Instruct: Given a question, retrieve relevant documents that answer the question.
Query: informed consent
Our understanding of coronary artery disease risk and the atherosclerotic process has changed greatly in recent years. For example, it is now known that angiographically apparent coronary artery plaque is not the major cause of myocardial infarction (MI). Rather, it is unstable, soft plaque that cannot be seen angiographically that is prone to rupture and result in infarction. Also important are changes in vascular reactivity resulting from diet. Cholesterol levels by themselves reveal little about a patient's coronary artery disease risk. Most infarctions occur in patients who have normal total cholesterol levels. At-risk patients can be identified using the ratio of total-to-high-density lipoprotein (HDL) cholesterol levels. The ratio of triglyceride to HDL cholesterol levels is also important. Simple steps to assess patients' risk in practice are outlined. Primary prevention trials demonstrate that coronary artery disease risk can be lowered dramatically with diet and drug therapy.
Two hundred thirty registered nurses and seventy physicians participated in a retrospective study scrutinizing placebo effects, prescribing patterns, and staff attitudes in a university-based general hospital setting. Despite copious experimental literature devoted to placebo effects over the past thirty years, the medical and surgical use of placebos seems to disregard experimental data. Although 80% of the staff had used placebos in the hospital, their knowledge of placebo effects was in many respects deficient. Within the hospital, 89% of placebo use was directed toward the amelioration of "pain"; the authors believe that emphasis should be placed on the education of staff to perceive emotional, social, and physiological concomitants of pain rather than resorting to a purely physicalistic approach. A need to acknowledge staff conflicts over the ethical use of placebos should be a significant part of this educational approach.
IMPORTANCE: Food and Drug Administration (FDA) guidance allows food manufacturers to determine whether additives to food are "generally recognized as safe" (GRAS). Manufacturers are not required to notify the FDA of a GRAS determination, although in some instances they notify the agency. The individuals that companies select to make these determinations may have financial conflicts of interest. OBJECTIVE: To determine the extent to which individuals selected by manufacturers to make GRAS determinations have conflicts of interest between their obligations to ensure that the use of the additive is safe and their financial relationships to the company. DESIGN Using conflict of interest criteria developed by a committee of the Institute of Medicine, we analyzed 451 GRAS notifications that were voluntarily submitted to the FDA between 1997 and 2012. MAIN OUTCOMES AND MEASURES: Number of GRAS notices submitted to the FDA; frequency of various types of relationships between decision maker and additive manufacturer; frequency of participation on GRAS panels by individuals; and number of GRAS safety determinations identified by the FDA that were not submitted to the agency. RESULTS: For the 451 GRAS notifications, 22.4% of the safety assessments were made by an employee of an additive manufacturer, 13.3% by an employee of a consulting firm selected by the manufacturer, and 64.3% by an expert panel selected by either a consulting firm or the manufacturer. A standing expert panel selected by a third party made none of these safety assessments. The 290 panels that made GRAS determinations had an average of 3.5 members, with a maximum of 7. Ten individuals served on 27 or more panels; 1 individual served on 128 panels (44.1%). At least 1 of the 10 individuals with the most frequent service was a member of 225 panels (77.6%). CONCLUSIONS AND RELEVANCE: Between 1997 and 2012, financial conflicts of interest were ubiquitous in determinations that an additive to food was GRAS. The lack of independent review in GRAS determinations raises concerns about the integrity of the process and whether it ensures the safety of the food supply, particularly in instances where the manufacturer does not notify the FDA of the determination. The FDA should address these concerns.
CONTEXT: While some studies have shown that physicians with healthy personal habits are especially likely to discuss prevention with their patients, to our knowledge no one has published information testing whether physician credibility and patient motivation to adopt healthier habits are enhanced by physician's disclosures of their own healthy behaviors. DESIGN: Two brief health education videos about improving diet and exercise were produced and shown to subjects (n1 = 66, n2 = 65) in an Emory University general medical clinic waiting room in Atlanta, Ga. In one video, the physician revealed an additional half minute of information about her personal healthy dietary and exercise practices and had a bike helmet and an apple visible on her desk (physician-disclosure video). In the other video, discussion of personal practices and the apple and bike helmet were not included (control video). RESULTS: Viewers of the physician-disclosure video considered the physician to be generally healthier, some-what more believable, and more motivating than did viewers of the control video. They also rated this physician to be specifically more believable and motivating regarding exercise and diet (P < or = .001). CONCLUSION: Physicians' abilities to motivate patients to adopt healthy habits can be enhanced by conveying their own healthy habits. Educational institutions should consider encouraging health professionals-in-training to practice and demonstrate healthy personal lifestyles.
The Princeton Consensus (Expert Panel) Conference is a multispecialty collaborative tradition dedicated to optimizing sexual function and preserving cardiovascular health. The third Princeton Consensus met November 8 to 10, 2010, and had 2 primary objectives. The first objective focused on the evaluation and management of cardiovascular risk in men with erectile dysfunction (ED) and no known cardiovascular disease (CVD), with particular emphasis on identification of men with ED who may require additional cardiologic work-up. The second objective focused on reevaluation and modification of previous recommendations for evaluation of cardiac risk associated with sexual activity in men with known CVD. The Panel's recommendations build on those developed during the first and second Princeton Consensus Conferences, first emphasizing the use of exercise ability and stress testing to ensure that each man's cardiovascular health is consistent with the physical demands of sexual activity before prescribing treatment for ED, and second highlighting the link between ED and CVD, which may be asymptomatic and may benefit from cardiovascular risk reduction.
A cross-sectional survey was conducted in order to describe the use of oral cobalamin among geriatricians, hematologists, and general practitioners, and to explore factors related to its use. The study population consisted of all geriatricians (n = 138) and hematologists (n = 317) listed in the Canadian Medical Directory plus a random sample of 307 general practitioners. The overall response rate was 40%. Intramuscular and oral cobalamin was prescribed by 76 and 32% of the respondents, respectively. Twenty seven percent reported using both oral and intramuscular cobalamin and 6% reported using only oral cobalamin. Only 25% of respondents indicated they were aware of a RCT demonstrating the efficacy of oral cobalamin prior to reading a synopsis of the study in the survey. After multivariate adjustment, only the belief that oral cobalamin was effective and certainty about who carried oral preparations remained independently associated with oral cobalamin use. Oral cobalamin has been shown to be an efficacious, cost efficient and safe method of treating cobalamin deficiency. Nonetheless, it is not used by the majority of physicians treating this condition. Strategies to promote the use of oral cobalamin should be directed at educating physicians of its efficacy and providing them with prescribing information on where it can be purchased.
ESC is to create an inventory of cardiovascular disease registries and a task force on data standardization
The strategy of "manufacturing uncertainty" has been used with great success by polluters and manufacturers of dangerous products to oppose public health and environmental regulation. This strategy entails questioning the validity of scientific evidence on which the regulation is based. While this approach is most identified with the tobacco industry, it has been used by producers of asbestos, benzene, beryllium, chromium, diesel exhaust, lead, plastics, and other hazardous products to avoid environmental and occupational health regulation. It is also central to the debate on global warming. The approach is now so common that it is unusual for the science not to be challenged by an industry facing regulation. Manufacturing uncertainty has become a business in itself; numerous technical consulting firms provide a service often called "product defense" or "litigation support." As these names imply, the usual objective of these activities is not to generate knowledge to protect public health but to protect a corporation whose products are alleged to have toxic properties. Evidence in the scientific literature of the funding effect--the close correlation between the results of a study desired by a study's funder and the reported results of that study--suggests that the financial interest of a study's sponsors should be taken into account when considering the study's findings. Similarly, the interpretation of data by scientists with financial conflicts should be seen in this light. Manufacturing uncertainty is antithetical to the public health principle that decisions be made using the best evidence currently available.
In November 1906, Richard Pearson Strong, then head of the Philippine Biological Laboratory, inoculated 24 men--inmates of Manila's Bilibid Prison--with a cholera vaccine that somehow had been contaminated with plague organisms; 13 men died. The governor-general of the Philippines appointed a general committee to investigate the affair, and the U.S. Senate demanded information about the episode. Although the Senate, the secretary of war, and even the president were kept informed of developments, no mainland investigations ensued. The general committee concluded that Strong was negligent for not having locks on his incubators and for leaving a visiting physician alone in the laboratory, where he might have mixed up the cholera and plague cultures on the fateful day. The committee's charge was referred to the attorney general, who found Strong innocent of criminal negligence, whereupon the governor-general exonerated Strong. Strong was despondent over Bilibid but recovered and developed a noteworthy career in American tropical medicine. In retrospect, the disaster at Bilibid presents an epitome of the problems surrounding the use of prisoner-subjects without authorization and without their voluntary consent. Far ahead of its time, the general committee recognized and condemned the shortcomings and urged reform, pleas the government ignored. The Bilibid episode remains, however, as a cautionary tale for those engaged in clinical research.
Aims To discover whether patients have the same expectations of benefit from taking the first and any additional drugs for the treatment of hypertension and to investigate any patient characteristics which predict willingness to take treatment. Methods This was an anonymous questionnaire survey carried out in a single primary care group. A random sample of patients from the practice list stratified by age and gender were surveyed to determine what benefit they required before deciding to receive first and subsequent drugs to treat hypertension. They were asked to indicate the largest number needing treatment for 5 years (NNT5) to prevent myocardial infarction in 1 (smallest benefit) that would persuade them of the need for treatment. Demographic information which might explain variability in enthusiasm for treatment was also collected. Results Participants required far higher benefit to consider drug treatment than expected with a mean NNT5 for the first treatment of 15.0 (95% CI 12.3, 17.8). Marginal benefit demanded for the addition of second and third treatments was at least as great with an NNT5 of 13.2 (95% CI 10.8, 15.7) and NNT5 of 11.0 (95% CI 8.6, 13.4). Additional factors influencing willingness to take treatment were gender with a difference in NNT5 between men and women of 7.1 (95% CI 1.7, 12.5), difficulty in making the decision (very easy vs very difficult) of 14.9 (95% CI 6.0, 23.8), and years in full time education 2.0 (95% CI 0.9, 3.0) for each additional year of education. Any slope of NNT5 with increasing number of tablets disappeared when gender, years in education, and difficulty in reaching a decision were taken into account simultaneously. Conclusions People may have greater expectation of benefit from antihypertensive drug treatment than it provides. They certainly do not view the addition of subsequent drugs as any lesser step than starting the first in terms of the benefit expected. Full understanding of both the risks and benefits may be of critical importance with those spending longer in full time education and those expending more effort in making the decision accepting more treatment. The discrepancy between benefit expected and that available demands further research into methods of determining patients’ expectations and informing individual patient decisions.
Sixty percent of the U.S. population experiences acute diarrheal illness each year, but little is understood regarding public knowledge and beliefs about the causes and treatment of these diseases. We performed a telephone survey of 2117 Tennessee residents regarding knowledge and practices associated with diarrheal illness. Bloody stool, dehydration, and persistent symptoms were the most common reasons for which the respondents would seek medical care. Although most acute diarrheal disease is self-limited, overuse of antimicrobials for treatment is common. Few people believed that stool cultures (4.5%) or antibiotics (6.9%) are routinely necessary for diarrhea. Over 60% of respondents believed that food is the most common source of diarrhea. Three-fourths believed that it is normal for uncooked meat to contain bacteria, and 45% believed it is legal to sell such products. These results have implications for medical providers, regulators, and public health in the management and prevention of diarrheal disease.
OBJECTIVE: To explore a potential "priming effect" of physician advice on patient responses to behavioral change interventions. DESIGN: Randomized controlled trial with a 3-month follow-up. SETTING: Four community-based group family medicine clinics in southeastern Missouri. PARTICIPANTS: Adult patients (N = 915). INTERVENTIONS: Printed educational materials designed to encourage patients to quit smoking, eat less fat, and increase physical activity. MAIN OUTCOME MEASURES: Recall, rating, and use of the educational materials; changes in smoking behavior, dietary fat consumption, and physical activity. RESULTS: Patients who received physician advice to quit smoking, eat less fat, or get more exercise prior to receiving intervention materials on the same topic were more likely to remember the materials, show them to others, and perceive the materials as applying to them specifically. They were also more likely to report trying to quit smoking (odds ratio [OR] = 1.54, 95% confidence interval [CI] = 0.95-2.40), quitting for at least 24 hours (OR = 1.85, 95% CI = 1.02-3.34), and making some changes in diet (OR = 1.35, 95% CI = 1.00-1.84) and physical activity (OR = 1.51, 95% CI = 0.95-2.40). CONCLUSIONS: Findings support an integrated model of disease prevention in which physician advice is a catalyst for change and is supported by a coordinated system of information and activities that can provide the depth of detail and individualization necessary for sustained behavioral change.
Five years ago, the Institute of Medicine (IOM) called for a national effort to make health care safe. Although progress since then has been slow, the IOM report truly "changed the conversation" to a focus on changing systems, stimulated a broad array of stakeholders to engage in patient safety, and motivated hospitals to adopt new safe practices. The pace of change is likely to accelerate, particularly in implementation of electronic health records, diffusion of safe practices, team training, and full disclosure to patients following injury. If directed toward hospitals that actually achieve high levels of safety, pay for performance could provide additional incentives. But improvement of the magnitude envisioned by the IOM requires a national commitment to strict, ambitious, quantitative, and well-tracked national goals. The Agency for Healthcare Research and Quality should bring together all stakeholders, including payers, to agree on a set of explicit and ambitious goals for patient safety to be reached by 2010.
The double-blind randomized controlled trial (RCT) is accepted by medicine as objective scientific methodology that, when ideally performed, produces knowledge untainted by bias. The validity of the RCT rests not just on theoretical arguments, but also on the discrepancy between the RCT and less rigorous evidence (the difference is sometimes considered an objective measure of bias). A brief overview of historical and recent developments in "the discrepancy argument" is presented. The article then examines the possibility that some of this "deviation from truth" may be the result of artifacts introduced by the masked RCT itself. Can an "unbiased" method produce bias? Among the experiments examined are those that augment the methodological stringency of a normal RCT in order to render the experiment less susceptible to subversion by the mind. This methodology, a hypothetical "platinum" standard, can be used to judge the "gold" standard. The concealment in a placebo-controlled RCT seems capable of generating a "masking bias." Other potential biases, such as "investigator self-selection," "preference," and "consent" are also briefly discussed. Such potential distortions indicate that the double-blind RCT may not be objective in the realist sense, but rather is objective in a "softer" disciplinary sense. Some "facts" may not exist independent of the apparatus of their production.
Controversial and ethically tenuous, the use of placebos is central to medicine but even more pivotal to psychosocial therapies. Scholars, researchers, and practitioners largely disagree about the conceptualization of placebos. While different professionals often confound the meanings of placebo effects with placebo responses, physicians continue to prescribe placebos as part of clinical practice. Our study aims to review attitudes and beliefs concerning placebos outside of clinical research. Herein we compare patterns of placebo use reported by academic psychiatrists with those reported by physicians from different specialties across Canadian medical schools. Using a web-based tool, we circulated an online survey to all 17 Canadian medical schools, with a special emphasis on psychiatry departments therein and in university-affiliated teaching hospitals. A variation on earlier efforts, our 5-minute, 21-question survey was anonymous. Among the 606 respondents who completed our online survey, 257 were psychiatrists. Our analysis revealed that psychiatrists prescribed significantly more subtherapeutic doses of medication than physicians in other specialties, although about 20% of both psychiatrists and nonpsychiatrists prescribed placebos regularly as part of routine clinical practice. However, compared with 6% of nonpsychiatrists, only 2% of psychiatrists deemed placebos of no clinical benefit. In addition, more than 60% of psychiatrists either agreed or strongly agreed that placebos had therapeutic effects relative to fewer than 45% of other practitioners. Findings from this pan-Canadian survey suggest that, compared with other physicians, psychiatrists seem to better value the influence placebos wield on the mind and body and maintain more favourable beliefs and attitudes toward placebo phenomena.
OBJECTIVES: To determine the counseling practices of a group of internists in the areas of smoking, exercise, and alcohol and seat belt use, and to determine the associations among physicians' personal health habits and their counseling practices. DESIGN: A random stratified sample of members and fellows of the American College of Physicians in 21 regions selected to represent all areas of the United States. Because of the relatively small proportion of women in this group, they were oversampled. SETTING: Physicians' practices. PARTICIPANTS: One thousand three hundred and forty-nine internists (members or fellows of the College) returned questionnaires, for a response rate of 75%; 52% defined themselves as general internists. INTERVENTIONS: A questionnaire was used to obtain information on internists' use of cigarettes, alcohol, and seat belts and their level of physical activity. Data were obtained on the indications used for counseling and the aggressiveness of counseling about each of these four habits. MEASUREMENTS AND MAIN RESULTS: Bivariate and logistic regression analyses were used to compare the tendencies of internist subgroups both in using various indications for counseling and in the thoroughness of counseling. Generalists were more likely than specialists to counsel at least once all patients who were at risk and to be more aggressive in counseling. Ninety percent of respondents counseled all of their patients who smoked, but 64.5% never discussed the use of seat belts. Only 3.8% of these internists currently smoked cigarettes, 11.3% drank alcohol daily, 38.7% were extremely or quite active, and 87.3% used seat belts all or most of the time. Among men internists, for every habit except alcohol use, personal health practices were substantially associated with counseling patients; for example, nonsmoking internists were more likely to counsel smokers, and very physically active internists were more likely to counsel about exercise. Among women internists, being very physically active was associated with counseling more patients about exercise and alcohol use. CONCLUSIONS: The low level of self-reported counseling among these internists suggests that further emphasis on training in these skills is needed. The association between personal and professional practices suggests that medical schools and housestaff training programs should support health promotion activities for future internists.
Many studies have documented the role of risk and protective factors for late life dementing illnesses, particularly Alzheimer's disease. A "Systematic Review" from the US Agency for Healthcare Research and Quality and the National Institute on Aging concluded that because the overall quality of evidence was low, recommendations for public health could not be made. In order to gain evidence for the efficacy of lifestyle interventions, we propose a "Modest Proposal" to study 10,000 subjects over 40 years randomly assigned to groups of low or high saturated fat in the diet, head injury, and high or low levels of mental activity, physical activity, or inactivity as well as smoking or non-smoking. This proposed study cannot be accomplished. The "Modest Proposal" illustrates that the absence of definitive evidence should not restrict physicians from making reasonable recommendations based on the evidence that is available.
BACKGROUND: In April 2009, experts on sexually transmitted diseases (STDs) were convened to review updates on STD prevention and treatment in preparation for the revision of the Centers for Disease Control and Prevention (CDC) STD Treatment Guidelines. At this meeting, there was a discussion of important updates on human papillomavirus (HPV), genital warts, and cervical cancer screening. METHODS: Key questions were identified with assistance from an expert panel, and systematic reviews of the literature were conducted searching the English-language literature of the PubMed computerized database (US National Library of Medicine). The available evidence was reviewed, and new information was incorporated in the 2010 CDC STD Treatment Guidelines. RESULTS: Two HPV vaccines are now available, the quadrivalent HPV vaccine and the bivalent HPV vaccine; either vaccine is recommended routinely for girls aged 11 or 12 years. The quadrivalent HPV vaccine may be given to boys and men aged 9-26 years. A new patient-applied treatment option for genital warts, sinecatechins 15% ointment, is available and recommended for treatment of external genital warts. This product is a mixture of active ingredients (catechins) from green tea. Finally, updated counseling guidelines and messages about HPV, genital warts, and cervical cancer are included. CONCLUSIONS: This manuscript highlights updates to the 2010 CDC STD Treatment Guidelines for HPV and genital warts. Important additions to the 2010 STD Treatment Guidelines include information on prophylactic HPV vaccine recommendations, new patient-applied treatment options for genital warts, and counseling messages for patients on HPV, genital warts, cervical cancer screening, and HPV tests.
Although consumers say they are concerned about nutrition and are aware that eating a healthful diet is important for good health, this knowledge does not always translate into healthful diet behaviors or motivate behavior change. In an effort to better understand consumer attitudes about nutrition and to explore alternatives for communicating dietary advice in language that is meaningful and motivates behavior change, the International Food Information Council (IFIC) conducted qualitative research with consumers (using focus groups) and registered dietitians (using telephone interviews) in 1998 and 1999. Results of the research are presented using dietary fat as a case study. Findings from the IFIC research were reported to the Dietary Guidelines Advisory Committee to assist the Committee in developing meaningful and action-oriented dietary advice related to dietary fat for inclusion in the 2000 Dietary Guidelines for Americans that would be motivating and easy for consumers to implement. The recommendation to moderate fat intake in the new dietary guideline, "Choose a diet that is low in saturated fat and cholesterol and moderate in total fat" is consistent with communication recommendations in the IFIC research. Further, the moderate fat message is empowering because it suggests an achievable dietary regimen and reduces guilt and worry about foods. It allows flexibility to enjoy desired foods and promotes using common sense when it comes to diet. Several issues emerged from the IFIC research that apply to general nutrition communications with consumers, whether it be through national nutrition recommendations or in one-on-one counseling situations: to be effective, messages to consumers about nutrition, and specifically dietary fat, must address sources of discomfort about dietary choices; they must engender a sense of empowerment; and they should motivate both by providing clear information that propels toward taking action and appeals to the need to make personal choices.
In the 1970s several states in the Great Lakes region became concerned about mercury contamination in lakes and rivers and were the first to issue local fish consumption advisories. In 2001, the Food and Drug Administration (FDA) advised pregnant women, nursing mothers, young children, and women who may become pregnant not to consume shark, swordfish, king mackerel, and tilefish and recommended that these women not exceed 12 ounces of other fish per week. In 2004, FDA reissued this advice jointly with the U.S. Environmental Protection Agency (EPA) and modified it slightly to provide information about consumption of canned tuna and more details about consumption of recreationally caught fish. Though several studies have examined consumers' awareness of the joint FDA and EPA advisory as well as different state advisories, few used representative data. We examined the changes in awareness and knowledge of mercury as a problem in fish using the pooled nationally representative 2001 and 2006 Food Safety Surveys (FSS) with sample sizes of 4482 in 2001 and 2275 in 2006. Our results indicated an increase in consumers' awareness of mercury as a problem in fish (69% in 2001 to 80% in 2006, p<.001). In our regression models, we found that in both years, parents having children less than 5 years of age were more aware of mercury in fish and knowledgeable about the information contained in the national advisories about mercury in fish (p<.01) than other adults. In both 2001 and 2006, women of childbearing age (aged 18-45) were less aware and knowledgeable about this information than other women. However, women of all age groups had larger gains in awareness and knowledge than their male counterparts during this time. Participants' race, education, income, region, fish preparation experiences, having a foodborne illness in the past year, and risk perceptions about the safety of food were significant predictors of their awareness and knowledge. Copyright © 2011 Elsevier Inc. All rights reserved.
The relationship between psychiatry and pharmaceutical companies has come under scrutiny during the past decade. Concerns are growing that financial ties of psychiatrists to the pharmaceutical industry may unduly influence professional judgments involving the primary interests of patients. Such conflicts of interest threaten the public trust in psychiatry. The goal of conflict of interest policies is to protect the integrity of professional judgment and to preserve public trust. The disclosure of individual and institutional financial relationships is a critical but limited first step in the process of identifying and responding to conflicts of interest. Conflict of interest policies and procedures can be strengthened by engaged psychiatrists, researchers, institutions, and professional associations in developing policies and consensus standards. Research on conflicts of interest can provide a stronger evidence base for policy design and implementation. Society has traditionally granted the medical profession considerable autonomy and may be willing to continue do so in the case of conflicts of interest. Nevertheless, concern is growing that stronger measures are needed. To avoid undue regulatory burdens, psychiatrists can play a vital role in designing responsible and reasonable conflict of interest policies that reduce the risks of bias and the loss of trust. Psychiatrists and the institutions that carry out research, education, clinical care, and practice guideline development must recognize public concerns about conflicts of interest and take effective measures soon to maintain public trust with a cultural change in the practice of psychiatry, from reactive treatment-seeking for mental illness to proactive advocacy for patients. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.
BACKGROUND: Evidence-based medicine is valuable to the extent that the evidence base is complete and unbiased. Selective publication of clinical trials--and the outcomes within those trials--can lead to unrealistic estimates of drug effectiveness and alter the apparent risk-benefit ratio. METHODS: We obtained reviews from the Food and Drug Administration (FDA) for studies of 12 antidepressant agents involving 12,564 patients. We conducted a systematic literature search to identify matching publications. For trials that were reported in the literature, we compared the published outcomes with the FDA outcomes. We also compared the effect size derived from the published reports with the effect size derived from the entire FDA data set. RESULTS: Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published. Whether and how the studies were published were associated with the study outcome. A total of 37 studies viewed by the FDA as having positive results were published; 1 study viewed as positive was not published. Studies viewed by the FDA as having negative or questionable results were, with 3 exceptions, either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies). According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive. Separate meta-analyses of the FDA and journal data sets showed that the increase in effect size ranged from 11 to 69% for individual drugs and was 32% overall. CONCLUSIONS: We cannot determine whether the bias observed resulted from a failure to submit manuscripts on the part of authors and sponsors, from decisions by journal editors and reviewers not to publish, or both. Selective reporting of clinical trial results may have adverse consequences for researchers, study participants, health care professionals, and patients. Copyright 2008 Massachusetts Medical Society.
BACKGROUND/AIMS: Herbal agents are popular and perceived as safe because they are supposedly 'natural'. We report 10 cases of toxic hepatitis implicating Herbalife products. METHODS: To determine the prevalence and outcome of hepatotoxicity due to Herbalife products. A questionnaire was sent to all public Swiss hospitals. Reported cases were subjected to causality assessment using the CIOMS criteria. RESULTS: Twelve cases of toxic hepatitis implicating Herbalife preparations (1998-2004) were retrieved, 10 sufficiently documented to permit causality analysis. Median age of patients was 51 years (range 30-69) and latency to onset was 5 months (0.5-144). Liver biopsy (7/10) showed hepatic necrosis, marked lymphocytic/eosinophilic infiltration and cholestasis in five patients. One patient with fulminant liver failure was successfully transplanted; the explant showed giant cell hepatitis. Sinusoidal obstruction syndrome was observed in one case. Three patients without liver biopsy presented with hepatocellular (2) or mixed (1) liver injury. Causality assessment of adverse drug reaction was classified as certain in two, probable in seven and possible in one case(s), respectively. CONCLUSIONS: We present a case series of toxic hepatitis implicating Herbalife products. Liver toxicity may be severe. A more detailed declaration of components and pro-active role of regulatory agencies would be desirable.
In a 1995 pivotal study, Kushner described the attitudes, practice behaviors, and barriers to the delivery of nutrition counseling by primary care physicians. This article recognized nutrition and dietary counseling as key components in the delivery of preventive services by primary care physicians. Kushner called for a multifaceted approach to change physicians' counseling practices. The prevailing belief today is that little has changed. Healthy People 2010 and the U.S. Preventive Task Force identify the need for physicians to address nutrition with patients. The 2010 objective was to increase to 75% the proportion of office visits that included ordering or providing diet counseling for patients with a diagnosis of cardiovascular disease, diabetes, or hypertension. At the midcourse review, the proportion actually declined from 42% to 40%. Primary care physicians continue to believe that providing nutrition counseling is within their realm of responsibility. Yet the gap remains between the proportion of patients who physicians believe would benefit from nutrition counseling and those who receive it from their primary care physician or are referred to dietitians and other healthcare professionals. The barriers cited in recent years continue to be those listed by Kushner: lack of time and compensation and, to a lesser extent, lack of knowledge and resources. The 2010 Surgeon General's Vision for a Healthy and Fit Nation and First Lady Obama's "Let's Move Campaign" spotlight the need for counseling adults and children on diet and physical activity.
The triptans, selective serotonin 5-HT1B/1D agonists, are very effective acute migraine drugs. Soon, seven different triptans will be clinically available at 13 different oral doses, making evidence-based selection guidelines necessary. Triptan trials have similar designs, facilitating meta-analysis. We wished to provide an evidence-based foundation for using triptans in clinical practice, and to review the methodological issues surrounding triptan trials. We asked pharmaceutical companies and the principal investigators of company-independent trials for the 'raw patient data' of all double-blind, randomized, controlled, clinical trials with oral triptans in migraine. All data were cross-checked with published or presented data. We calculated summary estimates across studies for important efficacy and tolerability parameters, and compared these with those from direct, head-to-head, comparator trials. Out of 76 eligible clinical trials, 53 (12 not yet published) involving 24089 patients met the criteria for inclusion. Mean results (and 95% confidence intervals) for sumatriptan 100 mg, the first available and most widely prescribed oral triptan, are 59% (57-60) for 2 h headache response (improvement from moderate or severe to mild or no pain); 29% (27-30) for 2 h pain free (improvement to no pain); 20% (18-21) for sustained pain free (pain free by 2 h and no headache recurrence or use of rescue medication 2-24 h post-dose), and 67% (63-70) for consistency (response in at least two out of three treated attacks); placebo-subtracted proportions for patients with at least one adverse event (AE) are 13% (8-18), for at least one central nervous system AE 6% (3-9), and for at least one chest AE 1.9% (1.0-2.7). Compared with these data: rizatriptan 10 mg shows better efficacy and consistency, and similar tolerability; eletriptan 80 mg shows better efficacy, similar consistency, but lower tolerability; almotriptan 12.5 mg shows similar efficacy at 2 h but better sustained pain-free response, consistency, and tolerability; sumatriptan 25 mg, naratriptan 2.5 mg and eletriptan 20 mg show lower efficacy and better tolerability; zolmitriptan 2.5 mg and 5 mg, eletriptan 40 mg, and rizatriptan 5 mg show very similar results. The results of the 22 trials that directly compared triptans show the same overall pattern. We received no data on frovatriptan, but publicly available data suggest substantially lower efficacy. The major methodological issues involve the choice of the primary endpoint, consistency over multiple attacks, how to evaluate headache recurrence, use of placebo-subtracted proportions to control for across-study differences, and the difference between tolerability and safety. In addition, there are a number of methodological issues specific for direct comparator trials, including encapsulation and patient selection. At marketed doses, all oral triptans are effective and well tolerated. Differences among them are in general relatively small, but clinically relevant for individual patients. Rizatriptan 10 mg, eletriptan 80 mg and almotriptan 12.5 mg provide the highest likelihood of consistent success. Sumatriptan features the longest clinical experience and the widest range of formulations. All triptans are contra-indicated in the presence of cardiovascular disease.