Ibuprofen and skin and soft tissue superinfections in children with varicella

PURPOSE: To investigate the possible association between ibuprofen use and dermatologic superinfections among children with recent varicella infection. METHODS: A retrospective cohort study of children in Harvard Pilgrim Health Care, a health maintenance organization in New England, was conducted. Outcomes and exposures of interest were identified from automated medical and pharmacy records. Exposure was defined by dispensing of ibuprofen before varicella to avoid potential confounding by indication. RESULTS: Between July 1, 1990 and September 30, 1994, 89 superinfections developed among 7,013 cases of varicella. The 30-day risk of superinfection was 7.2/10(3) cases (95% CI = 5.8-8.8/10(3) cases). Four of 169 children dispensed ibuprofen within 180 days of varicella developed superinfection. Relative to children without prior use, children with ibuprofen dispensed in the month prior to varicella were 3.1 times more likely to be diagnosed with a superinfection (95% CI = 0.1-19.7; P-value: 0.31). Restriction of outcomes to superinfections treated with systemic antibiotics increased the odds ratio to 5.1 (95% CI = 0.1-32.5; P-value: 0.22). CONCLUSIONS: The results of this study are consistent with a broad range of effects including no association and suggest that further study is needed.     

Influence of payor on use of invasive cardiac procedures and patient outcome after myocardial infarction in the United States. Participants in the National Registry of Myocardial Infarction

OBJECTIVES: We sought to determine the influence of payor status on the use and appropriateness of cardiac procedures. BACKGROUND: The use of invasive procedures affects the cost of cardiovascular care and may be influenced by payor status. METHODS: We compared treatment and outcomes of myocardial infarction among four payor groups: fee for service (FFS), health maintenance organization (HMO), Medicaid and uninsured. Multivariate comparison was performed on the use of invasive cardiac procedures, length of hospital stay and in-hospital mortality in 17,600 patients <65 years old enrolled in the National Registry of Myocardial Infarction from June 1994 to October 1995. To determine the appropriateness of coronary angiography, we compared its use in patients at low and high risk for cardiac events. RESULTS: Angiography was performed in 86% of FFS, 80% of HMO, 61% of Medicaid and 75% of uninsured patients. FFS patients were more likely to undergo angiography than HMO (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.13 to 1.42), Medicaid (OR 2.43, 95% CI 2.11 to 2.81) and uninsured patients (OR 1.99, 95% CI 1.76 to 2.25). Similar patterns for the use of coronary revascularization were found. Among those at low risk, FFS patients were as likely to undergo angiography as HMO patients but more likely than Medicaid and uninsured patients. For those at high risk, FFS patients were more likely to undergo angiography than patients in other payor groups. Adjusted mean length of stay (7.3 days) was similar among all payor groups, but adjusted mortality was higher in the Medicaid group (Medicaid vs. FFS: OR 1.55, 95% CI 1.19 to 2.01). CONCLUSIONS: Payor status is associated with the use and appropriateness of invasive cardiac procedures but not length of hospital stay after myocardial infarction. The higher in-hospital mortality in the Medicaid cohort merits further study.     

Restoration of rat liver L-threonine dehydratase activity by pyridoxamine 5''-phosphate: the half-transaminating activity of L-threonine dehydratase and its regulatory role

OBJECTIVE: The objective of this study is to estimate the risk of subarachnoid hemorrhage produced by oral contraceptive use. METHODS: Studies published since 1960 were identified using MEDLINE, Cumulated Index Medicus, Dissertation Abstracts On-line, and bibliographies of pertinent articles. Two independent reviewers screened published cohort and case-control studies that evaluated the risk of subarachnoid hemorrhage associated with oral contraceptives. Eleven of 21 pertinent studies met predefined quality criteria for inclusion in the meta-analysis. Relative risk (RR) estimations evaluating subarachnoid hemorrhage risk in oral contraceptive users compared with nonusers were extracted from each study by two independent reviewers. Study heterogeneity was assessed by design type, outcome measure (mortality versus incidence), exposure measure (current versus ever use), prevailing estrogen dose used, and control for smoking and hypertension. RESULTS: The overall summary RR of subarachnoid hemorrhage due to oral contraceptive use was 1.42 (95% CI, 1.12 to 1.80; p = 0.004). When the two study results failing to control for smoking were excluded from the analysis, a slightly greater effect was seen, with an RR of 1.55 (95% CI, 1.26 to 1.91; p < 0.0001). In the six studies controlling for smoking and hypertension the RR was 1.49 (95% CI, 1.20 to 1.85; p = 0.0003). High-estrogen oral contraceptives appeared to impart a greater risk than low-dose preparations in studies controlling for smoking, but the difference was not significant (high-dose RR, 1.94; 95% CI, 1.06 to 3.56; low-dose RR, 1.51; 95% CI, 1.18 to 1.92). CONCLUSIONS: This meta-analysis of observational studies suggests that oral contraceptive use produces a small increase in the risk of subarachnoid hemorrhage.     

Incidence and risk factors for serious hypoglycemia in older persons using insulin or sulfonylureas

BACKGROUND: Our knowledge about the risk of hypoglycemia associated with diabetes treatment is derived from studies that often exclude frail, elderly persons. OBJECTIVE: To determine the incidence and risk factors for developing serious hypoglycemia among older persons using sulfonylureas or insulin. METHODS: We conducted a population-based, retrospective cohort study of 19932 Tennessee Medicaid enrollees, aged 65 years or older, who used insulin or sulfonylureas from 1985 through 1989. The main end point was serious hypoglycemia defined as a hospitalization, emergency department admission, or death associated with hypoglycemic symptoms and a concomitant blood glucose determination of less than 2.8 mmol/L (< 50 mg/dL). RESULTS: We identified 586 persons with a first episode of serious hypoglycemia during 33,048 person-years of insulin or sulfonylurea use. The crude rates (per 100 person-years) of serious hypoglycemia were 1.23 (95% confidence interval [CI], 1.08-1.38) in users of sulfonylureas and 2.76 (95% CI, 2.47-3.06) among insulin users. Recent hospital discharge was the strongest predictor of subsequent hypoglycemia in older persons with diabetes. The adjusted relative risk of serious hypoglycemia occurring in days 1 through 30 after hospital discharge was 4.5 (95% CI, 3.5-5.7) compared with the risk associated with a hypoglycemic event occurring 366 or more days after hospital discharge. Other independent risk factors included advanced age (relative risk, 1.8; 95% CI, 1.4-2.3), black race (relative risk, 2.0; 95% CI, 1.7-2.4), and use of 5 or more concomitant medications (relative risk, 1.3; 95% CI, 1.1-1.5). CONCLUSIONS: In this population, the incidence of serious hypoglycemia is approximately 2 per 100 person-years, suggesting that many older adults can be safely treated with hypoglycemic drugs. Frail, elderly persons--the oldest-old, those using multiple medications, and those who are frequently hospitalized--are at a higher risk for drug-associated hypoglycemia. Such individuals may benefit from intensive education about the symptoms of hypoglycemia and close monitoring for adverse events related to diabetes treatment.     

A double-blind, randomized study of naproxen sodium, ibuprofen, and placebo in postoperative dental pain

In a double-blind, parallel, placebo-controlled study, 203 patients with post-operative dental pain following the extraction of one or two bony impacted third molars were randomized to receive a single dose of naproxen sodium 220 mg, ibuprofen 200 mg or placebo. Pain intensity and pain relief were assessed at intervals for 12 hours postdose. Both active drugs demonstrated superior analgesic efficacy over placebo. Naproxen sodium and ibuprofen were comparable both in onset of analgesic action and in pain relief. From 1 to 12 hours postdose, naproxen sodium showed a trend for superior analgesic efficacy compared with ibuprofen; this trend reached statistical significance at the 12-hour time point. Both drugs were well-tolerated and effective analgesics for postoperative dental pain.     

The effect of N-acetylcysteine on total serum anti-oxidant potential and urinary albumin excretion in critically ill patients

PURPOSE: Calcium channel blockers have been reported to increase the risk of gastrointestinal bleeding. We tested this hypothesis, and also assessed whether beta blockers decrease this risk. SUBJECTS AND METHODS: A nested case-control design within a population-based cohort of all 34,074 new users of beta blockers, angiotensin-converting enzyme (ACE) inhibitors, or calcium channel blockers in Saskatchewan, from 1990 to 1993 and followed up to March 1995, was used. We identified all 311 subjects hospitalized because of gastrointestinal bleeding during this period, each of whom was matched to 10 randomly selected controls. RESULTS: The rate of hospitalization for gastrointestinal bleeding was 3.0 per 1,000 per year. The adjusted rate ratio of gastrointestinal bleeding for current use of calcium channel blockers was 1.1 (95% confidence interval [CI] 0.8 to 1.4) and 0.66 (95% CI 0.44 to 0.98) for beta blockers compared with no current use of anti-hypertensive drugs. The adjusted rate ratio for ACE inhibitor use was 1.0 (95% CI 0.7 to 1.3) while that for diuretic use was 1.4 (95% CI 1.0 to 2.0). CONCLUSIONS: The use of calcium channel blockers does not appear to increase the risk of gastrointestinal bleeding in the first five years of treatment, while beta blockers may prevent this adverse event. The unexpected elevated risk associated with the use of diuretics needs to be investigated further.     

ACE inhibitor use is associated with hospitalization for severe hypoglycemia in patients with diabetes. DARTS/MEMO Collaboration. Diabetes Audit and Research in Tayside, Scotland. Medicines Monitoring Unit

OBJECTIVE: To evaluate the association between the use of ACE inhibitors and hospital admission for severe hypoglycemia and to explore the effects of potential confounding variables on this relationship. RESEARCH DESIGN AND METHODS: The association between the use of ACE inhibitors and the incidence of hypoglycemia is controversial. A recent study reported that 14% of all hospital admissions for hypoglycemia might be attributable to ACE inhibitors. We performed a nested case-control study, using a cohort of 6,649 diabetic patients taking insulin or oral antidiabetic drugs, on the Diabetes Audit and Research in Tayside, Scotland (DARTS) database. From 1 January 1993 to 30 April 1994, we identified 64 patients who had been admitted to Tayside hospitals with hypoglycemia and selected 440 control patients from the same cohort. RESULTS: Hypoglycemia was associated with the use of ACE inhibitors (odds ratio [OR] 3.2, 95% CI 1.2-8.3, P = 0.023), whereas use of beta-blockers and calcium antagonists was not associated with an increased risk of hospitalization for hypoglycemia with ORs of 0.9 (95% CI 0.3-3.3) and 1.7 (95% CI 0.2-2.1), respectively. There were significant differences between case and control patients in type of diabetes treatment, diabetes duration, place of routine diabetes care, and congestive cardiac failure. These differences did not confound the relationship between ACE inhibitors and hypoglycemia (adjusted OR 4.3, 95% CI 1.2-16.0). CONCLUSIONS: The results show that the association between ACE inhibitor therapy and hospital admission for severe hypoglycemia is not explained by these confounding factors. Although ACE inhibitors have distinct advantages over other antihypertensive drugs in diabetes, the risk of hypoglycemia should be considered.     

Reversible regulation of SHP-1 tyrosine phosphatase activity by oxidation

BACKGROUND AND PURPOSE: Randomized clinical trials testing aspirin in relatively low-risk, middle-aged people have consistently shown small increases in stroke associated with aspirin use. We analyzed the relationship between the regular use of aspirin and incident ischemic and hemorrhagic stroke among people aged 65 years or older participating in the Cardiovascular Health Study. METHODS: We conducted a multivariate analysis of incident stroke rates in a prospectively assessed, observational cohort of 5011 elderly people followed for a mean of 4.2 years. RESULTS: Participants had a mean age of 72 years, and 58% were women. Twenty-three percent used aspirin frequently, and 17% used aspirin infrequently at study entry. Frequent aspirin use was associated with an increased rate of ischemic stroke compared with nonusers (relative risk= 1.6; 95% confidence interval [CI], 1.2 to 2.2; P=0.001). After adjustment for other stroke risk factors, women who used aspirin frequently or infrequently at study entry had a 1.8-fold (95% CI, 1.2 to 2.8) and 1.6-fold (95% CI, 0.9 to 3.0) increased risk of ischemic stroke, respectively (P<0.01, test for trend), compared with nonusers. In men, aspirin use was not statistically significantly associated with stroke risk. Findings were similar when aspirin use in the years before the incident stroke was used in the modeling. Aspirin use at entry was also associated with a 4-fold (95% CI, 1.6 to 10.0) increase in risk of hemorrhagic stroke for both infrequent and frequent users of aspirin (P=0.003). CONCLUSIONS: Aspirin use was associated with increased risks of ischemic stroke in women and hemorrhagic stroke overall in this elderly cohort, after adjustment for other stroke predictors. The possibility exists of confounding by reasons for aspirin use rather than cause and effect. Whether regular aspirin use increases stroke risk for elderly people without cardiovascular disease can only be determined by randomized clinical trials.     

Epilepsy--a time for change?

OBJECTIVE: To examine the association between postmenopausal hormone use and cholecystectomy. METHODS: A prospective cohort study was performed, with follow-up every 2 years. Participants were 54,845 postmenopausal United States nurses, who reported both hormone use and cholecystectomy on mailed questionnaires. RESULTS: Cholecystectomy was reported by 1750 women during 8 years of follow-up. After adjusting for confounding factors, women currently using postmenopausal hormones were at an increased risk of cholecystectomy (relative risk [RR] 2.1, 95% confidence interval [CI] 1.9-2.4) compared to never-users. For current users, the risk of cholecystectomy increased with increasing duration of hormone use (RR 2.6, 95% CI 2.2-3.1 for 10 years or more) and higher doses of estrogen (RR 2.4, 95% CI 2.0-2.9 for users of 1.25 mg or more). Although the risk for past hormone users decreased substantially in women who had discontinued use 1-2.9 years ago (RR 1.6, 95% CI 1.2-2.0), a small risk persisted for women who had stopped taking hormones 5 or more years previously (RR 1.3, 95% CI 1.1-1.6). However, after controlling for time since last use, duration of past use had little or no effect on the risk of cholecystectomy (RR 1.4 and RR 1.7 for past users of less than 2 years and 10 or more years' duration, respectively). CONCLUSION: Women using postmenopausal hormones are at an increased risk of cholecystectomy. Women and their physicians should consider the spectrum of risks and benefits when deciding whether to take hormones.     

Association of road-traffic accidents with benzodiazepine use

BACKGROUND: Psychomotor studies suggest that commonly prescribed psychoactive drugs impair driving skills. We have examined the association between the use of psychoactive drugs and road-traffic accidents. METHODS: We used dispensed prescribing as a measure of exposure in a within-person case-crossover study of drivers aged 18 years and over, resident in Tayside, UK, who experienced a first road-traffic accident between Aug 1, 1992, and June 30, 1995, and had used a psychoactive drug (tricyclic antidepressant, benzodiazepine, selective serotonin-reuptake inhibitor, or other psychoactive drug [mainly major tranquillisers]) between Aug 1, 1992, and the date of the accident. For each driver, the risks of having a road-traffic accident while exposed and not exposed to a drug were compared. FINDINGS: 19386 drivers were involved in a first road-traffic accident during the study period. 1731 were users of any study drug. On the day of the accident, 189 individuals were taking tricyclic antidepressants (within-patient exposure odds ratio for an accident 0.93 [95% CI 0.72-1.21]), 84 selective serotonin-reuptake inhibitors (0.85 [0.55-1.33]), 235 benzodiazepines (1.62 [1.24-2.12]), and 47 other psychoactive drugs (0.88 [0.62-1.25]). The risk associated with benzodiazepine use decreased with increasing driver's age and was greater when the breath test for alcohol was positive. A dose-response relation was evident with benzodiazepines. The increased risk with benzodiazepines was significant for long-half-life drugs, used as anxiolytics, and for short-half-life hypnotics (all zopiclone). INTERPRETATION: Users of anxiolytic benzodiazepines and zopiclone were at increased risk of experiencing a road-traffic accident. Users of anxiolytic benzodiazepines and zopiclone should be advised not to drive.     

Risk factors for falls of hospitalized stroke patients

BACKGROUND AND PURPOSE: Patients with stroke are at a high risk for falling. We assessed the fall incidence and risk factors for patients hospitalized as the result of an acute stroke. METHODS: We studied a cohort of 720 stroke patients from 23 hospitals in The Netherlands. The data were abstracted from the medical and nursing records. RESULTS: We studied 346 women and 374 men with a median age of 75 years; 77% of the patients had had a cerebral infarct, 17% had had a hemorrhage, and 6% had had an undefined stroke. We recorded 104 patients (14%) who fell at least once; there were a total of 173 falls. The incidence of falls was 8.9/1000 patients per day. The daily incidence was 6.2/1000 patients for first falls and 17.9/1000 patients for second falls. Heart disease (relative risk [RR], 1.6; 95% confidence interval [CI], 1.0 to 2.4), mental decline (RR, 1.6; 95% CI, 1.0 to 2.4), and urinary incontinence (RR, 2.3; 95% CI, 1.3 to 4.1) were incremental risk factors for first falls, whereas the use of major psychotropic drugs lowered the fall risk (RR, 0.5; 95% CI, 0.3 to 0.8). The fall RR for patients with one previous fall was 2.2 (95% CI, 1.5 to 3.2), adjusted for the other risk factors. Most falls occurred during the day. Approximately 25% of the falls caused slight-to-severe injury, whereas three falls (2%) led to hip fractures. CONCLUSIONS: Stroke patients have at risk of falling. The identification of patients at risk may be a first step toward the implementation of fall-prevention measures for these patients.