Mohammed, Khaled

Importance Suicide is a leading cause of death among young people and an escalating public health crisis. Objective To assess the effectiveness and harms of available treatments for suicidal thoughts and behaviors among youths at heightened risk for suicide. Evidence Review A systematic review was conducted searching databases including MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, and various gray literature sources from January 1, 2000, to September 26, 2024. We included randomized clinical trials, comparative observational studies, and before-after studies of psychosocial interventions, pharmacologic interventions, neurotherapeutics, emerging therapies, and combination therapies. Eligible patients were youths (aged 5-24 years) with heightened risk for suicide, adolescents from racial and ethnic minority groups known to be at increased risk of suicide, or those exposed to crime or violence. Pairs of independent reviewers selected and appraised studies. Findings This review included 65 studies (33 randomized clinical trials, 13 comparative observational studies, and 19 before-after studies) reporting on 14 534 patients (median age, 15.1 years; 75.1% female patients). Psychosocial interventions comprised psychotherapy interventions (33 studies; cognitive behavioral therapy, dialectical behavioral therapy, collaborative assessment and management of suicidality, dynamic deconstructive psychotherapy, attachment-based family therapy, and family-focused therapy), acute (ie, 1-4 sessions or contacts) psychosocial interventions (19 studies; safety planning, family-based crisis management, motivational interviewing crisis interventions, continuity of care after crisis, and brief adjunctive treatments), and school- or community-based psychosocial interventions (13 studies; social network interventions, school-based skills interventions, suicide awareness or gatekeeper programs, and community-based, culturally tailored adjunct programs). Dialectical behavior therapy showed moderate strength of evidence for reducing suicidal ideation. Other categories of psychosocial treatments showed insufficient to low strength of evidence for reducing suicidal outcomes. None of the studies evaluated adverse events. The evidence base on pharmacologic treatment for youths at risk of suicide was largely nonexistent. Conclusions and Relevance This systematic review found that the current evidence on available interventions targeting youths at heightened risk of suicide is uncertain. Medication, neurotherapeutics, and emerging therapies remain unstudied among this population. The limited evidence base calls for the development of novel, developmentally and trauma-informed treatments, as well as multilevel interventions to target the increasing suicide risk among youths.

Abstract Background Early-stage breast cancer is among the most common cancer diagnoses. Adjuvant radiotherapy is an essential component of breast-conserving therapy, and several options exist for tailoring its extent and duration. This study assesses the comparative effectiveness of partial-breast irradiation (PBI) compared with whole-breast irradiation (WBI). Methods A systematic review was completed to identify relevant randomized clinical trials and comparative observational studies. Independent reviewers working in pairs selected studies and extracted data. Randomized trial results were pooled using a random effects model. Prespecified main outcomes were ipsilateral breast recurrence (IBR), cosmesis, and adverse events (AEs). Results Fourteen randomized clinical trials and 6 comparative observational studies with 17 234 patients evaluated the comparative effectiveness of PBI. PBI was not statistically significantly different from WBI for IBR at 5 years (RR = 1.34, 95% CI = 0.83 to 2.18; high strength of evidence [SOE]) and 10 years (RR = 1.29, 95% CI = 0.87 to 1.91; high SOE). Evidence for cosmetic outcomes was insufficient. Statistically significantly fewer acute AEs were reported with PBI compared with WBI, with no statistically significant difference in late AEs. Data from subgroups according to patient, tumor, and treatment characteristics were insufficient. Intraoperative radiotherapy was associated with higher IBR at 5, 10, and over than 10 years (high SOE) compared with WBI. Conclusions Ipsilateral breast recurrence was not statistically significantly different between PBI and WBI. Acute AEs were less frequent with PBI. This evidence supports the effectiveness of PBI among selected patients with early-stage, favorable-risk breast cancer who are similar to those represented in the included studies.

AbstractBackgroundWe sought to evaluate the association between vitamin D deficiency and the severity of coronavirus disease 2019 (COVID‐19) infection.MethodsMultiple databases from 1 January 2019 to 3 December 2020 were searched for observational studies evaluating the association between vitamin D deficiency and severity of COVID‐19 infection. Independent reviewers selected studies and extracted data for the review. The main outcomes of interest were mortality, hospital admission, length of hospital stay and intensive care unit admission.ResultsSeventeen observational studies with 2756 patients were included in the analyses. Vitamin D deficiency was associated with significantly higher mortality (odds ratio [OR]: 2.47, 95% confidence interval [CI]: 1.50–4.05; 12 studies; hazard ratio [HR]: 4.11, 95% CI: 2.40–7.04; 3 studies), higher rates of hospital admissions (OR: 2.18, 95% CI: 1.48–3.21; 3 studies) and longer hospital stays (0.52 days; 95% CI: 0.25–0.80; 2 studies) as compared to nonvitamin D deficient status. Subgroup analyses based on different cut‐offs for defining vitamin D deficiency, study geographic locations and latitude also showed similar trends.ConclusionsVitamin D deficiency is associated with greater severity of COVID‐19 infection. Further studies are warranted to determine if vitamin D supplementation can decrease the severity of COVID‐19.

Objectives: This systematic review evaluated the accuracy of triaxial and omnidirectional accelerometers for measuring physical activity and sedentary behavior in children. Design: Systematic review of the literature. Methods: We comprehensively searched several databases for studies published from January 1996 through June 2018 that reported diagnostic accuracy measures in children and adolescents (age 3-18 years) and compared accelerometers with energy expenditure using indirect calorimetry. Results: We included 11 studies that enrolled 570 participants. All studies used indirect calorimetry as the reference standard. Across the studies, median sensitivity ranged from 46% to 96% and median specificity ranged from 71% to 96%. Median area under the curve ranged from 69% to 98%. Conclusions: Accuracy measures were greatest when detecting sedentary behavior and lowest when detecting light physical activity. Accuracy was higher when the accelerometer was placed on the hip compared with the wrist. The current evidence suggests that triaxial and omnidirectional accelerometers are accurate in measuring sedentary behavior and physical activity levels in children.

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.

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.

Hepatocellular carcinoma (HCC) is a complex disease most commonly arising in the background of chronic liver disease. In the past two decades, there has been a significant increase in our understanding of both the clinical and molecular heterogeneity of HCC. There has been a robust increase in clinical trial activity in patients with poor prognostic factors, such as macrovascular invasion and extrahepatic spread (EHS). We aimed to synthesize the evidence for the treatment of patients with advanced HCC based on these baseline characteristics, including patients with both Child‐Pugh (CP) scores of A and B. A comprehensive search of several databases from each database inception to February 15, 2016 any language was conducted. We included 14 studies (three randomized controlled studies [RCTs] and 11 observational studies). We included studies that compared sorafenib, transarterial bland embolization/transarterial chemoembolization, yttrium‐90/radiation therapy, ablation (or combination), and no therapy. Two RCTs comparing sorafenib to best supportive care demonstrated a consistent improvement in overall survival (OS) for patients with advanced HCC and metastatic vascular invasion (MVI) and/or EHS and CP A liver disease (hazard ratio, 0.66 [95% confidence interval, 0.51‐0.87]; I 2 = 0%). Several observational studies evaluated locoregional therapies alone or in combination with other treatments and were limited by very‐low‐quality of evidence. This was true for both patients with EHS and MVI. Conclusion : In patients with advanced HCC and CP A liver function, sorafenib is the only treatment that has been shown to improve OS in randomized studies. High‐quality data supporting the use of other treatment modalities in this setting, or in the setting of patients with less compensated (CP B) liver disease, are lacking. (H epatology 2018;67:422‐435)