Effect of restricting contact between pharmaceutical company representatives and internal medicine residents on posttraining attitudes and behavior

CONTEXT: The long-term effect of policies restricting contact between residents and pharmaceutical company representatives (PCRs) during internal medicine training is unknown. The McMaster University Department of Medicine in Hamilton, Ontario, implemented a policy restricting PCR contact with trainees in 1992, whereas the Department of Medicine at the University of Toronto, Toronto, Ontario, has no such policy. OBJECTIVE: To determine if the presence of a restrictive policy and the frequency of contact with PCRs during internal medicine training predict attitudes and behavior several years after completion of training. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of the attitudes and behavior of 3 cohorts of physicians: University of Toronto trainees, prepolicy McMaster trainees, and postpolicy McMaster trainees. Surveys were mailed to 242 former University of Toronto and 57 former McMaster trainees who completed their internal medicine training between 1990 and 1996, with response rates of 163 (67%) and 42 (74%), respectively. MAIN OUTCOME MEASURES: Physician attitude, assessed by a question about the perceived helpfulness of PCR information, and behavior, assessed by whether physicians met with PCRs in the office and the frequency of contacts with PCRs (current contact score, consisting of conversations with PCRs, PCR-sponsored events attended, gifts, honoraria, and consulting fees received). RESULTS: In both the unadjusted and multiple regression analyses, postpolicy McMaster trainees were less likely to find information from PCRs beneficial in guiding their practice compared with Toronto and prepolicy McMaster trainees, with unadjusted odds ratios (ORs) of 0.44 (95% confidence interval [CI], 0.20-0.94) and 0.39 (95% CI, 0.13-1.22), respectively. All 3 groups were equally likely to report that they met with PCRs in their office in the past year (88%). Postpolicy McMaster trainees had a lower current contact score compared with Toronto (9.3 vs 10.9; P =.04) and prepolicy McMaster trainees (9.3 vs 10.8; P =.18). In multiple regression models, greater frequency of contact with PCRs during training was a predictor of increased perceived benefit of PCR information (OR, 1.29; 95% CI, 1.13-1.47) and was positively correlated with the current contact score (partial r = 0.49; P<.001). Number of PCR-sponsored rounds attended during training was not a consistent predictor of attitudes or behavior. CONCLUSIONS: Policies restricting PCR access to internal medicine trainees and the amount of contact during residency appear to affect future attitudes and behavior of physicians.     

Sex differences in evaluation and outcome of unstable angina

CONTEXT: The existence of sex bias in the delivery of cardiac care is controversial, and little is known about the association between sex and delivery of care and outcomes at an early point in the diagnostic sequence, such as when patients present for the evaluation of chest pain. OBJECTIVE: To test the hypothesis that female sex is negatively associated with care delivered to and outcomes of persons diagnosed as having unstable angina. DESIGN: Inception population-based cohort study with an average of 6 years of follow-up. SETTING: Emergency departments (EDs) in Olmsted County, Minnesota. PATIENTS: A total of 2271 Olmsted County residents (1306 men and 965 women) who presented to the ED for the first time with symptoms meeting criteria for unstable angina between 1985 and 1992. MAIN OUTCOME MEASURES: Use of cardiac procedures within 90 days of ED visit, overall mortality, and cardiac events (cardiac death, nonfatal myocardial infarction, nonfatal cardiac arrest, and congestive heart failure), compared by sex and Agency for Health Care Policy and Research cardiovascular risk category (low, intermediate, or high). RESULTS: Women were older (P<.001), more likely to have a history of hypertension (P = .001), and less likely to present with typical angina (P = .004) than men. Men were more likely than women to undergo noninvasive cardiac tests (relative risk [RR], 1.27; 95% confidence interval [CI], 1.14-1.40) as well as invasive cardiac procedures (RR, 1.72; 95% CI, 1.51-1.97). After adjustment, male sex was associated with a 24% increase in the use of cardiac procedures. Survival of both men and women in the high and intermediate risk categories was significantly lower than expected per the general population (P<.001). Women had a worse outcome than men, but after multivariate adjustment, male sex was associated with a trend toward an increase in the risk of death (RR, 1.23; 95% CI, 0.99-1.54) and significantly associated with increased risk of cardiac events (RR, 1.21; 95% CI, 1.03-1.42). CONCLUSIONS: Our population-based data indicate that after an ED visit for symptoms of unstable angina, the use of cardiac procedures was lower in women, but after taking into account baseline characteristics, men experienced worse outcomes.     

Effect of statins on risk of coronary disease: a meta-analysis of randomized controlled trials

CONTEXT: Lowering low-density lipoprotein cholesterol (LDL-C) is known to reduce risk of recurrent coronary heart disease in middle-aged men. However, this effect has been uncertain in elderly people and women. OBJECTIVE: To estimate the risk reduction of coronary heart disease and total mortality associated with statin drug treatment, particularly in elderly individuals and women. DATA SOURCES: Trials published in English-language journals were retrieved by searching MEDLINE (1966-December 1998), bibliographies, and authors' reference files. STUDY SELECTION: Studies in which participants were randomized to statin or control treatment for at least 4 years and clinical disease or death was the primary outcome were included in the meta-analysis (5 of 182 initially identified). DATA EXTRACTION: Information on sample size, study drug duration, type and dosage of statin drug, participant characteristics at baseline, reduction in lipids during intervention, and outcomes was abstracted independently by 2 authors (J.H. and S.V.) using a standardized protocol. Disagreements were resolved by consensus. DATA SYNTHESIS: Data from the 5 trials, with 30 817 participants, were included in this meta-analysis. The mean duration of treatment was 5.4 years. Stati n drug treatment was associated with a20% reduction in total cholesterol, 28% reduction in LDL-C, 13% reduction in triglycerides, and 5% increase in high-density lipoprotein cholesterol. Overall, statin drug treatment reduced risk 31 % in major coronary events (95% confidence interval [CI], 26%-36%) and 21 % in all-cause mortality (95% CI, 14%-28%). The risk reduction in major coronary events was similar between women (29%; 95% Cl, 13 %-42 %) and men (31 %; 95% CI, 26%-35%), and between persons aged at least 65 years (32%; 95% CI, 23%-39%) and persons younger than 65 years (31 %; 95% CI, 24%-36%). CONCLUSIONS: Our meta-analysis indicates that reduction in LDL-C associated with statin drug treatment decreases the risk of coronary heart disease and all-cause mortality. The risk reduction was similar for men and women and for elderly and middle-aged persons.     

Risk factors and incidence of posttransplant diabetes mellitus in Mexican kidney recipients

BACKGROUND: Many risk factors are associated with the development of posttransplant diabetes mellitus (PTDM), which has adverse effects on graft and patient survival. We report the incidence and risk factors associated with the development of PTDM in Mexican kidney recipients. METHODS: In a retrospective cohort study, we included kidney transplants performed between January 1, 1994 and December 31, 2000; all patients were followed up for at least 1 year posttransplantation. PTDM was defined as fasting blood glucose >126 mg/dL on at least two occasions. Statistical analysis included estimation of crude relative risk (RR) with 95% confidence intervals (CI). Adjusted RR and 95% CI by logistic regression were used. RESULTS: We studied 522 kidney recipients. Fifty three (10.1%) cases of PTDM were identified in this cohort. Cumulative dosage of prednisone (PDN) >13 g (RR 7.6, 95% CI 1.5-16.3 p <0.0001) and the presence of >or=1 acute rejection episodes (RR 3.7, 95% CI 1.2-11.6 p <0.001 were independent risk factors associated with the development of PTDM. Obesity (RR 2.6, 95% CI 0.8-8.7, p = 0.083) and age range of 40-49 years (RR 2.0; 95% CI 0.6-7.2, p = 0.093) were identified as marginal risk factors. CONCLUSIONS: The incidence of PTDM in kidney recipients was 10.1% in our population. Cumulative PDN dosage and presence of >or=1 acute rejection episodes were independent risk factors for the development of PTDM. These results are consistent with prior studies of the diabetogenic effect of the PDN. The relationship between acute rejection and PTDM deserves further investigation in order to learn more about the role that inflammatory mechanisms may play in this association.     

Assessing taxane-associated adverse events using the FDA adverse event reporting system database

Background:Taxanes are an essential class of antineoplastic agents used to treat various cancers and are a fundamental cause of hypersensitivity reactions. In addition, other adverse events, such as bone marrow toxicity and peripheral neuropathy, can lead to chemotherapy discontinuation. This study aimed to evaluate the safety of taxanes in the real world.Methods:Taxane-associated adverse events were identified by the Medical Dictionary for Regulatory Activities Preferred Terms and analyzed and compared by mining the US Food and Drug Administration Adverse Event Reporting System pharmacovigilance database from January 2004 to December 2019. Reported adverse events, such as hypersensitivity reaction, bone marrow toxicity, and peripheral neuropathy, were analyzed with the following signal detection algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma Poisson shrinker (MGPS), Bayesian confidence propagation neural network (BCPNN), and logistic regression methods. Adverse outcome events and death outcome rates were compared between different taxane groups using Pearson''s χ² test, whereas significance was determined at P < 0.05 with a 95% confidence interval (CI).Results:A total of 966 reports of hypersensitivity reactions, 1109 reports of bone marrow toxicity, and 1374 reports of peripheral neuropathy were analyzed. Compared with paclitaxel and docetaxel, bone marrow toxicity following the use of nab-paclitaxel had the highest ROR of 6.45 (95% two-sided CI, 6.05–6.88), PRR of 5.66, (χ² = 4342.98), information component of 2.50 (95% one-sided CI = 2.34), and empirical Bayes geometric mean of 5.64 (95% one-sided CI = 5.34). Peripheral neuropathy following the use of nab-paclitaxel showed a higher ROR of 12.78 (95% two-sided CI, 11.55–14.14), PRR of 12.16 (χ² = 4060.88), information component of 3.59 (95% one-sided CI = 3.25), and empirical Bayes geometric mean of 12.07 (95% one-sided CI = 11.09).Conclusions:The results showed that bone marrow toxicity and peripheral neuropathy were the major adverse events induced by taxanes. Nab-paclitaxel exhibited the highest potential for taxane-associated adverse events. Further research in the future is warranted to explain taxane-associated adverse effects in real-world circumstances.     

An ambulatory stabilisation program for children with newly diagnosed type 1 diabetes

OBJECTIVES: (i) To evaluate the benefits and adverse effects of a Diabetes Day Care Program (DDCP); and (ii) to compare outcomes in two cohorts diagnosed before and after implementing the DDCP ("pre-DDCP" and "post-DDCP"). DESIGN: Outcomes from the pre-DDCP cohort were compared with those of the post-DDCP cohort. SETTING: The study was conducted from March 2001 to October 2002 at the Children's Hospital at Westmead. PARTICIPANTS: The pre-DDCP cohort comprised all children newly diagnosed with type 1 diabetes from March 2000 to November 2000 (n = 49). The post-DDCP cohort were those diagnosed from November 2000 to August 2001 (n = 61). MAIN OUTCOME MEASURES: Length of stay, adverse events, insulin requirement and glycohaemoglobin (HbA(1c)) level over the first year after diagnosis were ascertained from medical records. Questionnaires to measure parents' knowledge of diabetes, emotional adjustment to diabetes, and responsibility for and conflict over specific diabetes management tasks were completed by parents at 6-monthly intervals. RESULTS: Median length of hospital stay decreased from 5.14 days (range, 2-10) to 1.70 days (range, 0-10) (P < 0.001). There were no differences between the two cohorts in insulin requirement at 12 months (pre-DDCP: 0.9 U/kg [95% CI, 0.8-1.0]; post-DDCP: 0.8 U/kg [95% CI, 0.7-0.9]; P = 0.22), HbA(1c) level at 12 months (pre-DDCP: 8.4% [95% CI, 8.0%-8.9%]; post-DDCP: 8.2% [95% CI, 7.9%-8.5%]; P = 0.37) and adverse events over the first year after diagnosis. Both groups reported similar scores for the parental questionnaires. CONCLUSIONS: Ambulatory stabilisation of children with type 1 diabetes provides similar metabolic outcomes for the child, and comparable levels of diabetes knowledge and similar psychosocial outcomes for the family, to inpatient stabilisation programs.     

The natural history of hepatitis C virus infection: host, viral, and environmental factors

CONTEXT: Hepatitis C virus (HCV) infection may resolve (viral clearance), persist without complications, or cause end-stage liver disease (ESLD). The frequency and determinants of these outcomes are poorly understood. OBJECTIVE: To assess the incidence and determinants of viral clearance and ESLD among persons who acquired HCV infection from injection drug use. DESIGN AND SETTING: Community-based prospective cohort study with enrollment in 1988-1989 and a median follow-up of 8.8 years. SUBJECTS: A total of 1667 persons aged 17 years or older with a history of injection drug use and an HCV antibody-positive test result during follow-up. MAIN OUTCOME MEASURES: Viral clearance was assessed in a subset of 919 patients and defined as failure to detect HCV RNA in at least 2 consecutive samples collected 5 or more months apart. End-stage liver disease was assessed at semiannual visits and by review of medical records and death certificates and defined by the presence of ascites, esophageal varices, or hepatic encephalopathy, or when ESLD was stated as a cause of death. RESULTS: Viral clearance was observed in 90 persons who were compared with 722 with persistent viremia, while the viremia of 107 was not resolved. Viral clearance occurred more often in nonblacks (adjusted odds ratio [OR], 5.15; 95% confidence interval [CI], 2.60-10.17) and those not infected with human immunodeficiency virus (HIV) (adjusted OR, 2.19; 95% CI, 1.26-3.47). Forty cases of ESLD were observed throughout follow-up (incidence, 3.1 per 1000 person-years). In a multivariate model, risk of ESLD was higher for persons aged 38 years or older at enrollment (adjusted relative incidence, 3.67; 95% CI, 1.96-6.88) and who reported ingestion of more than 260 g of alcohol per week (adjusted relative incidence, 3.60; 95% CI, 1.73-7.52). Of 210 patients without ESLD randomly selected for biopsy, only 2 had cirrhosis. CONCLUSIONS: Our results indicate that although HCV infection can be self-limited or associated with ESLD, the majority of adults have persistent viremia without clinically demonstrable liver disease. Further research is needed to explain the less frequent clearance of HCV infection among black persons and to improve utilization of treatment for those infected in the context of injection drug use. JAMA. 2000;284:450-456     

National surveillance of emergency department visits for outpatient adverse drug events

Context  Adverse drug events are common and often preventable causes of medical injuries. However, timely, nationally representative information on outpatient adverse drug events is limited. Objective  To describe the frequency and characteristics of adverse drug events that lead to emergency department visits in the United States. Design, Setting, and Participants  Active surveillance from January 1, 2004, through December 31, 2005, through the National Electronic Injury Surveillance System–Cooperative Adverse Drug Event Surveillance project. Main Outcome Measures  National estimates of the numbers, population rates, and severity (measured by hospitalization) of individuals with adverse drug events treated in emergency departments. Results  Over the 2-year study period, 21 298 adverse drug event cases were reported, producing weighted annual estimates of 701 547 individuals (95% confidence interval [CI], 509 642-893 452) or 2.4 individuals per 1000 population (95% CI, 1.7-3.0) treated in emergency departments. Of these cases, 3487 individuals required hospitalization (annual estimate, 117 318 [16.7%]; 95% CI, 13.1%-20.3%). Adverse drug events accounted for 2.5% (95% CI, 2.0%-3.1%) of estimated emergency department visits for all unintentional injuries and 6.7% (95% CI, 4.7%-8.7%) of those leading to hospitalization and accounted for 0.6% of estimated emergency department visits for all causes. Individuals aged 65 years or older were more likely than younger individuals to sustain adverse drug events (annual estimate, 4.9 vs 2.0 per 1000; rate ratio [RR], 2.4; 95% CI, 1.8-3.0) and more likely to require hospitalization (annual estimate, 1.6 vs 0.23 per 1000; RR, 6.8; 95% CI, 4.3-9.2). Drugs for which regular outpatient monitoring is used to prevent acute toxicity accounted for 41.5% of estimated hospitalizations overall (1381 cases; 95% CI, 30.9%-52.1%) and 54.4% of estimated hospitalizations among individuals aged 65 years or older (829 cases; 95% CI, 45.0%-63.7%). Conclusions  Adverse drug events among outpatients that lead to emergency department visits are an important cause of morbidity in the United States, particularly among individuals aged 65 years or older. Ongoing, population-based surveillance can help monitor these events and target prevention strategies.      

Claiming behaviour in a no-fault system of medical injury: a descriptive analysis of claimants and non-claimants

OBJECTIVES: (i) To determine the proportion of patients in New Zealand who claim compensation from the national no-fault compensation program after experiencing a compensable injury; and (ii) to identify characteristics of injured patients who are least likely to claim despite having sustained a compensable injury. DESIGN: We estimated the percentage of eligible patients who claim no-fault compensation by linking a national claims database (Accident Compensation Corporation) to records reviewed in the New Zealand Quality of Healthcare Study (NZQHS). Bivariate and multivariate analyses were used to investigate socioeconomic and sociodemographic differences between claimants and injured non-claimants. PARTICIPANTS AND SETTING: Patients who experienced an adverse event associated with care in NZ public hospitals in 1998 and claimed compensation with the ACC, the national no-fault insurer (n = 741). Patients identified by the NZQHS as having sustained an adverse event associated with hospital care in the same year who did not file a compensation claim (n = 839). MAIN OUTCOME MEASURES: Adverse events, compensable adverse events, and compensation claims. RESULTS: Among patients judged by NZQHS reviewers to be eligible for compensation, 2.9% (6/210) claimed. Odds of claiming after an adverse event were significantly lower for patients who were elderly (odds ratio [OR], 0.20; 95% CI, 0.14-0.28), from the most deprived areas (OR, 0.36; 95% CI, 0.23-0.57), or of Ma ori or Pacific ethnicity (OR, 0.47; 95% CI, 0.32-0.69 and OR, 0.26, 95% CI, 0.11-0.58). CONCLUSIONS: Despite few apparent institutional or economic barriers, the proportion of injured patients in NZ who seek compensation after sustaining a compensable injury is very low. Hence, substantial underclaiming occurs in both negligence and no-fault systems. The disproportionately low propensity of elderly, poor and minority patients to seek compensation also appears to be pervasive.