Objective  To determine if the risk of serious cardiovascular harm is increased by rosiglitazone compared with pioglitazone, the other thiazolidinedione marketed in the United States.

Design, Setting, and Patients  Nationwide, observational, retrospective, inception cohort of 227 571 Medicare beneficiaries aged 65 years or older (mean age, 74.4 years) who initiated treatment with rosiglitazone or pioglitazone through a Medicare Part D prescription drug plan from July 2006-June 2009 and who underwent follow-up for up to 3 years after thiazolidinedione initiation.

Main Outcome Measures  Individual end points of acute myocardial infarction (AMI), stroke, heart failure, and all-cause mortality (death), and composite end point of AMI, stroke, heart failure, or death, assessed using incidence rates by thiazolidinedione, attributable risk, number needed to harm, Kaplan-Meier plots of time to event, and Cox proportional hazard ratios for time to event, adjusted for potential confounding factors, with pioglitazone as reference.

Results  A total of 8667 end points were observed during the study period. The adjusted hazard ratio for rosiglitazone compared with pioglitazone was 1.06 (95% confidence interval [CI], 0.96-1.18) for AMI; 1.27 (95% CI, 1.12-1.45) for stroke; 1.25 (95% CI, 1.16-1.34) for heart failure; 1.14 (95% CI, 1.05-1.24) for death; and 1.18 (95% CI, 1.12-1.23) for the composite of AMI, stroke, heart failure, or death. The attributable risk for this composite end point was 1.68 (95% CI, 1.27-2.08) excess events per 100 person-years of treatment with rosiglitazone compared with pioglitazone. The corresponding number needed to harm was 60 (95% CI, 48-79) treated for 1 year.

Conclusion  Compared with prescription of pioglitazone, prescription of rosiglitazone was associated with an increased risk of stroke, heart failure, and all-cause mortality and an increased risk of the composite of AMI, stroke, heart failure, or all-cause mortality in patients 65 years or older.

Objective  To assess short-term respiratory morbidity in late preterm births compared with term births in a contemporary cohort of deliveries in the United States.

Design, Setting, and Participants  Retrospective collection of electronic data from 12 institutions (19 hospitals) across the United States on 233 844 deliveries between 2002 and 2008. Charts were abstracted for all neonates with respiratory compromise admitted to a neonatal intensive care unit (NICU), and late preterm births were compared with term births in regard to resuscitation, respiratory support, and respiratory diagnoses. A multivariate logistic regression analysis compared infants at each gestational week, controlling for factors that influence respiratory outcomes.

Main Outcome Measures  Respiratory distress syndrome, transient tachypnea of the newborn, pneumonia, respiratory failure, and standard and oscillatory ventilator support.

Results  Of 19 334 late preterm births, 7055 (36.5%) were admitted to a NICU and 2032 had respiratory compromise. Of 165 993 term infants, 11 980 (7.2%) were admitted to a NICU, 1874 with respiratory morbidity. The incidence of respiratory distress syndrome was 10.5% (390/3700) for infants born at 34 weeks' gestation vs 0.3% (140/41 764) at 38 weeks. Similarly, incidence of transient tachypnea of the newborn was 6.4%(n = 236) for those born at 34 weeks vs 0.4% (n = 155) at 38 weeks, pneumonia was 1.5% (n = 55) vs 0.1% (n = 62), and respiratory failure was 1.6% (n = 61) vs 0.2% (n = 63). Standard and oscillatory ventilator support had similar patterns. Odds of respiratory distress syndrome decreased with each advancing week of gestation until 38 weeks compared with 39 to 40 weeks (adjusted odds ratio [OR] at 34 weeks, 40.1; 95% confidence interval [CI], 32.0-50.3 and at 38 weeks, 1.1; 95% CI, 0.9-1.4). At 37 weeks, odds of respiratory distress syndrome were greater than at 39 to 40 weeks (adjusted OR, 3.1; 95% CI, 2.5-3.7), but the odds at 38 weeks did not differ from 39 to 40 weeks. Similar patterns were noted for transient tachypnea of the newborn (adjusted OR at 34 weeks, 14.7; 95% CI, 11.7-18.4 and at 38 weeks, 1.0; 95% CI, 0.8-1.2), pneumonia (adjusted OR at 34 weeks, 7.6; 95% CI, 5.2-11.2 and at 38 weeks, 0.9; 95% CI, 0.6-1.2), and respiratory failure (adjusted OR at 34 weeks, 10.5; 95% CI, 6.9-16.1 and at 38 weeks, 1.4; 95% CI, 1.0-1.9).

Conclusion  In a contemporary cohort, late preterm birth, compared with term delivery, was associated with increased risk of respiratory distress syndrome and other respiratory morbidity.

Objective  To analyze breast cancer risk, overall and by tumor subtype, in relation to 14 individual single-nucleotide polymorphisms (SNPs) previously linked to the disease, and in relation to a polygenic risk score.

Design, Setting, and Participants  Study of 10 306 women with breast cancer (mean age at diagnosis, 58 years) and 10 393 women without breast cancer who in 2005-2008 provided blood samples for genotyping in a large prospective study of UK women; and meta-analysis of these results and of other published results.

Main Outcome Measures  Estimated per-allele odds ratio (OR) for individual SNPs, and cumulative incidence of breast cancer to age 70 years in relation to a polygenic risk score based on the 4, 7, or 10 SNPs most strongly associated with risk.

Results  Odds ratios for breast cancer were greatest for FGFR2-rs2981582 and TNRC9-rs3803662 and, for these 2 SNPs, were significantly greater for estrogen receptor (ER)–positive than for ER-negative disease, both in our data and in meta-analyses of all published data (pooled per-allele ORs [95% confidence intervals] for ER-positive vs ER-negative disease: 1.30 [1.26-1.33] vs 1.05 [1.01-1.10] for FGFR2; interaction P < .001; and 1.24 [1.21-1.28] vs 1.12 [1.07-1.17] for TNRC9; interaction P < .001). The next strongest association was for 2q-rs13387042, for which the per-allele OR was significantly greater for bilateral than unilateral disease (1.39 [1.21-1.60] vs 1.15 [1.11-1.20]; interaction P = .008) and for lobular than ductal tumors (1.35 [1.23-1.49] vs 1.10 [1.05-1.15]; interaction P < .001). The estimated cumulative incidence (95% confidence interval) of breast cancer to age 70 years among women in the top and bottom fifths of a polygenic risk score based on 7 SNPs was 8.8% (8.3%-9.4%) and 4.4% (4.2%-4.8%), respectively. For ER-positive disease the corresponding risks were 7.4% (6.9%-8.0%) and 3.4% (3.1%-3.8%), respectively; while for ER-negative disease they were 1.4% (1.2%-1.6%) and 1.0% (0.8%-1.2%). The findings did not differ materially according to the number of SNPs included in the polygenic risk model.

Conclusions  The polygenic risk score was substantially more predictive of ER-positive than of ER-negative breast cancer, particularly for absolute risk.

Objective  To assess complication rates of different bariatric procedures and variability in rates of serious complications across hospitals and according to procedure volume and center of excellence (COE) status.

Design, Setting, and Patients  Involving 25 hospitals and 62 surgeons statewide, the Michigan Bariatric Surgery Collaborative (MBSC) administers an externally audited, prospective clinical registry. We evaluated short-term morbidity in 15 275 Michigan patients undergoing 1 of 3 common bariatric procedures between 2006 and 2009. We used multilevel regression models to assess variation in risk-adjusted complication rates across hospitals and the effects of procedure volume and COE designation (by the American College of Surgeons or American Society for Metabolic and Bariatric Surgery) status.

Main Outcome Measure  Complications occurring within 30 days of surgery.

Results  Overall, 7.3% of patients experienced perioperative complications, most of which were wound problems and other minor complications. Serious complications were most common after gastric bypass (3.6%; 95% confidence interval [CI], 3.2%-4.0%), followed by sleeve gastrectomy (2.2%; 95% CI, 1.2%-3.2%), and laparoscopic adjustable gastric band (0.9%; 95% CI, 0.6%-1.1%) procedures (P < .001). Mortality occurred in 0.04% (95% CI, 0.001%-0.13%) of laparoscopic adjustable gastric band, 0 sleeve gastrectomy, and 0.14% (95% CI, 0.08%-0.25%) of the gastric bypass patients. After adjustment for patient characteristics and procedure mix, rates of serious complications varied from 1.6% (95% CI, 1.3-2.0) to 3.5% (95% CI, 2.4-5.0) (risk difference, 1.9; 95% CI, 0.08-3.7) across hospitals. Average annual procedure volume was inversely associated with rates of serious complications at both the hospital level (<150 cases, 4.1%; 95% CI, 3.0%-5.1%; 150-299 cases, 2.7%; 95% CI, 2.2-3.2; and ≥300 cases, 2.3%; 95% CI, 2.0%-2.6%; P = .003) and surgeon level (<100 cases, 3.8%; 95% CI, 3.2%-4.5%; 100-249 cases, 2.4%; 95% CI, 2.1%-2.8%;≥250 cases, 1.9%; 95% CI, 1.4%-2.3%; P = .001). Adjusted rates of serious complications were similar in COE and non-COE hospitals (COE, 2.7%; 95% CI, 2.5%-3.1%; non-COE, 2.0%; 95% CI, 1.5%-2.4%; P = .41).

Conclusions  The frequency of serious complications among patients undergoing bariatric surgery in Michigan was relatively low. Rates of serious complications are inversely associated with hospital and surgeon procedure volume, but unrelated to COE accreditation by professional organizations.

Objective  To assess the association between delirium in elderly patients and long-term poor outcome, defined as mortality, institutionalization, or dementia, while controlling for important confounders.

Data Sources  A systematic search of studies published between January 1981 and April 2010 was conducted using the databases of MEDLINE, EMBASE, PsycINFO, and CINAHL.

Study Selection  Observational studies of elderly patients with delirium as a study variable and data on mortality, institutionalization, or dementia after a minimum follow-up of 3 months, and published in the English or Dutch language. Titles, abstracts, and articles were reviewed independently by 2 of the authors. Of 2939 references in the original search, 51 relevant articles were identified.

Data Extraction  Information on study design, characteristics of the study population, and outcome were extracted. Quality of studies was assessed based on elements of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cohort studies.

Data Synthesis  The primary analyses included only high-quality studies with statistical control for age, sex, comorbid illness or illness severity, and baseline dementia. Pooled-effect estimates were calculated with random-effects models. The primary analysis with adjusted hazard ratios (HRs) showed that delirium is associated with an increased risk of death compared with controls after an average follow-up of 22.7 months (7 studies; 271/714 patients [38.0%] with delirium, 616/2243 controls [27.5%]; HR, 1.95 [95% confidence interval {CI}, 1.51-2.52]; I², 44.0%). Moreover, patients who had experienced delirium were also at increased risk of institutionalization (7 studies; average follow-up, 14.6 months; 176/527 patients [33.4%] with delirium and 219/2052 controls [10.7%]; odds ratio [OR], 2.41 [95% CI, 1.77-3.29]; I², 0%) and dementia (2 studies; average follow-up, 4.1 years; 35/56 patients [62.5%] with delirium and 15/185 controls [8.1%]; OR, 12.52 [95% CI, 1.86-84.21]; I², 52.4%). The sensitivity, trim-and-fill, and secondary analyses with unadjusted high-quality risk estimates stratified according to the study characteristics confirmed the robustness of these results.

Conclusion  This meta-analysis provides evidence that delirium in elderly patients is associated with poor outcome independent of important confounders, such as age, sex, comorbid illness or illness severity, and baseline dementia.

Objective  To summarize evidence on primary Sjögren syndrome drug therapy from randomized controlled trials.

Data Sources  We searched MEDLINE and EMBASE for articles on drug therapy for primary Sjögren syndrome published between January 1, 1986, and April 30, 2010.

Study Selection  Controlled trials of topical and systemic drugs including adult patients with primary Sjögren syndrome were selected as the primary information source.

Results  The search strategy yielded 37 trials. A placebo-controlled trial found significant improvement in the Schirmer and corneal staining scores, blurred vision, and artificial tear use in patients treated with topical ocular 0.05% cyclosporine. Three placebo-controlled trials found that pilocarpine was associated with improvements in dry mouth (61%-70% vs 24%-31% in the placebo group) and dry eye (42%-53% vs 26%). Two placebo-controlled trials found that cevimeline was associated with improvement in dry mouth (66%-76% vs 35%-37% in the placebo group) and dry eye (39%-72% vs 24%-30%). Small trials (<20 patients) found no significant improvement in sicca outcomes for oral prednisone or hydroxychloroquine and limited benefits for immunosuppressive agents (azathioprine and cyclosporine). A large trial found limited benefits for oral interferon alfa-2a. Two placebo-controlled trials of infliximab and etanercept did not achieve the primary outcome (a composite visual analog scale measuring joint pain, fatigue, and dryness); neither did 2 small trials (<30 patients) testing rituximab, although significant results were observed in some secondary outcomes and improvement compared with baseline.

Conclusions  In primary Sjögren syndrome, evidence from controlled trials suggests benefits for pilocarpine and cevimeline for sicca features and topical cyclosporine for moderate or severe dry eye. Anti–tumor necrosis factor agents have not shown clinical efficacy, and larger controlled trials are needed to establish the efficacy of rituximab.