No abstract

Objective: Head-to-head randomized controlled trials (RCTs) are the gold standard for assessing comparative treatment effects. In the absence of direct comparisons between all possible antiepileptic drugs (AEDs), however, clinical decision-making in focal (partial onset) epilepsy relies on alternative evidence borne from indirect comparisons including network meta-analyses (NMAs) and from real-world evidence (RWE) studies. We review NMAs and observational RWE studies comparing AEDs in the adjunctive setting to compare the robustness of these methods and to formulate recommendations for future evidence development. Methods: A literature review identified NMAs and RWE studies comparing AEDs for the adjunctive treatment of focal seizures published between January 2008 and October 2018. NMAs were evaluated for robustness using a framework based on guidelines from the National Institute for Health and Care Excellence Decision Support Unit and the International Society for Pharmacoeconomics and OutcomesResearch. RWE studies were evaluated using the GRACE checklist. Results: From a total of 1993 records, 11 NMAs and six RWE studies were eligible. Key limitations identified in the NMAs include nonsystematic selection of RCTs, unexplored heterogeneity between included RCTs in terms of study and patient characteristics, and selection of AEDs and AED doses or dosing strategies that are not reflective of clinical practice. The main limitations of RWE studies concern sample size, design, and analysis methods. Approximately 90% of comparisons between individual AEDs were nonsignificant in the NMAs. None of the RWE studies adjusted for baseline differences between comparator groups; therefore, they lack the validity to make comparative conclusions. Significance: Current NMAs and RWE studies provide only nominal comparative evidence for AED treatments in focal epilepsy, and should be used with caution for decision-making due to their methodological limitations. To overcome these hurdles, adherence to methodological guidelines and concerted efforts to collect relevant outcome data in the real world are needed. |

Schizophrenia is a debilitating psychiatric disorder and patients experience significant comorbidity, especially cognitive and psychosocial deficits, already at the onset of disease. Previous research suggests that treatment during the earlier stages of disease reduces disease burden, and that a longer time of untreated psychosis has a negative impact on treatment outcomes. A targeted literature review was conducted to gain insight into the definitions currently used to describe patients with a recent diagnosis of schizophrenia in the early course of disease (‘early’ schizophrenia). A total of 483 relevant English-language publications of clinical guidelines and studies were identified for inclusion after searches of MEDLINE, MEDLINE In-Process, relevant clinical trial databases and Google for records published between January 2005 and October 2015. The extracted data revealed a wide variety of terminology and definitions used to describe patients with ‘early’ or ‘recent-onset’ schizophrenia, with no apparent consensus. The most commonly used criteria to define patients with early schizophrenia included experience of their first episode of schizophrenia or disease duration of less than 1, 2 or 5 years. These varied definitions likely result in substantial disparities of patient populations between studies and variable population heterogeneity. Better agreement on the definition of early schizophrenia could aid interpretation and comparison of studies in this patient population and consensus on definitions should allow for better identification and management of schizophrenia patients in the early course of their disease.

Background: Schizophrenia is a heterogeneous disorder with a burden that can vary greatly depending on the severity and the duration. Previous research has suggested that patients in the earlier stages of schizophrenia (typically first-episode schizophrenia) benefit from effective early treatment, however, a comprehensive review of the burden specifically in this population has not been undertaken. A systematic literature review was therefore conducted to characterize the clinical, economic, and humanistic burden, as reported in naturalistic studies of schizophrenia populations specifically at an early stage of disease in comparison with healthy controls, patients with chronic schizophrenia, and patients with other psychiatric disorders.

Background With obesity prevalence projected to increase, the demand for bariatric surgery will consequently rise. Enhanced recovery programmes aim for improved recovery, earlier discharge, and more efficient use of resources following surgery. This systematic literature review aimed to evaluate the evidence available on the effects of enhanced recovery programmes after three common bariatric procedures: laparoscopic Roux-en-Y gastric bypass (LRYGB), laparoscopic sleeve gastrectomy (LSG), and one anastomosis gastric bypass (OAGB). Methods MEDLINE, Embase, the Cochrane Library and the National Health Service Economic Evaluation Database were searched for studies published in 2012–2019 comparing outcomes with enhanced recovery programmes versus conventional care after bariatric surgery in Europe, the Middle East and Africa. Data were extracted and meta-analyses or descriptive analyses performed when appropriate using R. Results Of 1152 screened articles, seven relevant studies including 3592 patients were identified. Six reported outcomes for 1434 patients undergoing LRYGB; however, as only individual studies reported on LSG and OAGB these could not be included in the analyses. The meta-analysis revealed a significantly shorter mean duration of hospital-stay for LRYGB enhanced recovery programmes than conventional care (mean difference [95% CI]: -1.34 days [-2.01, -0.67]; p<0.0001), supported by sensitivity analysis excluding retrospective studies. Meta-analysis found no significant difference in 30-day readmission rate (risk ratio [95% CI]: 1.39 [0.84, 2.28]; p = 0.2010). Complication rates were inconsistently reported by Clavien-Dindo grade, but descriptive analysis showed generally higher low-grade rates for enhanced recovery programmes; the trend reversed for high-grade complications. Reoperation rates were rarely reported; no significant differences were seen. Conclusion These results support enhanced recovery programmes allowing shorter inpatient stay without significant differences in readmission rate following LRYGB, although complication and reoperation rate comparisons were inconclusive. Further research is needed to fill current data gaps including the lack of studies on LSG and OAGB.