Murad, Mohammad Hassan

Background Sudden unexpected death in epilepsy ( SUDEP ) is the leading cause of epilepsy‐related death. SUDEP shares many features with sudden cardiac death and sudden unexplained death in the young and may have a similar genetic contribution. We aim to systematically review the literature on the genetics of SUDEP . Methods and Results PubMed, MEDLINE Epub Ahead of Print, Ovid Medline In‐Process & Other Non‐Indexed Citations, MEDLINE , EMBASE , Cochrane Database of Systematic Reviews, and Scopus were searched through April 4, 2017. English language human studies analyzing SUDEP for known sudden death, ion channel and arrhythmia‐related pathogenic variants, novel variant discovery, and copy number variant analyses were included. Aggregate descriptive statistics were generated; data were insufficient for meta‐analysis. A total of 8 studies with 161 unique individuals were included; mean was age 29.0 (± SD 14.2) years; 61% males; ECG data were reported in 7.5% of cases; 50.7% were found prone and 58% of deaths were nocturnal. Cause included all types of epilepsy. Antemortem diagnosis of Dravet syndrome and autism (with duplication of chromosome 15) was associated with 11% and 9% of cases. The most frequently detected known pathogenic variants at postmortem were in Na + and K + ion channel subunits, as were novel potentially pathogenic variants (11%). Overall, the majority of variants were of unknown significance. Analysis of copy number variant was insignificant. Conclusions SUDEP case adjudication and evaluation remains limited largely because of crucial missing data such as ECG s. The most frequent pathogenic/likely pathogenic variants identified by molecular autopsy are in ion channel or arrhythmia‐related genes, with an ≈11% discovery rate. Comprehensive postmortem examination should include examination of the heart and brain by specialized pathologists and blood storage.

Abstract Background Osteoporosis and osteopenia are associated with increased fracture incidence in postmenopausal women. We aimed to determine the comparative effectiveness of various available pharmacological therapies. Methods We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science, and Scopus for randomized controlled trials that enrolled postmenopausal women with primary osteoporosis and evaluated the risk of hip, vertebral, or nonvertebral fractures. A network meta-analysis was conducted using the multivariate random effects method. Results We included 107 trials (193,987 postmenopausal women; mean age, 66 years; 55% white; median follow-up, 28 months). A significant reduction in hip fractures was observed with romosozumab, alendronate, zoledronate, risedronate, denosumab, estrogen with progesterone, and calcium in combination with vitamin D. A significant reduction in nonvertebral fractures was observed with abaloparatide, romosozumab, denosumab, teriparatide, alendronate, risedronate, zoledronate, lasofoxifene, tibolone, estrogen with progesterone, and vitamin D. A significant reduction in vertebral fractures was observed with abaloparatide, teriparatide, parathyroid hormone 1-84, romosozumab, strontium ranelate, denosumab, zoledronate, risedronate, alendronate, ibandronate, raloxifene, bazedoxifene, lasofoxifene, estrogen with progesterone, tibolone, and calcitonin. Teriparatide, abaloparatide, denosumab, and romosozumab were associated with the highest relative risk reductions, whereas ibandronate and selective estrogen receptor modulators had lower efficacy. The evidence for the treatment of fractures with vitamin D and calcium remains limited despite numerous large trials. Conclusions This network meta-analysis provides comparative effective estimates for the various available treatments to reduce the risk of fragility fractures in postmenopausal women.

Abstract Background Several treatments are available to reduce the risk of fragility fractures associated with osteoporosis. The choice of treatment requires knowledge of patients’ values and preferences. The aim of the present study was to summarize what is known about the values and preferences relevant to the management of osteoporosis in women. Methods We conducted a comprehensive search of several databases for studies reported in any language that had included women who had already started or were about to start any pharmacological therapy for osteoporosis. Pairs of reviewers independently selected the studies and extracted the data. The results were synthesized narratively. Results We included 26 studies reporting on 15,348 women (mean age, 66 years). The women considered the effectiveness and adverse events equally, followed by the convenience of taking the drug and its effect on daily routine (less frequent dosing was preferred, the oral route was preferred, and the injectable route was preferred over oral if given less frequently). The treatment cost and duration were less important factors for decision making. Fear of breast cancer and fear of resuming uterine bleeding were common reasons for not choosing estrogen therapy. Calcium and vitamin D were viewed as safe and natural. Across the studies, the preferences were not affected by age, previous drug exposure, or employment status. Conclusions Women starting osteoporosis medications value effectiveness and side effects equally and prefer medications given less frequently. Injectable drugs appear acceptable if given less frequently. More research on patient values and preferences is needed to guide decision making in osteoporosis.

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.

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.

Introduction Cumulative network meta-analysis (NMA) is a method to provide a global comparison of multiple treatments with real-time update to evidence users. Several studies investigated the ranking of cumulative NMA and the recommendations of practice guidelines. However, to the best of our knowledge, no study has evaluated the cumulative NMA ranking and prescription patterns. Here, we present a protocol for a meta-epidemiological investigation to compare the results of cumulative NMA with the recommendations in postmenopausal osteoporosis practice guidelines and with the actual prescriptions. Method and analysis We will use the data of primary trials from the upcoming postmenopausal osteoporosis clinical practice guideline of the Endocrine Society. We will conduct cumulative NMA using all eligible trials and generate hierarchy of treatment rankings by using the surface under the cumulative ranking curve. We will search practice guidelines in relevant society websites. Two review authors will extract the practice recommendations. We will use data from the Medical Expenditures Panel Survey, a US representative sample of the non-institutionalised population, to determine the prescription patterns. Ethics and dissemination Because all data will be retrieved from public databases, institutional review board approval is not required. We will publish our findings in a peer-reviewed journal and present key findings at conferences. Trial registration number UMIN000031894: Pre-results.

We performed a systematic review with network meta‐analysis (NMA) to compare the efficacy of different approaches in primary prevention of esophageal variceal bleeding and overall survival in patients with cirrhosis with large varices. Thirty‐two randomized clinical trials (RCTs) with 3,362 adults with cirrhosis with large esophageal varices and no prior history of bleeding, with a minimum of 12 months of follow‐up, were included. Nonselective beta‐blockers (NSBB), isosorbide‐mononitrate (ISMN), carvedilol, and variceal band ligation (VBL), alone or in combination, were compared with each other or placebo. Primary outcomes were reduction of all‐cause mortality and prevention of esophageal variceal bleeding. Random‐effects NMA was performed and summary estimates were expressed as odds ratio and 95% confidence intervals (OR; CI). Quality of evidence was critically appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. Moderate quality evidence supports NSBB monotherapy (0.70; 0.49‐1.00) or in combination with VBL (0.49; 0.23‐1.02) or ISMN (0.44; 0.21‐0.93) for decreasing mortality in patients with cirrhosis with large esophageal varices and no prior history of bleeding. Moderate‐quality evidence supports carvedilol (0.21; 0.08‐0.56) and VBL monotherapy (0.33; 0.19‐0.55) or in combination with NSBB (0.34; 0.14‐0.86), and low‐quality evidence supports NSBB monotherapy (0.64; 0.38‐1.07) for primary prevention of variceal bleeding. VBL carries a higher risk of serious adverse events compared with NSBB.Conclusion:NSBB monotherapy may decrease all‐cause mortality and the risk of first variceal bleeding in patients with cirrhosis with large esophageal varices. Additionally, NSBB carries a lower risk of serious complications compared with VBL. Therefore, NSBB may be the preferred initial approach for primary prophylaxis of esophageal variceal bleeding.