Murad, M. Hassan

Abstract Objective The objective is to formulate clinical practice guidelines for the pharmacological management of osteoporosis in postmenopausal women. Conclusions Evidence from clinical trials and insights from clinical experience with pharmacologic therapies for osteoporosis were critically evaluated in formulating this guideline for the management of postmenopausal osteoporosis. Patient preferences, data on adherence and persistence, and risks and benefits from the patient and provider perspectives were also considered in writing committee deliberations. A consensus by the Writing Committee members was achieved for four management principles: (i) The risk of future fractures in postmenopausal women should be determined using country-specific assessment tools to guide decision-making. (ii) Patient preferences should be incorporated into treatment planning. (iii) Nutritional and lifestyle interventions and fall prevention should accompany all pharmacologic regimens to reduce fracture risk. (iv) Multiple pharmacologic therapies are capable of reducing fracture rates in postmenopausal women at risk with acceptable risk-benefit and safety profiles.

Abstract Objective The objective is to formulate clinical practice guidelines for the treatment of diabetes in older adults. Conclusions Diabetes, particularly type 2, is becoming more prevalent in the general population, especially in individuals over the age of 65 years. The underlying pathophysiology of the disease in these patients is exacerbated by the direct effects of aging on metabolic regulation. Similarly, aging effects interact with diabetes to accelerate the progression of many common diabetes complications. Each section in this guideline covers all aspects of the etiology and available evidence, primarily from controlled trials, on therapeutic options and outcomes in this population. The goal is to give guidance to practicing health care providers that will benefit patients with diabetes (both type 1 and type 2), paying particular attention to avoiding unnecessary and/or harmful adverse effects.

Abstract Background The efficacy of lipid-lowering agents on patient-important outcomes in older individuals is unclear. Methods We included randomized trials that enrolled individuals aged 65 years or older and that included at least 1 year of follow-up. Pairs of reviewers selected and appraised the trials. Results We included 23 trials that enrolled 60,194 elderly patients. For primary prevention, statins reduced the risk of coronary artery disease [CAD; relative risk (RR): 0.79, 95% CI: 0.68 to 0.91] and myocardial infarction (MI; RR: 0.45, 95% CI: 0.31 to 0.66) but not all-cause or cardiovascular mortality or stroke. These effects were imprecise in patients with diabetes, but there was no significant interaction between diabetes status and the intervention effect. For secondary prevention, statins reduced all-cause mortality (RR: 0.80, 95% CI: 0.73 to 0.89), cardiovascular mortality (RR: 0.68, 95% CI: 0.58 to 0.79), CAD (RR: 0.68, 95% CI: 0.61 to 0.77), MI (RR: 0.68, 95% CI: 0.59 to 0.79), and revascularization (RR: 0.68, 95% CI: 0.61 to 0.77). Intensive (vs less-intensive) statin therapy reduced the risk of CAD and heart failure. Niacin did not reduce the risk of revascularization, and fibrates did not reduce the risk of stroke, cardiovascular mortality, or CAD. Conclusion High-certainty evidence supports statin use for secondary prevention in older individuals. Evidence for primary prevention is less certain. Data in older individuals with diabetes are limited; however, no empirical evidence has shown a significant difference based on diabetes status.

263 Background: In non-metastatic CRPC with short PSA doubling time, APA or ENZA with ADT have shown to slow development of metastasis. We performed an indirect comparison of APA and ENZA clinical effectiveness (efficacy and side effects) using network meta-analysis. Methods: A search of Medline, Embase, Cochrane Library, and Cochrane Central Register of Controlled Trials was performed to identify relevant RCTs. Collected data included hazard ratio (HR) and confidence interval (CI) for primary outcome of median time to metastasis free survival (MFS) and secondary outcomes of median time to overall survival (OS), PSA progression, initiation of cytotoxic therapy and number of adverse events (AE) in each study arm. Risk for bias was assessed using the Cochrane Collaboration’s tool. We used a fixed effects model using Bayesian approach to generate pooled estimates. Results: Two randomized trials (n=2608) were analyzed. SPARTAN trial compared APA plus ADT to ADT alone and PROSPER compared ENZA plus ADT to ADT alone. Risk of bias was low. There were no statistically significant differences between APA and ENZA in MFS, OS, median time to PSA progression and initiation of cytotoxic therapy. The MFS endpoint hazard ratio (HR) was 0.97 (95% CI 0.73-1.28) for comparing the two drugs. APA had fewer reports of hypertension (HR 0.54, 95% CI 0.31–0.91) compared to enzalutamide. However, no significant differences were observed in other AEs including grade 3 or higher AE, serious AE, AE leading to death or trial discontinuation. Common AEs (nausea, diarrhea, fall, dizziness, arthralgia, weight loss) and AEs of special interests (mental impairment disorders, seizures) were also comparable between APA and ENZA. Conclusions: In non-metastatic CRPC with short PSA doubling time, APA and ENZA showed similar time to metastasis free survival. APA was associated with lower incidence of hypertension than ENZA; otherwise, side effect profile was similar. Given similar efficacy and risk profile demonstrated in this study, clinical decision making should depend on other factors such as cost and availability.

Background. This systematic review was commissioned to identify new variables associated with transplant outcomes that are not currently collected by the Organ Procurement and Transplantation Network (OPTN). Methods. We identified 81 unique studies including 1 193 410 patients with median follow-up of 36 months posttransplant, reporting 108 unique risk factors. Results. Most risk factors (104) were recipient related; few (4) were donor related. Most risk factors were judged to be practical and feasible to routinely collect. Relative association measures were small to moderate for most risk factors (ranging between 1.0 and 2.0). The strongest relative association measure for a heart transplant outcome with a risk factor was 8.6 (recipient with the previous Fontan operation), for a kidney transplant 2.8 (sickle cell nephropathy as primary cause of end-stage renal disease), for a liver transplant 14.3 (recipient serum ferritin >500 µg/L), and for a lung transplant 6.3 (Burkholderia cepacia complex infection for 1 y or less). OPTN may consider some of these 108 variables for future collection to enhance transplant research and clinical care. Conclusions. Evidence-based approaches can be used to determine variables collected in databases and registries. Several candidate variables have been identified for OPTN.

OBJECTIVEDifferent CSF diversion procedures (ventriculoperitoneal, ventriculoatrial, and lumboperitoneal shunting) have been utilized for the treatment of idiopathic normal pressure hydrocephalus. More recently, endoscopic third ventriculostomy has been suggested as a reasonable alternative in some studies. The purpose of this study was to perform a systematic review and meta-analysis to assess overall rates of favorable outcomes and adverse events for each of these treatments. An additional objective was to determine the outcomes and complication rates in relation to the type of valve utilized (fixed vs programmable).METHODSMultiple databases (PubMed, Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus) were searched for studies involving patients with idiopathic ventriculomegaly, no secondary cause of hydrocephalus, opening pressure < 25 mm Hg on high-volume tap or drainage trial, and age > 60 years. Outcomes included the proportion of patients who showed improvement in gait, cognition, and bladder function. Adverse events considered in the analysis included postoperative ischemic/hemorrhagic complications, subdural fluid collections, seizures, need for revision surgery, and infection.RESULTSA total of 33 studies, encompassing 2461 patients, were identified. More than 75% of patients experienced improvement after shunting, without significant differences among the different techniques utilized. Overall, gait improvement was observed in 75% of patients, cognitive function improvement in more than 60%, and improvement of incontinence in 55%. Adjustable valves were associated with a reduction in revisions (12% vs 32%) and subdural collections (9% vs 22%) as compared to fixed valves.CONCLUSIONSOutcomes did not differ significantly among different CSF diversion techniques, and overall improvement was reported in more than 75% of patients. The use of programmable valves decreased the incidence of revision surgery and of subdural collections after surgery, potentially justifying the higher initial cost associated with these valves.

619 Background: Regorafenib (at a starting dose of 160 mg/day, rego 160), regorafenib (with a weekly dose escalation, rego 80+) and TAS-102, are suggested treatment options for refractory metastatic colorectal cancer (mCRC). We aimed to evaluate the comparative effectiveness evidence supporting these 3 strategies. Methods: We searched PubMed, Embase, and Cochrane CENTRAL, for randomized controlled trials evaluating TAS 102 or regorafenib in refractory mCRC patients who progressed on/intolerant of previous oxaliplatin, irinotecan, and fluoropyrimidine. Outcomes of interest included OS and PFS. The overall effect was pooled using the DerSimonian random effects model. We conducted network meta-analysis based on White’s multivariate meta-regression to pool evidence from direct and indirect comparisons. Results: Six trials (3 of regorafenib and 3 of TAS-102) at low risk of bias (2,445 patients) were included. Direct comparisons showed that Rego 160 and TAS-102 as monotherapy were superior to BSC in terms of PFS (Rego 160: HR = 0.4, CI 0.26 to 0.63; TAS-102: HR = 0.46, CI 0.40 to 0.52) and OS (Rego 160: HR = 0.67, CI 0.48 to 0.93; TAS-102: HR = 0.67, CI 0.57 to 0.80). Network analysis showed that there was no difference in PFS or OS between Rego 160 and TAS-102. Rego 80+ was superior to BSC in terms of OS (HR = 0.44, CI 0.23 to 0.84) and PFS (HR = 0.37, CI 0.21 to 0.66). There was a numerical advantage for Rego 80+ compared to TAS-102 and Rego 160 (see table). Conclusions: Regorafenib 160 and TAS-102 appear to have similar efficacy. Rego 80+ is shown to be superior to BSC. A trend for improved OS was observed with Rego 80+ versus Rego 160 or TAS 102. [Table: see text]

Objective To assess gender disparity in outcomes among hospitalised patients with acute myocardial infarction (AMI), acute decompensated heart failure (ADHF) or pneumonia. Design A retrospective cohort study. Setting A tertiary referral centre in Midwest, USA. Participants We evaluated 12 265 adult patients hospitalised with ADHF, 15 777 with AMI and 12 929 with pneumonia, from 1 January 1995 through 31 August 2015. Patients were selected using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Primary and secondary outcome measures Prevalence of comorbidities, 30-day mortality and 30-day readmission. Comorbidities were chosen from the 20 chronic conditions, specified by the Office of the Assistant Secretary for Health. Logistic regression analysis was conducted adjusting for multiple confounders. Results Prevalence of comorbidities was significantly different between men and women in all three conditions. After adjusting for age, length of stay, multicomorbidities and residence, there was no significant difference in 30-day mortality between men and women in AMI or ADHF, but men with pneumonia had slightly higher 30-day mortality with an OR of 1.19 (95% CI 1.06 to 1.34). There was no significant difference in 30-day readmission between men and women with AMI or pneumonia, but women with ADHF were slightly more likely to be readmitted within 30 days with OR 0.90 (95% CI 0.82 to 0.99). Conclusion Gender differences in the distribution of comorbidities exist in patients hospitalised with AMI, ADHF and pneumonia. However, there is minimal clinically meaningful impact of these differences on outcomes. Efforts to address gender difference may need to be diverted towards targeting overall population health, reducing race/ethnicity disparity and improving access to care.

Objective There exists a paucity of work in the development and testing of theoretical models specific to childhood health disparities even though they have been linked to the prevalence of adult health disparities including high rates of chronic disease. We conducted a systematic review and thematic analysis of existing models of health disparities specific to children to inform development of a unified conceptual framework. Methods We systematically reviewed articles reporting theoretical or explanatory models of disparities on a range of outcomes related to child health. We searched Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus (database inception to 9 July 2015). A metanarrative approach guided the analysis process. Results A total of 48 studies presenting 48 models were included. This systematic review found multiple models but no consensus on one approach. However, we did discover a fair amount of overlap, such that the 48 models reviewed converged into the unified conceptual framework. The majority of models included factors in three domains: individual characteristics and behaviours (88%), healthcare providers and systems (63%), and environment/community (56%), . Only 38% of models included factors in the health and public policies domain. Conclusions A disease-agnostic unified conceptual framework may inform integration of existing knowledge of child health disparities and guide future research. This multilevel framework can focus attention among clinical, basic and social science research on the relationships between policy, social factors, health systems and the physical environment that impact children's health outcomes.