Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73).

OBJECTIVE: To examine the traditional diet-heart hypothesis through recovery and analysis of previously unpublished data from the Minnesota Coronary Experiment (MCE) and to put findings in the context of existing diet-heart randomized controlled trials through a systematic review and meta-analysis. DESIGN: The MCE (1968-73) is a double blind randomized controlled trial designed to test whether replacement of saturated fat with vegetable oil rich in linoleic acid reduces coronary heart disease and death by lowering serum cholesterol. Recovered MCE unpublished documents and raw data were analyzed according to hypotheses prespecified by original investigators. Further, a systematic review and meta-analyses of randomized controlled trials that lowered serum cholesterol by providing vegetable oil rich in linoleic acid in place of saturated fat without confounding by concomitant interventions was conducted. SETTING: One nursing home and six state mental hospitals in Minnesota, United States. PARTICIPANTS: Unpublished documents with completed analyses for the randomized cohort of 9423 women and men aged 20-97; longitudinal data on serum cholesterol for the 2355 participants exposed to the study diets for a year or more; 149 completed autopsy files. INTERVENTIONS: Serum cholesterol lowering diet that replaced saturated fat with linoleic acid (from corn oil and corn oil polyunsaturated margarine). Control diet was high in saturated fat from animal fats, common margarines, and shortenings. MAIN OUTCOME MEASURES: Death from all causes; association between changes in serum cholesterol and death; and coronary atherosclerosis and myocardial infarcts detected at autopsy. RESULTS: The intervention group had significant reduction in serum cholesterol compared with controls (mean change from baseline -13.8%v-1.0%; P<0.001). Kaplan Meier graphs showed no mortality benefit for the intervention group in the full randomized cohort or for any prespecified subgroup. There was a 22% higher risk of death for each 30 mg/dL (0.78 mmol/L) reduction in serum cholesterol in covariate adjusted Cox regression models (hazard ratio 1.22, 95% confidence interval 1.14 to 1.32; P<0.001). There was no evidence of benefit in the intervention group for coronary atherosclerosis or myocardial infarcts. Systematic review identified five randomized controlled trials for inclusion (n=10,808). In meta-analyses, these cholesterol lowering interventions showed no evidence of benefit on mortality from coronary heart disease (1.13, 0.83 to 1.54) or all cause mortality (1.07, 0.90 to 1.27). CONCLUSIONS: Available evidence from randomized controlled trials shows that replacement of saturated fat in the diet with linoleic acid effectively lowers serum cholesterol but does not support the hypothesis that this translates to a lower risk of death from coronary heart disease or all causes. Findings from the Minnesota Coronary Experiment add to growing evidence that incomplete publication has contributed to overestimation of the benefits of replacing saturated fat with vegetable oils rich in linoleic acid.

[Current application of placebo in Chinese clinical studies in past 30 years].

To analyze and discuss placebo-related information in clinical research literatures in the past 30 years, including placebo's dosage form, ingredients, preparation process and quality control. Effort were made to research the CNKI. full-text database to preliminary find 700 placebo-related clinical research literature, screen out 301 eligible articles by hand, read the literatures to extract placebo-related information and make statistics and discussions. According to the results, Chinese randomized placebo-controlled clinical studies were characterized by diverse dosage forms of placebo with lack of reports for components, as evidenced by the only 17 literatures describing placebo's preparation or specific composition among the 301 literatures. Placebo-controlled clinical trials covered a wide range of disease spectra, but with a specific tropism of diseases in terms of system classification. Although placebo plays a key role in blinded clinical studies, researchers made less records of placebo, perhaps because they paid less attention to placebo or more attention to the research process or restricted by other objective conditions. Moreover, placebo production, quality control and quality evaluation also need to be further standardized.

A tale of two diseases: the history of inflammatory bowel disease.

'Inflammatory bowel disease' (IBD) sounds like a straightforward term - a disease of inflammation in the bowel. However, the history of IBD reveals a story of a nefariously complex set of idiopathic conditions. IBD defies definition, in part because its pathophysiology is not completely understood. For the same reason and despite substantial advances in research, IBD also defies cure. At best, IBD can be defined as a disease of disruption - disrupted physiology, microbiology, immunology and genetics. The term 'IBD' is most often used to describe two separate conditions: ulcerative colitis (UC) and Crohn's disease (CD). This paper reviews the history of IBD, considering the ever-evolving understanding of both UC and CD. Beyond its intrinsic interest, the history of IBD exemplifies a pattern that is becoming increasingly familiar in the 21st century - the story of a chronic, incurable disease that defies the best efforts to treat it.

An essential infusion for an essential organ.

Essential amino acid-based parenteral nutrition (PN) was found to be superior to hypertonic dextrose for patients with acute renal failure in a classical randomized trial that was published in 1973. However, subsequent trials were not able to duplicate this finding when this formulation was compared to hypertonic dextrose or to standard amino acid-based PN. As a result, this intervention has not been recommended in various guidelines for the nutrition support of patients with renal failure. However, all of these trials were relatively small, and none of them compared the intervention to a true control group-namely, patients who were not receiving any artificial nutrition. Because no trials have compared any form of artificial nutrition to no nutrition support in patients with acute renal failure, there really is no basis on which to make any level 1 evidence-based recommendation. Furthermore, a close look at all of the trials suggests that the essential amino acid-based formulation may be superior to the other types of intravenous nutrient supplementation to which it was compared. To determine whether this should be offered to patients with acute renal failure, we need data from one or more large, well-designed and executed, low risk of bias randomized trial(s) comparing essential amino acid-based PN to no nutrition therapy.

A brief history of placebos and clinical trials in psychiatry.

The history of placebos in psychiatry can be understood only in the context of randomized controlled trials (RCTs). Placebo treatments are as old as medicine itself, and are particularly effective in dealing with psychosomatic symptoms. In psychiatry, placebos have mainly been featured in clinical drug trials. The earliest controlled trial in psychiatry (not involving drugs) occurred in 1922, followed by the first crossover studies during the 1930s. Meanwhile the concept of randomization was developed during the interwar years by British statistician Ronald A Fisher, and introduced in 3 trials of tuberculosis drugs between 1947 and 1951. These classic studies established the RCT as the gold standard in pharmaceutical trials, and its status was cemented during the mid-1950s. Nevertheless, while the placebo became established as a standard measure of drug action, placebo treatments became stigmatized as unethical. This is unfortunate, as they constitute one of the most powerful therapies in psychiatry. In recent years, moreover, the dogma of the placebo-controlled trial as the only acceptable data for drug licensing is also being increasingly discredited. This backlash has had 2 sources: one is the recognition that the US Food and Drug Administration has been too lax in permitting trials controlled with placebos alone, rather than also using an active agent as a test of comparative efficacy. In addition, there is evidence that in the hands of the pharmaceutical industry, the scientific integrity of RCTs themselves has been degraded into a marketing device. The once-powerful placebo is thus threatened with extinction.

INCAP Oriente longitudinal study: 40 years of history and legacy.

Our purpose in this article is to describe the objectives, design, overall coverage, and main domains of data collection of the Institute of Nutrition of Central America and Panama Oriente Longitudinal Study and subsequent follow-up studies. This supplementary feeding trial targeted to pregnant and lactating women and children from birth to 7 y of age, conducted in 4 rural Guatemalan villages (1969-77) with a series of follow-up studies (1988-2007), is one of the richest sources of information on the effects of nutrition, growth, development, and human capital in the developing world, with outstanding data from gestation to adult age and 40 y of follow-up. Its results have influenced nutrition knowledge and policy with over 300 scientific publications. We present brief descriptions of preliminary studies that were critical for the success of the trial and the design and methods used during the trial and in the follow-up studies, in chronological order.

Assessing the quality of evidence from randomized, controlled drug and nutritional supplement trials conducted among nursing home residents between 1968 and 2004: what can we learn?

BACKGROUND: An estimated 1.5 million residents of nursing homes (NH) in the United States were prescribed an average of 7 to 8 medications each month. However, it is unknown which of these prescribed drugs and nutritional supplements have been tested for use among NH residents who often have distinct and complex needs compared with other geriatric patients. This pilot study addresses the quantity and quality of randomized, controlled drug and nutritional supplement trials that have been conducted among NH residents. METHOD: Using multiple search strategies and review protocol, I assessed the quality of evidence from randomized, controlled drug and nutritional supplement trials that had a parallel-group design, were conducted among NH residents, and were published in English between 1968 and October 2004. Internal validity of the trials was examined by assessing adequately reporting power calculation, drop-outs (completion fraction), randomization and allocation concealment, blind status, and intention-to-treat analysis. External validity of the trials was examined by assessing adequately reporting the sample description, the inclusion and exclusion criteria, the recruitment process, and comorbidities and harm. RESULT: Relatively few drug and nutritional supplements have been tested among NH residents by well-designed and executed randomized controlled trials (N = 42). The total number of participants (N = 7941) is small. The quality of many trials is poor. CONCLUSIONS: Given the limited number and poor quality of existing trials conducted among NH residents in this pilot study, I conclude that there is a limited body of evidence that could be used to establish quality of care standards or pay for performance criteria for drug therapy and nutritional supplements in NH. Long-term care providers face a great challenge in practicing evidence-based medicine in prescribing drugs and nutritional supplements.

A brief history of spa therapy.

Bathing in thermal water has an impressive history and continuing popularity. In this paper a brief overview of the use of water in medicine over the centuries is given.

[A century of progress in the knowledge and treatment of nephroblastoma]. / Un siècle de progrès dans la connaissance et le traitement du néphroblastome.

Since its initial description by Max Wilms over a century ago, nephroblastoma has benefited from considerable improvements both in terms of basic knowledge about it and management of it. Today, the majority of these very young patients can expect a long-term survival in excess of 90% at the price of a light therapy that combines surgical resection, chemotherapy based on ill-toxic agents, and in selected cases, radiotherapy of remarkably low toxicity. The contribution of large international studies will be emphasized here.