Kenneth M. Flegel

Frequency, severity and risk factors for adverse drug reactions in adult out-patients: A prospective study

To provide information on the frequency of adverse drug reactions in ambulatory patients we used intensive telephone surveillance to detect suspected reactions in 1026 patients seen at an internal medicine group practice over a 1-year period. Two hundred and ninety-two suspected reactions were detected. The majority of suspected reactions were mild, causing predominantly worry or discomfort. We used a published algorithm to assess the suspected reactions for drug causation with the following results: 40 (14%) unlikely; 193 (66%) possible; 56 (19%) probable; and 3 (1%) definite. The rate of probable or definite reactions was 49/1026 (5%) per patient and 58/3330 (2%) per drug course. Surprisingly, neither the age of the patient nor the number of other drugs he was taking modified the risk of a reaction to an individual newly-started drug. Our data suggest that fear of adverse reaction should not usually be a major factor in therapeutic decision making for an ambulatory patient even when the patient is old or already on multiple drugs.

Associations between ambient air pollution and daily mortality among persons with congestive heart failure

We conducted a mortality time series study to investigate the association between daily mortality for congestive heart failure (CHF), and daily concentrations of particles and gaseous pollutants in the ambient air of Montreal, Quebec, during the period 1984-1993. In addition, using data from the universal Quebec Health Insurance Plan, we identified individuals >/=65 years of age who, one year before death, had a diagnosis of CHF. Fixed-site air pollution monitors in Montreal provided daily mean levels of pollutants. We regressed the logarithm of daily counts of mortality on the daily mean levels of each pollutant, after accounting for seasonal and subseasonal fluctuations in the mortality time series, non-Poisson dispersion, weather variables, and other gaseous and particle pollutants. Using cause of death information, we did not find any associations between daily mortality for CHF and any air pollutants. The analyses of CHF defined from the medical record showed positive associations with coefficient of haze, the extinction coefficient, SO(2), and NO(2). For example, the mean percent increase in daily mortality for an increase in the coefficient of haze across the interquartile range was 4.32% (95% CI: 0.95-7.80%) and for NO(2) it was 4.08% (95% CI: 0.59-7.68%). These effects were generally higher in the warm season.

Adverse drug reactions in general pediatric outpatients

We used a recently developed diagnostic adverse drug reaction (ADR) algorithm and an intensive telephone surveillance program to monitor all courses of prescription and nonprescription drug therapy in a general pediatric group practice for 1 year. A total of 3181 different children visited the practice during the year and received 4244 separate courses of drug therapy. Adverse symptoms were noted in 473 (11.1%) of these courses of therapy. Of 534 total adverse symptoms, however, only 24 scored as definite and 176 as probable ADRs. The main ADRs noted were antibiotic-associated gastrointestinal complaints and rashes, and various manifestations of CNS stimulation with bronchodilators. Sociodemographic variables significantly associated with the risk of a definite or probable ADR were socioeconomic status (P less than 0.0001), ethnic origin (P = 0.0015), and age (P less than 0.05). Treatment-related risk factors included treatment by a practitioner outside the study practice (usually during nonoffice hours) (P less than 0.001) and administration of a dosage above the range recommended by the manufacturer (P less than 0.001). Half the ADRs were judged as inconsequential by the childrens parents, and most of the remainder resulted in only minor morbidity. Half were judged to be highly or probably preventable. Our results suggest that ADRs do not occur commonly in general pediatric outpatients and that most are mild and self-limited.

Economic assessment of troglitazone as an adjunct to sulfonylurea therapy in the treatment of type 2 diabetes.

OBJECTIVE To assess the economic efficiency of adding troglitazone to sulfonylurea therapy to improve glycemic control. BACKGROUND Despite the high prevalence of type 2 diabetes, existing treatment strategies often fail. New oral agents give a wider segment of the population with type 2 diabetes hope of achieving near-normal blood-glucose levels. Troglitazone, a novel chemical entity, is one promising new agent. METHODS We conducted an economic analysis based on glycemic-control data from a randomized clinical trial comparing troglitazone with placebo, each added to glyburide. A patient simulation model was used to translate these data to long-term outcomes associated with diabetes. Patients had poorly controlled type 2 diabetes mellitus despite glyburide therapy. Risk functions of developing and progressing through nephropathy, retinopathy, neuropathy, hypoglycemia, and macrovascular disease were developed from the Diabetes Control and Complications Trial and large epidemiologic studies. Cost estimates were based on data from 5 states, all payor databases, surveys, and literature. The main outcomes of the model were cost-consequences, number of patients developing each type of complication, mean time to development of the complication, cost per life-year gained (LYG), and cost per quality-adjusted life-year. RESULTS The model predicts that for every 1000 patients treated with troglitazone, the improved glycemic control could mean that 95 to 140 fewer patients would experience one of the most severe diabetic complications (eg, blindness, end-stage renal disease, amputation), which may increase life expectancy by 2.0 years. These benefits are obtained at an additional

Time to address stimulant abuse on our campuses.

2100 per LYG (undiscounted). The ratio remains <

Factors relevant to preventing embolic stroke in patients with non-rheumatic atrial fibrillation.

50,000 per LYG for most variations in input. CONCLUSIONS The clinical trial demonstrated that troglitazone + glyburide improves glycemic control compared with glyburide alone. Based on these results, the model estimates fewer diabetic complications at a cost well below accepted cost-effective thresholds.

Is it time for another medical curriculum revolution

Universities and colleges need to do more to protect our young adults from and educate them about the dangers of illicit stimulant use. Abuse of prescription medications such as methylphenidate and atomoxetine has been estimated at an alarming rate ranging from 5% to 35%.[1][1] Without action, some

Decision-making capacity in an age of control

Whether or not to treat patients with non-rheumatic atrial fibrillation with anticoagulants to prevent embolic stroke is a dilemma for physicians. If randomized trials, currently underway, demonstrate a beneficial effect, the dilemma will not be solved because not all of the relevant factors can be addressed by trials. We used current knowledge about non-rheumatic atrial fibrillation and a method of obtaining patient-derived weights for avoiding stroke from eight medically trained subjects, to determine the overall benefit of anticoagulants and to see what factors were relevant and what effect each might have in deciding whether to use anticoagulant therapy. Using standard assumptions, anticoagulants gave an expected benefit for all subjects. The expected benefit (expressed in terms of lives per 1000 saved due to anticoagulants) varied between 5.4 and 46.7. This benefit remained for all subjects when we did a sensitivity analysis for different rates of stroke prevented by anticoagulants and different rates of intracranial hemorrhage caused by anticoagulants. When we used different baseline rates of stroke and different impacts of major hemorrhagic complications the benefit disappeared for 3 and 4 subjects respectively. We found the factors that were most crucial to the decision will not be included in randomized trials; the weight that an individual would place on avoiding embolic stroke vs the risk of intracranial bleeding from anticoagulant therapy; and the rate of embolic stroke that could be expected for the subject at risk. Factors which will be measured in randomized trials, will change results less substantially: the increased risk of major hemorrhages; the proportion of strokes that could be prevented by treatment; the increase in risk of intracranial hemorrhage. This method of analysis suggests that for most patients anticoagulants are beneficial and that the most important factor in determining this result is the value that subjects put on different outcomes.

Ideas about medical reporting

Many physicians would agree that medical school was long and arduous, featuring some courses that ultimately proved of dubious relevance to their current practices. That might not be as true for younger physicians who trained during the time of widespread adoption of problem-based learning. In this

L'aptitude à décider en une ère de contrôle

“ …when you grow old, you will stretch out your hands, and someone else will gird you, and bring you where you do not wish to go.” John 21:18 Clinicians know that elderly people do not fear death so much as the process of dying. Because modern therapies are more effective at relieving pain,