So how special is special K? A systematic review and meta-analysis of ketamine for PTSD RCTs.

Background: PTSD is a significant mental health problem worldwide. Current evidence-based interventions suffer various limitations. Ketamine is a novel agent that is hoped to be incrementally better than extant interventions.Objective: Several randomized control trials (RCTs) of ketamine interventions for PTSD have now been published. We sought to systematically review and meta-analyse results from these trials to evaluate preliminary evidence for ketamine's incremental benefit above-and-beyond control interventions in PTSD treatment.Results: Omnibus findings from 52 effect sizes extracted across six studies (n = 221) yielded a small advantage for ketamine over control conditions at reducing PTSD symptoms (g = 0.27, 95% CI = 0.03, 0.51). However, bias-correction estimates attenuated this effect (adjusted g = 0.20, 95%, CI = -0.08, 0.48). Bias estimates indicated smaller studies reported larger effect sizes favouring ketamine. The only consistent timepoint assessed across RCTs was 24-hours post-initial infusion. Effects at 24-hours post-initial infusion suggest ketamine has a small relative advantage over controls (g = 0.35, 95% CI = 0.06, 0.64). Post-hoc analyses at 24-hours post-initial infusion indicated that ketamine was significantly better than passive controls (g = 0.44, 95% CI = 0.03, 0.85), but not active controls (g = 0.24, 95% CI = -0.30, 0.78). Comparisons one-week into intervention suggested no meaningful group differences (g = 0.24, 95% CI = 0.00, 0.48). No significant differences were evident for RCTs that examined effects two-weeks post initial infusion (g = 0.17, 95% CI = -0.10, 0.44).Conclusions: Altogether, ketamine-for-PTSD RCTs reveal a nominal initial therapeutic advantage relative to controls. However, bias and heterogeneity appear problematic. While rapid acting effects were observed, all control agents (including saline) also evidenced rapid acting effects. We argue blind penetration to be a serious concern, and that placebo is the likely mechanism behind reported therapeutic effects.

We systematically reviewed and meta-analysed all randomized control trials of ketamine intervention for PTSD.While ketamine was associated with a reduction in symptoms, the effect was generally not stronger than control conditions.By two-weeks post-initial infusion, no meaningful differences are evident between ketamine and controls.

Systematic review of dynamization vs exchange nailing for delayed/non-union femoral fractures.

AIM: To analyze the literature on efficacy of dynamamization vs exchange nailing in treatment of delayed and non-union femur fractures. METHODS: Ultimately, 31 peer-reviewed articles with 644 exchanged nailing patients and 131 dynamization patients were identified and analyzed. The following key words were inputted in different combinations in order to search the field of publications in its entirety: "non-union", "delayed union", "ununited", "femur fracture", "femoral fracture", "exchange nailing", "dynaiz(s)ation", "secondary nailing", "dynamic", "static", and "nail revision". The initial search yielded over 150 results, and was refined based on the inclusion criteria: Only studies reporting on humans, non-unions and delayed unions, and the usage of exchange nailing and/or dynamization as a secondary treatment after failed IM nailing. The resulting 66 articles were obtained through online journal access. The results were filtered further based on the exclusion criteria: No articles that failed to report overall union rates, differentiate between success rates of their reported techniques, or articles that analyzed less than 5 patients. RESULTS: Exchange nailing lead to fracture union in 84.785% of patients compared to the 66.412% of dynamization with statistically comparable durations until union (5.193 ± 2.310 mo and 4.769 ± 1.986 mo respectively). Dynamically locking exchange nails resulted in an average union time of 5.208 ± 2.475 mo compared to 5.149 ± 2.366 mo (P = 0.8682) in statically locked exchange nails. The overall union rate of the two procedures, statically and dynamically locked exchange nailing yielded union rates of 84.259% and 82.381% respectively. Therefore, there was no significant difference between the different locking methods of exchange nailing for union rate or time to union at a significance value of P < 0.05. The analysis showed exchange nailing to be the more successful choice in the treatment of femoral non-unions in respect to its higher success rate (491/567 EN, 24/57 dynam, P < 0.0001). However, there was no significant difference between the success rates of the two procedures for delayed union fractures (25/27 EN, 45/55 dynam, P = 0.3299). Nevertheless, dynamization was more efficient in the treatment of delayed unions (at rates comparable to exchange nailing) than in the treatment of non-unions. CONCLUSION: In conclusion, after examination of factors, dynamization is recommended treatment of delayed femur fractures, while exchange nailing is the treatment of choice for non-unions.

iPhemap: an atlas of phenotype to genotype relationships of human iPSC models of neurological diseases.

Disease modeling with induced pluripotent stem cells (iPSCs) is creating an abundance of phenotypic information that has become difficult to follow and interpret. Here, we report a systematic analysis of research practices and reporting bias in neurological disease models from 93 published articles. We find heterogeneity in current research practices and a reporting bias toward certain diseases. Moreover, we identified 663 CNS cell-derived phenotypes from 243 patients and 214 controls, which varied by mutation type and developmental stage in vitro We clustered these phenotypes into a taxonomy and characterized these phenotype-genotype relationships to generate a phenogenetic map that revealed novel correlations among previously unrelated genes. We also find that alterations in patient-derived molecular profiles associated with cellular phenotypes, and dysregulated genes show predominant expression in brain regions with pathology. Last, we developed the iPS cell phenogenetic map project atlas (iPhemap), an open submission, online database to continually catalog disease phenotypes. Overall, our findings offer new insights into the phenogenetics of iPSC-derived models while our web tool provides a platform for researchers to query and deposit phenotypic information of neurological diseases.