Titel: Magasinet
Adresse: http://www.jazzspecial.dk/index.php?id=104


Zithromax 500mg for sale

The More Than Just a http://www.jazzspecial.dk/can-you-get-zithromax-over-the-counter/ Jab Māori Influenza Vaccination Programme (MIVP) evaluation was prepared for the Ministry of Health by Research Evaluation Consultancy Ltd to understand zithromax 500mg for sale the impact of the MIVP on Māori influenza rates and equity.The key evaluation questions were. did MIVP impact on the equity of Māori influenza vaccination rates?. what aspects of the MIVP implementation made a difference for Māori?.

what are insights that providers and DHBs can use to improve MIVP or similar programmes and services targeting zithromax 500mg for sale Māori?. what are the considerations for the Ministry to improve MIVP or similar programmes and services to increase equity for Māori?. Findings from the evaluation The evaluation found that overall, the MIVP made a valuable contribution to improving Māori influenza vaccination equity rates.

In summary zithromax 500mg for sale. NIR recorded significantly higher vaccination rates for Māori than in previous years influenza vaccination rates for Māori 65+ increased from 45.8 percent in 2019 to 59 percent in 2020. This is significant given the small improvement observed between 2015 and 2019 the overall influenza equity gap for Māori 65+ reduced in 2020 from -12.1 percent to -8.4 percent.

While some of this increase will be due to buy antibiotics, the evidence suggested the MIVP also contributed to this increase. In addition, the evaluation identified three core strategies that made a difference for zithromax 500mg for sale whānau Māori. mobilising services to go into the community taking a whānau-centred approach focusing on Māori workforce capability and capacity.

Additional strategies include the need to identify and respond to barriers while considering the local context and, being diverse in the design and delivery of services. The critical learning zithromax 500mg for sale was that the delivery of vaccinations is More than just a jab. The MIVP delivered the ingredients for system transformation – ingredients informing delivery of this year’s Māori Influenza and Measles Vaccination Programme.

For further information, contact. The MIMVP contributes to zithromax 500mg for sale He Korowai Oranga. The Māori Health Strategy that has the overall aim of ensuring Māori enjoy high standards of health and wellbeing.

Whakamaua. The Māori Health Plan 2020–2025 guides implementation by ensuring health and wellbeing outcomes improve for Māori whānau, hapū and iwi – and that persistent equity gaps for Māori are addressed.SummaryThis study provides a statistical analysis of the four data collection years (2012 to 2015) of the National Gambling Study in order to assess how changes in gambling risk levels are associated with changes over time in health, wellbeing, disability, deprivation and social connectedness.

Zithromax chlamydia side effects

Zithromax
Ceclor
Ocuflox
Principen
Floxin
Omnicef
Best price for generic
1000mg 30 tablet $119.95
500mg 30 tablet $149.95
0.3% 5ml 2 solution $14.00
500mg 360 tablet $452.30
200mg 120 tablet $205.95
300mg 10 tablet $49.95
Long term side effects
No
No
No
Yes
No
No
Possible side effects
1000mg 60 tablet $224.95
500mg 90 tablet $359.95
0.3% 5ml 4 solution $24.00
500mg 120 tablet $178.80
200mg 360 tablet $524.95
300mg 30 tablet $134.95
Does work at first time
500mg 9 tablet $17.99
250mg 30 tablet $119.95
0.3% 5ml 4 solution $24.00
500mg 60 tablet $110.40
300mg 120 tablet $235.95
300mg 180 tablet $599.95
Best place to buy
No
No
No
Yes
No
Yes
Daily dosage
Online
No
Yes
No
No
Online
How long does stay in your system
Ask your Doctor
Yes
You need consultation
Ask your Doctor
You need consultation
You need consultation

DeepMind today announced its partnership with the European Molecular Biology zithromax chlamydia side effects Laboratory (EMBL), Europe's flagship laboratory go to website for the life sciences, to make the most complete and accurate database yet of predicted protein structure models for the human proteome. This will cover all ~20,000 proteins expressed by the human genome, and the data will be freely and openly available to the scientific community. The database and artificial intelligence system provide structural biologists with powerful new tools for examining a protein's three-dimensional structure, and offer a treasure trove of data that could unlock future advances and herald a new era for AI-enabled biology.AlphaFold's recognition in December 2020 by the organisers of the Critical Assessment of protein Structure Prediction (CASP) benchmark as a solution to the 50-year-old grand challenge of protein structure prediction was a zithromax chlamydia side effects stunning breakthrough for the field. The AlphaFold Protein Structure Database builds on this innovation and the discoveries of generations of scientists, from the early pioneers of protein imaging and crystallography, to the thousands of prediction specialists and structural biologists who've spent years experimenting with proteins since. The database zithromax chlamydia side effects dramatically expands the accumulated knowledge of protein structures, more than doubling the number of high-accuracy human protein structures available to researchers.

Advancing the understanding of these building blocks of life, which underpin every biological process in every living thing, will help enable researchers across a huge variety of fields to accelerate their work.Last week, the methodology behind the latest highly innovative version of AlphaFold, the sophisticated AI system announced last December that powers these structure predictions, and its open source code were published in Nature. Today's announcement coincides with a second Nature paper that provides the fullest picture of proteins that make up the human proteome, and the release of 20 additional organisms that are important for biological research."Our goal at DeepMind has always been to build AI and then zithromax chlamydia side effects use it as a tool to help accelerate the pace of scientific discovery itself, thereby advancing our understanding of the world around us," said DeepMind Founder and CEO Demis Hassabis, PhD. "We used AlphaFold to generate the most complete and accurate picture of the human proteome. We believe this represents the most significant zithromax chlamydia side effects contribution AI has made to advancing scientific knowledge to date, and is a great illustration of the sorts of benefits AI can bring to society."AlphaFold is already helping scientists to accelerate discoveryThe ability to predict a protein's shape computationally from its amino acid sequence -- rather than determining it experimentally through years of painstaking, laborious and often costly techniques -- is already helping scientists to achieve in months what previously took years. advertisement "The AlphaFold database is a perfect example of the virtuous circle of open science," said EMBL Director General Edith Heard.

"AlphaFold was zithromax chlamydia side effects trained using data from public resources built by the scientific community so it makes sense for its predictions to be public. Sharing AlphaFold predictions openly and freely will empower researchers everywhere http://mydatinghangovers.com/2012/04/quote-of-the-week-3/ to gain new insights and drive discovery. I believe that AlphaFold is truly a revolution for the life sciences, just as genomics was several decades ago and I am very proud that EMBL has been able to zithromax chlamydia side effects help DeepMind in enabling open access to this remarkable resource."AlphaFold is already being used by partners such as the Drugs for Neglected Diseases Initiative (DNDi), which has advanced their research into life-saving cures for diseases that disproportionately affect the poorer parts of the world, and the Centre for Enzyme Innovation (CEI) is using AlphaFold to help engineer faster enzymes for recycling some of our most polluting single-use plastics. For those scientists who rely on experimental protein structure determination, AlphaFold's predictions have helped accelerate their research. For example, zithromax chlamydia side effects a team at the University of Colorado Boulder is finding promise in using AlphaFold predictions to study antibiotic resistance, while a group at the University of California San Francisco has used them to increase their understanding of antibiotics biology.The AlphaFold Protein Structure DatabaseThe AlphaFold Protein Structure Database builds on many contributions from the international scientific community, as well as AlphaFold's sophisticated algorithmic innovations and EMBL-EBI's decades of experience in sharing the world's biological data.

DeepMind and EMBL's European Bioinformatics Institute (EMBL-EBI) are providing access to AlphaFold's predictions so that others can use the system as a tool to enable and accelerate research and open up completely new avenues of scientific discovery."This will be one of the most important datasets since the mapping of the Human Genome," said EMBL Deputy Director General, and EMBL-EBI Director Ewan Birney. "Making AlphaFold predictions accessible to the international scientific community zithromax chlamydia side effects opens up so many new research avenues, from neglected diseases to new enzymes for biotechnology and everything in between. This is a great new scientific tool, which complements existing technologies, and will allow us to push the boundaries of our understanding of the world."In addition to the human proteome, the database launches with ~350,000 structures including 20 biologically-significant organisms such as E.coli, fruit fly, mouse, zebrafish, malaria parasite and tuberculosis bacteria. Research into these organisms has been the subject of zithromax chlamydia side effects countless research papers and numerous major breakthroughs. These structures will enable researchers across a huge variety of fields -- from neuroscience to medicine -- to accelerate their work.The future of AlphaFoldThe database and system will be periodically updated as we continue to invest in future improvements to AlphaFold, and over the coming months we plan to vastly expand the coverage to almost every sequenced protein known to science -- over 100 million structures covering most of the UniProt reference database.To learn more, please see the Nature papers [cited below] describing the full method and the human proteome, and read the Authors' Notes.

See the open-source code to AlphaFold if you want to view the workings of zithromax chlamydia side effects the system, and Colab notebook to run individual sequences. To explore the structures, visit EMBL-EBI's searchable database that is open and free to all..

DeepMind today announced its partnership with the European Molecular Biology Laboratory (EMBL), Europe's flagship laboratory for the life sciences, to make the most complete and accurate database yet of predicted visit our website protein structure models for zithromax 500mg for sale the human proteome. This will cover all ~20,000 proteins expressed by the human genome, and the data will be freely and openly available to the scientific community. The database and artificial intelligence system provide structural biologists with powerful new tools for examining a protein's three-dimensional structure, and offer a zithromax 500mg for sale treasure trove of data that could unlock future advances and herald a new era for AI-enabled biology.AlphaFold's recognition in December 2020 by the organisers of the Critical Assessment of protein Structure Prediction (CASP) benchmark as a solution to the 50-year-old grand challenge of protein structure prediction was a stunning breakthrough for the field.

The AlphaFold Protein Structure Database builds on this innovation and the discoveries of generations of scientists, from the early pioneers of protein imaging and crystallography, to the thousands of prediction specialists and structural biologists who've spent years experimenting with proteins since. The database dramatically expands the accumulated knowledge of protein structures, more than doubling the number of high-accuracy human zithromax 500mg for sale protein structures available to researchers. Advancing the understanding of these building blocks of life, which underpin every biological process in every living thing, will help enable researchers across a huge variety of fields to accelerate their work.Last week, the methodology behind the latest highly innovative version of AlphaFold, the sophisticated AI system announced last December that powers these structure predictions, and its open source code were published in Nature.

Today's announcement coincides with a second Nature paper that provides the fullest picture of proteins that make up the human proteome, and the release of 20 additional organisms that are important for zithromax 500mg for sale biological research."Our goal at DeepMind has always been to build AI and then use it as a tool to help accelerate the pace of scientific discovery itself, thereby advancing our understanding of the world around us," said DeepMind Founder and CEO Demis Hassabis, PhD. "We used AlphaFold to generate the most complete and accurate picture of the human proteome. We believe this represents the most significant zithromax 500mg for sale contribution AI has made to advancing scientific knowledge to date, and is a great illustration of the sorts of benefits AI can bring to society."AlphaFold is already helping scientists to accelerate discoveryThe ability to predict a protein's shape computationally from its amino acid sequence -- rather than determining it experimentally through years of painstaking, laborious and often costly techniques -- is already helping scientists to achieve in months what previously took years.

advertisement "The AlphaFold database is a perfect example of the virtuous circle of open science," said EMBL Director General Edith Heard. "AlphaFold was trained using data from public resources built by the scientific community so it makes sense zithromax 500mg for sale for its predictions to be public. Sharing AlphaFold predictions openly and http://fieldrecordings.tv/kjerstin-rossi freely will empower researchers everywhere to gain new insights and drive discovery.

I believe that AlphaFold is truly a revolution for the life sciences, just as genomics was several decades ago and I am very proud that EMBL has been able to help DeepMind in enabling open access to this remarkable resource."AlphaFold is already being used by partners such as the Drugs for Neglected Diseases Initiative (DNDi), which has advanced their research into life-saving cures for diseases that disproportionately affect the poorer parts of the world, and the zithromax 500mg for sale Centre for Enzyme Innovation (CEI) is using AlphaFold to help engineer faster enzymes for recycling some of our most polluting single-use plastics. For those scientists who rely on experimental protein structure determination, AlphaFold's predictions have helped accelerate their research. For example, a team at the University of Colorado Boulder is finding promise in using AlphaFold predictions to study antibiotic resistance, while a group at the University of California San Francisco has used them to increase their understanding of antibiotics biology.The AlphaFold Protein Structure DatabaseThe AlphaFold Protein Structure Database builds on many contributions from the international zithromax 500mg for sale scientific community, as well as AlphaFold's sophisticated algorithmic innovations and EMBL-EBI's decades of experience in sharing the world's biological data.

DeepMind and EMBL's European Bioinformatics Institute (EMBL-EBI) are providing access to AlphaFold's predictions so that others can use the system as a tool to enable and accelerate research and open up completely new avenues of scientific discovery."This will be one of the most important datasets since the mapping of the Human Genome," said EMBL Deputy Director General, and EMBL-EBI Director Ewan Birney. "Making AlphaFold predictions accessible to the international scientific community zithromax 500mg for sale opens up so many new research avenues, from neglected diseases to new enzymes for biotechnology and everything in between. This is a great new scientific tool, which complements existing technologies, and will allow us to push the boundaries of our understanding of the world."In addition to the human proteome, the database launches with ~350,000 structures including 20 biologically-significant organisms such as E.coli, fruit fly, mouse, zebrafish, malaria parasite and tuberculosis bacteria.

Research into these organisms has been the subject of countless research papers zithromax 500mg for sale and numerous major breakthroughs. These structures will enable researchers across a huge variety of fields -- from neuroscience to medicine -- to accelerate their work.The future of AlphaFoldThe database and system will be periodically updated as we continue to invest in future improvements to AlphaFold, and over the coming months we plan to vastly expand the coverage to almost every sequenced protein known to science -- over 100 million structures covering most of the UniProt reference database.To learn more, please see the Nature papers [cited below] describing the full method and the human proteome, and read the Authors' Notes. See the open-source code to AlphaFold if you want to view the workings of the system, and Colab notebook to run individual sequences zithromax 500mg for sale.

To explore the structures, visit EMBL-EBI's searchable database that is open and free to all..

What may interact with Zithromax?

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

How to take zithromax

NCHS Data Brief site No how to take zithromax. 286, September 2017PDF Versionpdf icon (374 KB)Anjel Vahratian, Ph.D.Key findingsData from the National Health Interview Survey, 2015Among those aged 40–59, perimenopausal women (56.0%) were more likely than postmenopausal (40.5%) and premenopausal (32.5%) women to sleep less than 7 hours, on average, in a 24-hour period.Postmenopausal women aged 40–59 were more likely than premenopausal women aged 40–59 to have trouble falling asleep (27.1% compared with 16.8%, respectively), and staying asleep (35.9% compared with 23.7%), four times or more in the past week.Postmenopausal women aged 40–59 (55.1%) were more likely than premenopausal women aged 40–59 (47.0%) to not wake up feeling well rested 4 days or more in the past week.Sleep duration and quality are important contributors to health and wellness. Insufficient sleep how to take zithromax is associated with an increased risk for chronic conditions such as cardiovascular disease (1) and diabetes (2). Women may be particularly vulnerable to sleep problems during times of reproductive hormonal change, such as after the menopausal transition. Menopause is “the permanent cessation how to take zithromax of menstruation that occurs after the loss of ovarian activity” (3).

This data brief describes sleep duration and sleep quality among nonpregnant women aged 40–59 by menopausal status. The age range selected for this analysis reflects the focus on midlife sleep health. In this analysis, 74.2% of women are how to take zithromax premenopausal, 3.7% are perimenopausal, and 22.1% are postmenopausal. Keywords. Insufficient sleep, menopause, National Health Interview Survey Perimenopausal women were more likely than premenopausal and postmenopausal women to sleep less than 7 hours, on average, in a 24-hour period.More than one in three nonpregnant women aged 40–59 how to take zithromax slept less than 7 hours, on average, in a 24-hour period (35.1%) (Figure 1).

Perimenopausal women were most likely to sleep less than 7 hours, on average, in a 24-hour period (56.0%), compared with 32.5% of premenopausal and 40.5% of postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to sleep less than 7 hours, on average, in a 24-hour period. Figure 1 how to take zithromax. Percentage of nonpregnant women aged 40–59 who slept less than 7 hours, on average, in a 24-hour period, by menopausal status. United States, 2015image icon1Significant quadratic trend by menopausal status (p how to take zithromax <.

0.05).NOTES. Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had how to take zithromax a menstrual cycle and their last menstrual cycle was 1 year ago or less. Women were premenopausal if they still had a menstrual cycle. Access data table for Figure 1pdf icon.SOURCE how to take zithromax.

NCHS, National Health Interview Survey, 2015. The percentage of women aged 40–59 who had trouble falling asleep four times or more in the past week varied by menopausal status.Nearly one in five nonpregnant women aged 40–59 how to take zithromax had trouble falling asleep four times or more in the past week (19.4%) (Figure 2). The percentage of women in this age group who had trouble falling asleep four times or more in the past week increased from 16.8% among premenopausal women to 24.7% among perimenopausal and 27.1% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to have trouble falling asleep four times or more in the past week. Figure 2 how to take zithromax.

Percentage of nonpregnant women aged 40–59 who had trouble falling asleep four times or more in the past week, by menopausal status. United States, how to take zithromax 2015image icon1Significant linear trend by menopausal status (p <. 0.05).NOTES. Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and how to take zithromax their last menstrual cycle was 1 year ago or less.

Women were premenopausal if they still had a menstrual cycle. Access data how to take zithromax table for Figure 2pdf icon.SOURCE. NCHS, National Health Interview Survey, 2015. The percentage of women aged 40–59 who had trouble staying asleep four times or more in the past week varied by menopausal status.More than one in four nonpregnant women aged 40–59 had how to take zithromax trouble staying asleep four times or more in the past week (26.7%) (Figure 3). The percentage of women aged 40–59 who had trouble staying asleep four times or more in the past week increased from 23.7% among premenopausal, to 30.8% among perimenopausal, and to 35.9% among postmenopausal women.

Postmenopausal women were significantly more likely than premenopausal women to have trouble staying asleep four times or more in the past week. Figure 3 how to take zithromax. Percentage of nonpregnant women aged 40–59 who had trouble staying asleep four times or more in the past week, by menopausal status. United States, 2015image icon1Significant linear trend by menopausal status (p < how to take zithromax. 0.05).NOTES.

Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their last menstrual cycle how to take zithromax was 1 year ago or less. Women were premenopausal if they still had a menstrual cycle. Access data table how to take zithromax for Figure 3pdf icon.SOURCE. NCHS, National Health Interview Survey, 2015.

The percentage of women aged 40–59 who did not wake up feeling well rested 4 days or more in the past week varied by menopausal status.Nearly one in two nonpregnant women aged 40–59 did not wake up feeling well rested 4 days or more in the past week (48.9%) (Figure 4). The percentage of women in this age group who did not wake up feeling well rested 4 days or more in the past week increased from 47.0% how to take zithromax among premenopausal women to 49.9% among perimenopausal and 55.1% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to not wake up feeling well rested 4 days or more in the past week. Figure 4 how to take zithromax. Percentage of nonpregnant women aged 40–59 who did not wake up feeling well rested 4 days or more in the past week, by menopausal status.

United States, 2015image icon1Significant linear trend by menopausal status (p <. 0.05).NOTES. Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their last menstrual cycle was 1 year ago or less. Women were premenopausal if they still had a menstrual cycle.

Access data table for Figure 4pdf icon.SOURCE. NCHS, National Health Interview Survey, 2015. SummaryThis report describes sleep duration and sleep quality among U.S. Nonpregnant women aged 40–59 by menopausal status. Perimenopausal women were most likely to sleep less than 7 hours, on average, in a 24-hour period compared with premenopausal and postmenopausal women.

In contrast, postmenopausal women were most likely to have poor-quality sleep. A greater percentage of postmenopausal women had frequent trouble falling asleep, staying asleep, and not waking well rested compared with premenopausal women. The percentage of perimenopausal women with poor-quality sleep was between the percentages for the other two groups in all three categories. Sleep duration changes with advancing age (4), but sleep duration and quality are also influenced by concurrent changes in women’s reproductive hormone levels (5). Because sleep is critical for optimal health and well-being (6), the findings in this report highlight areas for further research and targeted health promotion.

DefinitionsMenopausal status. A three-level categorical variable was created from a series of questions that asked women. 1) “How old were you when your periods or menstrual cycles started?. €. 2) “Do you still have periods or menstrual cycles?.

€. 3) “When did you have your last period or menstrual cycle?. €. And 4) “Have you ever had both ovaries removed, either as part of a hysterectomy or as one or more separate surgeries?. € Women were postmenopausal if they a) had gone without a menstrual cycle for more than 1 year or b) were in surgical menopause after the removal of their ovaries.

Women were perimenopausal if they a) no longer had a menstrual cycle and b) their last menstrual cycle was 1 year ago or less. Premenopausal women still had a menstrual cycle.Not waking feeling well rested. Determined by respondents who answered 3 days or less on the questionnaire item asking, “In the past week, on how many days did you wake up feeling well rested?. €Short sleep duration. Determined by respondents who answered 6 hours or less on the questionnaire item asking, “On average, how many hours of sleep do you get in a 24-hour period?.

€Trouble falling asleep. Determined by respondents who answered four times or more on the questionnaire item asking, “In the past week, how many times did you have trouble falling asleep?. €Trouble staying asleep. Determined by respondents who answered four times or more on the questionnaire item asking, “In the past week, how many times did you have trouble staying asleep?. € Data source and methodsData from the 2015 National Health Interview Survey (NHIS) were used for this analysis.

NHIS is a multipurpose health survey conducted continuously throughout the year by the National Center for Health Statistics. Interviews are conducted in person in respondents’ homes, but follow-ups to complete interviews may be conducted over the telephone. Data for this analysis came from the Sample Adult core and cancer supplement sections of the 2015 NHIS. For more information about NHIS, including the questionnaire, visit the NHIS website.All analyses used weights to produce national estimates. Estimates on sleep duration and quality in this report are nationally representative of the civilian, noninstitutionalized nonpregnant female population aged 40–59 living in households across the United States.

The sample design is described in more detail elsewhere (7). Point estimates and their estimated variances were calculated using SUDAAN software (8) to account for the complex sample design of NHIS. Linear and quadratic trend tests of the estimated proportions across menopausal status were tested in SUDAAN via PROC DESCRIPT using the POLY option. Differences between percentages were evaluated using two-sided significance tests at the 0.05 level. About the authorAnjel Vahratian is with the National Center for Health Statistics, Division of Health Interview Statistics.

The author gratefully acknowledges the assistance of Lindsey Black in the preparation of this report. ReferencesFord ES. Habitual sleep duration and predicted 10-year cardiovascular risk using the pooled cohort risk equations among US adults. J Am Heart Assoc 3(6):e001454. 2014.Ford ES, Wheaton AG, Chapman DP, Li C, Perry GS, Croft JB.

Associations between self-reported sleep duration and sleeping disorder with concentrations of fasting and 2-h glucose, insulin, and glycosylated hemoglobin among adults without diagnosed diabetes. J Diabetes 6(4):338–50. 2014.American College of Obstetrics and Gynecology. ACOG Practice Bulletin No. 141.

Management of menopausal symptoms. Obstet Gynecol 123(1):202–16. 2014.Black LI, Nugent CN, Adams PF. Tables of adult health behaviors, sleep. National Health Interview Survey, 2011–2014pdf icon.

2016.Santoro N. Perimenopause. From research to practice. J Women’s Health (Larchmt) 25(4):332–9. 2016.Watson NF, Badr MS, Belenky G, Bliwise DL, Buxton OM, Buysse D, et al.

Recommended amount of sleep for a healthy adult. A joint consensus statement of the American Academy of Sleep Medicine and Sleep Research Society. J Clin Sleep Med 11(6):591–2. 2015.Parsons VL, Moriarity C, Jonas K, et al. Design and estimation for the National Health Interview Survey, 2006–2015.

National Center for Health Statistics. Vital Health Stat 2(165). 2014.RTI International. SUDAAN (Release 11.0.0) [computer software]. 2012.

Suggested citationVahratian A. Sleep duration and quality among women aged 40–59, by menopausal status. NCHS data brief, no 286. Hyattsville, MD. National Center for Health Statistics.

2017.Copyright informationAll material appearing in this report is in the public domain and may be reproduced or copied without permission. Citation as to source, however, is appreciated.National Center for Health StatisticsCharles J. Rothwell, M.S., M.B.A., DirectorJennifer H. Madans, Ph.D., Associate Director for ScienceDivision of Health Interview StatisticsMarcie L. Cynamon, DirectorStephen J.

Blumberg, Ph.D., Associate Director for Science.

NCHS Data zithromax 500mg for sale useful site Brief No. 286, September 2017PDF Versionpdf icon (374 KB)Anjel Vahratian, Ph.D.Key findingsData from the National Health Interview Survey, 2015Among those aged 40–59, perimenopausal women (56.0%) were more likely than postmenopausal (40.5%) and premenopausal (32.5%) women to sleep less than 7 hours, on average, in a 24-hour period.Postmenopausal women aged 40–59 were more likely than premenopausal women aged 40–59 to have trouble falling asleep (27.1% compared with 16.8%, respectively), and staying asleep (35.9% compared with 23.7%), four times or more in the past week.Postmenopausal women aged 40–59 (55.1%) were more likely than premenopausal women aged 40–59 (47.0%) to not wake up feeling well rested 4 days or more in the past week.Sleep duration and quality are important contributors to health and wellness. Insufficient sleep is associated with an increased risk for chronic conditions such as cardiovascular zithromax 500mg for sale disease (1) and diabetes (2).

Women may be particularly vulnerable to sleep problems during times of reproductive hormonal change, such as after the menopausal transition. Menopause is “the permanent cessation of menstruation that occurs after the loss of ovarian activity” (3) zithromax 500mg for sale. This data brief describes sleep duration and sleep quality among nonpregnant women aged 40–59 by menopausal status.

The age range selected for this analysis reflects the focus on midlife sleep health. In this analysis, 74.2% zithromax 500mg for sale of women are premenopausal, 3.7% are perimenopausal, and 22.1% are postmenopausal. Keywords.

Insufficient sleep, menopause, National Health Interview Survey Perimenopausal women were more likely than premenopausal and postmenopausal women to sleep less than 7 zithromax 500mg for sale hours, on average, in a 24-hour period.More than one in three nonpregnant women aged 40–59 slept less than 7 hours, on average, in a 24-hour period (35.1%) (Figure 1). Perimenopausal women were most likely to sleep less than 7 hours, on average, in a 24-hour period (56.0%), compared with 32.5% of premenopausal and 40.5% of postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to sleep less than 7 hours, on average, in a 24-hour period.

Figure 1 zithromax 500mg for sale. Percentage of nonpregnant women aged 40–59 who slept less than 7 hours, on average, in a 24-hour period, by menopausal status. United States, zithromax 500mg for sale 2015image icon1Significant quadratic trend by menopausal status (p <.

0.05).NOTES. Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their last menstrual cycle zithromax 500mg for sale was 1 year ago or less.

Women were premenopausal if they still had a menstrual cycle. Access data table for Figure zithromax 500mg for sale 1pdf icon.SOURCE. NCHS, National Health Interview Survey, 2015.

The percentage of women zithromax 500mg for sale aged 40–59 who had trouble falling asleep four times or more in the past week varied by menopausal status.Nearly one in five nonpregnant women aged 40–59 had trouble falling asleep four times or more in the past week (19.4%) (Figure 2). The percentage of women in this age group who had trouble falling asleep four times or more in the past week increased from 16.8% among premenopausal women to 24.7% among perimenopausal and 27.1% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to have trouble falling asleep four times or more in the past week.

Figure 2 zithromax 500mg for sale. Percentage of nonpregnant women aged 40–59 who had trouble falling asleep four times or more in the past week, by menopausal status. United States, 2015image icon1Significant linear zithromax 500mg for sale trend by menopausal status (p <.

0.05).NOTES. Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were zithromax 500mg for sale perimenopausal if they no longer had a menstrual cycle and their last menstrual cycle was 1 year ago or less.

Women were premenopausal if they still had a menstrual cycle. Access data zithromax 500mg for sale table for Figure 2pdf icon.SOURCE. NCHS, National Health Interview Survey, 2015.

The percentage of zithromax 500mg for sale women aged 40–59 who had trouble staying asleep four times or more in the past week varied by menopausal status.More than one in four nonpregnant women aged 40–59 had trouble staying asleep four times or more in the past week (26.7%) (Figure 3). The percentage of women aged 40–59 who had trouble staying asleep four times or more in the past week increased from 23.7% among premenopausal, to 30.8% among perimenopausal, and to 35.9% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to have trouble staying asleep four times or more in the past week.

Figure 3 zithromax 500mg for sale. Percentage of nonpregnant women aged 40–59 who had trouble staying asleep four times or more in the past week, by menopausal status. United States, 2015image icon1Significant linear trend by zithromax 500mg for sale menopausal status (p <.

0.05).NOTES. Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were zithromax 500mg for sale perimenopausal if they no longer had a menstrual cycle and their last menstrual cycle was 1 year ago or less.

Women were premenopausal if they still had a menstrual cycle. Access data table for Figure zithromax 500mg for sale 3pdf icon.SOURCE. NCHS, National Health Interview Survey, 2015.

The percentage of women aged 40–59 who did not wake up feeling well rested 4 days or more in the past week varied by menopausal status.Nearly one in two nonpregnant women aged 40–59 did not wake up feeling well rested 4 days or more in the past week (48.9%) (Figure 4). The percentage of women in this age group who did not zithromax 500mg for sale wake up feeling well rested 4 days or more in the past week increased from 47.0% among premenopausal women to 49.9% among perimenopausal and 55.1% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to not wake up feeling well rested 4 days or more in the past week.

Figure 4 zithromax 500mg for sale. Percentage of nonpregnant women aged 40–59 who did not wake up feeling well rested 4 days or more in the past week, by menopausal status. United States, 2015image icon1Significant linear trend by menopausal status (p <.

0.05).NOTES. Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their last menstrual cycle was 1 year ago or less.

Women were premenopausal if they still had a menstrual cycle. Access data table for Figure 4pdf icon.SOURCE. NCHS, National Health Interview Survey, 2015.

SummaryThis report describes sleep duration and sleep quality among U.S. Nonpregnant women aged 40–59 by menopausal status. Perimenopausal women were most likely to sleep less than 7 hours, on average, in a 24-hour period compared with premenopausal and postmenopausal women.

In contrast, postmenopausal women were most likely to have poor-quality sleep. A greater percentage of postmenopausal women had frequent trouble falling asleep, staying asleep, and not waking well rested compared with premenopausal women. The percentage of perimenopausal women with poor-quality sleep was between the percentages for the other two groups in all three categories.

Sleep duration changes with advancing age (4), but sleep duration and quality are also influenced by concurrent changes in women’s reproductive hormone levels (5). Because sleep is critical for optimal health and well-being (6), the findings in this report highlight areas for further research and targeted health promotion. DefinitionsMenopausal status.

A three-level categorical variable was created from a series of questions that asked women. 1) “How old were you when your periods or menstrual cycles started?. €.

2) “Do you still have periods or menstrual cycles?. €. 3) “When did you have your last period or menstrual cycle?.

€. And 4) “Have you ever had both ovaries removed, either as part of a hysterectomy or as one or more separate surgeries?. € Women were postmenopausal if they a) had gone without a menstrual cycle for more than 1 year or b) were in surgical menopause after the removal of their ovaries.

Women were perimenopausal if they a) no longer had a menstrual cycle and b) their last menstrual cycle was 1 year ago or less. Premenopausal women still had a menstrual cycle.Not waking feeling well rested. Determined by respondents who answered 3 days or less on the questionnaire item asking, “In the past week, on how many days did you wake up feeling well rested?.

€Short sleep duration. Determined by respondents who answered 6 hours or less on the questionnaire item asking, “On average, how many hours of sleep do you get in a 24-hour period?. €Trouble falling asleep.

Determined by respondents who answered four times or more on the questionnaire item asking, “In the past week, how many times did you have trouble falling asleep?. €Trouble staying asleep. Determined by respondents who answered four times or more on the questionnaire item asking, “In the past week, how many times did you have trouble staying asleep?.

€ Data source and methodsData from the 2015 National Health Interview Survey (NHIS) were used for this analysis. NHIS is a multipurpose health survey conducted continuously throughout the year by the National Center for Health Statistics. Interviews are conducted in person in respondents’ homes, but follow-ups to complete interviews may be conducted over the telephone.

Data for this analysis came from the Sample Adult core and cancer supplement sections of the 2015 NHIS. For more information about NHIS, including the questionnaire, visit the NHIS website.All analyses used weights to produce national estimates. Estimates on sleep duration and quality in this report are nationally representative of the civilian, noninstitutionalized nonpregnant female population aged 40–59 living in households across the United States.

The sample design is described in more detail elsewhere (7). Point estimates and their estimated variances were calculated using SUDAAN software (8) to account for the complex sample design of NHIS. Linear and quadratic trend tests of the estimated proportions across menopausal status were tested in SUDAAN via PROC DESCRIPT using the POLY option.

Differences between percentages were evaluated using two-sided significance tests at the 0.05 level. About the authorAnjel Vahratian is with the National Center for Health Statistics, Division of Health Interview Statistics. The author gratefully acknowledges the assistance of Lindsey Black in the preparation of this report.

ReferencesFord ES. Habitual sleep duration and predicted 10-year cardiovascular risk using the pooled cohort risk equations among US adults. J Am Heart Assoc 3(6):e001454.

2014.Ford ES, Wheaton AG, Chapman DP, Li C, Perry GS, Croft JB. Associations between self-reported sleep duration and sleeping disorder with concentrations of fasting and 2-h glucose, insulin, and glycosylated hemoglobin among adults without diagnosed diabetes. J Diabetes 6(4):338–50.

2014.American College of Obstetrics and Gynecology. ACOG Practice Bulletin No. 141.

Management of menopausal symptoms. Obstet Gynecol 123(1):202–16. 2014.Black LI, Nugent CN, Adams PF.

Tables of adult health behaviors, sleep. National Health Interview Survey, 2011–2014pdf icon. 2016.Santoro N.

Perimenopause. From research to practice. J Women’s Health (Larchmt) 25(4):332–9.

2016.Watson NF, Badr MS, Belenky G, Bliwise DL, Buxton OM, Buysse D, et al. Recommended amount of sleep for a healthy adult. A joint consensus statement of the American Academy of Sleep Medicine and Sleep Research Society.

J Clin Sleep Med 11(6):591–2. 2015.Parsons VL, Moriarity C, Jonas K, et al. Design and estimation for the National Health Interview Survey, 2006–2015.

National Center for Health Statistics. Vital Health Stat 2(165). 2014.RTI International.

SUDAAN (Release 11.0.0) [computer software]. 2012. Suggested citationVahratian A.

Sleep duration and quality among women aged 40–59, by menopausal status. NCHS data brief, no 286. Hyattsville, MD.

National Center for Health Statistics. 2017.Copyright informationAll material appearing in this report is in the public domain and may be reproduced or copied without permission. Citation as to source, however, is appreciated.National Center for Health StatisticsCharles J.

Rothwell, M.S., M.B.A., DirectorJennifer H. Madans, Ph.D., Associate Director for ScienceDivision of Health Interview StatisticsMarcie L. Cynamon, DirectorStephen J.

Blumberg, Ph.D., Associate Director for Science.

Zithromax pfizer

That they are ‘following the science’ has become the watchword of many politicians during the present zithromax, especially when imposing or prolonging lockdowns zithromax pfizer or other liberty-restricting regulations. The scientists who advise politicians however are usually careful to add that the decision what to restrict and when is ultimately a political one. In science, as in medical practice, there is a delicate balance to be maintained between confidence in zithromax pfizer the best available information, and the necessary caveat that the assumptions and calculations on which that information is based are subject to further scientific enquiry.

For politicians and the public, moreover, as for patients, whether those informing them are judged to be trustworthy is a necessary consideration, a judgement determined by a variety of personal and political contingencies and circumstances. Ethics, by contrast, unable to appeal to scientific consensus (however revisable) or political authority (however reversible), let alone a confidence-inspiring bedside manner, must rest the case for its essentially contestable assumptions and arguments being judged trustworthy, on its willingness to admit all reasoned voices (including zithromax pfizer occasionally those that question reason itself) to a conversation that is potentially unending, but in the process often highly enlightening.That conversation is contributed to in this issue of the Journal by several reasoned voices, mostly on ethical aspects of the buy antibiotics zithromax. Relevant to issues on which politicians claim to be ‘following the science’, but also raising fundamental ethical questions, is this month’s feature article.

In Ethics of Selective Restriction of Liberty in a zithromax,1 Cameron and colleagues consider ‘if and when it may be ethically acceptable to impose selective liberty-restricting measures in zithromax pfizer order to reduce the negative impacts of a zithromax by preventing particularly vulnerable groups [for example, the elderly in buy antibiotics] of the community from contracting the disease’ [and thereby, for example, increasing the disease burden]. €˜Preventing harm to others when this is least restrictive option’, they argue, ‘fails to adequately accommodate the complexity of the issue or the difficult choices that must be made’. Instead, they propose ‘a dualist consequentialist approach, weighing utility at both a population and individual level’, thereby taking account of ‘two relevant values to be promoted or maximised.

Well-being and liberty’, as well as the value of equality, zithromax pfizer ‘protected through the application of an additional proportionality test’. The authors then propose an algorithm to take account of the different values and variables which need to be weighed up. They conclude zithromax pfizer.

€˜Selective restriction of liberty is justified when the problem is grave, the expected utility of the liberty restriction is high and significantly greater than the alternatives and the costs of the liberty restrictions are relatively small both at a population and individual level… Discrimination can be justified under these conditions when it is proportionate and limited to a very specific public health challenge’. The arguments and conclusions of the feature article are discussed in the two Commentaries2 3.In buy antibiotics controlled human zithromax pfizer studies. Worries about local community impact and demands for local engagement,4 Eyal and Lee review recent arguments which express ‘concern about undue usage of local residents’ direly needed scarce resources at a time of great need and even about their unintended ’ – and hence a requirement for ‘either avoiding controlled trials (CHIs) or engaging local communities before conducting CHIs’.

They then examine and compare the evidence of such adverse (and some potentially positive) effects of CHIs with those of conventional field trials and argue that ‘both small and large negative effects on struggling communities are likelier in field trials than in CHIs’. €˜Whether or not local community engagement is necessary for urgent treatment studies in a zithromax’, they conclude, ‘the case for its engagement is stronger prior to zithromax pfizer field trials than prior to controlled human studies’.In Payment of buy antibiotics challenge trials. Underpayment is a bigger worry than overpayment,5 Blumenthal Barby and Ubel consider the impact not on communities but on individuals, and specifically on ‘how much people should be paid for their participation in buy antibiotics challenge trials’.

Noting recent worries about ‘incentivising people with large amounts of money’, they argue that ‘higher payment that accounts for participant time, and for pains, burdens and willingness to take risks’ constitutes neither ‘undue inducement’ (for which the remedy is strengthening informed consent processes and minimising risks) nor ‘unjust inducement’ of individuals zithromax pfizer from ‘already disadvantaged groups’. Evidence of recruitment to challenge trials worldwide suggests, on the contrary, that participants ‘come from all walks of life’. Nor are these authors convinced that ‘offering substantial payment waters down zithromax pfizer the auistic motives of those involved’.

€˜auism and payment’ they argue, ‘frequently coexist. Teachers, physicians, public defenders – they all dedicate their lives to helping people. But few do without compensation.’In zithromax pfizer Money is not everything.

Experimental evidence that payments do not increase willingness to be vaccinated against buy antibiotics6, Sprengholz and colleagues report on an ‘experiment investigating the impact of payments and the communication of individual and prosocial benefits of high vaccination rates on vaccination intentions.’ In November 2020 over 1,000 ‘individuals from a German non-probabilistic sample’ were asked about their intentions. The ‘results revealed that none of these interventions or their combinations increased willingness to be vaccinated shortly after a treatment becomes available.’ Given that this experiment was conducted before treatments became available and only in Germany, the authors suggest that these results ‘should be generalised with caution’, but that ‘decision makers’ also ‘should be cautious about introducing monetary incentives and instead focus on interventions that increase confidence in treatment safety first’.In Voluntary buy antibiotics zithromax pfizer vaccination of children. A social responsibility,7 Brusa and Barilan observe a zithromax paradox.

€˜while we rely on low quality evidence when harming children by school deprivation and social distancing, zithromax pfizer we insist on a remarkably high level of safety data to benefit them with vaccination’. The consequent exclusion of children from vaccination, they argue, is unjust and not in ‘the best interest of the child as a holistic value encompassing physical, psychological, social and spiritual well-being’, something which ‘there is no scientific method for evaluating’. Society, rather, ‘has the political responsibility to factor in the overall impact of the zithromax on children’s well-being’ and the ‘ultimate choice is a matter of paediatric informed consent.

Moreover, jurisdictions that permit non-participation in established childhood vaccination programmes should also permit zithromax pfizer choice of treatments outside of the approved programmes.’ The authors conclude by outlining ‘a prudent and ethical scheme for gradual incorporation of minors in vaccination programmes that includes a rigorous postvaccination monitoring.’In Challenging misconceptions about clinical ethics support during buy antibiotics and beyond. A legal update and future considerations,8 Brierley, Archard and Cave note that the ‘buy antibiotics zithromax has highlighted the lack of formal ethics processes in most UK hospitals… at a time of unprecedented need for such support’. Unlike Research Ethics Committees (RECs), Clinical Ethics Committees (CECs) in the UK have neither any ‘well-funded governing authority,’ nor the decision-making capacity over clinical zithromax pfizer questions which RECs have over research.

In 2001 the ‘three central functions of CECs’ were described as ‘education, policy development and case review’. But more recently ‘the role of some was expanding’ and in 2020 the UK General Medical Council ‘mentioned for the first time the value zithromax pfizer in seeking advice from CECs to resolve disagreements’. Misunderstanding of CEC’s role however began to arise when some courts appeared to ‘perceive CECs as an alternative dispute resolution mechanism’ rather than as providing ‘ethics support, with treatment decisions remaining with the clinical team and those providing their consent.’ The future role of CECs, as well as the nature of patient involvement in them, the authors conclude, will depend on a choice between the ‘flexibility and diversity of the current ethical support system’ and ‘greater standardisation, governance and funding’.Important ethical issues not directly related to buy antibiotics are discussed in this issue’s remaining papers.

In Institutional conflict of interest. Attempting to crack the deferiprone mystery,9 Schafer identifies, places in zithromax pfizer historical context, and analyses ethical issues raised by the ‘ mystery’ of why between 2009 and 2015 ‘a third of patients with thalassaemia in Canada’s largest hospital were switched from first-line licensed drugs to regimens of deferiprone, an unlicensed drug of unproven safety and efficacy’. He then considers ‘institutional conflict of interest’ as ‘a possible explanatory hypothesis’.The perils of a broad approach to public interest in health data research.

A response to Ballantyne and Schaefer10 by Grewal and Newson and Ballantyne and Schaefer’s response In defence of a broad approach to public interest in health data research11 debate legal and philosophical aspects of whether ‘public interest’, and how narrowly or broadly this is conceived, is the most appropriate justification of consent waivers for secondary research on health information.In Do we really know how many clinical trials are conducted ethically,12 Yarborough presents evidence in support of the argument that 'research ethics committee practices zithromax pfizer need to be strengthed' and then suggests 'initial steps we could take to strengthen them'.Finally, and returning to how ‘science’ is perceived, in Lessons from Frankenstein 200 years on. Brain organoids, chimaeras and other ‘monsters’13, Koplin and Massie make a crucial observation. In ‘bioethical debates, Frankenstein is usually evoked zithromax pfizer as a warning against interfering with the natural order or “playing God”’.

But in the novel, Frankenstein’s ‘most serious moral error’ was made ‘not when he decided to pursue his scientific breakthrough (one which might, after all, have helped save lives), but when he failed to consider his moral obligations to the creature he created.’ Today, when, like Frankenstein, ‘modern scientists are creating and manipulating life in unprecedented ways’ such as brain organoids and chimaeras, Koplin and Massie argue, ‘two key insights’ can be drawn from Mary Shelley’s 1818 novel. First, ‘if we have created an entity in order to experiment on it’ we need ‘to extend much consideration to its interests and preferences, not least because ‘scientists cannot always rely on existing regulations to anticipate moral issues associated with the creation of new kinds of organisms’. And second zithromax pfizer.

€˜we should be wary of any prejudice we feel towards beings that look and behave differently from us’ and should ‘interrogate any knee-jerk intuitions we have about the moral status of unfamiliar kinds of beings.’Ethics statementsPatient consent for publicationNot required.IntroductionThalassaemia is an inherited anaemia that exerts an enormous disease burden worldwide.1 Along with sickle cell disease, it is one of the two most common single gene disorders. Indeed, ‘the alpha and beta thalassaemias are the most common inherited single-gene disorders in the world…’2A newly published study by Olivieri, Sabouhanian and Gallie3 analyses and assesses the comparative efficacy and safety zithromax pfizer profile of two drugs. Deferiprone (Ferriprox.

Apotex) and zithromax pfizer deferasirox (Exfade. Novartis). Both of these ‘iron-chelating’ drugs remove (‘chelate’) iron deposited, as a result of transfusions, in the tissues of patients with thalassaemia.The present-day first-line chelator, deferasirox, was zithromax pfizer licensed by the US FDA in 2005.

The evidence for its safety and effectiveness was judged to be substantial and, accordingly, the FDA licensed it as a first-line agent. The prime advantage of deferasirox, in comparison to deferoxamine, an older drug that was formerly the gold standard of iron-chelating therapy for thalassaemia, is that deferasirox is orally active (that is, taken in pill form), while deferoxamine is more burdensome for patients because it has to be taken parenterally (that is, via injection). Deferiprone, like deferasirox, is taken zithromax pfizer orally but has not been licensed anywhere as first-line treatment.

The FDA withheld market approval for deferiprone because there were/are no controlled trials demonstrating direct treatment benefit. Although the FDA did eventually approve deferiprone, in 2011, it gave approval only as a last-resort treatment for zithromax pfizer those patients in whom other chelators had been tried unsuccessfully.1The data presented by Olivieri et al in their PLOS ONE paper indicate that the drugs differ significantly with respect to their effectiveness and safety. This commentary explores some of the ethical issues raised by the PLOS data.Historical contextIn order to understand properly the significance of the PLOS ONE Study some historical context will be helpful.

What follows is a brief sketch of that context.2In 1993 Dr Nancy Olivieri, a specialist in blood diseases at Toronto’s Hospital for Sick Children (HSC or ‘Sick Kids’) and Professor of Pediatrics and Medicine at the University of Toronto (U of zithromax pfizer T), signed a contract with Apotex, a generic drug company, to continue studies of deferiprone, the early promise of which she had already reported in the literature. Olivieri’s thalassaemia research was initially supported by the Medical Research Council of Canada, but now she sought additional funding to extend her clinical trials. Apotex contributed this additional funding, thereby obtaining worldwide patents on the still-experimental drug.Despite early promise, by 1996 Olivieri’s research began to indicate that deferiprone might be inadequately effective in many patients, posing risks of potentially serious harm.

Olivieri communicated to Apotex her intention to inform patients of this unexpected risk and she proposed also to amend the zithromax pfizer study’s consent forms. She wished to continue amended studies of the drug, and to publish her findings.Apotex responded to Olivieri that they disagreed with her interpretation of the data and the company’s CEO threatened her with ‘all legal remedies’ should she inform patients or publish her findings. In issuing these threats, Apotex relied on a confidentiality clause in a legal contract zithromax pfizer Olivieri had signed with Apotex in 1993.

This contract prohibited disclosure ‘to any third party’ without the express permission of Apotex.3Despite the objections raised by Apotex, Olivieri saw it as her professional duty to disclose her findings. The Research Ethics Board (REB) of Sick Kids Hospital reached the zithromax pfizer same conclusion. In compliance with instructions from the Hospital’s REB, Olivieri duly informed both her patients and the regulatory authorities.When Olivieri later identified a second risk—that liver damage progressed during deferiprone exposure—Apotex issued additional legal warnings.

Olivieri nevertheless proceeded to inform her patients of this additional risk and published her findings.Since patient safety, research integrity and academic freedom were all at stake in this dispute, Olivieri appealed for assistance, repeatedly, to senior officials at both the U of T and Sick Kids Hospital. Neither the University nor the Hospital provided the support she requested zithromax pfizer. In the words of the Report of the Committee of Inquiry on the Case Involving Dr Nancy Olivieri, the HSC, the U of T, and Apotex Inc4:The HSC and the U of T did not provide effective support either for Dr Olivieri and her rights, or for the principles of research and clinical ethics, and of academic freedom, during the first two and a half years of this controversy.Instead, both the University and the Hospital ‘took actions that were harmful to Dr.

Olivieri’s interests and professional reputation and disrupted her work’.4 The harmful actions included firing Olivieri from her position as Director of the Hemoglobinopathy Program at Sick Kids Hospital and referring her zithromax pfizer for discipline to the College of Physicians and Surgeons of Ontario (CPSO).Only later did it emerge that, during this period of conflict, the U of T was negotiating with Apotex for a major donation towards building the University’s proposed new molecular medicine building. Some speculated that the University’s failure to support Olivieri may not have been unconnected from its desire to appease a wealthy corporate donor. This speculation was reinforced when it was discovered that the then President of the University, Robert Prichard, had secretly lobbied the government of Canada for changes in drug patent law, changes that would favour Apotex.4Apotex proceeded zithromax pfizer to sue Olivieri for defaming both the company and their drug.

She sued the company for defaming her.The Canadian Association of University Teachers (CAUT) and the U of T Faculty Association (UTFA), to whom Olivieri appealed for assistance after being rebuffed by the U of T and HSC, viewed the underlying issue as one of academic freedom. Both CAUT and UTFA provided support, including legal advice, to Olivieri.Thus began what is widely acknowledged to be the greatest scandal in Canadian academic history. Commissions of inquiry, books and articles (both zithromax pfizer scholarly and popular) proliferated, not to mention newspaper and television stories.

John le Carré’s novel The Constant Gardener and the Hollywood movie based on the book both appeared to draw heavily on the Olivieri-Apotex scandal. An inquiry into the dispute commissioned by Sick Kids Hospital (the Naimark Inquiry)5 zithromax pfizer absolved Apotex of wrongdoing but suggested that Olivieri was seriously at fault.5 She was charged with research misconduct and failures of patient care and was referred first to the Hospital’s Medical Advisory Council and subsequently to the disciplinary committee of the CPSO. Unsurprisingly, these widely publicised referrals were prejudicial to Olivieri’s reputation.The CAUT then commissioned an independent inquiry.6 The 540-page CAUT report on the Olivieri/Apotex affair4 gave a markedly different account of the scandal from that offered by the hospital-commissioned Naimark Report.

A few excerpts from the CAUT report will convey its central findings:Apotex issued more legal warnings zithromax pfizer to deter Dr. Olivieri from communicating this second unexpected risk of L1 (deferiprone) to anyone. However, she was legally and ethically obligated to communicate the risk to those taking or prescribing the drug as there were potential safety implications for patients, and she fulfilled these obligations despite the legal warnings.Apotex acted against the public interest in issuing legal warnings to Dr.

Olivieri to deter her from zithromax pfizer communicating about risks of L1.Apotex’s legal warnings violated Dr. Olivieri’s academic freedom.7Shortly after the CAUT report absolved Olivieri of misconduct, the CPSO published the findings of its inquiry. The CPSO report exonerated Olivieri of all misconduct zithromax pfizer charges.

Indeed, their report concluded that her conduct had been ‘commendable’.6 This favourable verdict did not, however, bring an end to litigation.In 2004, 8 years after the first legal threats had been issued, Apotex signed a mediated settlement with Olivieri. Nevertheless, litigation zithromax pfizer continued for another 10 years. Those unfamiliar with the workings of the law may wonder how it is possible for litigation to continue for such a long period after a mediated settlement.

Litigation continued because Apotex alleged that Olivieri had violated their agreement. Olivieri insisted that she was in compliance with the terms zithromax pfizer of the settlement. Court decisions were appealed by both parties.

A final settlement was not reached between Olivieri zithromax pfizer and Apotex until 2014.8 Shades of Jarndyce v. Jarndyce in Charles Dicken’s novel Bleak House.The HSC settled its dispute with Olivieri in 2006 and, although her research programme at the Hospital continued, she ceased to provide clinical care to HSC patients. From 1997 to 2009, Olivieri served as zithromax pfizer Director of the University Health Network (UHN) Hemoglobinopathy Program.

She continued, as she had since 1997, to assist in the clinical care of UHN patients with thalassaemia and to enrol them in her research studies. In March 2009, however, Olivieri was dismissed by zithromax pfizer UHN from her position as Director. No reason was given for her dismissal (Personal communication.

Olivieri, 2019).The PLOS ONE Study data3 show that, after Olivieri’s dismissal from her position as Director, the UHN thalassaemia Clinic began almost immediately to switch patients to (unlicensed) deferiprone. Olivieri has described how her UHN research work, from this time forward, was marginalised (https://inthepatientsinterest.org/wp-content/uploads/2019/12/2018-12-20-GallieOlivieri-to-SmithHodges.pdf).Meanwhile, Freedom of Information (FOI) requests filed by Olivieri zithromax pfizer after her dismissal revealed that Apotex was supplying unrestricted educational grants to UHN’s thalassaemia programme as well as providing research support. The FOI requests filed by Olivieri also revealed that Apotex was strategising with the programme’s new director about how best to obtain licensing for deferiprone from the regulator (Health Canada).9 With this dramatic background as historical context, we commence our discussion of the ethical implications of the PLOS ONE paper.Findings of the PLOS ONE paperIn their 2019 PLOS ONE study Olivieri et al conclude, based on a retrospective review of patient data at Toronto’s UHN, that deferiprone is inadequately effective and associated with serious toxicity.

Their review also confirms that, by contrast, deferasirox is effective and associated with relatively few adverse effects.3Olivieri et al report that ‘[b]etween 2009 and 2015, a third of patients transfused zithromax pfizer and managed in Canada’s largest transfusion programme were switched from first-line, licensed drugs to regimens of unlicensed deferiprone’.3 This finding raises the ethically troubling question. How and why were so many locally transfused patients at UHN treated over such a long time period with an unlicensed drug of unproven safety and efficacy?. This zithromax pfizer ethical concern is followed immediately by another related concern.

Why did the UHN thalassaemia programme continue to treat large numbers of its patients with deferiprone—despite ongoing evidence of inadequate effectiveness and serious (and often irreversible) adverse effects?. 3To recapitulate. The PLOS ONE paper demonstrates that a substantial proportion of zithromax pfizer UHN patients with thalassaemia was switched, between the years 2009 and 2015, from first-line licensed therapies (deferasirox or deferoxamine) to deferiprone.

During this entire period, deferiprone was unlicensed in Canada. To this day in every jurisdiction in which deferiprone has been licensed zithromax pfizer it has been licensed only as ‘last resort’ therapy. The ethical concern is to explain and to explore possible justifications for how and why so many patients at one particular thalassaemia treatment centre were prescribed a drug whose safety and efficacy were unproven in face of availability of licensed effective drugs.

The urgency of the concern derives partly from the paper’s finding that those patients who were switched to deferiprone displayed evidence of increases in body iron zithromax pfizer and experienced the harms associated with body iron increase.3 This finding raises a second troubling ethical question. Why were patients not switched back to a first-line licensed therapy after they began to experience serious adverse effects from treatment with unlicensed deferiprone?. How and why?.

In a sustained effort to discover answers to zithromax pfizer these questions, Olivieri and Gallie have been in communication since 2015, by email and in personal meetings, with senior officials at UHN. Olivieri and Gallie report, however, that no definitive answers have yet been provided to any of their questions. FOI requests were filed but they, too, failed to produce definitive answers zithromax pfizer.

(Olivieri and Gallie to Smith &. Porter, 2019, https://inthepatientsinterest.org/wp-content/uploads/2019/12/2019-04-23-OlivieriGallie-to-SmithPorter.pdf).10 I, too, wrote to the CEO/President of UHN and to the Chief of Medical Staff, in an attempt zithromax pfizer to discover answers to a number of the ethical questions posed in this commentary. The hospital, however, has not responded to any of my questions.11Olivieri and Gallie have recently posted documentation of their correspondence with senior UHN administrators (https://inthepatientsinterest.org/).

In September 2019 the UHN administration responded to the PLOS ONE paper by revealing that it had conducted a ‘Review of chelation practice in the red blood cell disorders program at UHN’. However, as Olivieri and Gallie document on the web, the hospital’s ‘Review’ does not address any of the safety concerns flagged in the PLOS ONE zithromax pfizer paper (https://inthepatientsinterest.org/wp-content/uploads/2019/12/Letter-to-Smith-and-Hodges-2-12-19.pdf). Nor does the ‘Review’ address any of the ethical concerns raised here.Despite UHN’s apparent reluctance to provide the information requested, here’s what we know or can reasonably infer.

Deferiprone was unlicensed in Canada during the relevant period, that is, zithromax pfizer from 2009 to 2015. €˜Unlicensed’ is different from ‘off-label’, the latter referring to a drug that has been licensed but is being provided for an indication other than that for which it is approved. Prescription of any unlicensed drug to Canadian patients can be accomplished only in one of two mutually exclusive zithromax pfizer ways.

Either through Health Canada’s ‘Special Access Program (SAP)’ or via an REB approved clinical trial. It has to be one or the other since, as Health Canada’s Guidance Document7 makes clear, patients cannot be simultaneously treated through SAP and in a research trial.12 Under the SAP, the treating physician must confirm to Health Canada that ‘conventional therapies have failed, or are unsuitable or unavailable’. Although some zithromax pfizer of the UHN patients’ records indicate that deferiprone was released under the SAP, Olivieri et al report that they ‘could identify no explanation for a proposed switch to deferiprone that was supported by evidence of failure of licensed therapy prescribed as recommended’3.

Indeed, the authors write that many patients appear to have been switched to deferiprone despite optimal responses, or improvements during treatment with first-line therapies. Here’s the relevant paragraph from their PLOS ONE article:Deferiprone was prescribed to 41 study zithromax pfizer patients between 2009 and 2015. We could identify in the electronic medical records no explanation for a proposed switch to deferiprone that was supported by evidence of failure of licensed therapy prescribed as recommended.

There was no indication zithromax pfizer that any patient switched to deferiprone over these 6 years had ‘failed’ therapy with either deferoxamine or deferasirox. Many patients were recorded as tolerant of at least one and (in most), both licensed first-line chelating agents. Some had sustained minor adverse events during deferasirox that had resolved by the time deferiprone was prescribed.3In other words, according to the data found in UHN patient records, there is no evidence that the patients with thalassaemia who were switched to deferiprone met Health Canada’s eligibility criteria under SAP.

Since deferiprone is licensed only as a ‘last resort’ therapy, its employment to treat patients who can tolerate either of the first-line therapies might improperly expose those patients to risks of serious medical harms, up to and including death.On the other hand, one should also consider the alternate possibility that, over the 6-year period studied by zithromax pfizer Olivieri et al, deferiprone was prescribed as part of a clinical trial. In favour of this hypothesis, one notes that the UHN physician primarily responsible for the widespread prescribing of deferiprone during the relevant time period claimed, in 2011, that deferiprone was provided to patients under a study approved by the REB of the UHN.8 UHN physicians also made this identical claim in a publicly available letter to the US FDA.9 Moreover, in response to an FOI application filed by Olivieri, UHN claimed that deferiprone was provided at UHN during a clinical trial (the data of which are protected from scrutiny under FOI laws), and not under SAP (the data of which are not protected from scrutiny under FOI). However, Olivieri et al have been unable to find any record of registration for such a trial, as required by Canadian Clinical Trial guidelines.13 Requests to the UHN administration for confirmation that a clinical trial existed remain unanswered.14 zithromax pfizer My own efforts to find some registration record for this putative clinical trial of deferiprone have been equally unsuccessful.15Two core ethical principles.

Harm-minimisation and informed consentIf the deferiprone used to treat UHN patients with thalassaemia was obtained from Apotex as part of a randomised clinical trial, responsibility for approving the trial would fall to the UHN’s REB. In Canada, both researchers and REBs are governed by the Tri-Council Policy Statement (TCPS) ‘Ethical Conduct for Research Involving Humans’.10 The 1998 version of this policy statement (TCPS1) and the subsequent 2010 version (TCPS2), both applicable to research trials during this period, stipulate that zithromax pfizer clinical trials must be designed so that harm to research subjects will be minimised.16 For example, TCPS1 specifies, in section 1.5, that ‘Research subjects must not be subjected to unnecessary risks of harm’. TCPS2, under the rubric ‘Core Principles’, requires similarly that clinical trials must ‘ensure that participants are not exposed to unnecessary risks’.Data presented by Olivieri et al in their PLOS ONE Study indicate that UHN patients exposed to unlicensed deferiprone, either as monotherapy or in combination with low dose of a first-line chelator (‘combination therapy’), experienced significant harms as a result of poor iron control, but very few if any compensating benefits.We provide new evidence of inadequate reduction in hepatic iron, a 17% incidence of new diabetes and new liver dysfunction in 65% of patients, many who were challenged and rechallenged with deferiprone despite elevated liver enzymes developed during previous exposure.

We identified no evidence of ‘cardio-protective’ effect during deferiprone therapy.3In zithromax pfizer light of PLOS ONE Study data indicating serious adverse events (SAEs) for patients switched to deferiprone from first-line drugs one is led to question why the study protocol did not, in anticipation of such a contingency, provide for a resumption of licensed therapy for patients doing poorly on the unlicensed drug. Moreover, the investigators were obliged to report adverse events to the hospital’s REB. Were the adverse events so reported?.

And if they were then why did the zithromax pfizer UHN REB not seek to protect patient safety by insisting that licensed therapy be resumed for deferiprone-harmed patients?. In an effort to establish whether the deferiprone ‘clinical trial’ satisfied the TCPS harm-minimisation principle, I made inquiries about how the adverse findings described by the PLOS ONE paper were reported to the hospital’s REB and also how they were reported to the regulatory authorities, that is, Health Canada and the US FDA. But my queries, like those made previously by Olivieri and Gallie, have not succeeded in eliciting this ethically relevant information.17 Neither UHN nor its thalassaemia zithromax pfizer clinic responded to my letters of inquiry.

It is known, however, from a publicly available 2011 document, that physicians in the UHN thalassaemia clinic strongly supported the market approval of deferiprone by the FDA.18 This support is difficult to reconcile with the toxicities recorded in UHN patient records. So, a final verdict on the issue of whether the UHN deferiprone ‘clinical trial design’ violated the TCPS harm-minimisation principle cannot be reached until those involved in conducting and monitoring clinical trials at UHN make available the zithromax pfizer relevant information. An independent public inquiry may be necessary to achieve the necessary degree of accountability.Reference has been made, above, to the TCPS core ethical requirement of harm-minimisation, applicable in Canada both to researchers and to REBs.

It is important to note, however, that TCPS2, like its predecessor, TCPS1 (and, indeed, like virtually every postwar code of research ethics) also stipulates as a second ‘core principle’ that ‘Researchers shall provide to prospective participants, or authorised third parties, full disclosure of all information necessary for making an informed decision’.19 Moreover, as the then-current TCPS guidelines make clear, ‘consent is an ongoing process’. So, assurance should be given to prospective participants that they ‘will be given in a timely manner throughout the course of the research project, information that is relevant to their decision to continue or withdraw from participation’.20 (My emphasis) zithromax pfizer. Finally, TCPS2 imposes on researchers the additional ethical requirement that they disclose to research subjects ‘information concerning the possibility of commercialisation of research findings, and the presence of any real, potential or perceived conflicts of interest on the part of the researchers, their institutions or the research sponsors’.21 There is also an expectation that conflicts of interest will be disclosed to the REB.

Whether there was adequate disclosure of Apotex funding either to research subjects or to the UHN REB zithromax pfizer is still unknown.Thus, in order to assess the ethical adequacy of the putative UHN thalassaemia clinical trial one must inquire whether UHN patients/subjects were given adequate risk information when they were first enrolled, subsequently, when they were switched from treatment with deferasirox or deferoxamine to treatment with deferiprone and then, finally, when they experienced SAEs. That is, in order to know whether the putative deferiprone clinical trial conformed to established principles of research ethics, one would need to know whether patients/research subjects understood that they were being switched from licensed first-line drugs of proven efficacy to an unlicensed and unproven third-line drug. One would zithromax pfizer also need to know whether the deferiprone ‘research subjects’ were informed about conflicts of interest arising from Apotex donations (A) to the UHN.

(B) To the hospital’s thalassaemia programme,22 as well as the hoped-for commercialisation of deferiprone via Health Canada and FDA licensing.If there was a failure to obtain ongoing informed consent and/or a failure to disclose conflicts of interest (to patients and to the REB) then this would constitute a violation of research ethics. Unfortunately, my attempts to elicit the clinical trial’s consent to research information from the UHN and its thalassaemia clinic met with as little success as earlier attempts made by the PLOS ONE authors.23REB review. Safety monitoringAlthough every clinical trial requires safety monitoring, those trials which involve non-negligible risk of significant harm to patients/subjects require especially rigorous safety monitoring.24 Because the exposure of deferiprone to zithromax pfizer UHN patients posed risks of organ dysfunction and death, the need for safety monitoring was exigent.

As the TCPS1 and TCPS2 both make clear, those who conduct research have an obligation to monitor and protect the safety of their research subjects.Moreover, it is now widely recognised that individuals closely involved with the design and conduct of a trial may not be able to be fully objective in reviewing interim data for any emerging concerns.25 Hence the importance of REBs, part of whose role is to provide safety monitoring initially and, for ongoing trials, over the entire period of the trial. In order to assess the adequacy of the safety monitoring for the UHN ‘deferiprone trial’ one would need to know whether the hospital’s REB was provided with regular and accurate reports of SAEs and what actions this REB took in response to those reports.It has become common practice in North America ‘that for any controlled trial of any size that will compare rates of mortality or major morbidity’, a data safety monitoring board (DSMB) will be established.26,11 12 A DSMB is constituted by a panel of independent (and otherwise unbiased) individuals with expertise pertinent zithromax pfizer to reviewing trial data on a regular ongoing basis. Its role is to advise the sponsors regarding the safety of trial subjects and to recommend early termination where indicated, for example, on grounds of patient safety.27Since there are no specifically Canadian requirements with respect to the establishment of DSMBs, Canadian REBs tend to follow FDA guidelines.

Those guidelines recommend that a DSMB should be established when the study end point is such that a highly favourable or unfavourable result at an interim analysis zithromax pfizer might ethically require termination of the study. Advance information suggesting the possibility of serious toxicity with the study treatment is another a priori reason for safety concern that would justify the establishment of a DSMB.12For reasons given above, the UHN deferiprone trial appears to have been a prime candidate for the establishment of a DSMB. But it is not known whether the study’s research protocol, purportedly submitted for approval to the hospital’s REB, included a DSMB.

Nor is it zithromax pfizer known whether a DSMB was established and reported regularly to the trial’s sponsors. Data on the toxicity of deferiprone, provided by Olivieri et al from their retrospective study of UHN patient records, suggest that had a DSMB existed for this putative clinical trial the trial might, on grounds of patient safety, have been a candidate for premature cancellation. Lacunae in our knowledge of the safety monitoring provisions of the deferiprone ‘clinical trial’ make it difficult to reach any firm zithromax pfizer conclusion as to whether the ‘trial’ met prevailing safety monitoring requirements.The apparent unwillingness of the UHN to answer questions relating to safety monitoring might mean that an inquiry is needed to fill in our knowledge gaps and thereby make ethical evaluation possible.

For the findings of such an inquiry to be minimally credible it should be carried out by individuals who possess the requisite scientific/medical expertise and who are independent of the hospital and its thalassaemia clinic and who are demonstrably impartial. An inquiry carried out, for example, by someone whose research has been funded by Apotex and/or by an expert with close professional and personal zithromax pfizer ties to one or more of the physicians in the UHN thalassaemia clinic would not satisfy the hospital’s duty of accountability for patient safety.Ethical concernsA RecapitulationThe serious complications experienced by deferiprone-exposed UHN patients, as described by Olivieri et al in their PLOS ONE article, raise a number of ethically important questions. How could an unlicensed drug of unproven efficacy and safety—a drug that has been questioned by regulatory agencies such that it is licensed only as a “last resort” therapy—have been administered to so many patients over a period of so many years when two licensed drugs, both proven adequately safe and effective and licensed as first-line therapies, were available?.

How did UHN physicians gain access to deferiprone from Health Canada when there is little evidence in UHN patient records that the deferiprone-exposed patients satisfied Health Canada’s criteria for Special Access?. Why was a putative UHN REB-approved research study involving deferiprone not zithromax pfizer registered as a clinical trial?. Did the trial design include a DSMB, to protect patient safety and, if not, why not?.

Were SAEs reported to the UHN REB and to regulators, as zithromax pfizer required?. Were deferiprone-treated UHN patients with thalassaemia adequately informed of the unlicensed status, unproven efficacy and reported toxicities of deferiprone?. Were deferiprone-exposed patients informed of harms they zithromax pfizer themselves had sustained during deferiprone from this exposure?.

28 Did the evidence of systematic treatment failure, as outlined in the PLOS ONE paper, raise red flags for thalassaemia clinic physicians and for the REB of UHN?. And if serious problems were flagged what actions were taken to protect patient safety?. Institutional conflict of interestThe literature on biomedical conflicts of interest tends to focus on the ways in which financial support of individual researchers by the pharmaceutical industry can adversely affect both research integrity and patient safety.13–16 But similar ethical problems arise at the macro level when institutions, such as hospitals and clinics, depend on drug company funding to support patient care and clinical research.13 15 Notable scandals associated with institutional conflicts of interest include the David Healy/Eli Lilly scandal at Toronto’s Centre for Addictions and Mental Health (CAMH),13 the Aubrey Blumsohn/Proctor and Gamble scandal at Sheffield University (UK)17 and the Carl Elliott/Janssen Pharmaceuticals scandal at the University of Minnesota.17 The underlying pattern in each of these scandals involves (A) a biomedical researcher who is concerned about patient safety coming into conflict with (B) a pharmaceutical company which funds both the researcher’s hospital and university and (C) a failure by the institutions involved vigorously to defend patient safety and research integrity when doing so might offend a wealthy sponsor.It should not be assumed that corporate influence on university medical centres is necessarily zithromax pfizer exerted by means of threats or other direct forms of intervention.

The mere presence of corporate funding can be sufficient to produce a corporate-friendly result. This point is illustrated by a recent STAT article, zithromax pfizer a propos the financial support which Purdue Pharma provided to Massachusetts General Hospital. The very title of the article encapsulates the ethical problem of institutional conflict of interest.

€˜Purdue Pharma zithromax pfizer cemented ties with universities and hospitals to expand opioid sales, documents contend’.18 Nor should it be supposed that the problem of institutional conflict of interest arises exclusively in the context of biomedical research. A recent Guardian article on the Mobil Oil Corporation describes how ‘Oil giant Mobil sought to make tax-exempt donations to leading universities … to promote the company’s interests and undermine environmental regulation, according to internal documents from the early 1990s obtained by the Guardian’.19As mentioned above, deferiprone, whose safety and efficacy are the central concern of Olivieri et al’s PLOS ONE paper, is manufactured by Apotex. When we seek to understand why deferiprone was so frequently prescribed to UHN patients, from zithromax pfizer 2009 to 2016, despite its being unlicensed and despite evidence of poor patient outcomes,3 it may be relevant to note that Apotex provided substantial funding to the UHN thalassaemia clinic.29 Moreover, a publicly displayed UHN banner lists ‘Apotex Inc – Barry and Honey Sherman’ as having donated between $1 million and $5 million to the hospital itself.30As every biomedical researcher understands, correlation is not causation.

Nevertheless, the correlation between industry funding of hospitals, on the one hand, and industry-friendly decisions made by researchers and administrators at those hospitals, on the other, is worth pondering. Physicians and researchers who speak or write critically of drugs manufactured by wealthy donor companies may find that their careers are jeopardised. Nancy Olivieri’s dismissal from two Apotex-funded teaching hospitals illustrates this phenomenon as does the termination of psychiatrist David Healy from Toronto’s CAMH.13 Healy’s appointment zithromax pfizer as Head of the CAMH Mood Disorders Clinic was rescinded almost immediately after he gave a public lecture at the hospital—a lecture in which he called for further research into the potentially adverse effects of Eli Lilly’s antidepressant drug, Prozac.

Healy was particularly concerned about SSRI-induced suicidal ideation. After his lecture the hospital decided that he was not ‘a good fit’ zithromax pfizer with their programme and terminated his appointment. Shortly thereafter the hospital opened its Eli Lilly wing.13UHN, like every other research and teaching hospital in Canada, receives most of its funding, directly or indirectly, from governments.20 ,31 Nevertheless, UHN, again like other hospitals, faces ongoing pressure to find additional sources of revenue to support both patient care and clinical research.32 The pharmaceutical industry is a prime source of much-needed ‘top-up’ financial support for Canadian hospital research and clinical care.21 Hospital administrators, researchers and clinicians are thereby placed, willy nilly, in a conflict-of-interest situation.

Because of funding zithromax pfizer exigencies, hospitals and other healthcare institutions, like individual physicians and researchers, have a strong vested interest in pleasing corporate sponsors and encouraging their ongoing support. Moreover, institutional administrators, not unlike individual researchers and clinicians, typically experience a need to express their gratitude to donors by returning kindness for kindness and benefit for benefit. Thus, both the need for ongoing corporate sponsorship and the need to reciprocate for past corporate generosity create for hospital administrators (as well as for researchers and clinicians who work within hospitals) a conflict-of-interest situation in which their decision making may be skewed, consciously or unconsciously, in favour of the benefactors’ products.13 15 16 21Here’s an example of the manner in which an institutional conflict-of-interest situation can potentially bias the judgement of hospital administrators.

Hospitals are required zithromax pfizer to exercise their disinterested judgement in the appointment of medical and scientific staff and in the ethical monitoring of research. This moral obligation follows directly from their fundamental commitment to promote and defend patient safety and research integrity. To illustrate zithromax pfizer.

UHN’s website, under the heading Purpose, Values and Principles, declares that ‘[o]ur Primary Value and above all else. The needs of patients zithromax pfizer come first’.22 It would be difficult to find any hospital whose Mission Statement did not proclaim a similar commitment to the primacy of patient well-being. In a similar vein, the UHN website, under the heading Information for Patients, subheaded Our Mission, declares.

€˜We believe that health equity is achieved when each person is. Enabled to choose the best care and treatment based on the most current knowledge available’.From this fundamental commitment, it follows that healthcare institutions are obliged rigorously to monitor the quality of care provided zithromax pfizer to their patients and research subjects. As an important element of protecting patient safety, hospitals are required to appoint the most qualified and competent candidates to clinical and research positions.

But, as noted above, conflicts of interest are a risk factor for bias, conscious or unconscious, in personnel decisions.22 So, when a research hospital depends on corporate donations there is a risk that physicians and researchers may be appointed to key positions because they are known to be zithromax pfizer sympathetic to the donors’ product(s) rather than because they are the best qualified and the most competent. Contrariwise, physicians and researchers believed to be unsympathetic to the donors’ products are at risk of losing their jobs or of not being hired in the first place. The cases of Olivieri, Healy and Blumsohn illustrate this point.13 17As explained above, we know from the extensive literature on conflict of interest that when research and clinical care are funded by industry there is a marked tendency for both to favour the sponsors’/donors’ products.13 15 16 18 Significantly, the UHN itself explicitly recognises the danger to patient safety zithromax pfizer posed by systemic biases.

Its Mission Statement commits the hospital to ensuring that every patient is ‘[m]ade aware of existing systemic biases to support the best possible health decisions’.22 Unfortunately, it is not possible at present to ascertain whether UHN conformed to this ethical commitment in the case of its deferiprone research/treatment clinic. In order to make such an ethical determination we would need to know the mechanism by which the UHN thalassaemia clinic gained access to deferiprone and whether the clinic provided information about systemic bias to patients with thalassaemia and to the hospital’s REB.ConclusionsHospitals worldwide proclaim that their primary commitment is to meet the needs of their patients. Institutional codes of ethics and mission zithromax pfizer statements insist that patient needs come first.

Indeed, meeting ‘patient needs’ is agreed to be the fundamental value to which all other hospital goals should be subordinated. Toronto’s UHN declares zithromax pfizer unequivocally that it shares this value. €˜[t]he needs of patients come first’.22Although patients have many and various needs, the need for safety must be counted as the sine qua non.

If the need zithromax pfizer for safety is not met then other needs become irrelevant.The findings of Olivieri et al in their PLOS ONE paper raise many troubling questions about the safety of patients in UHN’s thalassaemia clinic. One would expect that when top UHN officials became aware of the PLOS ONE data they would immediately have recognised the ethical red flags. Hospitals are ethically obliged both to investigate thoroughly possible safety failures and to rectify any problems identified.Over a period of several years, both before and after the publication of their research findings, Drs Olivieri and Gallie communicated regularly with UHN officials (https://inthepatientsinterest.org/).

Multiple safety concerns were brought to the hospital’s zithromax pfizer attention. Numerous questions were asked by the PLOS ONE authors and specific concerns were raised. To date, zithromax pfizer the hospital has not definitively addressed these issues.

I posed a series of ethically salient questions to these same hospital officials (see online supplementary appendix A). My queries zithromax pfizer were ignored. There was no response from UHN.Supplemental materialIf a healthcare institution such as UHN claims that patient safety is its top priority then when safety issues are raised, it necessarily incurs an obligation of accountability.

It would, for example, scarcely be adequate for a hospital, such as UHN, unilaterally to investigate alleged failures, declare that there has been no violation of patient care standards, and then to stonewall all further inquiries, whether those inquiries originate from its own medical staff, as was the case with Olivieri and Gallie, or from outside scholars, as was the case with me.When an unlicensed drug is prescribed to hospital patients, over a period of years, as happened in the UHN thalassaemia programme, it is surely the hospital’s obligation to answer questions about how and why this extraordinary practice occurred. When hospital records reveal that patients switched from licensed to unlicensed medication, have experienced serious harms, up to and including death, it is surely the hospital’s obligation to answer in a conscientious and complete manner zithromax pfizer all the ethically troubling questions that have been identified. This obligation of accountability is owed both to patients and to staff.

Thus far, UHN has not been willing to accept the implications of its own mission statement zithromax pfizer (https://www.uhn.ca/corporate/AboutUHN/Quality_Patient_Safety).The PLOS ONE Study by Olivieri Sabouhanian and Gallie spurs us to inquire whether the benefits which accrue to society from corporate sponsorship of healthcare institutions may, on balance, be outweighed by the associated harms. Admittedly, for governments committed to constraining public expenditures, the transfer of substantial healthcare costs to private corporations represents a benefit for public finances. But, as we zithromax pfizer have seen, when one considers this financial benefit, one ought also to take into account the spectrum of negative consequences potentially generated by institutional conflicts of interest.

The price for our continued acceptance of corporate funding of scientific research and clinical care may be the erosion of public trust. Arguably, it would be preferable if our research hospital were to aim instead for the complete elimination of systemic biases.Data availability statementAll data relevant to the study are included in the article or uploaded as supplementary informationEthics statementsPatient consent for publicationNot required.AcknowledgmentsThe author thanks the editors of JME and two JME reviewers for their criticisms of and suggestions for change to an earlier version of this paper..

That they are ‘following the science’ has become the zithromax 500mg for sale watchword of many politicians during the present zithromax, especially when imposing or prolonging lockdowns or other liberty-restricting regulations. The scientists who advise politicians however are usually careful to add that the decision what to restrict and when is ultimately a political one. In science, as in medical practice, there is a delicate balance to be maintained between confidence in the zithromax 500mg for sale best available information, and the necessary caveat that the assumptions and calculations on which that information is based are subject to further scientific enquiry.

For politicians and the public, moreover, as for patients, whether those informing them are judged to be trustworthy is a necessary consideration, a judgement determined by a variety of personal and political contingencies and circumstances. Ethics, by contrast, unable to appeal to scientific consensus (however revisable) or political authority (however reversible), let alone a confidence-inspiring bedside manner, must rest the case for its essentially contestable assumptions and arguments being judged trustworthy, on its willingness to admit all reasoned voices (including occasionally those zithromax 500mg for sale that question reason itself) to a conversation that is potentially unending, but in the process often highly enlightening.That conversation is contributed to in this issue of the Journal by several reasoned voices, mostly on ethical aspects of the buy antibiotics zithromax. Relevant to issues on which politicians claim to be ‘following the science’, but also raising fundamental ethical questions, is this month’s feature article.

In Ethics of Selective Restriction zithromax 500mg for sale of Liberty in a zithromax,1 Cameron and colleagues consider ‘if and when it may be ethically acceptable to impose selective liberty-restricting measures in order to reduce the negative impacts of a zithromax by preventing particularly vulnerable groups [for example, the elderly in buy antibiotics] of the community from contracting the disease’ [and thereby, for example, increasing the disease burden]. €˜Preventing harm to others when this is least restrictive option’, they argue, ‘fails to adequately accommodate the complexity of the issue or the difficult choices that must be made’. Instead, they propose ‘a dualist consequentialist approach, weighing utility at both a population and individual level’, thereby taking account of ‘two relevant values to be promoted or maximised.

Well-being and liberty’, as well as the value of equality, zithromax 500mg for sale ‘protected through the application of an additional proportionality test’. The authors then propose an algorithm to take account of the different values and variables which need to be weighed up. They conclude zithromax 500mg for sale.

€˜Selective restriction of liberty is justified when the problem is grave, the expected utility of the liberty restriction is high and significantly greater than the alternatives and the costs of the liberty restrictions are relatively small both at a population and individual level… Discrimination can be justified under these conditions when it is proportionate and limited to a very specific public health challenge’. The arguments zithromax 500mg for sale and conclusions of the feature article are discussed in the two Commentaries2 3.In buy antibiotics controlled human studies. Worries about local community impact and demands for local engagement,4 Eyal and Lee review recent arguments which express ‘concern about undue usage of local residents’ direly needed scarce resources at a time of great need and even about their unintended ’ – and hence a requirement for ‘either avoiding controlled trials (CHIs) or engaging local communities before conducting CHIs’.

They then examine and compare the evidence of such adverse (and some potentially positive) effects of CHIs with those of conventional field trials and argue that ‘both small and large negative effects on struggling communities are likelier in field trials than in CHIs’. €˜Whether or not local community engagement is necessary for urgent treatment studies in a zithromax’, they conclude, ‘the case for its zithromax 500mg for sale engagement is stronger prior to field trials than prior to controlled human studies’.In Payment of buy antibiotics challenge trials. Underpayment is a bigger worry than overpayment,5 Blumenthal Barby and Ubel consider the impact not on communities but on individuals, and specifically on ‘how much people should be paid for their participation in buy antibiotics challenge trials’.

Noting recent worries about ‘incentivising people with large amounts of money’, they argue that ‘higher payment that accounts for participant time, and for pains, burdens and willingness to zithromax 500mg for sale take risks’ constitutes neither ‘undue inducement’ (for which the remedy is strengthening informed consent processes and minimising risks) nor ‘unjust inducement’ of individuals from ‘already disadvantaged groups’. Evidence of recruitment to challenge trials worldwide suggests, on the contrary, that participants ‘come from all walks of life’. Nor are zithromax 500mg for sale these authors convinced that ‘offering substantial payment waters down the auistic motives of those involved’.

€˜auism and payment’ they argue, ‘frequently coexist. Teachers, physicians, public defenders – they all dedicate their lives to helping people. But few do without compensation.’In Money zithromax 500mg for sale is not everything.

Experimental evidence that payments do not increase willingness to be vaccinated against buy antibiotics6, Sprengholz and colleagues report on an ‘experiment investigating the impact of payments and the communication of individual and prosocial benefits of high vaccination rates on vaccination intentions.’ In November 2020 over 1,000 ‘individuals from a German non-probabilistic sample’ were asked about their intentions. The ‘results revealed that none of these interventions or their combinations increased willingness to be vaccinated shortly after a treatment zithromax 500mg for sale becomes available.’ Given that this experiment was conducted before treatments became available and only in Germany, the authors suggest that these results ‘should be generalised with caution’, but that ‘decision makers’ also ‘should be cautious about introducing monetary incentives and instead focus on interventions that increase confidence in treatment safety first’.In Voluntary buy antibiotics vaccination of children. A social responsibility,7 Brusa and Barilan observe a zithromax paradox.

€˜while we rely on low quality evidence when harming children by school deprivation and zithromax 500mg for sale social distancing, we insist on a remarkably high level of safety data to benefit them with vaccination’. The consequent exclusion of children from vaccination, they argue, is unjust and not in ‘the best interest of the child as a holistic value encompassing physical, psychological, social and spiritual well-being’, something which ‘there is no scientific method for evaluating’. Society, rather, ‘has the political responsibility to factor in the overall impact of the zithromax on children’s well-being’ and the ‘ultimate choice is a matter of paediatric informed consent.

Moreover, jurisdictions that permit non-participation in established childhood vaccination programmes should also permit choice of treatments outside of the approved programmes.’ The authors conclude by outlining ‘a prudent and ethical scheme for gradual incorporation of minors in vaccination programmes that includes a zithromax 500mg for sale rigorous postvaccination monitoring.’In Challenging misconceptions about clinical ethics support during buy antibiotics and beyond. A legal update and future considerations,8 Brierley, Archard and Cave note that the ‘buy antibiotics zithromax has highlighted the lack of formal ethics processes in most UK hospitals… at a time of unprecedented need for such support’. Unlike Research Ethics Committees (RECs), Clinical Ethics Committees (CECs) in zithromax 500mg for sale the UK have neither any ‘well-funded governing authority,’ nor the decision-making capacity over clinical questions which RECs have over research.

In 2001 the ‘three central functions of CECs’ were described as ‘education, policy development and case review’. But more recently ‘the role of some was expanding’ and in 2020 the UK General Medical Council ‘mentioned for zithromax 500mg for sale the first time the value in seeking advice from CECs to resolve disagreements’. Misunderstanding of CEC’s role however began to arise when some courts appeared to ‘perceive CECs as an alternative dispute resolution mechanism’ rather than as providing ‘ethics support, with treatment decisions remaining with the clinical team and those providing their consent.’ The future role of CECs, as well as the nature of patient involvement in them, the authors conclude, will depend on a choice between the ‘flexibility and diversity of the current ethical support system’ and ‘greater standardisation, governance and funding’.Important ethical issues not directly related to buy antibiotics are discussed in this issue’s remaining papers.

In Institutional conflict of interest. Attempting to crack the deferiprone mystery,9 Schafer identifies, zithromax 500mg for sale places in historical context, and analyses ethical issues raised by the ‘ mystery’ of why between 2009 and 2015 ‘a third of patients with thalassaemia in Canada’s largest hospital were switched from first-line licensed drugs to regimens of deferiprone, an unlicensed drug of unproven safety and efficacy’. He then considers ‘institutional conflict of interest’ as ‘a possible explanatory hypothesis’.The perils of a broad approach to public interest in health data research.

A response to Ballantyne and Schaefer10 by Grewal and Newson and Ballantyne and Schaefer’s response In defence of a broad approach to public interest in health data research11 debate legal and philosophical aspects of whether ‘public interest’, and how narrowly or broadly this is conceived, is the most appropriate justification of consent waivers for secondary research on health information.In Do we really know how many clinical trials are conducted ethically,12 Yarborough presents evidence in support of the argument that 'research ethics committee practices need to zithromax 500mg for sale be strengthed' and then suggests 'initial steps we could take to strengthen them'.Finally, and returning to how ‘science’ is perceived, in Lessons from Frankenstein 200 years on. Brain organoids, chimaeras and other ‘monsters’13, Koplin and Massie make a crucial observation. In ‘bioethical debates, Frankenstein is usually evoked as a warning against interfering with the zithromax 500mg for sale natural order or “playing God”’.

But in the novel, Frankenstein’s ‘most serious moral error’ was made ‘not when he decided to pursue his scientific breakthrough (one which might, after all, have helped save lives), but when he failed to consider his moral obligations to the creature he created.’ Today, when, like Frankenstein, ‘modern scientists are creating and manipulating life in unprecedented ways’ such as brain organoids and chimaeras, Koplin and Massie argue, ‘two key insights’ can be drawn from Mary Shelley’s 1818 novel. First, ‘if we have created an entity in order to experiment on it’ we need ‘to extend much consideration to its interests and preferences, not least because ‘scientists cannot always rely on existing regulations to anticipate moral issues associated with the creation of new kinds of organisms’. And second zithromax 500mg for sale.

€˜we should be wary of any prejudice we feel towards beings that look and behave differently from us’ and should ‘interrogate any knee-jerk intuitions we have about the moral status of unfamiliar kinds of beings.’Ethics statementsPatient consent for publicationNot required.IntroductionThalassaemia is an inherited anaemia that exerts an enormous disease burden worldwide.1 Along with sickle cell disease, it is one of the two most common single gene disorders. Indeed, ‘the alpha and beta thalassaemias are the most common zithromax 500mg for sale inherited single-gene disorders in the world…’2A newly published study by Olivieri, Sabouhanian and Gallie3 analyses and assesses the comparative efficacy and safety profile of two drugs. Deferiprone (Ferriprox.

Apotex) and deferasirox zithromax 500mg for sale (Exfade. Novartis). Both of these zithromax 500mg for sale ‘iron-chelating’ drugs remove (‘chelate’) iron deposited, as a result of transfusions, in the tissues of patients with thalassaemia.The present-day first-line chelator, deferasirox, was licensed by the US FDA in 2005.

The evidence for its safety and effectiveness was judged to be substantial and, accordingly, the FDA licensed it as a first-line agent. The prime advantage of deferasirox, in comparison to deferoxamine, an older drug that was formerly the gold standard of iron-chelating therapy for thalassaemia, is that deferasirox is orally active (that is, taken in pill form), while deferoxamine is more burdensome for patients because it has to be taken parenterally (that is, via injection). Deferiprone, like deferasirox, zithromax 500mg for sale is taken orally but has not been licensed anywhere as first-line treatment.

The FDA withheld market approval for deferiprone because there were/are no controlled trials demonstrating direct treatment benefit. Although the FDA did eventually approve deferiprone, in 2011, it gave approval only as a last-resort treatment for those patients in whom other chelators had been zithromax 500mg for sale tried unsuccessfully.1The data presented by Olivieri et al in their PLOS ONE paper indicate that the drugs differ significantly with respect to their effectiveness and safety. This commentary explores some of the ethical issues raised by the PLOS data.Historical contextIn order to understand properly the significance of the PLOS ONE Study some historical context will be helpful.

What follows is a brief sketch of that context.2In 1993 Dr Nancy Olivieri, a specialist in blood diseases at Toronto’s Hospital for Sick Children (HSC or ‘Sick Kids’) and Professor of Pediatrics and Medicine at the University of Toronto (U of T), signed a contract with Apotex, a generic drug company, to continue studies of deferiprone, the early promise of which she zithromax 500mg for sale had already reported in the literature. Olivieri’s thalassaemia research was initially supported by the Medical Research Council of Canada, but now she sought additional funding to extend her clinical trials. Apotex contributed this additional funding, thereby obtaining worldwide patents on the still-experimental drug.Despite early promise, by 1996 Olivieri’s research began to indicate that deferiprone might be inadequately effective in many patients, posing risks of potentially serious harm.

Olivieri communicated to Apotex her intention to zithromax 500mg for sale inform patients of this unexpected risk and she proposed also to amend the study’s consent forms. She wished to continue amended studies of the drug, and to publish her findings.Apotex responded to Olivieri that they disagreed with her interpretation of the data and the company’s CEO threatened her with ‘all legal remedies’ should she inform patients or publish her findings. In issuing these threats, Apotex zithromax 500mg for sale relied on a confidentiality clause in a legal contract Olivieri had signed with Apotex in 1993.

This contract prohibited disclosure ‘to any third party’ without the express permission of Apotex.3Despite the objections raised by Apotex, Olivieri saw it as her professional duty to disclose her findings. The Research Ethics Board (REB) of Sick Kids Hospital zithromax 500mg for sale reached the same conclusion. In compliance with instructions from the Hospital’s REB, Olivieri duly informed both her patients and the regulatory authorities.When Olivieri later identified a second risk—that liver damage progressed during deferiprone exposure—Apotex issued additional legal warnings.

Olivieri nevertheless proceeded to inform her patients of this additional risk and published her findings.Since patient safety, research integrity and academic freedom were all at stake in this dispute, Olivieri appealed for assistance, repeatedly, to senior officials at both the U of T and Sick Kids Hospital. Neither the University nor the zithromax 500mg for sale Hospital provided the support she requested. In the words of the Report of the Committee of Inquiry on the Case Involving Dr Nancy Olivieri, the HSC, the U of T, and Apotex Inc4:The HSC and the U of T did not provide effective support either for Dr Olivieri and her rights, or for the principles of research and clinical ethics, and of academic freedom, during the first two and a half years of this controversy.Instead, both the University and the Hospital ‘took actions that were harmful to Dr.

Olivieri’s interests and professional reputation and disrupted her work’.4 The harmful actions included firing Olivieri from her position as Director of the Hemoglobinopathy Program at Sick Kids Hospital and referring her for discipline to the zithromax 500mg for sale College of Physicians and Surgeons of Ontario (CPSO).Only later did it emerge that, during this period of conflict, the U of T was negotiating with Apotex for a major donation towards building the University’s proposed new molecular medicine building. Some speculated that the University’s failure to support Olivieri may not have been unconnected from its desire to appease a wealthy corporate donor. This speculation was reinforced when it was discovered that the then President of the University, Robert Prichard, had secretly lobbied the government of Canada for changes in drug patent law, changes that would favour Apotex.4Apotex proceeded to zithromax 500mg for sale sue Olivieri for defaming both the company and their drug.

She sued the company for defaming her.The Canadian Association of University Teachers (CAUT) and the U of T Faculty Association (UTFA), to whom Olivieri appealed for assistance after being rebuffed by the U of T and HSC, viewed the underlying issue as one of academic freedom. Both CAUT and UTFA provided support, including legal advice, to Olivieri.Thus began what is widely acknowledged to be the greatest scandal in Canadian academic history. Commissions of inquiry, books and articles (both scholarly and popular) proliferated, not to mention newspaper and television stories zithromax 500mg for sale.

John le Carré’s novel The Constant Gardener and the Hollywood movie based on the book both appeared to draw heavily on the Olivieri-Apotex scandal. An inquiry into the dispute commissioned by Sick Kids Hospital (the Naimark Inquiry)5 absolved Apotex of wrongdoing but suggested that Olivieri was seriously at fault.5 She was charged with research misconduct and failures of zithromax 500mg for sale patient care and was referred first to the Hospital’s Medical Advisory Council and subsequently to the disciplinary committee of the CPSO. Unsurprisingly, these widely publicised referrals were prejudicial to Olivieri’s reputation.The CAUT then commissioned an independent inquiry.6 The 540-page CAUT report on the Olivieri/Apotex affair4 gave a markedly different account of the scandal from that offered by the hospital-commissioned Naimark Report.

A few excerpts from the CAUT report will convey its zithromax 500mg for sale central findings:Apotex issued more legal warnings to deter Dr. Olivieri from communicating this second unexpected risk of L1 (deferiprone) to anyone. However, she was legally and ethically obligated to communicate the risk to those taking or prescribing the drug as there were potential safety implications for patients, and she fulfilled these obligations despite the legal warnings.Apotex acted against the public interest in issuing legal warnings to Dr.

Olivieri to deter her from communicating about risks of zithromax 500mg for sale L1.Apotex’s legal warnings violated Dr. Olivieri’s academic freedom.7Shortly after the CAUT report absolved Olivieri of misconduct, the CPSO published the findings of its inquiry. The CPSO report exonerated zithromax 500mg for sale Olivieri of all misconduct charges.

Indeed, their report concluded that her conduct had been ‘commendable’.6 This favourable verdict did not, however, bring an end to litigation.In 2004, 8 years after the first legal threats had been issued, Apotex signed a mediated settlement with Olivieri. Nevertheless, litigation continued for another zithromax 500mg for sale 10 years. Those unfamiliar with the workings of the law may wonder how it is possible for litigation to continue for such a long period after a mediated settlement.

Litigation continued because Apotex alleged that Olivieri had violated their agreement. Olivieri insisted that she was in compliance with the terms of zithromax 500mg for sale the settlement. Court decisions were appealed by both parties.

A final zithromax 500mg for sale settlement was not reached between Olivieri and Apotex until 2014.8 Shades of Jarndyce v. Jarndyce in Charles Dicken’s novel Bleak House.The HSC settled its dispute with Olivieri in 2006 and, although her research programme at the Hospital continued, she ceased to provide clinical care to HSC patients. From 1997 to 2009, Olivieri served zithromax 500mg for sale as Director of the University Health Network (UHN) Hemoglobinopathy Program.

She continued, as she had since 1997, to assist in the clinical care of UHN patients with thalassaemia and to enrol them in her research studies. In March 2009, however, zithromax 500mg for sale Olivieri was dismissed by UHN from her position as Director. No reason was given for her dismissal (Personal communication.

Olivieri, 2019).The PLOS ONE Study data3 show that, after Olivieri’s dismissal from her position as Director, the UHN thalassaemia Clinic began almost immediately to switch patients to (unlicensed) deferiprone. Olivieri has described how her UHN research work, from this time forward, was marginalised (https://inthepatientsinterest.org/wp-content/uploads/2019/12/2018-12-20-GallieOlivieri-to-SmithHodges.pdf).Meanwhile, Freedom of Information (FOI) requests filed by Olivieri after her dismissal revealed that Apotex was supplying unrestricted educational zithromax 500mg for sale grants to UHN’s thalassaemia programme as well as providing research support. The FOI requests filed by Olivieri also revealed that Apotex was strategising with the programme’s new director about how best to obtain licensing for deferiprone from the regulator (Health Canada).9 With this dramatic background as historical context, we commence our discussion of the ethical implications of the PLOS ONE paper.Findings of the PLOS ONE paperIn their 2019 PLOS ONE study Olivieri et al conclude, based on a retrospective review of patient data at Toronto’s UHN, that deferiprone is inadequately effective and associated with serious toxicity.

Their review also confirms that, by contrast, deferasirox is effective and associated with relatively few adverse effects.3Olivieri et al report that ‘[b]etween 2009 and 2015, a third of patients transfused and managed in Canada’s largest zithromax 500mg for sale transfusion programme were switched from first-line, licensed drugs to regimens of unlicensed deferiprone’.3 This finding raises the ethically troubling question. How and why were so many locally transfused patients at UHN treated over such a long time period with an unlicensed drug of unproven safety and efficacy?. This ethical concern is followed immediately by another related zithromax 500mg for sale concern.

Why did the UHN thalassaemia programme continue to treat large numbers of its patients with deferiprone—despite ongoing evidence of inadequate effectiveness and serious (and often irreversible) adverse effects?. 3To recapitulate. The PLOS ONE paper demonstrates that a substantial proportion of UHN patients with thalassaemia was switched, between the years 2009 and 2015, from zithromax 500mg for sale first-line licensed therapies (deferasirox or deferoxamine) to deferiprone.

During this entire period, deferiprone was unlicensed in Canada. To this day in every jurisdiction in which deferiprone has been licensed zithromax 500mg for sale it has been licensed only as ‘last resort’ therapy. The ethical concern is to explain and to explore possible justifications for how and why so many patients at one particular thalassaemia treatment centre were prescribed a drug whose safety and efficacy were unproven in face of availability of licensed effective drugs.

The urgency of the concern derives partly from the paper’s finding that those patients who were switched to deferiprone displayed evidence of increases in body iron and experienced the harms associated with body iron increase.3 This finding raises a second zithromax 500mg for sale troubling ethical question. Why were patients not switched back to a first-line licensed therapy after they began to experience serious adverse effects from treatment with unlicensed deferiprone?. How and why?.

In a sustained effort to discover zithromax 500mg for sale answers to these questions, Olivieri and Gallie have been in communication since 2015, by email and in personal meetings, with senior officials at UHN. Olivieri and Gallie report, however, that no definitive answers have yet been provided to any of their questions. FOI requests were filed but they, too, failed to produce definitive answers zithromax 500mg for sale.

(Olivieri and Gallie to Smith &. Porter, 2019, https://inthepatientsinterest.org/wp-content/uploads/2019/12/2019-04-23-OlivieriGallie-to-SmithPorter.pdf).10 zithromax 500mg for sale I, too, wrote to the CEO/President of UHN and to the Chief of Medical Staff, in an attempt to discover answers to a number of the ethical questions posed in this commentary. The hospital, however, has not responded to any of my questions.11Olivieri and Gallie have recently posted documentation of their correspondence with senior UHN administrators (https://inthepatientsinterest.org/).

In September 2019 the UHN administration responded to the PLOS ONE paper by revealing that it had conducted a ‘Review of chelation practice in the red blood cell disorders program at UHN’. However, as Olivieri and Gallie document on the web, the hospital’s ‘Review’ does not address any of the safety zithromax 500mg for sale concerns flagged in the PLOS ONE paper (https://inthepatientsinterest.org/wp-content/uploads/2019/12/Letter-to-Smith-and-Hodges-2-12-19.pdf). Nor does the ‘Review’ address any of the ethical concerns raised here.Despite UHN’s apparent reluctance to provide the information requested, here’s what we know or can reasonably infer.

Deferiprone was unlicensed in Canada during the relevant period, that is, from 2009 to 2015 zithromax 500mg for sale. €˜Unlicensed’ is different from ‘off-label’, the latter referring to a drug that has been licensed but is being provided for an indication other than that for which it is approved. Prescription of any unlicensed drug to Canadian patients can be accomplished zithromax 500mg for sale only in one of two mutually exclusive ways.

Either through Health Canada’s ‘Special Access Program (SAP)’ or via an REB approved clinical trial. It has to be one or the other since, as Health Canada’s Guidance Document7 makes clear, patients cannot be simultaneously treated through SAP and in a research trial.12 Under the SAP, the treating physician must confirm to Health Canada that ‘conventional therapies have failed, or are unsuitable or unavailable’. Although some of the UHN patients’ records indicate that deferiprone was released under the SAP, Olivieri et al report that they ‘could identify no explanation for zithromax 500mg for sale a proposed switch to deferiprone that was supported by evidence of failure of licensed therapy prescribed as recommended’3.

Indeed, the authors write that many patients appear to have been switched to deferiprone despite optimal responses, or improvements during treatment with first-line therapies. Here’s the relevant paragraph from zithromax 500mg for sale their PLOS ONE article:Deferiprone was prescribed to 41 study patients between 2009 and 2015. We could identify in the electronic medical records no explanation for a proposed switch to deferiprone that was supported by evidence of failure of licensed therapy prescribed as recommended.

There was no indication that any patient switched to zithromax 500mg for sale deferiprone over these 6 years had ‘failed’ therapy with either deferoxamine or deferasirox. Many patients were recorded as tolerant of at least one and (in most), both licensed first-line chelating agents. Some had sustained minor adverse events during deferasirox that had resolved by the time deferiprone was prescribed.3In other words, according to the data found in UHN patient records, there is no evidence that the patients with thalassaemia who were switched to deferiprone met Health Canada’s eligibility criteria under SAP.

Since deferiprone is licensed only as a ‘last resort’ therapy, its employment to treat patients who can tolerate either of the first-line therapies might improperly expose those patients to risks of serious medical harms, up to and including death.On the other hand, one should also zithromax 500mg for sale consider the alternate possibility that, over the 6-year period studied by Olivieri et al, deferiprone was prescribed as part of a clinical trial. In favour of this hypothesis, one notes that the UHN physician primarily responsible for the widespread prescribing of deferiprone during the relevant time period claimed, in 2011, that deferiprone was provided to patients under a study approved by the REB of the UHN.8 UHN physicians also made this identical claim in a publicly available letter to the US FDA.9 Moreover, in response to an FOI application filed by Olivieri, UHN claimed that deferiprone was provided at UHN during a clinical trial (the data of which are protected from scrutiny under FOI laws), and not under SAP (the data of which are not protected from scrutiny under FOI). However, Olivieri et al have been unable to find any record of registration for such a trial, as required by Canadian Clinical Trial guidelines.13 Requests to the UHN administration zithromax 500mg for sale for confirmation that a clinical trial existed remain unanswered.14 My own efforts to find some registration record for this putative clinical trial of deferiprone have been equally unsuccessful.15Two core ethical principles.

Harm-minimisation and informed consentIf the deferiprone used to treat UHN patients with thalassaemia was obtained from Apotex as part of a randomised clinical trial, responsibility for approving the trial would fall to the UHN’s REB. In Canada, zithromax 500mg for sale both researchers and REBs are governed by the Tri-Council Policy Statement (TCPS) ‘Ethical Conduct for Research Involving Humans’.10 The 1998 version of this policy statement (TCPS1) and the subsequent 2010 version (TCPS2), both applicable to research trials during this period, stipulate that clinical trials must be designed so that harm to research subjects will be minimised.16 For example, TCPS1 specifies, in section 1.5, that ‘Research subjects must not be subjected to unnecessary risks of harm’. TCPS2, under the rubric ‘Core Principles’, requires similarly that clinical trials must ‘ensure that participants are not exposed to unnecessary risks’.Data presented by Olivieri et al in their PLOS ONE Study indicate that UHN patients exposed to unlicensed deferiprone, either as monotherapy or in combination with low dose of a first-line chelator (‘combination therapy’), experienced significant harms as a result of poor iron control, but very few if any compensating benefits.We provide new evidence of inadequate reduction in hepatic iron, a 17% incidence of new diabetes and new liver dysfunction in 65% of patients, many who were challenged and rechallenged with deferiprone despite elevated liver enzymes developed during previous exposure.

We identified no evidence of zithromax 500mg for sale ‘cardio-protective’ effect during deferiprone therapy.3In light of PLOS ONE Study data indicating serious adverse events (SAEs) for patients switched to deferiprone from first-line drugs one is led to question why the study protocol did not, in anticipation of such a contingency, provide for a resumption of licensed therapy for patients doing poorly on the unlicensed drug. Moreover, the investigators were obliged to report adverse events to the hospital’s REB. Were the adverse events so reported?.

And if they were then why did the UHN REB not seek to protect patient safety by insisting that licensed therapy be resumed for deferiprone-harmed zithromax 500mg for sale patients?. In an effort to establish whether the deferiprone ‘clinical trial’ satisfied the TCPS harm-minimisation principle, I made inquiries about how the adverse findings described by the PLOS ONE paper were reported to the hospital’s REB and also how they were reported to the regulatory authorities, that is, Health Canada and the US FDA. But my queries, like those made previously by Olivieri and Gallie, have not succeeded in eliciting this ethically relevant information.17 Neither UHN nor its thalassaemia clinic zithromax 500mg for sale responded to my letters of inquiry.

It is known, however, from a publicly available 2011 document, that physicians in the UHN thalassaemia clinic strongly supported the market approval of deferiprone by the FDA.18 This support is difficult to reconcile with the toxicities recorded in UHN patient records. So, a final zithromax 500mg for sale verdict on the issue of whether the UHN deferiprone ‘clinical trial design’ violated the TCPS harm-minimisation principle cannot be reached until those involved in conducting and monitoring clinical trials at UHN make available the relevant information. An independent public inquiry may be necessary to achieve the necessary degree of accountability.Reference has been made, above, to the TCPS core ethical requirement of harm-minimisation, applicable in Canada both to researchers and to REBs.

It is important to note, however, that TCPS2, like its predecessor, TCPS1 (and, indeed, like virtually every postwar code of research ethics) also stipulates as a second ‘core principle’ that ‘Researchers shall provide to prospective participants, or authorised third parties, full disclosure of all information necessary for making an informed decision’.19 Moreover, as the then-current TCPS guidelines make clear, ‘consent is an ongoing process’. So, assurance should be given to prospective participants that they ‘will be given in a timely manner throughout the course of the zithromax 500mg for sale research project, information that is relevant to their decision to continue or withdraw from participation’.20 (My emphasis). Finally, TCPS2 imposes on researchers the additional ethical requirement that they disclose to research subjects ‘information concerning the possibility of commercialisation of research findings, and the presence of any real, potential or perceived conflicts of interest on the part of the researchers, their institutions or the research sponsors’.21 There is also an expectation that conflicts of interest will be disclosed to the REB.

Whether there was adequate disclosure of Apotex funding either to research subjects or to the UHN REB is still unknown.Thus, in zithromax 500mg for sale order to assess the ethical adequacy of the putative UHN thalassaemia clinical trial one must inquire whether UHN patients/subjects were given adequate risk information when they were first enrolled, subsequently, when they were switched from treatment with deferasirox or deferoxamine to treatment with deferiprone and then, finally, when they experienced SAEs. That is, in order to know whether the putative deferiprone clinical trial conformed to established principles of research ethics, one would need to know whether patients/research subjects understood that they were being switched from licensed first-line drugs of proven efficacy to an unlicensed and unproven third-line drug. One would also need to know whether the deferiprone ‘research subjects’ were informed about conflicts of interest zithromax 500mg for sale arising from Apotex donations (A) to the UHN.

(B) To the hospital’s thalassaemia programme,22 as well as the hoped-for commercialisation of deferiprone via Health Canada and FDA licensing.If there was a failure to obtain ongoing informed consent and/or a failure to disclose conflicts of interest (to patients and to the REB) then this would constitute a violation of research ethics. Unfortunately, my attempts to elicit the clinical trial’s consent to research information from the UHN and its thalassaemia clinic met with as little success as earlier attempts made by the PLOS ONE authors.23REB review. Safety monitoringAlthough every clinical trial requires safety monitoring, those trials which involve non-negligible risk of significant harm to patients/subjects require especially rigorous safety monitoring.24 Because the exposure of deferiprone to UHN patients posed risks of organ dysfunction and death, the need for safety zithromax 500mg for sale monitoring was exigent.

As the TCPS1 and TCPS2 both make clear, those who conduct research have an obligation to monitor and protect the safety of their research subjects.Moreover, it is now widely recognised that individuals closely involved with the design and conduct of a trial may not be able to be fully objective in reviewing interim data for any emerging concerns.25 Hence the importance of REBs, part of whose role is to provide safety monitoring initially and, for ongoing trials, over the entire period of the trial. In order to assess the adequacy of the safety monitoring for the UHN ‘deferiprone trial’ one would need to know whether the hospital’s REB was provided with regular and accurate reports of SAEs and what actions this REB took in response to those reports.It has become common practice in North America ‘that for any controlled trial of any size that will compare rates of mortality or major morbidity’, a data safety monitoring board (DSMB) will be established.26,11 12 A DSMB is constituted by a panel of independent (and otherwise unbiased) individuals with expertise pertinent to reviewing zithromax 500mg for sale trial data on a regular ongoing basis. Its role is to advise the sponsors regarding the safety of trial subjects and to recommend early termination where indicated, for example, on grounds of patient safety.27Since there are no specifically Canadian requirements with respect to the establishment of DSMBs, Canadian REBs tend to follow FDA guidelines.

Those guidelines recommend that a DSMB should be established when the study end point is such zithromax 500mg for sale that a highly favourable or unfavourable result at an interim analysis might ethically require termination of the study. Advance information suggesting the possibility of serious toxicity with the study treatment is another a priori reason for safety concern that would justify the establishment of a DSMB.12For reasons given above, the UHN deferiprone trial appears to have been a prime candidate for the establishment of a DSMB. But it is not known whether the study’s research protocol, purportedly submitted for approval to the hospital’s REB, included a DSMB.

Nor is it known whether a DSMB was established and reported regularly to the trial’s sponsors zithromax 500mg for sale. Data on the toxicity of deferiprone, provided by Olivieri et al from their retrospective study of UHN patient records, suggest that had a DSMB existed for this putative clinical trial the trial might, on grounds of patient safety, have been a candidate for premature cancellation. Lacunae in our knowledge of the safety monitoring provisions of the deferiprone ‘clinical trial’ make it difficult to zithromax 500mg for sale reach any firm conclusion as to whether the ‘trial’ met prevailing safety monitoring requirements.The apparent unwillingness of the UHN to answer questions relating to safety monitoring might mean that an inquiry is needed to fill in our knowledge gaps and thereby make ethical evaluation possible.

For the findings of such an inquiry to be minimally credible it should be carried out by individuals who possess the requisite scientific/medical expertise and who are independent of the hospital and its thalassaemia clinic and who are demonstrably impartial. An inquiry carried out, for example, by someone whose research has been funded by Apotex and/or by an expert with close professional and personal ties to one or more of the physicians in the UHN thalassaemia clinic would not satisfy the hospital’s duty of accountability for patient safety.Ethical concernsA RecapitulationThe serious complications experienced by deferiprone-exposed zithromax 500mg for sale UHN patients, as described by Olivieri et al in their PLOS ONE article, raise a number of ethically important questions. How could an unlicensed drug of unproven efficacy and safety—a drug that has been questioned by regulatory agencies such that it is licensed only as a “last resort” therapy—have been administered to so many patients over a period of so many years when two licensed drugs, both proven adequately safe and effective and licensed as first-line therapies, were available?.

How did UHN physicians gain access to deferiprone from Health Canada when there is little evidence in UHN patient records that the deferiprone-exposed patients satisfied Health Canada’s criteria for Special Access?. Why was a putative UHN REB-approved research study involving deferiprone not zithromax 500mg for sale registered as a clinical trial?. Did the trial design include a DSMB, to protect patient safety and, if not, why not?.

Were SAEs reported to the UHN REB and to regulators, as zithromax 500mg for sale required?. Were deferiprone-treated UHN patients with thalassaemia adequately informed of the unlicensed status, unproven efficacy and reported toxicities of deferiprone?. Were deferiprone-exposed patients informed of harms they themselves zithromax 500mg for sale had sustained during deferiprone from this exposure?.

28 Did the evidence of systematic treatment failure, as outlined in the PLOS ONE paper, raise red flags for thalassaemia clinic physicians and for the REB of UHN?. And if serious problems were flagged what actions were taken to protect patient safety?. Institutional conflict of interestThe literature on biomedical conflicts of interest tends to focus on the ways in which financial support of individual researchers by the pharmaceutical industry can adversely affect both research integrity and patient safety.13–16 But similar ethical problems arise at the macro level when institutions, such as hospitals and clinics, depend on drug company funding to support patient care and clinical research.13 15 Notable scandals associated with institutional conflicts of interest include the David Healy/Eli Lilly scandal at zithromax 500mg for sale Toronto’s Centre for Addictions and Mental Health (CAMH),13 the Aubrey Blumsohn/Proctor and Gamble scandal at Sheffield University (UK)17 and the Carl Elliott/Janssen Pharmaceuticals scandal at the University of Minnesota.17 The underlying pattern in each of these scandals involves (A) a biomedical researcher who is concerned about patient safety coming into conflict with (B) a pharmaceutical company which funds both the researcher’s hospital and university and (C) a failure by the institutions involved vigorously to defend patient safety and research integrity when doing so might offend a wealthy sponsor.It should not be assumed that corporate influence on university medical centres is necessarily exerted by means of threats or other direct forms of intervention.

The mere presence of corporate funding can be sufficient to produce a corporate-friendly result. This point is illustrated by a recent STAT article, a zithromax 500mg for sale propos the financial support which Purdue Pharma provided to Massachusetts General Hospital. The very title of the article encapsulates the ethical problem of institutional conflict of interest.

€˜Purdue Pharma cemented ties with universities and hospitals to expand opioid sales, documents contend’.18 Nor should it zithromax 500mg for sale be supposed that the problem of institutional conflict of interest arises exclusively in the context of biomedical research. A recent Guardian article on the Mobil Oil Corporation describes how ‘Oil giant Mobil sought to make tax-exempt donations to leading universities … to promote the company’s interests and undermine environmental regulation, according to internal documents from the early 1990s obtained by the Guardian’.19As mentioned above, deferiprone, whose safety and efficacy are the central concern of Olivieri et al’s PLOS ONE paper, is manufactured by Apotex. When we seek to understand why deferiprone was so frequently prescribed to UHN patients, from 2009 to 2016, despite its being unlicensed and despite evidence of poor patient outcomes,3 it may be relevant to note that Apotex provided substantial funding to the UHN thalassaemia clinic.29 Moreover, a publicly zithromax 500mg for sale displayed UHN banner lists ‘Apotex Inc – Barry and Honey Sherman’ as having donated between $1 million and $5 million to the hospital itself.30As every biomedical researcher understands, correlation is not causation.

Nevertheless, the correlation between industry funding of hospitals, on the one hand, and industry-friendly decisions made by researchers and administrators at those hospitals, on the other, is worth pondering. Physicians and researchers who speak or write critically of drugs manufactured by wealthy donor companies may find that their careers are jeopardised. Nancy Olivieri’s dismissal from two Apotex-funded teaching hospitals illustrates this phenomenon as does the termination of psychiatrist David Healy from Toronto’s CAMH.13 Healy’s appointment zithromax 500mg for sale as Head of the CAMH Mood Disorders Clinic was rescinded almost immediately after he gave a public lecture at the hospital—a lecture in which he called for further research into the potentially adverse effects of Eli Lilly’s antidepressant drug, Prozac.

Healy was particularly concerned about SSRI-induced suicidal ideation. After his lecture the hospital decided that he was not ‘a good zithromax 500mg for sale fit’ with their programme and terminated his appointment. Shortly thereafter the hospital opened its Eli Lilly wing.13UHN, like every other research and teaching hospital in Canada, receives most of its funding, directly or indirectly, from governments.20 ,31 Nevertheless, UHN, again like other hospitals, faces ongoing pressure to find additional sources of revenue to support both patient care and clinical research.32 The pharmaceutical industry is a prime source of much-needed ‘top-up’ financial support for Canadian hospital research and clinical care.21 Hospital administrators, researchers and clinicians are thereby placed, willy nilly, in a conflict-of-interest situation.

Because of funding exigencies, hospitals and other healthcare zithromax 500mg for sale institutions, like individual physicians and researchers, have a strong vested interest in pleasing corporate sponsors and encouraging their ongoing support. Moreover, institutional administrators, not unlike individual researchers and clinicians, typically experience a need to express their gratitude to donors by returning kindness for kindness and benefit for benefit. Thus, both the need for ongoing corporate sponsorship and the need to reciprocate for past corporate generosity create for hospital administrators (as well as for researchers and clinicians who work within hospitals) a conflict-of-interest situation in which their decision making may be skewed, consciously or unconsciously, in favour of the benefactors’ products.13 15 16 21Here’s an example of the manner in which an institutional conflict-of-interest situation can potentially bias the judgement of hospital administrators.

Hospitals are required to exercise their disinterested judgement zithromax 500mg for sale in the appointment of medical and scientific staff and in the ethical monitoring of research. This moral obligation follows directly from their fundamental commitment to promote and defend patient safety and research integrity. To illustrate zithromax 500mg for sale.

UHN’s website, under the heading Purpose, Values and Principles, declares that ‘[o]ur Primary Value and above all else. The needs of patients come first’.22 It would be difficult to find any hospital whose Mission Statement did not proclaim a similar commitment to the zithromax 500mg for sale primacy of patient well-being. In a similar vein, the UHN website, under the heading Information for Patients, subheaded Our Mission, declares.

€˜We believe that health equity is achieved when each person is. Enabled to choose the best care and treatment based on the most current knowledge available’.From this fundamental commitment, it follows that healthcare institutions zithromax 500mg for sale are obliged rigorously to monitor the quality of care provided to their patients and research subjects. As an important element of protecting patient safety, hospitals are required to appoint the most qualified and competent candidates to clinical and research positions.

But, as noted above, conflicts of interest are a risk factor for bias, conscious or unconscious, in personnel decisions.22 So, when a research hospital depends on corporate donations there is a risk zithromax 500mg for sale that physicians and researchers may be appointed to key positions because they are known to be sympathetic to the donors’ product(s) rather than because they are the best qualified and the most competent. Contrariwise, physicians and researchers believed to be unsympathetic to the donors’ products are at risk of losing their jobs or of not being hired in the first place. The cases of Olivieri, Healy and Blumsohn illustrate this point.13 17As explained above, we know from the extensive literature on conflict of interest that when research and clinical care are funded by industry zithromax 500mg for sale there is a marked tendency for both to favour the sponsors’/donors’ products.13 15 16 18 Significantly, the UHN itself explicitly recognises the danger to patient safety posed by systemic biases.

Its Mission Statement commits the hospital to ensuring that every patient is ‘[m]ade aware of existing systemic biases to support the best possible health decisions’.22 Unfortunately, it is not possible at present to ascertain whether UHN conformed to this ethical commitment in the case of its deferiprone research/treatment clinic. In order to make such an ethical determination we would need to know the mechanism by which the UHN thalassaemia clinic gained access to deferiprone and whether the clinic provided information about systemic bias to patients with thalassaemia and to the hospital’s REB.ConclusionsHospitals worldwide proclaim that their primary commitment is to meet the needs of their patients. Institutional codes zithromax 500mg for sale of ethics and mission statements insist that patient needs come first.

Indeed, meeting ‘patient needs’ is agreed to be the fundamental value to which all other hospital goals should be subordinated. Toronto’s UHN declares unequivocally that zithromax 500mg for sale it shares this value. €˜[t]he needs of patients come first’.22Although patients have many and various needs, the need for safety must be counted as the sine qua non.

If the need for safety is not met then other needs become irrelevant.The findings of Olivieri et al in their PLOS zithromax 500mg for sale ONE paper raise many troubling questions about the safety of patients in UHN’s thalassaemia clinic. One would expect that when top UHN officials became aware of the PLOS ONE data they would immediately have recognised the ethical red flags. Hospitals are ethically obliged both to investigate thoroughly possible safety failures and to rectify any problems identified.Over a period of several years, both before and after the publication of their research findings, Drs Olivieri and Gallie communicated regularly with UHN officials (https://inthepatientsinterest.org/).

Multiple safety concerns were brought to the hospital’s attention zithromax 500mg for sale. Numerous questions were asked by the PLOS ONE authors and specific concerns were raised. To date, the hospital zithromax 500mg for sale has not definitively addressed these issues.

I posed a series of ethically salient questions to these same hospital officials (see online supplementary appendix A). My queries were zithromax 500mg for sale ignored. There was no response from UHN.Supplemental materialIf a healthcare institution such as UHN claims that patient safety is its top priority then when safety issues are raised, it necessarily incurs an obligation of accountability.

It would, for example, scarcely be adequate for a hospital, such as UHN, unilaterally to investigate alleged failures, declare that there has been no violation of patient care standards, and then to stonewall all further inquiries, whether those inquiries originate from its own medical staff, as was the case with Olivieri and Gallie, or from outside scholars, as was the case with me.When an unlicensed drug is prescribed to hospital patients, over a period of years, as happened in the UHN thalassaemia programme, it is surely the hospital’s obligation to answer questions about how and why this extraordinary practice occurred. When hospital records reveal that patients switched from licensed to unlicensed medication, have experienced serious harms, up to and including death, it is surely zithromax 500mg for sale the hospital’s obligation to answer in a conscientious and complete manner all the ethically troubling questions that have been identified. This obligation of accountability is owed both to patients and to staff.

Thus far, UHN has not been willing to accept the implications of its own mission statement (https://www.uhn.ca/corporate/AboutUHN/Quality_Patient_Safety).The PLOS ONE Study by Olivieri Sabouhanian and Gallie spurs us to inquire whether zithromax 500mg for sale the benefits which accrue to society from corporate sponsorship of healthcare institutions may, on balance, be outweighed by the associated harms. Admittedly, for governments committed to constraining public expenditures, the transfer of substantial healthcare costs to private corporations represents a benefit for public finances. But, as we have seen, when one considers this financial zithromax 500mg for sale benefit, one ought also to take into account the spectrum of negative consequences potentially generated by institutional conflicts of interest.

The price for our continued acceptance of corporate funding of scientific research and clinical care may be the erosion of public trust. Arguably, it would be preferable if our research hospital were to aim instead for the complete elimination of systemic biases.Data availability statementAll data relevant to the study are included in the article or uploaded as supplementary informationEthics statementsPatient consent for publicationNot required.AcknowledgmentsThe author thanks the editors of JME and two JME reviewers for their criticisms of and suggestions for change to an earlier version of this paper..

Levaquin vs zithromax

Once upon a time, in a levaquin vs zithromax land not far away, there was a horrible zithromax that instilled terror in every town and home. Although most people who became infected showed no symptoms or recovered within a week, in a small fraction of cases the illness progressed, causing loss of reflexes and muscle control, paralysis and, sometimes, death. Children were especially levaquin vs zithromax vulnerable, so parents watched anxiously for any sign of , often keeping them away from swimming pools, movie theaters, bowling alleys, anywhere where there were crowds and the dreaded microbe might lurk. Travel and business were sometimes curtailed between places with outbreaks, and public health authorities imposed quarantines on healthy people who may have been exposed, in order to halt the spread of the disease.

In the first half of the 1950s, with no cure and no treatment, more than 200,000 Americans were disabled by the poliozithromax. The zithromax was second only to the atomic levaquin vs zithromax bomb as to what Americans feared most. Then, on April 12, 1955, public health officials at the University of Michigan announced that a “safe, effective, and potent” treatment had been found. This set off a national celebration that recalled the end of World War II.

Church bells levaquin vs zithromax rang, car horns honked, people wept with relief. President Eisenhower invited the treatment’s inventor, Jonas Salk, to the White House. In a Rose Garden ceremony, the former Supreme Allied Commander told the scientist in a trembling voice, “I should like to say to you that when I think of the countless thousands of American parents and grandparents who are hereafter to be spared the agonizing fears of the annual epidemic of poliomyelitis, when I think of all the agony that these people will be spared seeing their loved ones suffering in bed, I must say to you I have no words in which adequately to express the thanks of myself and all the people I know—all 164 million Americans, to say nothing of all the people in the world that will profit from your discovery.” But, alas, not everyone joined the party and expressed such gratitude. One group in particular did not levaquin vs zithromax welcome the treatment as a breakthrough.

Chiropractors actively opposed the vaccination campaign that followed Salk’s triumph. Many practitioners dismissed the role of contagious pathogens and adhered to the founding principle of chiropractic that all disease originated in the spine. Just a few years after the introduction of the treatment, as the number of polio cases was declining rapidly, an article in the Journal of levaquin vs zithromax the National Chiropractic Association asked, “Has the Test Tube Fight Against Polio Failed?. € It recommended that, rather than take the treatment, once stricken, “Chiropractic adjustments should be given of the entire spine during the first three days of polio.” Opposition to the polio treatment and to vaccination in general continued in the ranks such that even four decades later, long after polio had been eradicated from the United States, as many as one third of chiropractors still believed that there was no scientific proof that vaccination prevents any disease, including polio.

That belief and resistance continues to this day, with some chiropractors campaigning against state vaccination mandates. I was shocked when levaquin vs zithromax I first learned about chiropractors’ opposition to the polio treatment. The treatment is widely viewed as one of medicine’s greatest success stories. Why would anyone have opposed it?.

My shock turned into excitement, however, when I began to recognize the chiropractors’ pattern of arguments was uncannily similar to those I was familiar with from creationists who deny evolutionary levaquin vs zithromax science. And once I perceived those parallels, my excitement became an epiphany when I realized that the same general pattern of arguments—a denialist playbook—has been deployed to reject other scientific consensuses from the health effects of tobacco to the existence and causes of climate change. The same playbook is now being used to deny facts concerning the buy antibiotics zithromax. In brief, the six principal plays in the levaquin vs zithromax denialist playbook are.

Doubt the ScienceQuestion Scientists’ Motives and IntegrityMagnify Disagreements among Scientists and Cite Gadflies as AuthoritiesExaggerate Potential HarmAppeal to Personal FreedomReject Whatever Would Repudiate A Key Philosophy The purpose of the denialism playbook is to advance rhetorical arguments that give the appearance of legitimate debate when there is none. My purpose here is to penetrate that rhetorical fog, and to show that these are the predictable tactics of those clinging to an untenable position. If we hope to find any cure for (or treatment against) science denialism, scientists, journalists and the public need to be able recognize, understand and anticipate these plays levaquin vs zithromax. To illustrate how the playbook works—and sadly, it is very effective –I will break down the chiropractor and creationist versions, which have endured for many decades in spite of overwhelming evidence, and point out parallels to the antibiotics rhetoric.

THE PLAYBOOK 1. Doubt the levaquin vs zithromax Science The first tactic of denialism is to raise objections to scientific evidence or interpretations. This may take the form of seemingly legitimate specific arguments against a scientific claim. For example, chiropractors sought other explanations besides treatment efficacy to account for the decline of infectious diseases.

€œThe Center for Disease Control statistics make it clear that the majority of diseases that are now routinely vaccinated against were disappearing before either the cause was levaquin vs zithromax discovered or the treatment developed,” stated a 1995 letter to the editor of Dynamic Chiropractic magazine. In polio’s case, this argument does not hold up against the facts that. (a) the disease was surging in the 1950s. (b) the treatment levaquin vs zithromax was proven effective in a massive double-blind, placebo-controlled trial.

And (c) s declined precipitously after the introduction of the treatment. Alternatively, some statements are blanket arguments against an entire scientific discipline. For example, Henry Morris, whose 1961 book The Genesis levaquin vs zithromax Flood is credited with reviving the creationism movement, alleged. €œSince there is no real scientific evidence that evolution is occurring at present or ever occurred in the past, it is reasonable to conclude that evolution is not a fact of science, as many claim.

In fact, it is not even science at all, but an arbitrary system built upon faith in universal naturalism.” 2. Question Scientists’ Motives and Integrity As a growing body of consistent evidence can be hard to explain away, levaquin vs zithromax one fallback is to impugn the source. In the vaccination arena, this often takes the form of alleging financial conflicts of interest on the part of scientists, greed on the part of manufacturers, and complicity of government officials. €œIt appears that the scientific foundation on which these treatments have been erected is fragile enough that only compulsory laws, expensive public relations efforts, outrageous propaganda, and expensive advertising must ensue for compliance to be maintained,” wrote one author in American Chiropractor.

Salk, by the way, filed no levaquin vs zithromax patent. In the evolution arena, scientists are often accused of being part of a conspiracy to undermine religion through educational systems. Kenneth Cumming, of the Institute for Creation Research, objected to a PBS series on evolution by drawing a parallel to the 9/11 attackers. €œAmerica is being attacked from within levaquin vs zithromax through its public schools by a militant religious movement of philosophical naturalists (i.e., atheists) under the guise of secular Darwinism.

Both desire to alter the life and thinking of our nation.” One noteworthy counter to such assertions is the Clergy Letter Project, which has gained the support of more than 15,000 Christian clergy for the teaching of evolution. 3. Magnify Disagreements among Scientists and Cite Gadflies as Authorities In all scientific arenas, there is honest disagreement about the interpretation of levaquin vs zithromax evidence. However, these differences are deliberately inflated by denialists to imply a lack of consensus on more fundamental points, while often propounding the contradictory views of a few unqualified outliers.

An example of the latter is how some chiropractors have seized on the anti-vaccination stance of one critic, Viera Scheibner. Her claim that there is no evidence levaquin vs zithromax for treatment efficacy or safety is cited repeatedly, while overlooking the fact that her training and expertise is in geology, not medicine. In the evolution arena, differences of interpretation among scientists are relished by antievolution voices. For example, the initial discovery of a new fossil hominid usually elicits some different interpretations and expressions of uncertainty in the scientific community.

Creationists often mischaracterize these normal dynamics of scientific discourse as levaquin vs zithromax “skepticism” over the significance of such finds so as to discount them. By overblowing legitimate disagreements and propounding “alternatives” to evolution, denialists often make appeals to “teach the controversy,” when no such controversy exists in the scientific community. Different interpretations of a fossil do not negate the discomfiting evidence for the antiquity of human ancestors. Antievolution leaders in the levaquin vs zithromax U.S.

Also include a small number of scholars whose credentials are in other disciplines. For example, the abovementioned Henry Morris was an engineer, not a biologist. Phillip E levaquin vs zithromax. Johnson, whose book Darwin on Trial inspired many adherents to the intelligent design movement, was a law professor with no formal training in biology.

A lack of credentials or status within the scientific community is often seen not as a liability but as a virtue. Scientists Pascal Diethelm and Martin McKee note, “Denialists are usually not deterred by the extreme isolation of their theories, but rather see it levaquin vs zithromax as the indication of their intellectual courage against the dominant orthodoxy and the accompanying political correctness, often comparing themselves to Galileo.” 4. Exaggerate Potential Harm When the evidence contradicts a position, another recourse is to try to incite fear. No treatment or medicine is 100 percent safe, without any risk of side effects.

Chiropractors have long levaquin vs zithromax emphasized the potential side effects of treatments, for example in a statement in Dynamic Chiropractic offering a litant of possible effects. €œdeath, encephalopathy, demyelinating diseases, brachial neuritis, Guillain-Barré syndrome, s generated by treatment agents, anaphylaxis, subacute sclerosing panencephalitis, seizure disorder, optic neuritis, arthritis,” and so on. However, they generally fail to acknowledge the serious consequences of s that would be prevented by vaccination. But what harm could arise from knowing a bit about levaquin vs zithromax evolution?.

Well, Hitler, of course!. “Of the many factors that produced the Nazi Holocaust and World War II,” wrote one critic in the Journal of Creation, “one of the most important was Darwin’s notion that evolutionary progress occurs mainly as a result of the elimination of the weak in the struggle for survival.” It is an oft-repeated argument that has no bearing of course on the veracity of Darwin’s theory. Vaccination foes levaquin vs zithromax have lobbed similar accusations, likening physicians who administer treatments to Nazi doctors and alleging that treatments violate the 1947 Nuremberg Code of medical ethics. 5.

Appeal to Personal Freedom If fear is not persuasive, there is another fallback position that resonates strongly with Americans. The freedom levaquin vs zithromax of choice. The American Chiropractic Association leaned on this cherished notion when it established its official vaccination policy. €œSince the scientific community acknowledges that the use of treatments is not without risk, the American Chiropractic Association supports each individual’s levaquin vs zithromax right to freedom of choice in his/her own health care based on an informed awareness of the benefits and possible adverse effects of vaccination.

The ACA is supportive of a conscience clause or waiver in compulsory vaccination laws… providing an elective course of action regarding vaccination.” Likewise, the International Chiropractic Association “questions the wisdom of mass vaccination programs” and views compulsory programs as an infringement of “the individual’s right to freedom of choice.” Similarly, the teaching of evolution in public schools is viewed as an assault upon the religious freedom of those who oppose it. Those holding this view advocate for disclaimers on textbooks (“just a theory”), the teaching of “alternative” views of the history of life (Genesis or intelligent design), or the freedom to opt out of the evolution curriculum of biology classes. Notably, the levaquin vs zithromax U.S. Supreme Court has rejected challenges to compulsory vaccination partly on the grounds that individual belief cannot subordinate the safety of an entire community.

And U.S. Courts have repeatedly struck down attempts to subvert the teaching of evolution as religiously motivated and violations of the establishment clause of the First Amendment levaquin vs zithromax of the U.S. Constitution. 6.

Reject Whatever Would Repudiate a Key Philosophy Once the levaquin vs zithromax courts have spoken, and the scientific evidence grows to be overwhelming, one might think that denialists would be out of plays. But there is one last line of defense that reveals the nucleus of denial. It is not that some scientific claim is untrue. It is that it is unacceptable levaquin vs zithromax in light of some philosophical commitment.

The science must be summarily rejected. Chiropractic was founded in the early 20th century on the assertion that all disease has its origins in misalignments of the spine. €œChiropractors have found in every disease that is supposed to be contagious, a cause in the levaquin vs zithromax spine,” claimed Bartlett Joshua Palmer, the son of chiropractic founder Daniel David Palmer. Acceptance of germ theory and vaccination would repudiate the founding premise of the profession that all disease stems from vertebral misalignments.

Therefore, that premise cannot be questioned. With respect levaquin vs zithromax to evolution, Henry Morris made it plain. €œWhen science and the Bible differ, science has obviously misinterpreted its data.” Any credence granted to evolutionary science is a threat to a worldview based on interpretation of the Bible. David Cloud, a publisher of Bible study materials argues.

€œIf the Bible does not mean what it says, levaquin vs zithromax there is no way to know what it does mean. Historian of science and author Naomi Oreskes has coined a term for this stance. €œimplicatory denial”—the rejection of scientific findings because we don’t like their implications. As these positions are reinforced by family or community, they harden into part levaquin vs zithromax of one’s identity.

€œIn this way, cultural identity starts to override facts,” Norwegian climate psychologist Per Espen Stoknes has said. €œAnd my identity trumps truth any day.” Psychologists Elliot Aronson and Carol Tavris write in the Atlantic. €œ[W]hen people feel a strong connection to a political party, leader, ideology, or belief, they are more likely to levaquin vs zithromax let that allegiance do their thinking for them and distort or ignore the evidence that challenges those loyalties.” The denialist playbook is now erupting around the antibiotics. Although buy antibiotics is new, the reactions to public health measures, scientific claims, and expert advice are not.

Attitudes and behaviors concerning the threat posed by the antibiotics (doubting the science), the efficacy of lockdowns and mask wearing (freedoms being eroded) and alternative treatments (gadflies over experts) are being driven as much or more by rhetoric than by evidence. Polls indicate that despite the devastating health and economic impacts of the zithromax, with respect to a potential treatment we are nowhere near as united as Americans were in 1955 levaquin vs zithromax. But as epidemiologist Michael Osterholm noted in June, “Eventually there won't be any blue states or red states. There won't be any blue cities or red rural areas.

It'll all be buy antibiotics colored.” Now, sadly, there is no denying that.PANAMA Vampire bats monitored at the Smithsonian Tropical Research Institute have fewer interactions with levaquin vs zithromax family and friends when ill, biologists say. But they do not seem to stay apart intentionally—instead sick bats are simply too lethargic to call out to or groom one another. CANADA The last fully intact ice shelf in Canada collapsed into the Arctic Ocean this summer. Located in the levaquin vs zithromax territory of Nunavut, the Milne Ice Shelf lost 80 square kilometers of ice—40 percent of its area—in just two days.

CHILE Living 6,700 meters above sea level, a yellow-rumped leafeared mouse found at the summit of the dormant volcano Llullaillaco is the highest-dwelling mammal ever documented. It remains unclear how the animal survives the oxygen scarcity and freezing temperatures at this elevation. RUSSIA An analysis of ancient woolly rhino DNA from Siberia revealed that the population size was stable for thousands of years before the mammal's extinction 14,000 years ago, suggesting that a warming climate—not hunting by humans—most likely triggered levaquin vs zithromax its demise. ETHIOPIA Paleoanthropologists unearthed a 1.4-million-year old hand ax made from a hippo's leg bone.

Together with recently discovered stone tools, the ax indicates that Homo erectus had a diverse tool kit several hundred thousand years earlier than scientists had suspected. ANTARCTICA Contrary to researchers' expectations, methane-eating microbes failed to rapidly contain the first methane leak detected on levaquin vs zithromax the Antarctic seafloor. The finding means more of the potent greenhouse gas may have been pouring into the atmosphere than previously thought.With black holes, what you see is not what you get. The ring of light visible around a black hole’s silhouette originates from a radius of about 5GM/c2, where G is Newton’s constant, M is the black hole mass and c is the speed of light.

This ring is larger than the event horizon of a nonspinning black hole by a factor of 2.5—or up levaquin vs zithromax to five with the addition of spin. And so, truth in advertising requires me to tell you the Event Horizon Telescope did not actually image the event horizon of the supermassive black hole in the galaxy M87, but rather the light from much farther out. For a distant observer, the difference between the light ring and the horizon is academic, but for an astronaut en route into the black hole, the difference is existential. Entering the ultimate prison levaquin vs zithromax walls associated with the horizon implies a death sentence, with no opportunity for sharing the experience with the outside world.

After less than a day, the astronaut’s body will reach the singularity and be torn apart by gravitational tidal force. In 1939, Albert Einstein wrote a paper in Annals of Mathematics doubting that black holes exist in nature. Now, black holes are in vogue—so much so levaquin vs zithromax that the 2020 Nobel prize in physics was awarded to three scientists who have studied them. This gave me reason to celebrate, as the founding director of Harvard’s Black Hole Initiative, which brings together astronomers, physicists, mathematicians and philosophers, all dedicated to research on black holes.

Karl Schwarzschild would have been delighted to join our celebration. Unfortunately, he died on the German-Russian front during World War I over a levaquin vs zithromax century ago, just half a year after deriving the nonspinning black hole solution to Einstein’s equations. One of the recipients of the 2020 Nobel, Roger Penrose, demonstrated that black holes are a robust prediction of Einstein’s general theory of relativity, and in doing so invented a new mathematical tool to depict spacetimes, called Penrose diagrams. He also showed that it is possible to extract energy from a spinning black hole as if it were a flywheel, through the so-called Penrose process.

His cosmic censorship hypothesis protects our ability to make predictions about the future of universe from the pathology of black hole singularities, where the spacetime curvature blows up and Einstein's theory breaks levaquin vs zithromax down. This conjecture asserts that all singularities are hidden behind an event horizon so that matter approaching them has no causal effect on what happens outside the horizon. Just as they say about Las Vegas, "whatever happens inside the horizon, stays inside the horizon." The two other Nobel laureates in physics this year, Reinhard Genzel and Andrea Ghez, demonstrated that a black hole weighing four million suns resides at the center of our own Milky Way galaxy. The discovery of quasars more than half a century ago implied that levaquin vs zithromax supermassive black holes form generically at the centers of galaxies.

By monitoring the motion of massive stars around the center of our own galaxy in real time, as if they were planets orbiting a star, they demonstrated the existence of a black hole there. Prior to their work, it was unclear whether a black hole is associated with the stationary radio source Sagittarius A*. Not only did they measure the levaquin vs zithromax mass of the black hole, but they also tested Einstein's theory of gravity. The stars they discovered move in two orbital planes.

In a new paper with Giacomo Fragione, we showed that the black hole spin must therefore be small, or else it would blur the strict orbital planes of the stars over their lifetime. The teams led by levaquin vs zithromax Genzel and Ghez were engaged in intense competition, elevating their efforts to great heights. This was a wonderful demonstration of how rivalry promotes good science. One of the stars traced by Genzel and Ghez, labeled S2, completes an orbit around the galactic center every 16 years.

The related advice I gave astronomy students is to focus their Ph.D levaquin vs zithromax. Project on a source like S2 that evolves over a timescale of a decade or two, so that they will continue to learn new things about the source throughout their careers. If Stephen Hawking was alive, he would have been a worthy contender for this year's Nobel prize, since his work paralleled that of Penrose on classical general relativity, with the addition of the quantum mechanical aspect of black hole evaporation. Black holes are simple and complex at the same time levaquin vs zithromax.

They are described by mass, charge and spin, yet as Jacob Bekenstein first recognized, they carry a huge entropy. It would be remarkable to have a field trip to the nearest black hole and study it up close. The journey would be practical over a human lifetime if there is levaquin vs zithromax one in the solar system. Even though black holes are the darkest objects when left on their own, they appear as the brightest sources of light when dressed up with a shroud of matter, making them perfect symbols of Halloween.

Outflows from supermassive black holes shape the evolution of entire galaxies. These beasts stop growing only because they become so levaquin vs zithromax energetic that they shove their food off their dining table. One gets a lot more out of black holes than one might expect based on their small size. No wonder we never get tired of thinking and talking about them..

Once upon a time, in a land zithromax 500mg for sale not far away, there was a horrible zithromax that instilled terror http://thetrunkseries.com/?p=179 in every town and home. Although most people who became infected showed no symptoms or recovered within a week, in a small fraction of cases the illness progressed, causing loss of reflexes and muscle control, paralysis and, sometimes, death. Children were especially vulnerable, so parents watched anxiously for any sign of , often keeping them zithromax 500mg for sale away from swimming pools, movie theaters, bowling alleys, anywhere where there were crowds and the dreaded microbe might lurk. Travel and business were sometimes curtailed between places with outbreaks, and public health authorities imposed quarantines on healthy people who may have been exposed, in order to halt the spread of the disease.

In the first half of the 1950s, with no cure and no treatment, more than 200,000 Americans were disabled by the poliozithromax. The zithromax was second only to the atomic bomb as to what Americans feared most zithromax 500mg for sale. Then, on April 12, 1955, public health officials at the University of Michigan announced that a “safe, effective, and potent” treatment had been found. This set off a national celebration that recalled the end of World War II.

Church bells rang, zithromax 500mg for sale car horns honked, people wept with relief. President Eisenhower invited the treatment’s inventor, Jonas Salk, to the White House. In a Rose Garden ceremony, the former Supreme Allied Commander told the scientist in a trembling voice, “I should like to say to you that when I think of the countless thousands of American parents and grandparents who are hereafter to be spared the agonizing fears of the annual epidemic of poliomyelitis, when I think of all the agony that these people will be spared seeing their loved ones suffering in bed, I must say to you I have no words in which adequately to express the thanks of myself and all the people I know—all 164 million Americans, to say nothing of all the people in the world that will profit from your discovery.” But, alas, not everyone joined the party and expressed such gratitude. One group in particular did not zithromax 500mg for sale welcome the treatment as a breakthrough.

Chiropractors actively opposed the vaccination campaign that followed Salk’s triumph. Many practitioners dismissed the role of contagious pathogens and adhered to the founding principle of chiropractic that all disease originated in the spine. Just a few years after the introduction of the treatment, as the number of polio cases was declining rapidly, an article in the Journal of the National Chiropractic Association zithromax 500mg for sale asked, “Has the Test Tube Fight Against Polio Failed?. € It recommended that, rather than take the treatment, once stricken, “Chiropractic adjustments should be given of the entire spine during the first three days of polio.” Opposition to the polio treatment and to vaccination in general continued in the ranks such that even four decades later, long after polio had been eradicated from the United States, as many as one third of chiropractors still believed that there was no scientific proof that vaccination prevents any disease, including polio.

That belief and resistance continues to this day, with some chiropractors campaigning against state vaccination mandates. I was shocked when zithromax 500mg for sale I first learned about chiropractors’ opposition to the polio treatment. The treatment is widely viewed as one of medicine’s greatest success stories. Why would anyone have opposed it?.

My shock turned into excitement, however, when I began to recognize the chiropractors’ pattern of arguments was uncannily similar to those I was familiar zithromax 500mg for sale with from creationists who deny evolutionary science. And once I perceived those parallels, my excitement became an epiphany when I realized that the same general pattern of arguments—a denialist playbook—has been deployed to reject other scientific consensuses from the health effects of tobacco to the existence and causes of climate change. The same playbook is now being used to deny facts concerning the buy antibiotics zithromax. In brief, the six principal plays zithromax 500mg for sale in the denialist playbook are.

Doubt the ScienceQuestion Scientists’ Motives and IntegrityMagnify Disagreements among Scientists and Cite Gadflies as AuthoritiesExaggerate Potential HarmAppeal to Personal FreedomReject Whatever Would Repudiate A Key Philosophy The purpose of the denialism playbook is to advance rhetorical arguments that give the appearance of legitimate debate when there is none. My purpose here is to penetrate that rhetorical fog, and to show that these are the predictable tactics of those clinging to an untenable position. If we hope to find any cure zithromax 500mg for sale for (or treatment against) science denialism, scientists, journalists and the public need to be able recognize, understand and anticipate these plays. To illustrate how the playbook works—and sadly, it is very effective –I will break down the chiropractor and creationist versions, which have endured for many decades in spite of overwhelming evidence, and point out parallels to the antibiotics rhetoric.

THE PLAYBOOK 1. Doubt the Science The first tactic of denialism is to raise objections to scientific evidence or interpretations zithromax 500mg for sale. This may take the form of seemingly legitimate specific arguments against a scientific claim. For example, chiropractors sought other explanations besides treatment efficacy to account for the decline of infectious diseases.

€œThe Center for Disease Control zithromax 500mg for sale statistics make it clear that the majority of diseases that are now routinely vaccinated against were disappearing before either the cause was discovered or the treatment developed,” stated a 1995 letter to the editor of Dynamic Chiropractic magazine. In polio’s case, this argument does not hold up against the facts that. (a) the disease was surging in the 1950s. (b) the treatment was proven effective zithromax 500mg for sale in a massive double-blind, placebo-controlled trial.

And (c) s declined precipitously after the introduction of the treatment. Alternatively, some statements are blanket arguments against an entire scientific discipline. For example, Henry Morris, whose 1961 book The Genesis Flood is credited with reviving the creationism movement, alleged zithromax 500mg for sale. €œSince there is no real scientific evidence that evolution is occurring at present or ever occurred in the past, it is reasonable to conclude that evolution is not a fact of science, as many claim.

In fact, it is not even science at all, but an arbitrary system built upon faith in universal naturalism.” 2. Question Scientists’ Motives and Integrity As a growing body of consistent evidence can be hard zithromax 500mg for sale to explain away, one fallback is to impugn the source. In the vaccination arena, this often takes the form of alleging financial conflicts of interest on the part of scientists, greed on the part of manufacturers, and complicity of government officials. €œIt appears that the scientific foundation on which these treatments have been erected is fragile enough that only compulsory laws, expensive public relations efforts, outrageous propaganda, and expensive advertising must ensue for compliance to be maintained,” wrote one author in American Chiropractor.

Salk, by the way, zithromax 500mg for sale filed no patent. In the evolution arena, scientists are often accused of being part of a conspiracy to undermine religion through educational systems. Kenneth Cumming, of the Institute for Creation Research, objected to a PBS series on evolution by drawing a parallel to the 9/11 attackers. €œAmerica is zithromax 500mg for sale being attacked from within through its public schools by a militant religious movement of philosophical naturalists (i.e., atheists) under the guise of secular Darwinism.

Both desire to alter the life and thinking of our nation.” One noteworthy counter to such assertions is the Clergy Letter Project, which has gained the support of more than 15,000 Christian clergy for the teaching of evolution. 3. Magnify Disagreements among Scientists and Cite Gadflies as Authorities In all scientific arenas, there zithromax 500mg for sale is honest disagreement about the interpretation of evidence. However, these differences are deliberately inflated by denialists to imply a lack of consensus on more fundamental points, while often propounding the contradictory views of a few unqualified outliers.

An example of the latter is how some chiropractors have seized on the anti-vaccination stance of one critic, Viera Scheibner. Her claim that there is no evidence zithromax 500mg for sale for treatment efficacy or safety is cited repeatedly, while overlooking the fact that her training and expertise is in geology, not medicine. In the evolution arena, differences of interpretation among scientists are relished by antievolution voices. For example, the initial discovery of a new fossil hominid usually elicits some different interpretations and expressions of uncertainty in the scientific community.

Creationists often mischaracterize these normal dynamics of scientific discourse as “skepticism” over the significance of such finds so as to discount them zithromax 500mg for sale. By overblowing legitimate disagreements and propounding “alternatives” to evolution, denialists often make appeals to “teach the controversy,” when no such controversy exists in the scientific community. Different interpretations of a fossil do not negate the discomfiting evidence for the antiquity of human ancestors. Antievolution leaders zithromax 500mg for sale in the U.S.

Also include a small number of scholars whose credentials are in other disciplines. For example, the abovementioned Henry Morris was an engineer, not a biologist. Phillip E zithromax 500mg for sale. Johnson, whose book Darwin on Trial inspired many adherents to the intelligent design movement, was a law professor with no formal training in biology.

A lack of credentials or status within the scientific community is often seen not as a liability but as a virtue. Scientists Pascal Diethelm and Martin McKee note, “Denialists are usually not deterred by the extreme isolation of their theories, but rather see it as the indication of their zithromax 500mg for sale intellectual courage against the dominant orthodoxy and the accompanying political correctness, often comparing themselves to Galileo.” 4. Exaggerate Potential Harm When the evidence contradicts a position, another recourse is to try to incite fear. No treatment or medicine is 100 percent safe, without any risk of side effects.

Chiropractors have long emphasized the potential side effects of treatments, for example in a statement zithromax 500mg for sale in Dynamic Chiropractic offering a litant of possible effects. €œdeath, encephalopathy, demyelinating diseases, brachial neuritis, Guillain-Barré syndrome, s generated by treatment agents, anaphylaxis, subacute sclerosing panencephalitis, seizure disorder, optic neuritis, arthritis,” and so on. However, they generally fail to acknowledge the serious consequences of s that would be prevented by vaccination. But what harm could arise from zithromax 500mg for sale knowing a bit about evolution?.

Well, Hitler, of course!. “Of the many factors that produced the Nazi Holocaust and World War II,” wrote one critic in the Journal of Creation, “one of the most important was Darwin’s notion that evolutionary progress occurs mainly as a result of the elimination of the weak in the struggle for survival.” It is an oft-repeated argument that has no bearing of course on the veracity of Darwin’s theory. Vaccination foes have lobbed similar accusations, likening zithromax 500mg for sale physicians who administer treatments to Nazi doctors and alleging that treatments violate the 1947 Nuremberg Code of medical ethics. 5.

Appeal to Personal Freedom If fear is not persuasive, there is another fallback position that resonates strongly with Americans. The freedom zithromax 500mg for sale of choice. The American Chiropractic Association leaned on this cherished notion when it established its official vaccination policy. €œSince the scientific community acknowledges that the use of treatments is not without risk, the American Chiropractic Association supports each individual’s zithromax 500mg for sale right to freedom of choice in his/her own health care based on an informed awareness of the benefits and possible adverse effects of vaccination.

The ACA is supportive of a conscience clause or waiver in compulsory vaccination laws… providing an elective course of action regarding vaccination.” Likewise, the International Chiropractic Association “questions the wisdom of mass vaccination programs” and views compulsory programs as an infringement of “the http://www.darmsanierung-hund.de/ individual’s right to freedom of choice.” Similarly, the teaching of evolution in public schools is viewed as an assault upon the religious freedom of those who oppose it. Those holding this view advocate for disclaimers on textbooks (“just a theory”), the teaching of “alternative” views of the history of life (Genesis or intelligent design), or the freedom to opt out of the evolution curriculum of biology classes. Notably, the zithromax 500mg for sale U.S. Supreme Court has rejected challenges to compulsory vaccination partly on the grounds that individual belief cannot subordinate the safety of an entire community.

And U.S. Courts have repeatedly struck down attempts to subvert the teaching of evolution as religiously motivated and violations of the establishment clause of the First zithromax 500mg for sale Amendment of the U.S. Constitution. 6.

Reject Whatever Would Repudiate a Key Philosophy Once the courts have spoken, and the scientific evidence grows to be overwhelming, one might think that zithromax 500mg for sale denialists would be out of plays. But there is one last line of defense that reveals the nucleus of denial. It is not that some scientific claim is untrue. It is that it is unacceptable zithromax 500mg for sale in light of some philosophical commitment.

The science must be summarily rejected. Chiropractic was founded in the early 20th century on the assertion that all disease has its origins in misalignments of the spine. €œChiropractors have found zithromax 500mg for sale in every disease that is supposed to be contagious, a cause in the spine,” claimed Bartlett Joshua Palmer, the son of chiropractic founder Daniel David Palmer. Acceptance of germ theory and vaccination would repudiate the founding premise of the profession that all disease stems from vertebral misalignments.

Therefore, that premise cannot be questioned. With respect to evolution, Henry Morris made zithromax 500mg for sale it plain. €œWhen science and the Bible differ, science has obviously misinterpreted its data.” Any credence granted to evolutionary science is a threat to a worldview based on interpretation of the Bible. David Cloud, a publisher of Bible study materials argues.

€œIf the Bible does not mean what it says, zithromax 500mg for sale there is no way to know what it does mean. Historian of science and author Naomi Oreskes has coined a term for this stance. €œimplicatory denial”—the rejection of scientific findings because we don’t like their implications. As these positions are reinforced by family or community, they harden into part of zithromax 500mg for sale one’s identity.

€œIn this way, cultural identity starts to override facts,” Norwegian climate psychologist Per Espen Stoknes has said. €œAnd my identity trumps truth any day.” Psychologists Elliot Aronson and Carol Tavris write in the Atlantic. €œ[W]hen people feel a strong connection to a political party, leader, ideology, or belief, they are more likely to let that allegiance do their thinking for them and distort or ignore the evidence that challenges those loyalties.” The denialist playbook zithromax 500mg for sale is now erupting around the antibiotics. Although buy antibiotics is new, the reactions to public health measures, scientific claims, and expert advice are not.

Attitudes and behaviors concerning the threat posed by the antibiotics (doubting the science), the efficacy of lockdowns and mask wearing (freedoms being eroded) and alternative treatments (gadflies over experts) are being driven as much or more by rhetoric than by evidence. Polls indicate that despite the devastating health and economic zithromax 500mg for sale impacts of the zithromax, with respect to a potential treatment we are nowhere near as united as Americans were in 1955. But as epidemiologist Michael Osterholm noted in June, “Eventually there won't be any blue states or red states. There won't be any blue cities or red rural areas.

It'll all be buy antibiotics colored.” Now, sadly, there is no denying that.PANAMA Vampire bats monitored at zithromax 500mg for sale the Smithsonian Tropical Research Institute have fewer interactions with family and friends when ill, biologists say. But they do not seem to stay apart intentionally—instead sick bats are simply too lethargic to call out to or groom one another. CANADA The last fully intact ice shelf in Canada collapsed into the Arctic Ocean this summer. Located in the territory of Nunavut, the Milne zithromax 500mg for sale Ice Shelf lost 80 square kilometers of ice—40 percent of its area—in just two days.

CHILE Living 6,700 meters above sea level, a yellow-rumped leafeared mouse found at the summit of the dormant volcano Llullaillaco is the highest-dwelling mammal ever documented. It remains unclear how the animal survives the oxygen scarcity and freezing temperatures at this elevation. RUSSIA An analysis of ancient woolly rhino DNA from Siberia revealed that the population size was stable zithromax 500mg for sale for thousands of years before the mammal's extinction 14,000 years ago, suggesting that a warming climate—not hunting by humans—most likely triggered its demise. ETHIOPIA Paleoanthropologists unearthed a 1.4-million-year old hand ax made from a hippo's leg bone.

Together with recently discovered stone tools, the ax indicates that Homo erectus had a diverse tool kit several hundred thousand years earlier than scientists had suspected. ANTARCTICA Contrary to researchers' expectations, methane-eating microbes zithromax 500mg for sale failed to rapidly contain the first methane leak detected on the Antarctic seafloor. The finding means more of the potent greenhouse gas may have been pouring into the atmosphere than previously thought.With black holes, what you see is not what you get. The ring of light visible around a black hole’s silhouette originates from a radius of about 5GM/c2, where G is Newton’s constant, M is the black hole mass and c is the speed of light.

This ring is larger than the event horizon of zithromax 500mg for sale a nonspinning black hole by a factor of 2.5—or up to five with the addition of spin. And so, truth in advertising requires me to tell you the Event Horizon Telescope did not actually image the event horizon of the supermassive black hole in the galaxy M87, but rather the light from much farther out. For a distant observer, the difference between the light ring and the horizon is academic, but for an astronaut en route into the black hole, the difference is existential. Entering the ultimate prison walls associated with the horizon implies a death sentence, with no opportunity for sharing the experience with the outside world zithromax 500mg for sale.

After less than a day, the astronaut’s body will reach the singularity and be torn apart by gravitational tidal force. In 1939, Albert Einstein wrote a paper in Annals of Mathematics doubting that black holes exist in nature. Now, black holes zithromax 500mg for sale are in vogue—so much so that the 2020 Nobel prize in physics was awarded to three scientists who have studied them. This gave me reason to celebrate, as the founding director of Harvard’s Black Hole Initiative, which brings together astronomers, physicists, mathematicians and philosophers, all dedicated to research on black holes.

Karl Schwarzschild would have been delighted to join our celebration. Unfortunately, he died on the German-Russian front during World War I over a century ago, zithromax 500mg for sale just half a year after deriving the nonspinning black hole solution to Einstein’s equations. One of the recipients of the 2020 Nobel, Roger Penrose, demonstrated that black holes are a robust prediction of Einstein’s general theory of relativity, and in doing so invented a new mathematical tool to depict spacetimes, called Penrose diagrams. He also showed that it is possible to extract energy from a spinning black hole as if it were a flywheel, through the so-called Penrose process.

His cosmic censorship hypothesis protects our ability to make predictions about the future of universe from the pathology zithromax 500mg for sale of black hole singularities, where the spacetime curvature blows up and Einstein's theory breaks down. This conjecture asserts that all singularities are hidden behind an event horizon so that matter approaching them has no causal effect on what happens outside the horizon. Just as they say about Las Vegas, "whatever happens inside the horizon, stays inside the horizon." The two other Nobel laureates in physics this year, Reinhard Genzel and Andrea Ghez, demonstrated that a black hole weighing four million suns resides at the center of our own Milky Way galaxy. The discovery of quasars zithromax 500mg for sale more than half a century ago implied that supermassive black holes form generically at the centers of galaxies.

By monitoring the motion of massive stars around the center of our own galaxy in real time, as if they were planets orbiting a star, they demonstrated the existence of a black hole there. Prior to their work, it was unclear whether a black hole is associated with the stationary radio source Sagittarius A*. Not only zithromax 500mg for sale did they measure the mass of the black hole, but they also tested Einstein's theory of gravity. The stars they discovered move in two orbital planes.

In a new paper with Giacomo Fragione, we showed that the black hole spin must therefore be small, or else it would blur the strict orbital planes of the stars over their lifetime. The teams led by Genzel and Ghez were engaged in intense competition, elevating their zithromax 500mg for sale efforts to great heights. This was a wonderful demonstration of how rivalry promotes good science. One of the stars traced by Genzel and Ghez, labeled S2, completes an orbit around the galactic center every 16 years.

The related zithromax 500mg for sale advice I gave astronomy students is to focus their Ph.D. Project on a source like S2 that evolves over a timescale of a decade or two, so that they will continue to learn new things about the source throughout their careers. If Stephen Hawking was alive, he would have been a worthy contender for this year's Nobel prize, since his work paralleled that of Penrose on classical general relativity, with the addition of the quantum mechanical aspect of black hole evaporation. Black holes are simple and zithromax 500mg for sale complex at the same time.

They are described by mass, charge and spin, yet as Jacob Bekenstein first recognized, they carry a huge entropy. It would be remarkable to have a field trip to the nearest black hole and study it up close. The journey would be practical over a human lifetime if there is one in zithromax 500mg for sale the solar system. Even though black holes are the darkest objects when left on their own, they appear as the brightest sources of light when dressed up with a shroud of matter, making them perfect symbols of Halloween.

Outflows from supermassive black holes shape the evolution of entire galaxies. These beasts stop growing only because they become so energetic that they shove their food zithromax 500mg for sale off their dining table. One gets a lot more out of black holes than one might expect based on their small size. No wonder we never get tired of thinking and talking about them..