Ahmed, Ahmed T.

Background: Antidepressants are among the most prescribed medications in the United States. The aim of this study was to explore the prevalence of antidepressant prescriptions and investigate sex differences and age-sex interactions in adults enrolled in the Right Drug, Right Dose, Right Time: Using Genomic Data to Individualize Treatment (RIGHT) study. Materials and Methods: We conducted a retrospective analysis of the RIGHT study. Using electronic prescriptions, we assessed 12-month prevalence of antidepressant treatment. Sex differences and age-sex interactions were evaluated using multivariable logistic regression and flexible recursive smoothing splines. Results: The sample consisted of 11,087 participants (60% women). Antidepressant prescription prevalence was 22.24% (27.96% women, 13.58% men). After adjusting for age and enrollment year, women had significantly greater odds of antidepressant prescription (odds ratio = 2.29; 95% confidence interval = 2.07, 2.54). Furthermore, selective serotonin reuptake inhibitors (SSRIs) had a significant age-sex interaction. While SSRI prescriptions in men showed a sustained decrease with age, there was no such decline for women until after reaching ∼50 years of age. There are important limitations to consider in this study. Electronic prescription data were cross-sectional; information on treatment duration or adherence was not collected; this cohort is not nationally representative; and enrollment occurred over a broad period, introducing confounding by changes in temporal prescribing practices. Conclusions: Underscored by the significant interaction between age and sex on odds of SSRI prescription, our results warrant age to be incorporated as a mediator when investigating sex differences in mental illness, especially mood disorders and their treatment.

CONTEXT: Unplanned PICU readmissions within 48 hours of discharge (to home or a different hospital setting) are considered a quality metric of critical care. OBJECTIVE: We sought to determine identifiable risk factors associated with early unplanned PICU readmissions. DATA SOURCES: A comprehensive search of Medline, Embase, the Cochrane Database of Systematic Reviews, and Scopus was conducted from each database’s inception to July 16, 2018. STUDY SELECTION: Observational studies of early unplanned PICU readmissions (<48 hours) in children (<18 years of age) published in any language were included. DATA EXTRACTION: Two reviewers selected and appraised studies independently and abstracted data. A meta-analysis was performed by using the random-effects model. RESULTS: We included 11 observational studies in which 128 974 children (mean age: 5 years) were evaluated. The presence of complex chronic diseases (odds ratio 2.42; 95% confidence interval 1.06 to 5.55; I2 79.90%) and moderate to severe disability (odds ratio 2.85; 95% confidence interval 2.40 to 3.40; I2 11.20%) had the highest odds of early unplanned PICU readmission. Other significant risk factors included an unplanned index admission, initial admission to a general medical ward, spring season, respiratory diagnoses, and longer initial PICU stay. Readmission was less likely after trauma- and surgery-related index admissions, after direct admission from home, or during the summer season. Modifiable risk factors, such as evening or weekend discharge, revealed no statistically significant association. Included studies were retrospective, which limited our ability to account for all potential confounders and establish causality. CONCLUSIONS: Many risk factors for early unplanned PICU readmission are not modifiable, which brings into question the usefulness of this quality measure.

Abstract Background Ketamine, a glutamate N-methyl-d-aspartate receptor antagonist, has shown rapid antidepressant effects in treatment-resistant depression. We conducted a systematic review of studies evaluating the efficacy of intravenous ketamine augmentation in treatment-resistant depression patients with bipolar disorder. Methods Major databases were searched for open-label and randomized controlled trials (RCT). Two independent reviewers screened and selected the studies that met the inclusion criteria. Studies were selected following the standard Cochrane methodology, and the findings are reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Methodological quality of the included studies was assessed using standardized measures. Results A total of 1442 articles were screened. Five studies were included in the systematic review (3 RCTs and 2 open-label studies) enrolling 110 subjects (mean age, 45.54 ± 12.65 years; 68.18% female). All the RCTs and open-label studies showed improvement in depressions symptoms after receiving a single infusion of ketamine. Included studies also suggested improvement in suicidal ideation and anhedonia after ketamine infusion. Dissociation and transient increase in blood pressure were the most common reported adverse effects with ketamine. Ketamine infusions did not increase mania symptoms. Conclusions Limited data show efficacy and feasibility of intravenous racemic ketamine in treatment-resistant bipolar depression. Further studies with larger sample size are required to strengthen the evidence.

Background: Stiffness is a common reason for suboptimal clinical outcomes after primary total knee arthroplasty (pTKA). There is a lack of consensus regarding its definition, which is often conflated with its histopathologic subcategory—i.e., arthrofibrosis. There is value in refining the definition of acquired idiopathic stiffness in an effort to select for patients with arthrofibrosis. We conducted a systematic review and meta-analysis to establish a consensus definition of acquired idiopathic stiffness, determine its prevalence after pTKA, and identify potential risk factors for its development. Methods: MEDLINE, Embase, Cochrane Controlled Register of Trials (CENTRAL), and Scopus databases were searched from 2002 to 2017. Studies that included patients with stiffness after pTKA were screened with strict inclusion and exclusion criteria to isolate the subset of patients with acquired idiopathic stiffness unrelated to known extrinsic or surgical causes. Three authors independently assessed study eligibility and risk of bias and collected data. Outcomes of interest were then analyzed according to age, sex, and body mass index (BMI). Results: In the 35 included studies (48,873 pTKAs), the mean patient age was 66 years. In 63% of the studies, stiffness was defined as a range of motion of <90° or a flexion contracture of >5° at 6 to 12 weeks postoperatively. The prevalence of acquired idiopathic stiffness after pTKA was 4%, and this did not differ according to age (4%, I 2 = 95%, among patients <65 years old and 5%, I 2 = 96%, among those ≥65 years old; p = 0.238). The prevalence of acquired idiopathic stiffness was significantly lower in males (1%, I 2 = 85%) than females (3%, I 2 = 95%) (p < 0.0001) as well as in patients with a BMI of <30 kg/m 2 (2%, I 2 = 94%) compared with those with a BMI of ≥30 kg/m 2 (5%, I 2 = 97%) (p = 0.027). Conclusions: Contemporary literature supports the following definition for acquired idiopathic stiffness: a range of motion of <90° persisting for >12 weeks after pTKA in patients in the absence of complicating factors including preexisting stiffness. The mean prevalence of acquired idiopathic stiffness after pTKA was 4%; females and obese patients were at increased risk. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Study Design. Systematic review and meta-analysis of observational studies. Objective. The aim of the study is to evaluate different treatment modalities in the management of sacrococcygeal chordoma. Summary of Background Data. Chordomas are primary malignant bone tumors associated with considerable morbidity and mortality. Methods. We searched MEDLINE, EMBASE, Cochrane Central-Register of Controlled Trials, and Scopus from inception to July 2015. Eligible studies included patients with sacrococcygeal chordoma treated exclusively with surgery, radiotherapy, or both. Two reviewers independently assessed the eligibility of potential studies, risk of bias, and extracted data. Outcomes of interest were all-cause mortality, progression-free survival, and metastases. We analyzed further surgical outcomes by resection margin. All outcomes were assessed at 60 months and more than 60 months following intervention. Results. We included 33 noncomparative studies reporting on 501 patients (mean age 57 years). Overall mortality rate was (16%) after surgical resection with adjuvant radiotherapy and (28%) after surgical resection, and (43%) after radiotherapy (P = 0.28). All-cause mortality following wide surgical resection was (32%) compared to (40%) after marginal resection (P = 0.51). Overall progression-free survival rate was (58%) after surgical resection with adjuvant radiotherapy and (55%) after surgery (P = 0.92). However, at more than 60 months follow-up, progression-free survival rates were significantly higher (P = 0.024) following surgical resection with adjuvant radiotherapy (74%) in comparison to surgery (55%) and radiotherapy (36%). Overall progression-free survival rates were nonsignificantly higher after wide surgical resection (66%) than marginal resection (33%) (P = 0.16). However, at 60 months follow-up, progression-free survival rates were significantly higher following wide surgical resection (73%) than marginal resection (33%) (P = 0.047). Conclusion. Sacrococcygeal chordoma is a difficult to treat disease entity. Until comparative studies become available, wide surgical resection and multidisciplinary management are the recommended approaches to improve patient outcomes. Level of Evidence: 3

Antidepressants have reduced the symptom burden for many Major Depressive Disorder (MDD) patients, but drug‐related side effects and treatment resistance continue to present major challenges. Pharmacogenomics represents one approach to enhance antidepressant efficacy and avoid adverse reactions, but concerns remain with regard to the overall “value equation,” and several barriers must be overcome to achieve the full potential of MDD pharmacogenomics.

Abstract Objective: Multiple interventions are available to reduce excess body weight in children. We appraised the quality of evidence supporting each intervention and assessed the effectiveness on different obesity-related outcomes. Methods: We conducted a systematic search for systematic reviews of randomized controlled trials evaluating pediatric obesity interventions applied for ≥6 months. We assessed the quality of evidence for each intervention using GRADE (Grading of Recommendation, Assessment, Development, and Evaluation) approach. Results: From 16 systematic reviews, we identified 133 eligible randomized controlled trials. Physical activity interventions reduced systolic blood pressure and fasting glucose (low to moderate quality of evidence). Dietary interventions with low-carbohydrate diets had a similar effect to low-fat diets in terms of body mass index (BMI) reduction (moderate quality of evidence). Educational interventions reduced waist circumference, BMI, and diastolic blood pressure (low quality of evidence). Pharmacological interventions reduced BMI (metformin, sibutramine, orlistat) and waist circumference (sibutramine, orlistat) and increased high-density lipoprotein cholesterol (sibutramine) but also raised systolic and diastolic blood pressure (sibutramine). Surgical interventions (laparoscopic adjustable gastric banding, Roux-en-Y gastric bypass, sleeve gastrectomy) resulted in the largest BMI reduction (moderate quality of evidence). Combined interventions consisting of dietary modification, physical activity, behavioral therapy, and education significantly reduced systolic and diastolic blood pressure, BMI, and triglycerides. Combined parent–child interventions and parent-only interventions had similar effects on BMI (low quality of evidence). Conclusions: Several childhood obesity interventions are effective in improving metabolic and anthropometric measures. A comprehensive multicomponent intervention, however, appears to have the best overall outcomes.