Systematic review of rehabilitation intervention outcomes of adult and paediatric patients with infectious encephalitis.

OBJECTIVE: Although a range of rehabilitation interventions have been applied to restore function after infectious encephalitis, there is a lack of literature summarising the benefits of these interventions. This systematic review aims to synthesise current scientific knowledge on outcome measures following rehabilitative interventions among children and adults with infectious encephalitis, with a specific focus on the influence of the age, sex, baseline status and intervention type. SEARCH STRATEGY: Five scholarly databases (MEDLINE, Embase, PsycINFO, CINAHL and Cochrane Central Register of Controlled Trials), three sources of grey literature (Google, Google Scholar and Grey Matters) and reference lists of included publications were systematically searched. Literature published before 15 December 2017 and focused on patients with infectious encephalitis in any rehabilitation setting were included. Quality assessment was completed using the Downs and Black rating scale. RESULTS: Of the 12 737 reference titles screened, 20 studies were included in this review. All of the studies had sample sizes of less than 25 patients and received a score of less than 15 out of 31 points on the Downs and Black rating scale. Findings showed a variety of interventions has been applied to alleviate sequelae from infectious encephalitis, including using cognitive therapy (nine studies), behavioural therapy (five studies), physical therapy (two studies) or two or more therapies (four studies). There was inconclusive evidence on the effect of sex, age and baseline functional abilities on outcomes. Due to clinical and methodological heterogeneity between studies, meta-analyses were not performed. CONCLUSION: Evidence suggests the potential for a beneficial effect of rehabilitation interventions in patients with infectious encephalitis. Future research is required to identify all effect modifiers and to determine the effect of time in the natural course of recovery. An enhanced set of known effect modifiers will support the process of future evaluation of a client-centred rehabilitation intervention. TRIAL REGISTRATION NUMBER: CRD42015029217.

Genetic contribution to lipid levels in early life based on 158 loci validated in adults: the FAMILY study.

The contribution of polymorphisms associated with adult lipids in early life is unknown. We studied 158 adult lipid polymorphisms in 1440 participants (544 children, 544 mothers and 324 fathers) of the Family Atherosclerosis Monitoring In early life (FAMILY) birth cohort. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) measurements were collected at birth, 3 and 5 years of age. Polymorphisms were genotyped using the Illumina Cardio-Metabochip array. Genotype scores (GS) were calculated for TC, HDL-C, LDL-C and TG. Linear and mixed-effects regressions adjusted for sex, age and population stratification were performed. The GS was associated with LDL-C level at 3 and 5 years (ß = 0.017 ± 0.003, P = 2.9 × 10-8; ß = 0.020 ± 0.003, P = 5.7 × 10-9) and from birth to 5 years (ß = 0.013 ± 0.003, P = 2.6 × 10-7). The GS was associated with TC level at 3 and 5 years (ß = 0.009 ± 0.002, P = 9.1 × 10-7; ß = 0.009 ± 0.002, P = 7.7 × 10-6). CETP rs3764261 was associated with the HDL-C level from birth to 5 years (ß = 0.064 ± 0.014, P = 7.4 × 10-6). AMPD3 rs2923084 was associated with the HDL-C level at 5 years (ß = 0.096 ± 0.024, P = 9.7 × 10-5). Known loci associated with blood lipids in adults are associated with TC, LDL-C and HDL-C, but not TG in early life. Genetically predisposed children may benefit from early lipid lowering preventative strategies.

Rehabilitation interventions in children and adults with infectious encephalitis: a systematic review protocol.

INTRODUCTION: Many encephalitis survivors can benefit from rehabilitation. However, there is currently no comprehensive review describing rehabilitation intervention outcomes among children and adults with infectious encephalitis. This is a protocol for a systematic review that will summarise the current literature on outcomes following rehabilitative interventions among children and adults with infectious encephalitis. With a sufficient sample size, a sex-stratified analysis of the findings will also be presented, as variability between male and female patients with neurological disorders, including encephalitis, regarding outcomes after rehabilitative interventions has been noted in the literature. METHODS AND ANALYSIS: This review will systematically search MEDLINE, MEDLINE In-Process, EMBASE, Cochrane Central Register of Controlled Trials, and PsycINFO using the concepts 'encephalitis' and 'rehabilitation'. Grey literature will be searched using Grey Matters: A practical search tool for evidence-based medicine and the Google search engine. In addition, reference lists of eligible articles will be screened for any relevant studies. 2 reviewers will independently evaluate the retrieved studies based on predetermined eligibility criteria and perform a quality assessment on eligible studies. ETHICS AND DISSEMINATION: The results from this review hold the potential to advance our knowledge on the value of rehabilitative interventions targeting children and adults with infectious encephalitis and any sex differences among patients with regard to rehabilitative intervention outcomes. The authors will publish findings from this review in a peer-reviewed scientific journal (electronic and in-print) and present the results at national and international conferences. TRIAL REGISTRATION NUMBER: CRD42015029217.

Should we have blind faith in bioinformatics software? Illustrations from the SNAP web-based tool.

Bioinformatics tools have gained popularity in biology but little is known about their validity. We aimed to assess the early contribution of 415 single nucleotide polymorphisms (SNPs) associated with eight cardio-metabolic traits at the genome-wide significance level in adults in the Family Atherosclerosis Monitoring In earLY Life (FAMILY) birth cohort. We used the popular web-based tool SNAP to assess the availability of the 415 SNPs in the Illumina Cardio-Metabochip genotyped in the FAMILY study participants. We then compared the SNAP output with the Cardio-Metabochip file provided by Illumina using chromosome and chromosomal positions of SNPs from NCBI Human Genome Browser (Genome Reference Consortium Human Build 37). With the HapMap 3 release 2 reference, 201 out of 415 SNPs were reported as missing in the Cardio-Metabochip by the SNAP output. However, the Cardio-Metabochip file revealed that 152 of these 201 SNPs were in fact present in the Cardio-Metabochip array (false negative rate of 36.6%). With the more recent 1000 Genomes Project release, we found a false-negative rate of 17.6% by comparing the outputs of SNAP and the Illumina product file. We did not find any 'false positive' SNPs (SNPs specified as available in the Cardio-Metabochip by SNAP, but not by the Cardio-Metabochip Illumina file). The Cohen's Kappa coefficient, which calculates the percentage of agreement between both methods, indicated that the validity of SNAP was fair to moderate depending on the reference used (the HapMap 3 or 1000 Genomes). In conclusion, we demonstrate that the SNAP outputs for the Cardio-Metabochip are invalid. This study illustrates the importance of systematically assessing the validity of bioinformatics tools in an independent manner. We propose a series of guidelines to improve practices in the fast-moving field of bioinformatics software implementation.