Physician interpretations and textbook definitions of blinding terminology in randomized controlled trials

CONTEXT: When clinicians assess the validity of randomized controlled trials (RCTs), they commonly evaluate the blinding status of individuals in the RCT. The terminology authors often use to convey blinding status (single, double, and triple blinding) may be open to various interpretations. OBJECTIVE: To determine physician interpretations and textbook definitions of RCT blinding terms. DESIGN AND SETTING: Observational study undertaken at 3 Canadian university tertiary care centers between February and May 1999. PARTICIPANTS: Ninety-one internal medicine physicians who responded to a survey. MAIN OUTCOME MEASURES: Respondents identified which of the following groups they thought were blinded in single-, double-, and triple-blinded RCTs: participants, health care providers, data collectors, judicial assessors of outcomes, data analysts, and personnel who write the article. Definitions from 25 systematically identified textbooks published since 1990 providing definitions for single, double, or triple blinding. RESULTS: Physician respondents identified 10, 17, and 15 unique interpretations of single, double, and triple blinding, respectively, and textbooks provided 5, 9, and 7 different definitions of each. The frequencies of the most common physician interpretation and textbook definition were 75% (95% confidence interval [CI], 65%-83%) and 74% (95% CI, 52%-90%) for single blinding, 38% (95% CI, 28%-49%) and 43% (95% CI, 24%-63%) for double blinding, and 18% (95% CI, 10%-28%) and 14% (95% CI, 0%-58%) for triple blinding, respectively. CONCLUSIONS: Our study suggests that both physicians and textbooks vary greatly in their interpretations and definitions of single, double, and triple blinding. Explicit statements about the blinding status of specific groups involved in RCTs should replace the current ambiguous terminology.     

A comprehensive view of sex-specific issues related to cardiovascular disease

Cardiovascular disease (CVD) is the leading cause of mortality in women. In fact, CVD is responsible for a third of all deaths of women worldwide and half of all deaths of women over 50 years of age in developing countries. The prevalence of CVD risk factor precursors is increasing in children. Retrospective analyses suggest that there are some clinically relevant differences between women and men in terms of prevalence, presentation, management and outcomes of the disease, but little is known about why CVD affects women and men differently. For instance, women with diabetes have a significantly higher CVD mortality rate than men with diabetes. Similarly, women with atrial fibrillation are at greater risk of stroke than men with atrial fibrillation. Historically, women have been underrepresented in clinical trials. The lack of good trial evidence concerning sex-specific outcomes has led to assumptions about CVD treatment in women, which in turn may have resulted in inadequate diagnoses and suboptimal management, greatly affecting outcomes. This knowledge gap may also explain why cardiovascular health in women is not improving as fast as that of men. Over the last decades, mortality rates in men have steadily declined, while those in women remained stable. It is also becoming increasingly evident that gender differences in cultural, behavioural, psychosocial and socioeconomic status are responsible, to various degrees, for the observed differences between women and men. However, the interaction between sex-and gender-related factors and CVD outcomes in women remains largely unknown.     

ORIGINAL ARTICLE Effect of Ketotifen Fumarate,Olopatadine, and Levocabastine on Ocular Active Anaphylaxis in the Guinea Pig and Ocular Immediate Hypersensitivity in the Albino Rat

Purpose: To study the effects of ketotifen fumarate, olopatadine, and levocabastine on ocular active anaphylaxis in guinea pigs and on ocular immediate hypersensitivity in albino rats. Methods: Clinical grading scores and Evans blue dye leakage to eyelids and to eyeballs were assessed in five treatment groups (n = 10): ketotifen fumarate 0.025%, olopatadine 0.1%, levocabastine 0.05%, negative control, and positive control. Results: At 20 minutes after challenge, edema scores for ketotifen-treated guinea pigs were statistically significantly lower than those for levocabastine or olopatadine. Active treatment significantly reduced vascular leakage in both models. Ketotifen significantly reduced vascular leakage in eyelids compared with the other drugs. In guinea pigs, vascular leakage in eyeballs was significantly reduced with ketotifen fumarate compared with olopatadine and levocabastine. Conclusions: In the guinea pig model, ketotifen was more effective than olopatadine and levocabastine at reducing conjunctival edema and vascular permeability in eyelids and eyeballs. In the rat model, ketotifen was more effective at reducing vascular permeability in eyelids than olopatadine and levocabastine.     

Expansion of large granular lymphocytes (natural killer cells) with limited antigen expression (CD2+, CD3-, CD4-, CD8-, CD16+, NKH-1-) in a human immunodeficiency virus-positive homosexual man

Lymphoid neoplasms associated with acquired immune deficiency syndrome (AIDS) are mostly of B-cell type and rarely of T-cell origin. The authors report a case of a homosexual HIV antibody-positive, HTLV-1 antibody-negative man who developed T-lymphoproliferative disorder (TGLD) after he experienced a viral-like illness. The lymphoproliferative disorder was characterized by increased peripheral blood large granular lymphocytes (LGL) with azurophilic granules (natural killer [NK] cells) which had limited antigen expression: CD2+, CD3-, CD4-, CD8-, CD16+, NKH-1-. The LGL failed to express T-cell or T-cell-related antigens, with the exception of CD2. No functional or gene rearrangement studies were performed on the patient's lymphocytes. However, the results of immunophenotyping, including CD25, W26, and HLA-DR, were suggestive of an inactive state, and the negative finding for CD3 antigen was consistent with unarranged gene T-cell receptors. This is the first reported case of TGLD in an HIV antibody-positive patient.     

Pneumothorax preceding pulmonary blastoma in a child

Serial plain radiographic, ultrasound and CT findings of an unusual case of pulmonary blastoma are described with a review of the literature.     

Missed opportunities for prevention in general internal medicine

BACKGROUND: According to the Canadian Society of Internal Medicine, the Canadian general internist is in the ideal position to promote patient health through disease prevention. To explore the general internist's contribution to disease prevention, the authors quantified the extent to which opportunities for prevention were addressed by the general internal medicine (GIM) service in an acute care teaching hospital in Calgary. METHODS: The authors interviewed 100 adult patients before discharge from the hospital's GIM service between May 14, 1997, and Dec. 2, 1997. The number of potential opportunities for preventive intervention were identified for each patient from 10 possible interventions recommended by the Canadian Task Force on the Periodic Health Examination (now the Canadian Task Force on Preventive Health Care): breast cancer screening, Papanicolaou smear for cervical cancer, counselling on menopausal hormone replacement therapy, digital rectal examination for prostate cancer, smoking cessation counselling, cholesterol measurement, therapy or monitoring for hypertension, influenza vaccination, pneumococcal vaccination and colorectal cancer screening. The authors determined which interventions the patient had undergone before the current admission to hospital and, using patient recall and postdischarge medical chart review, which opportunities for intervention were addressed by the GIM service during the current admission. An opportunity for preventive intervention was considered as addressed by the GIM service if it was performed during the current admission or if the general internist informed the patient or the patient's family physician of the need for such intervention in the near future. RESULTS: Among the 10 preventive interventions considered, a mean of 3.8 potential opportunities for prevention were identified for each patient. Of these, 46.5% had been addressed before the current admission, and 8.7% were addressed by the GIM service during the admission. Therefore, at the time of discharge, a mean of 55.2% of opportunities had been addressed. Among the opportunities not previously addressed, the GIM service most frequently addressed digital rectal examination for prostate cancer and cholesterol measurement. INTERPRETATION: General internists are discharging patients without sufficiently addressing opportunities for disease prevention. Preventive care protocols may be needed to limit the frequency of missed opportunities for prevention in patients admitted to tertiary care GIM services.     

Estimation of Ochratoxin A in human blood of healthy Tunisian population

Human exposure to Ochratoxin A (OTA) has been investigated in many Mediterranean countries, where OTA was found with a higher frequency in foodstuffs and blood samples. The aim of this study was to assess OTA concentrations in human blood serum in Tunisia and to evaluate the impact of several factors (age, origin, sex) on these prevalence reference values. One hundred and seven blood serum samples from healthy subjects were analyzed using a solid-phase extraction linked to a high-performance liquid chromatography (HPLC) method. OTA values ranged from 0 to 3.43 ng/mL with a mean value of 0.49±0.67 ng/mL. OTA levels were higher in the Sahal group. Our results reflect OTA concentration previously detected for human blood in Tunisia. Origin, but not age and sex, may affect the OTA reference values.