Initial metformin or sulphonylurea exposure and cancer occurrence among patients with type 2 diabetes mellitus.

AIM: This was a retrospective cohort study of type 2 diabetes patients, to evaluate the association between initial metformin or sulphonylurea treatment and cancer incidence. METHODS: Patients identified in the UK Clinical Practice Research Datalink (CPRD), previously General Practice Research Database, during 1995-2008 who were initially stabilized on OHA monotherapy, including metformin, sulphonylurea, thiazolidinediones (TZDs) or meglitinides, were included in the cohort. New diagnoses of cancer, including malignant solid tumours and haematological malignancies, occurring during the follow-up were identified from the cohort. Age-standardized incidence rates were estimated and compared between metformin and sulphonylurea exposure groups. RESULTS: The age standardized incidences of cancer were 7.5 and 8.5 per 1000 person-years for the metformin and sulphonylurea exposure groups, respectively. After adjusting for potential confounders, the hazard ratios (HR) for malignant solid tumours and haematological malignancies were 1.06 (95% CI: 0.98, 1.15) and 0.98 (95% CI: 0.67, 1.43) for sulphonylurea group as compared to the metformin group, respectively. For individual cancers, the HRs were 1.17 (95% CI: 0.95, 1.44), 1.04 (95% CI: 0.83, 1.31) and 0.88 (95% CI: 0.71, 1.11) for colorectal cancer, breast cancer and prostate cancer, respectively. CONCLUSION: This study provides evidence that cancer incidence in the first few years after starting metformin or sulphonylurea therapy in type 2 diabetes patients is not much affected by choice of hypoglycaemic drug class.

Erythropoiesis-stimulating agents in oncology: a study-level meta-analysis of survival and other safety outcomes.

BACKGROUND: Cancer patients often develop the potentially debilitating condition of anaemia. Numerous controlled studies indicate that erythropoiesis-stimulating agents (ESAs) can raise haemoglobin levels and reduce transfusion requirements in anaemic cancer patients receiving chemotherapy. To evaluate recent safety concerns regarding ESAs, we carried out a meta-analysis of controlled ESA oncology trials to examine whether ESA use affects survival, disease progression and risk of venous-thromboembolic events. METHODS: This meta-analysis included studies from the 2006 Cochrane meta-analysis, studies published/updated since the 2006 Cochrane report, and unpublished trial data from Amgen and Centocor Ortho Biotech. The 60 studies analysed (15 323 patients) were conducted in the settings of chemotherapy/radiochemotherapy, radiotherapy only treatment or anaemia of cancer. Data were summarised using odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Results indicated that ESA use did not significantly affect mortality (60 studies: OR=1.06; 95% CI: 0.97-1.15) or disease progression (26 studies: OR=1.01; 95% CI: 0.90-1.14), but increased the risk for venous-thromoboembolic events (44 studies: OR=1.48; 95% CI: 1.28-1.72). CONCLUSION: Though this meta-analysis showed no significant effect of ESAs on survival or disease progression, prospectively designed, future randomised clinical trials will further examine the safety and efficacy of ESAs when used according to the revised labelling information.

Analyses of mortality risk in patients with dementia treated with galantamine.

OBJECTIVE: To analyze mortality data from patients with Alzheimer's disease (AD), Alzheimer's plus cerebrovascular disease (AD + CVD) or vascular dementia (VaD). METHODS: (1) Meta-analysis of mortality data from double-blind, placebo-controlled, randomized trials; and (2) recontact study to collect additional longer term mortality data from previous galantamine trial participants. RESULTS (META-ANALYSIS): Across 12 trials (< or =6 months duration), there was no increased risk of mortality associated with the use of galantamine (n = 4116) compared with that of placebo (n = 2386) (OR galantamine/placebo: 0.67, 95% CI 0.41-1.10). RESULTS (RECONTACT STUDY): Median survival was 79 months for patients with AD (n = 478) and 59 months for patients with AD + CVD (n = 180) or VaD (n = 145). Prolonged galantamine treatment (> vs < or =6 months) was not associated with decreased survival time (75 vs 61 months respectively; P = 0.02). Cox regression analyses were consistent with the Kaplan-Meier analyses. CONCLUSIONS: We found no short-term or longer term evidence of increased risk of mortality associated with the use of galantamine in patients with AD, AD + CVD or VaD.

Pharmacogenetic modulation of combined hormone replacement therapy by progesterone-metabolism genotypes in postmenopausal breast cancer risk.

Combined hormone replacement therapy (CHRT) containing estrogens and progestins is associated with breast cancer risk. The authors evaluated interactions between CHRT use and progestin metabolism genotypes at CYP3A4 and the progesterone receptor (PGR) and their effects on breast cancer risk using the population-based Women's Insights and Shared Experiences (WISE) Study (1999-2002) of postmenopausal Caucasian women (522 breast cancer cases, 708 controls). The authors observed an elevated risk of ductal tumors in women with 3 or more years of CHRT use and PGR 331A alleles compared with those who had neither factor (odds ratio = 3.35, 95% confidence interval (CI): 1.13, 9.99; two-sided p(interaction) = 0.035). They also observed an elevated risk of progesterone receptor-positive tumors in women who had had 3 or more years of CHRT use and PGR 331A alleles compared with those who had neither factor (odds ratio = 3.82, 95% CI: 1.26, 11.55; p = 0.028). Finally, they observed an increased risk of estrogen receptor-negative tumors in women without CHRT exposure and CYP3A4*1B alleles compared with those who had neither factor (odds ratio = 6.46, 95% CI: 2.02, 20.66; p = 0.024), although the biologic interpretation of this result requires further study. When stratified by recency of use, PGR effects were observed only in current CHRT users, while CYP3A4 effects were observed only in former CHRT users. Breast cancer risk in women who have used CHRT may be influenced by genetic factors involved in progestin metabolism.

Healing diabetic neuropathic foot ulcers: are we getting better?

AIM: To benchmark by year the likelihood that an individual with a diabetic neuropathic foot ulcer will heal over more than a 10-year period. PATIENTS AND METHODS: A cohort study within a multicentre wound care network of individuals with a diabetic neuropathic foot ulcer who were treated by a standard wound care algorithm. The main outcome was a healed wound by the 20th week of care stratified by calendar year. RESULTS: We evaluated 27 193 individuals with a neuropathic foot ulcer. Between 1988 and 1990 approximately 66% of patients did not heal. By 1999 this percentage had decreased to 49%. The change in the rate of failure to heal is very closely associated with an increase over time in the proportion of patients seen with wounds identified as prognostically favourable using a previously published prognostic model (i.e. individuals with wounds < or = 2 cm2, wounds < or = 2 months old, and wounds of grade < or = 2). Nevertheless, even among those most likely to heal, the likelihood of failing to heal went from 62% prior to 1991 to 32% in 2000. CONCLUSIONS: We have shown that individuals with a diabetic neuropathic foot ulcer seeking care are more likely to heal today than 10 years ago. The primary reason for this improvement is that individuals are seeking care when their wounds are most easily treated and these are now more likely to heal.

Dermatology position paper on the revision of the 1982 ACR criteria for systemic lupus erythematosus.

The 1982 ACR classification criteria have become de facto diagnostic criteria for systemic lupus erythematosus (SLE), but a review of the criteria is necessary to include recent diagnostic tests. The criteria were not developed with the help of dermatologists, and assign too much weight to the skin as one expression of a multiorgan disease. Consequently, patients with skin diseases are classified as SLE based mostly on skin symptoms. We discuss specific problems with each dermatologic criterion, but changes must await a new study. We suggest the following guidelines for such a study, aimed at revision of the criteria. 1) The SLE patient group should be recruited in part by dermatologists. 2) The study should evaluate an appropriate international ethnic/racial mix, including late onset SLE as well as pediatric patients. 3) All patients should have current laboratory and clinical evaluations, as suggested in the paper, to assure the criteria can be up-to-date. This includes anti-SS-A and anti-SS-B antibodies and skin biopsies for suspected cutaneous lupus erythematosus except for nonscarring alopecia and oral ulcers. 4) The study should be based on a series of transparent power calculations. 5) The control groups should represent relevant differential diagnoses in numbers large enough to assess diagnostic problems that might be specific to these differential diagnoses. In order to demonstrate specificity of the criteria with a 95% confidence interval between 90 and 100%, each control group of the above should have at least 73 patients.

Risk of venous thromboembolism from oral contraceptives containing gestodene and desogestrel versus levonorgestrel: a meta-analysis and formal sensitivity analysis.

Controversy exists regarding whether oral contraceptives (OCs) containing desogestrel and gestodene are associated with an increased risk of venous thromboembolism (VTE) versus OCs containing levonorgestrel. We were interested in synthesizing the available data, exploring explanations for mixed results, and characterizing the degree of uncontrolled confounding that could have produced a spurious association. We performed a meta-analysis and formal sensitivity analysis of studies that examined the relative risk of VTE for desogestrel and gestodene versus levonorgestrel. Twelve studies, all observational, were included. The summary relative risk (95% CI) was 1.7 (1.3-2.1; heterogeneity p = 0.09). If real, the incremental risk of VTE would be about 11 per 100,000 women per year. An association was present when accounting for duration of use and when restricted to the first year of use in new users. However, in the sensitivity analysis, the association abated in many, but not all, scenarios in which an unmeasured confounding factor increased the risk of VTE three to fivefold and in nearly all examined scenarios in which the factor increased the risk 10-fold. The summary relative risk of 1.7 does not appear to be caused by depletion of susceptibles, but is sensitive to a modest degree of unmeasured confounding. Whether such confounding occurred is unknown. However, given this sensitivity, this issue probably cannot be settled unequivocally with observational data. In the absence of a definitive answer, this apparent increased risk, together with its uncertainty and small magnitude and its important consequences, should be considered when selecting an OC for a given woman.

Selective serotonin reuptake inhibitors and myocardial infarction.

BACKGROUND: Depression is an independent risk factor for myocardial infarction (MI). Selective serotonin reuptake inhibitors (SSRIs) may reduce this risk through attenuation of serotonin-mediated platelet activation in addition to treatment of depression itself. METHODS AND RESULTS: case-control study of first MI in smokers 30 to 65 years of age was conducted among all 68 hospitals in an 8-county area during a 28-month period. Cases were patients hospitalized with a first MI. Approximately 4 community control subjects per case were randomly selected from the same geographic area using random digit dialing. Detailed information regarding use of antidepressant medication as well as other clinical and demographic data were obtained by telephone interview. A total of 653 cases of first MI and 2990 control subjects participated. After adjustment, using multivariable logistic regression, for age, sex, race, education, exercise, quantity smoked per day, body mass index, aspirin use, family history of MI, number of physician encounters, and history of coronary disease, diabetes, hypertension, or hypercholesterolemia, the odds ratio for MI among current SSRI users compared with nonusers was 0.35 (95% CI 0.18, 0.68; P<0.01). Non-SSRI antidepressant users had a nonsignificant reduction in MI risk with wide confidence intervals (adjusted odds ratio 0.48, CI 0.17, 1.32; P=0.15). However, analysis of this group was limited by the small number of exposed subjects. CONCLUSIONS: The use of SSRIs may confer a protective effect against MI. This could be attributable to the inhibitory effect SSRIs have on serotonin-mediated platelet activation or possibly amelioration of other factors associated with increased risk for MI in depression.

Sleep quality, estradiol levels, and behavioral factors in late reproductive age women.

OBJECTIVE: To estimate the prevalence of perceived poor sleep in women aged 35-49 years and to correlate sleep quality with levels of gonadal steroids and predictors of poor sleep. METHODS: A cohort of 218 black and 218 white women aged 35-47 years at enrollment (aged 37-49 at final follow-up) with regular menstrual cycles was identified through random digit dialing for a longitudinal study of ovarian aging correlates. Data obtained at four assessment periods, including enrollment, over a 2-year interval were collected between days 1 and 6 (mean = 3.9) of the menstrual cycle. The primary outcome measure was subjects' rating of sleep quality at each assessment period. Associations of sleep quality with hormone levels (estradiol, follicle-stimulating hormone, luteinizing hormone, testosterone, and dehydroepiandrosterone sulfate) and other clinical, behavioral, and demographic variables were examined in bivariable and multivariable analyses. RESULTS: Approximately 17% of subjects reported poor sleep at each assessment period. Significant independent associations with poor sleep included greater incidence of hot flashes (odds ratio [OR] 1.52; 95% confidence interval [CI] 1.08, 2.12, P =.02), higher anxiety levels (OR 1.03; 95% CI 1.00, 1.06, P =.04), higher depression levels (OR 1.05; 95% CI 1.02, 1.07, P <.001), greater caffeine consumption (OR 1.25; 95% CI 1.04, 1.49, P =.02), and lower estradiol levels in women aged 45-49 (OR 0.53; 95% CI 0.34, 0.84, P =.006), after adjustment for current use of sleep medications. CONCLUSION: Both hormonal and behavioral factors were associated with sleep quality. Estradiol levels are an important factor in poor sleep reported by women in the 45-49 age group. Further evaluation of estrogen treatment for poor sleep of women 45 years and older is warranted.

Effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in men more than 65 years of age.

PURPOSE: Because the effects of androgen replacement on lipoprotein levels are uncertain, we sought to determine the effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in elderly men. SUBJECTS AND METHODS: One hundred and eight healthy men more than 65 years of age who had serum testosterone concentrations >1 SD below the mean for young men were randomly assigned to receive either testosterone (54 men; 6 mg/day) or placebo (54 men) transdermally in a double-blind fashion for 36 months. Serum concentrations of lipids and apolipoproteins were measured, and cardiovascular events recorded. RESULTS: Serum total cholesterol concentrations decreased in both the testosterone-treated men and placebo-treated men, but the 3-year mean (+/- SD) decreases in the two groups (testosterone treated, -17 +/- 29 mg/dL; placebo treated, -12 +/- 38 mg/dL) were not significantly different from each other (P = 0.4). Similarly, serum low-density lipoprotein (LDL) cholesterol levels decreased in both treatment groups, but the decreases in the two groups (testosterone treated, -16 +/- 24 mg/dL; placebo treated, -16 +/- 33 mg/dL) were similar (P = 1.0). Levels of high-density lipoprotein (HDL) cholesterol, triglycerides, and apolipoproteins A-I and B did not change. Lipoprotein(a) levels increased in both groups by similar amounts (testosterone treated, 3 +/- 9 mg/dL; placebo treated, 4 +/- 6 mg/dL; P = 1.0). The number of cardiovascular events was small and did not differ significantly between the testosterone-treated men (9 events) and the placebo-treated men (5 events) during the 3-year study (relative risk = 1.8; 95% confidence interval: 0.7 to 5.0). CONCLUSIONS: As compared with placebo, transdermal testosterone treatment of healthy elderly men for 3 years did not affect any of the lipid or apolipoprotein parameters that we measured. The effect of testosterone treatment on cardiovascular events was unclear, because the number of events was small.

Pediatric Crohn's disease: risk factors for postoperative recurrence.

OBJECTIVE: Postoperative recurrence of Crohn's disease in adults has been extensively studied; however, the course of Crohn's disease after surgery in children has not been well defined. The aim of this study was to examine the postoperative course of pediatric Crohn's disease and the factors that may predict early postoperative recurrence. METHODS: We identified 100 resective surgeries in 79 children with Crohn's disease seen at the Children's Hospital of Philadelphia between 1978 and 1996. A retrospective, multivariable analysis of factors potentially influencing postoperative clinical recurrence was performed. Preoperative and postoperative height measurements were compared, and z scores were computed for height-for-age. Two-tailed t test was used for the analysis. RESULTS: Clinical recurrence rates were 17% at 1 yr, 38% at 3 yr, and 60% at 5 yr. Patients with colonic Crohn's disease had a significantly shorter postoperative recurrence-free interval (median 1.2 yr) than patients with ileocecal (median 4.4 yr) or diffuse disease (median 3.0 yr) (p = 0.01). On multivariable analysis, a high Pediatric Crohn's Disease Activity Index at the time of surgery (p = 0.01) and preoperative use of 6-mercaptopurine (6-MP) (p < 0.005) were also independently associated with higher postoperative recurrence rates. There was a significant improvement in z scores for height (p = 0.04) after surgery. CONCLUSIONS: In children undergoing resective surgery for Crohn's disease, high rates of postoperative Crohn's disease recurrence are associated with severe disease at the time of surgery, colonic Crohn's disease, and the preoperative use of 6-MP. Patients who require preoperative use of 6-MP are likely to suffer from a more aggressive disease and would benefit from postoperative 6-MP prophylaxis. Height growth was improved after intestinal resection for Crohn's disease.

Adjustments for center in multicenter studies: an overview.

Increasingly, investigators rely on multicenter or multigroup studies to demonstrate effectiveness and generalizability. Authors too often overlook the analytic challenges in these study designs: the correlation of outcomes and exposures among patients within centers, confounding of associations by center, and effect modification of treatment or exposure across center. Correlation or clustering, resulting from the similarity of outcomes among patients within a center, requires an adjustment to confidence intervals and P values, especially in observational studies and in randomized multicenter studies in which treatment is allocated by center rather than by individual patient. Multicenter designs also warrant testing and adjustment for the potential bias of confounding by center, and for the presence of effect modification or interaction by center. This paper uses examples from the recent biomedical literature to highlight the issues and analytic options.

Who will enroll? Predicting participation in a phase II AIDS vaccine trial.

BACKGROUND: The problems of underenrollment and selective enrollment may undermine AIDS vaccine trials. If prospective study subjects' stated willingness to participate (WTP) in hypothetical vaccine trials predicts future enrollment, then measuring WTP before recruitment may enhance the enrollment in, and ethics of, such trials. METHODS: We prospectively studied changes over an 18-month period in the stated WTP in, and knowledge of, a hypothetical AIDS vaccine trial among 610 Philadelphia residents at high risk for HIV infection. Of these people, 499 were subsequently recruited to participate in an actual, phase II AIDS vaccine trial. We used multivariable logistic regression and the area under the receiver-operating characteristic (ROC) curve to model predictors of actual enrollment. RESULTS: Actual enrollment rates were 8.3%, 6.8%, 15.8%, and 29.0% among those who had initially said they were "definitely not," "probably not," "probably," and "definitely" willing to participate, respectively (p =.006). The area under the ROC curve was 0.65, indicating a modest ability of stated WTP to differentiate those who enroll from those who do not. Knowledge of basic vaccine trial concepts, though unrelated to enrollment, increased over an 18-month period with repeated education sessions (p <.0001), whereas stated WTP declined over this same period (p <.0001). CONCLUSION: Although other factors not captured by stated WTP may also influence future enrollment, prospectively assessing stated WTP may augment the validity of the informed consent process, help prevent underenrollment, and clarify the population from which the study sample is drawn.

Comparative effects of carvedilol and metoprolol on left ventricular ejection fraction in heart failure: results of a meta-analysis.

BACKGROUND: Both metoprolol and carvedilol improve cardiac function and prolong survival in patients with heart failure. Carvedilol has broader antiadrenergic effects than metoprolol, but it is not clear whether this characteristic is associated with greater benefits on cardiac function during long-term treatment. STUDY DESIGN: We performed a meta-analysis of all 19 randomized controlled trials of carvedilol or metoprolol that measured left ventricular ejection fraction before and after an average of 8.3 +/- 0.1 months of treatment in 2184 patients with chronic heart failure. The mean daily doses were 58 +/- 1 mg of carvedilol and the equivalent of 162 +/- 1 mg of extended-release metoprolol. In the 15 placebo-controlled trials, the mean ejection fraction increased more in the trials of carvedilol than in the trials of metoprolol (placebo-corrected increases of +0.065 and +0.038, respectively), P = .0002. In the 4 active-controlled trials that compared metoprolol directly with carvedilol, the mean ejection fraction also increased more in the carvedilol groups than in the metoprolol groups (+0.084 on carvedilol and +0.057 on metoprolol, respectively), P = .009. The difference in favor of carvedilol in the active-controlled trials was nearly identical to the difference observed in the placebo-controlled trials and was apparent in patients with and without coronary artery disease. CONCLUSION: Long-term treatment with carvedilol produces greater effects on left ventricular ejection fraction than metoprolol when both drugs are prescribed in doses similar to those that have been shown to prolong life.

Effectiveness of platelet releasate for the treatment of diabetic neuropathic foot ulcers.

OBJECTIVE: The goal of this study was to specifically estimate the effectiveness of platelet releasate, a widely available treatment administered by a proprietary group of wound care centers (WCCs) for the treatment of diabetic neuropathic foot ulceration. RESEARCH DESIGN AND METHODS: Treatment effectiveness was estimated in a retrospective cohort study controlling for treatment selection bias using logistic regression-derived propensity scores. RESULTS: Platelet releasate was more effective than standard care. The relative risk for a wound to heal after treatment with platelet releasate compared with standard care at a WCC varied from 1.14 (95% CI 1.03-1.27) to 1.59 (1.49-1.70). The effect was greatest in those with the most severe wounds, i.e., large wounds that affect deeper anatomical structures. CONCLUSIONS: Within the limitations of the ability of propensity score analysis to control for selection bias, platelet releasate is more effective than standard therapy. This effect is more pronounced in more severe wounds. Unfortunately, severe wounds have not been evaluated in randomized clinical trials of new interventions. We encourage the inclusion of these patients in future trials.

Risk of acute first myocardial infarction and use of nicotine patches in a general population.

OBJECTIVES: To determine if nicotine patches, both as prescribed and used over-the-counter, increase the risk of first myocardial infarction (MI). BACKGROUND: Although nicotine patches improve smoking cessation rates, case reports have raised the hypothesis that they may increase the risk of MI. METHODS: A population-based case-control study among 68 hospitals in an eight-county region surrounding Philadelphia was performed to determine if nicotine patches increase the risk of first MI. Cases were smokers (current or within the prior year) admitted to all hospitals in the region with a first MI. Controls were smokers (current or within the prior year) without prior MI selected from the same region using random-digit dialing. Data were collected by telephone interviews and chart reviews. The study had 80% power to detect an odds ratio (OR) of 2.5. RESULTS: A total of 653 cases and 2,990 controls were interviewed. There was no association between nicotine patches and MI (OR 0.46; 95% CI: 0.09, 1.47), and the confidence interval (CI) excluded an effect from nicotine patches equal to that from cigarette smoking itself (OR < 2.5). Among those who abstained from smoking, the OR for use of nicotine patches was 0.25 (95% CI: 0.01, 1.67); among those who smoked concomitantly, the OR for patch use was 0.83 (95% CI: 0.09, 3.81). Adjustment for confounding did not alter the study's findings (OR adjusted for confounders that could mask a harmful effect of patches: 0.70; 95% CI: 0.20, 2.46). CONCLUSIONS: Nicotine patches, as used in actual practice, do not appear to be associated with an increased risk of MI.

Effect of ethnicity on denial of authorization for emergency department care by managed care gatekeepers.

OBJECTIVE: After a pilot study suggested that African American patients enrolled in managed care organizations (MCOs) were more likely than whites to be denied authorization for emergency department (ED) care through gatekeeping, the authors sought to determine the association between ethnicity and denial of authorization in a second, larger study at another hospital. METHODS: A retrospective cohort design was used, with adjustment for triage score, age, gender, day and time of arrival at the ED, and type of MCO. RESULTS: African Americans were more likely to be denied authorization for ED visits by the gatekeepers representing their MCOs even after adjusting for confounders, with an odds ratio of 1.52 (95% CI = 1.18 to 1.94). CONCLUSIONS: African Americans were more likely than whites to be denied authorization for ED visits. The observational study design raises the possibility that incomplete control of confounding contributed to or accounted for the association between ethnicity and gatekeeping decisions. Nevertheless, the questions that these findings raise about equity of gatekeeping indicate a need for additional research in this area.

Perioperative beta-blocker withdrawal and mortality in vascular surgical patients.

OBJECTIVE: Our purpose was to determine the effect of postoperative beta-blocker withdrawal on mortality and cardiovascular events after vascular surgery. METHODS: Detailed data were collected on perioperative cardiovascular medication use and discontinuation and cardiovascular risk factors among consecutive major vascular surgical procedures at two university hospitals. RESULTS: A total of 140 patients received beta-blockers preoperatively. Mortality in the 8 patients who had beta-blockers discontinued postoperatively (50%) was significantly greater than in 132 patients who had beta-blockers continued (1.5%, odds ratio 65.0, P<.001). The effect of beta-blocker discontinuation was unaffected by adjustment by stratification for risk factors (all P< or =.01), for contraindications to restarting beta-blockers (P = .006), and by multivariable analyses adjusting for potential confounders (adjusted odds ratio 17.0, P =.01). beta-Blocker discontinuation also was associated with increased cardiovascular mortality (0% vs 29%, P =.005) and postoperative myocardial infarction (odds ratio 17.7, P =.003). CONCLUSION: Discontinuing beta-blockers immediately after vascular surgery may increase the risk of postoperative cardiovascular morbidity and mortality.

Risk factors for delayed healing of neuropathic diabetic foot ulcers: a pooled analysis.

OBJECTIVE: To estimate the effect of various risk factors on the probability that neuropathic diabetic foot ulcers will heal within 20 weeks of care. DESIGN AND SETTING: A pooled or meta-analysis of individual patient data from the standard care arms of 5 randomized clinical trials was conducted. We analyzed 586 subjects with diabetes mellitus who had a neuropathic diabetic foot ulcer. All patients received good wound care, debridement, and "off-loading" of the wound. MAIN OUTCOME MEASURE: Multivariable logistic regression was used to calculate the magnitude of the association of each risk factor with patients having healed wounds. RESULTS: Logistic regression odds ratios (ORs; 95% confidence intervals [95% CIs]) revealed that those patients with a diabetic neuropathic foot ulcer that healed within 20 weeks using standard care were more likely to have a smaller wound (OR = 0.67; 95% CI, 0.55-0.81), a wound that existed for a shorter period (OR = 0.73; 95% CI, 0.61-0.87), and be nonwhite (OR = 0.64; 95% CI, 0.43-0.96) compared with patients whose wounds did not heal within 20 weeks. The patient's age (OR = 0.99; 95% CI, 0.89-1.01), serum level of glycosylated hemoglobin at the start of the study (OR = 1.03; 95% CI, 0.97-1.10), and sex (OR = 1. 02; 95% CI, 0.69-1.50) were unassociated with the probability of wound healing. Substantial heterogeneity was not found among the studies. CONCLUSIONS: A standard care regimen for diabetic neuropathic foot ulcers is most likely to be effective for patients who have wounds that are small and of brief duration. This information should help dermatologists decide initially whether to use standard care, to try a new treatment, or to refer the patient to a specialty center.

Comparability of perioperative morbidity between abdominal myomectomy and hysterectomy for women with uterine leiomyomas.

OBJECTIVE: The aim of this study was to compare the perioperative morbidity associated with abdominal myomectomy with that of hysterectomy. STUDY DESIGN: This was a retrospective cohort study of 394 women at an academic medical center. Main outcome measured was perioperative morbidity, with the following secondary outcomes: febrile morbidity, hemorrhage, unintended major surgical procedures, life-threatening events, and rehospitalization. RESULTS: Morbidity was associated with myomectomy and hysterectomy in 39% and 40% of cases, respectively. The crude odds ratio for morbidity of myomectomy with respect to hysterectomy was 0.93 (95% confidence interval, 0.63-1.40). Women who underwent myomectomy were significantly younger, weighed less, and had a smaller preoperative uterine size. In a multivariable analysis that accounted for these differences the odds ratio increased to 1.46 (95% confidence interval, 0.77-2.77) but still was not statistically elevated. The study had >90% power to detect a clinically relevant 15% absolute difference in overall morbidity between the 2 groups. CONCLUSION: No clinically significant difference in perioperative morbidity between myomectomy and hysterectomy was detected. Myomectomy should be considered a safe alternative to hysterectomy.