Rehabilitation for patients with sepsis: A systematic review and meta-analysis

<div><p>The objective of this systematic review was to determine whether rehabilitation impacts clinically relevant outcomes among adult patients with sepsis. Randomized controlled trials from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PEDro, and the World Health Organization International Clinical Trials Platform Search Portal, as well as conference proceedings and reference lists of relevant articles were collected. Two reviewers independently identified randomized controlled trials on the rehabilitation of patients with sepsis, and the two reviewers independently abstracted trial level data including population characteristics, interventions, comparisons, and clinical outcomes. Our primary outcomes were quality of life (QOL), activity of daily living (ADL), and mortality. Our secondary outcomes were length of stay, return to work, muscle strength, delirium, and all adverse events. The quality of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We included two trials enrolling 75 patients. The mean difference (95% confidence interval [CI]) of physical function and physical role in QOL measured by SF-36 were 21.10 (95% CI: 6.57–35.63) and 44.40 (95% CI: 22.55–66.05), respectively. Rehabilitation did not significantly decrease intensive care unit (ICU) mortality (risk ratio, 2.02 [95% CI: 0.46–8.91], <i>I</i>² = 0%; n = 75). ICU length of stay and hospital length of stay and muscle strength were not statistically significantly different and no adverse events were reported in both studies. The certainty of the evidence for these outcomes was “very low.” Data on ADL, return to work, and delirium were not available in any of the trials. Rehabilitation of patients with sepsis might not decrease ICU mortality, but might improve QOL. Further, well-designed trials measuring important outcomes will be needed to determine the benefit and harm of rehabilitation among patients with sepsis.</p></div

Summary of findings.

<p>Summary of findings.</p

Assessment of risk of bias in included trials.

<p>Assessment of risk of bias in included trials.</p

Effect of rehabilitation on ICU mortality.

<p>Effect of rehabilitation on ICU mortality.</p

Characteristics of included studies.

<p>Characteristics of included studies.</p

Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow diagram.

<p>Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow diagram.</p

Resequencing and Association Analysis of <i>PTPRA</i>, a Possible Susceptibility Gene for Schizophrenia and Autism Spectrum Disorders

<div><p>Background</p><p>The <i>PTPRA</i> gene, which encodes the protein RPTP-α, is critical to neurodevelopment. Previous linkage studies, genome-wide association studies, controlled expression analyses and animal models support an association with both schizophrenia and autism spectrum disorders, both of which share a substantial portion of genetic risks.</p><p>Methods</p><p>We sequenced the protein-encoding areas of the <i>PTPRA</i> gene for single nucleotide polymorphisms or small insertions/deletions (InDel) in 382 schizophrenia patients. To validate their association with the disorders, rare (minor allele frequency <1%), missense mutations as well as one InDel in the 3′UTR region were then genotyped in another independent sample set comprising 944 schizophrenia patients, 336 autism spectrum disorders patients, and 912 healthy controls.</p><p>Results</p><p>Eight rare mutations, including 3 novel variants, were identified during the mutation-screening phase. In the following association analysis, L59P, one of the two missense mutations, was only observed among patients of schizophrenia. Additionally, a novel duplication in the 3′UTR region, 174620_174623dupTGAT, was predicted to be located within a Musashi Binding Element.</p><p>Major Conclusions</p><p>No evidence was seen for the association of rare, missense mutations in the <i>PTPRA</i> gene with schizophrenia or autism spectrum disorders; however, we did find some rare variants with possibly damaging effects that may increase the susceptibility of carriers to the disorders.</p></div

Targeted sequencing areas of the <i>PTPRA</i> Gene.

<p>Targeted sequencing areas of the <i>PTPRA</i> Gene.</p

In silico functional effect prediction for rs61742029 and L59P.

<p>In silico functional effect prediction for rs61742029 and L59P.</p

Structure of the <i>PTPRA</i> gene, RPTP-α, and position of discovered rare missense mutations.

<p>Structure of the <i>PTPRA</i> gene, RPTP-α, and position of discovered rare missense mutations.</p