Objective To investigate the associations between obstructive sleep apnea (OSA) and maternal and neonatal morbidities in a cohort of obese gravid women. Methods Participants were enrolled in a prospective observational study designed to screen for OSA and describe the possible risk factors for and outcomes of OSA among obese (BMI 30 kg/m2 or higher) pregnant women. Women underwent an overnight sleep study using a portable home monitor. Studies were manually scored by a central masked Sleep Reading Center using American Academy of Sleep Medicine diagnostic criteria. An apnea hypopnea index of 5 or greater was considered diagnostic of OSA. Perinatal outcomes were compared between women with and without OSA. Results Among 175 women, OSA prevalence was 15.4% (13 mild, 9 moderate, 5 severe). Compared with no-OSA (AHI<5), the OSA group had a higher BMI (46.8 ±12.2 vs. 38.1± 7.5 kg/m2, p=0.002) and more chronic hypertension (55.6 vs. 32.4%, p=0.02). Maternal complications included: maternal death (n=1, amniotic fluid embolus [no-OSA group]) and cardiac arrest (n=1, intraoperative at cesarean delivery [OSA group]). One previable birth and two stillbirths occurred in the no-OSA group. Among live births, OSA was associated with more frequent cesarean delivery (65.4 vs. 32.8%, p=0.003), preeclampsia (42.3 vs. 16.9, p=0.005), and NICU admission (46.1 vs. 17.8, p=0.002). After controlling for BMI, maternal age, and diabetes, OSA (OR 3.55 [1.1–11.3]), prior preeclampsia (OR 2.79 [1.09–7.19]), and hypertension (4.25 [1.67–10.77]) were associated with developing preeclampsia. Conclusion OSA among obese pregnant women is associated with more frequent preeclampsia, neonatal intensive care unit admissions, and cesarean delivery.

The purpose of this randomized trial was to evaluate the efficacy of the Mindfulness-Based Stress Reduction for Breast Cancer (MBSR [BC]) program in improving psychological and physical symptoms and quality of life among breast cancer survivors (BCSs) who completed treatment.Outcomes were assessed immediately after 6 weeks of MBSR(BC) training and 6 weeks later to test efficacy over an extended timeframe. Patients and MethodsA total of 322 BCSs were randomly assigned to either a 6-week MBSR(BC) program (n = 155) or a usual care group (n = 167). Psychological (depression, anxiety, stress, and fear of recurrence) and physical symptoms (fatigue and pain) and quality of life (as related to health) were assessed at baseline and at 6 and 12 weeks. Linear mixed models were used to assess MBSR(BC) effects over time, and participant characteristics at baseline were also tested as moderators of MBSR(BC) effects. ResultsResults demonstrated extended improvement for the MBSR(BC) group compared with usual care in both psychological symptoms of anxiety, fear of recurrence overall, and fear of recurrence problems and physical symptoms of fatigue severity and fatigue interference (P , .01). Overall effect sizes were largest for fear of recurrence problems (d = 0.35) and fatigue severity (d = 0.27). Moderation effects showed BCSs with the highest levels of stress at baseline experienced the greatest benefit from MBSR(BC). ConclusionThe MBSR(BC) program significantly improved a broad range of symptoms among BCSs up to 6 weeks after MBSR(BC) training, with generally small to moderate overall effect sizes.

BackgroundDiabetes mellitus (DM), a metabolic disease, is characterized by impaired fasting glucose levels. Type 2 DM is adult onset diabetes. Long non-coding RNAs (lncRNAs) regulate gene expression and multiple studies have linked lncRNAs to human diseases.MethodsSerum samples obtained from 96 participating veterans at JAH VA were deposited in the Research Biospecimen Repository. We used a two-stage strategy to identify an lncRNA whose levels correlated with T2DM. Initially we screened five serum samples from diabetic and non-diabetic individuals using lncRNA arrays. Next, GAS5 lncRNA levels were analyzed in 96 serum samples using quantitative PCR. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff GAS5 for diagnosis of DM.ResultsOur results demonstrate that decreased GAS5 levels in serum were associated with diabetes in a cohort of US military veterans. The ROC analysis revealed an optimal cutoff GAS5 value of less than or equal to 10. qPCR results indicated that individuals with absolute GAS5 < 10 ng/μl have almost twelve times higher odds of having diabetes (Exact Odds Ratio [OR] = 11.79 (95% CI: 3.97, 37.26), p < 0.001). Analysis indicated area under curve (AUC) of ROC of 0.81 with 85.1% sensitivity and 67.3% specificity in distinguishing non-diabetic from diabetic subjects. The positive predictive value is 71.4%.ConclusionlncRNA GAS5 levels are correlated to prevalence of T2DM.General SignificanceAssessment of GAS5 in serum along with other parameters offers greater accuracy in identifying individuals at-risk for diabetes.

Background Community health workers (CHWs) are lay individuals who are trained to serve as liaisons between members of their communities and healthcare providers and services. Methods A systematic review was conducted to synthesize evidence from all prospective controlled studies on effectiveness of CHW programs in improving screening mammography rates. Studies reported in English and conducted in the United States were included if they: (1) evaluated a CHW intervention designed to increase screening mammography rates in women 40 years of age or older without a history of breast cancer; (2) were a randomized controlled trial (RCT), case-controlled study, or quasi-experimental study; and (3) evaluated a CHW intervention outside of a hospital setting. Results Participation in a CHW intervention was associated with a statistically significant increase in receipt of screening mammography [Risk Ratio (RR):1.06 (favoring intervention); 95% Confidence Interval (CI:1.02, 1.11),p=0.003]. The effect remained when pooled data from only RCTs were included in meta-analysis (RR:1.07,95% CI:1.03,1.12,p=0.0005), but was not present using pooled data from only quasi-experimental studies (RR:1.03,95% CI:0.89,1.18,p=0.71). In RCTs, participants recruited from medical settings (RR:1.41,95% CI:1.09,1.82,p=0.008), programs conducted in urban settings (RR:1.23,95% CI:1.09,1.39,p=0.001), and programs where CHWs were matched to intervention participants on race or ethnicity (RR:1.58, 95%CI:1.29,1.93,p=0.0001) demonstrated stronger effects on increasing mammography screening rates. Conclusions CHW interventions are effective for increasing screening mammography in certain settings and populations. Impact CHW interventions are especially associated with improvements in rate of screening mammography in medical settings, urban settings, and in participants who are racially or ethnically concordant with the CHW.

Bisphosphonates in multiple myeloma: an updated network meta-analysis (Review)

BackgroundThere is a need to synthesise the results of numerous randomised controlled trials evaluating the addition of therapies to androgen deprivation therapy (ADT) for men with metastatic hormone-sensitive prostate cancer (mHSPC). This systematic review aims to assess the effects of adding abiraterone acetate plus prednisone/prednisolone (AAP) to ADT.MethodsUsing our framework for adaptive meta-analysis (FAME), we started the review process before trials had been reported and worked collaboratively with trial investigators to anticipate when eligible trial results would emerge. Thus, we could determine the earliest opportunity for reliable meta-analysis and take account of unavailable trials in interpreting results. We searched multiple sources for trials comparing AAP plus ADT versus ADT in men with mHSPC. We obtained results for the primary outcome of overall survival (OS), secondary outcomes of clinical/radiological progression-free survival (PFS) and grade III–IV and grade V toxicity direct from trial teams. Hazard ratios (HRs) for the effects of AAP plus ADT on OS and PFS, Peto Odds Ratios (Peto ORs) for the effects on acute toxicity and interaction HRs for the effects on OS by patient subgroups were combined across trials using fixed-effect meta-analysis.FindingsWe identified three eligible trials, one of which was still recruiting (PEACE-1 (NCT01957436)). Results from the two remaining trials (LATITUDE (NCT01715285) and STAMPEDE (NCT00268476)), representing 82% of all men randomised to AAP plus ADT versus ADT (without docetaxel in either arm), showed a highly significant 38% reduction in the risk of death with AAP plus ADT (HR = 0.62, 95% confidence interval [CI] = 0.53–0.71, p = 0.55 × 10−10), that translates into a 14% absolute improvement in 3-year OS. Despite differences in PFS definitions across trials, we also observed a consistent and highly significant 55% reduction in the risk of clinical/radiological PFS (HR = 0.45, 95% CI = 0.40–0.51, p = 0.66 × 10−36) with the addition of AAP, that translates to a 28% absolute improvement at 3 years. There was no evidence of a difference in the OS benefit by Gleason sum score, performance status or nodal status, but the size of the benefit may vary by age. There were more grade III–IV acute cardiac, vascular and hepatic toxicities with AAP plus ADT but no excess of other toxicities or death.InterpretationAdding AAP to ADT is a clinically effective treatment option for men with mHSPC, offering an alternative to docetaxel for men who are starting treatment for the first time. Future research will need to address which of these two agents or whether their combination is most effective, and for whom.

BackgroundLung cancer is considered a terminal illness with a five-year survival rate of about 16%. Informed decision-making related to the management of a disease requires accurate prognosis of the disease with or without treatment. Despite the significance of disease prognosis in clinical decision-making, systematic assessment of prognosis in patients with lung cancer without treatment has not been performed. We conducted a systematic review and meta-analysis of the natural history of patients with confirmed diagnosis of lung cancer without active treatment, to provide evidence-based recommendations for practitioners on management decisions related to the disease. Specifically, we estimated overall survival when no anticancer therapy is provided.MethodsRelevant studies were identified by search of electronic databases and abstract proceedings, review of bibliographies of included articles, and contacting experts in the field. All prospective or retrospective studies assessing prognosis of lung cancer patients without treatment were eligible for inclusion. Data on mortality was extracted from all included studies. Pooled proportion of mortality was calculated as a back-transform of the weighted mean of the transformed proportions using the random-effects model. To perform meta-analysis of median survival, published methods were used to pool the estimates as mean and standard error under the random-effects model. Methodological quality of the studies was examined.ResultsSeven cohort studies (4,418 patients) and 15 randomized controlled trials (1,031 patients) were included in the meta-analysis. All studies assessed mortality without treatment in patients with non-small cell lung cancer (NSCLC). The pooled proportion of mortality without treatment in cohort studies was 0.97 (95% CI: 0.96 to 0.99) and 0.96 in randomized controlled trials (95% CI: 0.94 to 0.98) over median study periods of eight and three years, respectively. When data from cohort and randomized controlled trials were combined, the pooled proportion of mortality was 0.97 (95% CI: 0.96 to 0.98). Test of interaction showed a statistically non-significant difference between subgroups of cohort and randomized controlled trials. The pooled mean survival for patients without anticancer treatment in cohort studies was 11.94 months (95% CI: 10.07 to 13.8) and 5.03 months (95% CI: 4.17 to 5.89) in RCTs. For the combined data (cohort studies and RCTs), the pooled mean survival was 7.15 months (95% CI: 5.87 to 8.42), with a statistically significant difference between the two designs. Overall, the studies were of moderate methodological quality.ConclusionSystematic evaluation of evidence on prognosis of NSCLC without treatment shows that mortality is very high. Untreated lung cancer patients live on average for 7.15 months. Although limited by study design, these findings provide the basis for future trials to determine optimal expected improvement in mortality with innovative treatments.

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