“Fishing” for the Origins of the “Eskimos and Heart Disease” Story: Facts or Wishful Thinking?

During the 1970s, 2 Danish investigators, Bang and Dyerberg, on being informed that the Greenland Eskimos had a low prevalence of coronary artery disease (CAD) set out to study the diet of this population. Bang and Dyerberg described the “Eskimo diet” as consisting of large amounts of seal and whale blubber (ie, fats of animal origin) and suggested that this diet was a key factor in the alleged low incidence of CAD. This was the beginning of a proliferation of studies that focused on the cardioprotective effects of the “Eskimo diet.” In view of data, which accumulated on this topic during the past 40 years, we conducted a review of published literature to examine whether mortality and morbidity due to CAD are indeed lower in Eskimo/Inuit populations compared with their Caucasian counterparts. Most studies found that the Greenland Eskimos and the Canadian and Alaskan Inuit have CAD as often as the non-Eskimo populations. Notably, Bang and Dyerberg's studies from the 1970s did not investigate the prevalence of CAD in this population; however, their reports are still routinely cited as evidence for the cardioprotective effect of the “Eskimo diet.” We discuss the possible motives leading to the misinterpretation of these seminal studies.     

In-hospital observation after antibiotic switch in pneumonia: a national evaluation

Purpose

To evaluate the clinical benefit of in-hospital observation after the switch from intravenous (IV) to oral antibiotics in a large Medicare population. Retrospective studies of relatively small size indicate that the practice of in-hospital observation after the switch from IV to oral antibiotics for patients hospitalized with community-acquired pneumonia (CAP) is unnecessary.

Methods

We performed a retrospective examination of the US Medicare National Pneumonia Project database. Eligible patients were discharged with an ICD-9-CM diagnosis consistent with community-acquired pneumonia and divided into 2 groups: 1) a “not observed” cohort, in which patients were discharged on the same day as the switch from IV to oral antibiotics and 2) an “observed for 1 day” cohort, in which patients remained hospitalized for 1 day after the switch from IV to oral antibiotics. We compared clinical outcomes between these 2 cohorts.

Results

A total of 39,242 cases were sampled, representing 4341 hospitals in all 50 states and the District of Columbia. There were 5248 elderly patients who fulfilled eligibility criteria involving a length of stay of no more than 7 hospital days (2536 “not observed” and 2712 “observed for 1 day” patients). Mean length of stay was 3.8 days for the “not observed” cohort and 4.5 days for the “observed for 1 day” cohort (P <.0001). There was no significant difference in 14-day hospital readmission rate (7.8% in the “not observed” cohort vs 7.2% “observed for 1 day” cohort, odds ratio 0.91; 95% confidence interval [CI] 0.74-1.12; P =.367) and 30-day mortality rate (5.1% “not observed” cohort vs 4.4% in the “observed for 1 day” cohort, odds ratio 0.86; 95% CI, 0.67-1.11; P =.258) between the “not observed” and “observed for 1 day” cohorts.

Conclusions

Our analysis of the US Medicare Pneumonia Project database provides further evidence that the routine practice of in-hospital observation after the switch from IV to oral antibiotics for patients with CAP may be avoided in patients who are clinically stable although these findings should be verified in a large randomized controlled trial.     

Perspectives on "chronic Lyme disease"

There is much controversy about the treatment of Lyme disease with respect to 2 poorly defined entities: “chronic Lyme disease” and “posttreatment Lyme disease syndrome.” In the absence of direct evidence that these conditions are the result of a persistent infection, some mistakenly advocate extended antibiotic therapy (≥6 months), which can do great harm and has resulted in at least 1 death. The purpose of this brief report is to review what is known from clinical research about these conditions to assist both practicing physicians and lawmakers in making sound and safe decisions with respect to treatment.     

Evidence-Based Endocrinology

Evidence-based medicine is the judicious, conscientious, and explicit use of the best available evidence from clinical research in making clinical decisions. This definition recognizes a hierarchy of evidence that arranges study designs by their susceptibility to bias. The top of the hierarchy includes n-of-1 trials, systematic reviews of randomized trials, and single randomized trials reporting patient-important outcomes. The bottom of the hierarchy includes physiologic studies and unsystematic clinical observations. The definition posits that evidence alone is never enough to guide clinical decisions. In addition to evidence from clinical research, decision making requires careful and expert assessment of the patient's circumstances and elicitation of the patient's values and preferences. The latter should drive decisions, particularly when the trade-offs (of benefit and risk) are close or unclear. The evidence-based medicine process involves: (i) asking an answerable question; (ii) acquiring the best available evidence; (iii) appraising the evidence to judge the strength of inference of its results; and (iv) applying the results to the individual patient. Evidence-based endocrinology is hindered by limited high-level evidence assessing patient-important outcomes, limited systematic summaries of this evidence, lack of time, and lack of systematic training of endocrinologists in evidence-based medicine. Current endocrine practice may require a redesign to enhance the role of endocrinologists as information brokers for colleagues and patients. In the last 10 years, evidence-based medicine has matured as a philosophy of clinical care and medical education. An appraisal of its role in endocrinology awaits the pervasion of its principles into all of endocrine practice.     

Hypertension and outcomes research From clinical trials to clinical epidemiology

Outcomes research seeks to identify effective evidence-based methods of providing the best medical care. While randomized clinical trials (RCT) usually provide the clearest answers, they are often not done or not practicable. More than a decade after the introduction of calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors, clinical trial data about their effect on major disease endpoints in patients with hypertension are still not available. The primary alternatives are the use of randomized trials that include surrogate endpoints, such as level of blood pressure or extent of carotid atherosclerosis, and the use of observational studies that include major disease endpoints. Both approaches, their strengths and limitations, are discussed in detail. The possibility of residual confounding limits the strength of inferences that can be drawn from observational studies. Similarly, the possibility of important drug effects, other than those involving the surrogate endpoint, limits the inferences that can be drawn from randomized trials that rely solely on surrogate outcomes as guides to therapy. In the absence of evidence from large clinical trials that include major disease endpoints, treatment decisions and guidelines need to synthesize the best available information from a variety of sources. Consistency of findings across various study designs, outcomes, and populations is critical to the practice of evidence-based medicine and the effort to maximize the health benefits of antihypertensive therapies.     

Psychiatric Comorbidity and Other Psychological Factors in Patients with “Chronic Lyme Disease”

Background

There is no evidence of current or previous Borrelia burgdorferi infection in most patients evaluated at university-based Lyme disease referral centers. Instead, psychological factors likely exacerbate the persistent diffuse symptoms or “Chronic Multisymptom Illness” (CMI) incorrectly ascribed to an ongoing chronic infection with B. burgdorferi. The objective of this study was to assess the medical and psychiatric status of such patients and compare these findings to those from patients without CMI.

Methods

There were 240 consecutive patients who underwent medical evaluation and were screened for clinical disorders (eg, depression and anxiety) with diagnoses confirmed by structured clinical interviews at an academic Lyme disease referral center in New Jersey. Personality disorders, catastrophizing, and negative and positive affect also were evaluated, and all factors were compared between groups and with functional outcomes.

Results

Of our sample, 60.4% had symptoms that could not be explained by current Lyme disease or another medical condition other than CMI. After adjusting for age and sex, clinical disorders were more common in CMI than in the comparison group (P <.001, odds ratio 3.54, 95% confidence interval, 1.97-6.55), but personality disorders were not significantly more common. CMI patients had higher negative affect, lower positive affect, and a greater tendency to catastrophize pain (P <.001) than did the comparison group. Except for personality disorders, all psychological factors were related to worse functioning. Our explanatory model based on these factors was confirmed.

Conclusions

Psychiatric comorbidity and other psychological factors are prominent in the presentation and outcome of some patients who inaccurately ascribe longstanding symptoms to “chronic Lyme disease.”     

Why we do not have—and will not have—the integrated and “smart” alarm systems that technology would allow us to have today

Background

Many authors have been advocating “smart alarm systems” for more than 30 years, and technology for such systems has been described in the literature for more than 20 years. Such systems do not exist today.

Goals

Incoming data would be analyzed to reject artifact. Multiple inputs would be used to determine alarm conditions. Information would be passed to the best person to address the problem. If the primary person failed to respond, a backup person would be notified.

The Problem

One might show a statistical improvement in patient outcome with a new system, but there would always be patients who would have had an alarm under the old system, and who did not have an alarm with the new system. Only if Congress would exempt the alarm integrators from liability, as the vaccine makers are protected, could such a system be built.     

An additional basic science for clinical medicine: I. The constraining fundamental paradigms

The four main conceptual paradigms of basic biomedical research are that the explication of mechanisms is a primary goal of science; that scientific data must be "hard"; that formulation of hypotheses and counter-hypotheses is a principal creative challenge; and that experiments are the main mechanism for using scientific methods to conduct investigations. Although suitable for the spectacular accomplishments of biomedical research, these paradigms do not offer a satisfactory foundation for the additional basic science needed in the managerial decisions of patient care. For these decisions, the primary scientific goal is usually prediction rather than explication alone; the crucial data often involve "soft" information about clinical and personal phenomena; and the main creative challenge is to develop an improved methodology for getting adequate data and making unbiased comparisons. Although the experiments conducted as randomized clinical trials have been scientifically helpful, the improved methods will have to include evidence obtained in the often unplanned "experiments" of ordinary clinical practice.     

Benefits of an “angina clinic” for patients with coronary artery disease: A demonstration of health status measures as markers of health care quality

Objective Our purpose was to determine the efficacy of health status measurement in quantifying improvements in quality of care provided by an “angina clinic.” Study Design In a pretest-posttest, nonequivalent control group design in the outpatient clinics of a Veterans Affairs Medical Center, 535 patients with coronary disease were followed up, without intervention, for 3 months and were defined as the “usual-care” group. Concurrently, a clinical trial that optimized the antianginal medications of 100 patients with chronic, stable coronary disease was conducted and defined as the “angina clinic” group. The 3-month change in scores for the Seattle Angina Questionnaire, a valid, reliable, and responsive disease-specific health status measure for patients with coronary disease, was used as the main outcome measure. Results After baseline differences between groups were controlled, the “angina clinic” conferred substantial improvement on patient symptom control (3-month benefit in angina frequency +9.4, P < .001; in angina stability +14.7, P < .001), treatment satisfaction (+8.6, P < .001), quality of life (+6.8, P < .001), and physical limitations resulting from coronary disease (+3.6, P = .047). Only the changes in physical limitation were not clinically significant. Conclusion Disease-specific health status measures can provide valuable insights into the quality of care associated with innovations in health care delivery. These results suggest that patients in a clinical trial optimizing antianginal medications had greater improvements in symptom control, treatment satisfaction, and quality of life compared with similar patients receiving “usual care” in a general medicine clinic. (Am Heart J 2002;143:145-50.)     

Conflicting clinical trials and the uncertainty of treating mild hypertension

Recommendations to treat patients with mild hypertension are based principally on six randomized clinical trials conducted in three countries between 1964 and 1979. To determine whether the methods and results of these randomized clinical trials justify the current therapeutic policy, a clinical epidemiologic analysis of the data was performed focusing on (1) clinical versus statistical significance, (2) clinical heterogeneity of patients' baseline state, (3) suitable management of the untreated control patients, and (4) choice of outcome events. This analysis suggested that the results of available studies are better suited to public health decisions (number of cardiovascular deaths prevented nationwide) than personal health decisions (whether treatment does more good than harm for individual patients), and that current evidence does not justify a uniform policy of treating all asymptomatic patients with mild hypertension.     

The Emerging Role of Biomarkers in Atrial Fibrillation

Improved diagnostic techniques have identified various biomarkers that might play an important role in prediction of atrial fibrillation (AF) and related outcomes (cardio- and cerebrovascular events, and mortality and rhythm outcomes). Biomarkers can include blood markers (eg, von Willebrand factor, D-dimer, natriuretic peptides, etc), urine (eg, proteinuria, estimated glomerular filtration rate, or creatinine clearance), cardiac imaging (echocardiography; transthoracic or transoesophageal), or cerebral imaging (eg, computed tomography or magnetic resonance imaging), which can provide additional refinement to clinical stroke risk stratification for identification of “high risk” subjects. Although inclusion of some blood-based biomarkers (eg, von Willebrand factor, D-dimer) in existing clinical stroke risk stratification schemes might improve their predictive value for identifying “high risk” patients, this concept might be outdated and overtaken by new developments in thromboprophylaxis (which now focus on initial identification of “low risk” patients who do not need any antithrombotic therapy, followed by patients with 1 or more stroke risk factors, to whom anticoagulation can be offered), and additional questionable practicality in “everyday” practice. Biomarkers could be applied as a “rule out” approach or as surrogates of anticoagulation efficacy in trials of new antithrombotic strategies. The present review aims to provide an update of the role of biomarkers in AF, with particular focus on AF outcomes.     

Five year time course of celiac disease serology during gluten free diet: results of a community based “CD-Watch” program

Background

Little information is available on the effect of a follow-up strategy in celiac disease patients during gluten-free diet.

Aims

To assess 5 year time course of t-transglutaminase antibodies (t-TG) in celiac disease patients enrolled in a community based follow-up program.

Methods

Annual t-TG testing and periodical clinic visit in 2245 patients.

Results

Proportion of patients with negative t-TG progressively increased from 83% to 93% during the 5-year follow-up: poor adherence to gluten-free diet (HR 4.764), long duration of gluten-free diet (HR 0.929) and female gender (HR 1.472) were independently associated with serological outcome. In individual patients, 69% tested t-TG “persistently negative”, 1% “persistently positive” and 30% “intermittently negative or positive”. By applying mathematical modelling to t-TG conversion rates observed in this latter group at beginning and end of the follow-up program, the predicted proportion of t-TG negative population increased from 90% to 95% over 5 years.

Conclusions

Time-course of t-TG serology in the community fluctuates in 1/3 of celiac disease patients suggesting inconstant adherence to gluten-free diet and need of follow-up strategy. Periodical serological and clinical follow-up is a viable and efficacious strategy to promote adherence to gluten-free diet as inferred from time-course of t-TG serology.     

Impact of Lifelong Exercise “Dose” on Left Ventricular Compliance and Distensibility

Background

Sedentary aging has deleterious effects on the cardiovascular system, including decreased left ventricular compliance and distensibility (LVCD). Conversely, Masters level athletes, who train intensively throughout adulthood, retain youthful LVCD.

Objectives

The purpose of this study was to test the hypothesis that preservation of LVCD may be possible with moderate lifelong exercise training.

Methods

Healthy seniors (n = 102) were recruited from predefined populations, screened for lifelong patterns of exercise training, and stratified into 4 groups: “sedentary” (<2 sessions/week); “casual” (2 to 3 sessions/week); “committed” (4 to 5 sessions/week); and “competitive” Masters level athletes (6 to 7 sessions/week). Right heart catheterization and echocardiography were performed while preload was manipulated using lower body negative pressure and rapid saline infusion to define LV pressure–volume relationships and Frank-Starling curves.

Results

Peak oxygen uptake and LV mass increased with escalating doses of lifelong exercise, with little change in systolic function. At baseline, LV distensibility was greater in committed (21%) and competitive (36%) exercisers than in sedentary subjects. Group LV stiffness constants (sedentary: 0.062 ± 0.039; casual: 0.079 ± 0.052; committed: 0.055 ± 0.033; and competitive: 0.035 ± 0.033) revealed: 1) increased stiffness in sedentary subjects compared to competitive athletes, whereas lifelong casual exercise had no effect; and 2) greater compliance in committed exercisers than in sedentary or casual exercisers.

Conclusions

Low doses of casual, lifelong exercise do not prevent the decreased compliance and distensibility observed with healthy, sedentary aging. In contrast, 4 to 5 exercise sessions/week throughout adulthood prevent most of these age-related changes. As LV stiffening has been implicated in the pathophysiology of many cardiovascular conditions affecting the elderly, this “dose” of exercise training may have important implications for prevention of cardiovascular disease.     

Pretransfusion trigger platelet counts and dose for prophylactic platelet transfusions

PURPOSE OF REVIEW: To assess critically both the blood platelet counts that prompt a platelet transfusion (i.e. trigger) in various clinical settings in patients with thrombocytopenia caused by marrow failure and the dose of platelets infused (i.e. number per each transfusion) for optimal hemostasis, feasibility, and safety. RECENT FINDINGS: Definitive studies (e.g. well-designed, prospective, randomized clinical trials) are not available either historically or at present to support evidence-based decisions. Instead, retrospective reviews and anecdotal reports provide observational data to assist in best guess clinical practices. SUMMARY: Reasonable clinical practice, until more definitive data become available, is to transfuse enough platelets per each transfusion to maintain the blood platelet count >10 x 10/L in stable nonbleeding patients, >20 x 10(9)/L in unstable nonbleeding patients, and >50 x 10(9)/L in bleeding patients or in those undergoing invasive procedures.     

Blood Pressure Variability: A Novel and Important Risk Factor

Blood pressure is a continuous, not a static, variable. Individuals exhibiting similar clinic or home blood pressure can differ considerably with respect to their average day and nighttime values, beat-by-beat blood pressure variation during wakefulness and sleep, responses to mental and physical stimuli, and intersession and seasonal variation. There now is evidence that several such representations of blood pressure variability, if augmented, increase cardiovascular risk independent of the average of conventionally acquired blood pressure readings. As well, recent retrospective analyses of published trial data have concluded that antihypertensive drug classes differ in their effects on intersession blood pressure variability and associated risk of stroke. If the goal of the hypertension community is to optimize personalized cardiovascular risk assessment and to attenuate fully such risk, future efforts should be directed at determining which representation of blood pressure variability estimates individual cardiovascular risk best, establishing “normal” and “high- risk” variability distributions, testing the hypothesis that attenuating such variability specifically through drug or device therapy reduces cardiovascular risk more than blood pressure reduction per se, and integrating such data into clinical practice.     

An Intranet-based system for inpatient billing in an academic medical center

Academic physicians face great economic challenges. There is therefore a growing need to increase the efficiency of academic practice. One potential target for improving the “business” of medicine is inpatient billing. Currently many academic centers use “yellow” cards for inpatient billing. This is an inefficient system for capturing patient charges. We describe an Intranet-based system for inpatient billing that improves physician “productivity,” reduces billing lag time, and increases the collection rate and total revenues.     

Biologic and clinical significance of molecular profiling in Chronic Lymphocytic Leukemia

CLL is extremely heterogeneous in its clinical course, with some patients living decades with no need for treatment whilst others have a rapidly aggressive clinical course. A major focus of research has been to try to identify those biological factors that influence this heterogeneity. The goal of therapy has been to maintain the best quality of life and treat only when patients become symptomatic from their disease. For the majority of patients this means following a “watch and wait” approach to determine the rate of progression of the disease and assess for development of symptoms. Any alteration to this approach will require identification of criteria that define patients sufficiently “high-risk” that they gain benefit by introduction of early therapy. The use of molecular profiling to suggest particular therapies is currently appropriate only in defining the treatment of the minority of patients with 17p deletions or p53 mutations and in all other circumstances remains a clinical trial question.     

Integrating quality into the cycle of therapeutic development

The quality of healthcare, particularly as reflected in current practice versus the available evidence, has become a major focus of national health policy discussions. Key components needed to provide quality care include: 1) development of quality indicators and performance measures from specific practice guidelines, 2) better ways to disseminate such guidelines and measures, and 3) development of support tools to promote standardized practice. Although rational decision-making and development of practice guidelines have relied upon results of randomized trials and outcomes studies, not all questions can be answered by randomized trials, and many treatment decisions necessarily reflect physiology, intuition, and experience when treating individuals. Debate about the role of "evidence-based medicine" also has raised questions about the value of applying trial results in practice, and some skepticism has arisen about whether advocated measures of clinical effectiveness, the basic definition of quality, truly reflect a worthwhile approach to improving medical practice. We provide a perspective on this issue by describing a model that integrates quantitative measurements of quality and performance into the development cycle of existing and future therapeutics. Such a model would serve as a basic approach to cardiovascular medicine that is necessary, but not sufficient, to those wishing to provide the best care for their patients.     

Les réseaux asthme : trait d'union entre l'hôpital et la ville

The WHO defines and justifies patient education as a continuous process that is focused on treatment and centred on the patient. Here, the authors review the general principals of the patient education process as applied to asthmatics. This can be described in four steps: the informed diagnosis, the education contract, the plan of action, and the evaluation. They then describe their experience with a “school for asthma” linking, in a town-hospital partnership, allergy-pulmonary specialists working in a public hospital or private clinic, generalists in private practice, nurse educators and physiotherapists, all in contact with the patient and his family. The first trial of group education could not be analysed and the follow-up of individual cases did not succeed. A new “school for asthma” is now being developed. This educational project is being organized along three axes: 1) an individual approach coupled with medical consultation for diagnosis and educational follow-up with the patient, 2) collective management of patients through thematic seminars, 3) continuous training cycles aimed at the personnel involved in each theme. “Asthma and pregnancy” is the theme currently being developed as an example.