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ObjectivePrioritisation of important treatment uncertainties for ‘Common Conditions Affecting the Hand and Wrist’ via a UK-based James Lind Alliance Priority Setting Partnership.SettingThis process was funded by a national charitable organisation and based in the UK.ParticipantsAnyone with experience of common conditions affecting the adult hand and wrist, including patients, carers and healthcare professionals. All treatment modalities delivered by a hand specialist, including therapists, surgeons or other allied professionals, were considered.InterventionsEstablished James Lind Alliance Priority Setting Partnership methods were employed.Electronic and paper questionnaires identified potential uncertainties. These were subsequently confirmed using relevant, up-to-date systematic reviews. A final list of top 10 research uncertainties was developed via a face-to-face workshop with representation from patients and clinicians. Impact of research was sought by surveying hand clinicians electronically.Outcome measuresThe survey responses and prioritisation—both survey and workshop based.ResultsThere were 889 individually submitted questions from the initial survey, refined to 59 uncertainties across 32 themes. Eight additional uncertainties were added from published literature before prioritisation by 261 participants and the workshop allowed the final top 10 list to be finalised. The top 10 has so far contributed to the award of over £3.8 million of competitively awarded funding.ConclusionsThe Common Conditions in the Hand and Wrist Priority Setting Partnership identified important research questions and has allowed research funders to identify grant applications which are important to both patients and clinicians

Background Dupuytren's disease is a progressive fibroproliferative disorder which can result in fixed flexion contractures of digits and impaired hand function. Standard treatment involves surgical release or excision followed by post-operative hand therapy and splinting, however the evidence supporting night splinting is of low quality and equivocal. Methods A multi-centre, pragmatic, open, randomised controlled trial was conducted to evaluate the effect of night splinting on self-reported function, finger extension and satisfaction in patients undergoing fasciectomy or dermofasciectomy. 154 patients from 5 regional hospitals were randomised after surgery to receive hand therapy only (n = 77) or hand therapy with night-splinting (n = 77). Primary outcome was self-reported function using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. Secondary outcomes were finger range of motion and patient satisfaction. Primary analysis was by intention to treat. Results 148 (96%) patients completed follow-up at 12 months. No statistically significant differences were observed on the DASH questionnaire (0-100 scale: adjusted mean diff. 0.66, 95%CI - 2.79 to 4.11, p = 0.703), total extension deficit of operated digits (degrees: adjusted mean diff 5.11, 95%CI -2.33 to 12.55, p = 0.172) or patient satisfaction (0-10 numerical rating scale: adjusted mean diff -0.35, 95%CI -1.04 to 0.34, p = 0.315) at 1 year post surgery. Similarly, in a secondary per protocol analysis no statistically significant differences were observed between the groups in any of the outcomes. Conclusions No differences were observed in self-reported upper limb disability or active range of motion between a group of patients who were all routinely splinted after surgery and a group of patients receiving hand therapy and only splinted if and when contractures occurred. Given the added expense of therapists' time, thermoplastic materials and the potential inconvenience to patients having to wear a device, the routine addition of night-time splinting for all patients after fasciectomy or dermofasciectomy is not recommended except where extension deficits reoccur. Trial registration The trial was registered as an International Standard Randomised Controlled Trial ISRCTN57079614

Retrospective Cohort. There is currently no validated patient reported outcome measure (PROM) for Dupuytren's disease. We have performed a retrospective analysis of QuickDASH scores taken before and after surgery for Dupuytren's disease to assess the validity and responsiveness of the QuickDASH and evaluate its suitability to being a PROM for this condition. To determine the eligibility of the QuickDASH score as a Patient Reported Outcome Measure for Dupuytren's disease. Patients were identified from the hand therapy database that had surgery performed between January 2006 and April 2008 who had documented pre- and post-operative QuickDASH scores. 69 patients were identified with complete datasets with a mean change in QuickDASH score of −7.14 (p < 0.001) and an improvement of extension deficit by 68.1 degrees (p < 0.001) at a mean 110 day follow-up. The change in QuickDASH score did not correlate with the change in extension deficit. The effect size was 0.545 and the standardised response mean was 0.580. The QuickDASH is an acceptable PROM for Dupuytren's surgery with limitations. Further research is needed examining PROMs with this common condition. n/a.

The purpose of the study was to explore the relationship between preoperative flexion contracture (FC) and self-reported disability in patients undergoing surgical release by fasciectomy or dermofasciectomy. The study design used was a prospective observational study: Dupuytren’s disease (DD) is a fibroproliferative disorder of the palmar fascia and may lead to functional deficits requiring surgical intervention. Outcomes are usually reported using digital range of motion although recent studies have also included patient-rated outcome measures with the extensively validated Disabilities of the Arm, Shoulder, and Hand (DASH) Questionnaire commonly used. One hundred fifty-four patients consecutively enrolled in a prospective randomized trial were assessed before surgery for active range of movement using goniometry and self-reported functioning using DASH questionnaire. The small finger was affected in 69% of patients with a mean FC of 77.8 degrees (standard deviation = 43.5°). The mean DASH score was 16 points (range, 0–62). The correlation between severity of FC in all four fingers and DASH was weak ( r = 0.264, p = 0.001). At individual digital level, the correlation between FC and DASH was weak in the index ( r = 0.26), middle ( r = 0.28), and ring ( r = 0.21) fingers but almost absent in the small finger ( r = 0.07). These results show that the relationship between severity of FC and functional disability measured by the DASH questionnaire appear to be very weak or even absent. Level of evidence: Level III prospective cohort study.

To say that \"the people lying in shop doorways and parkades around Victoria are not a problem for folks living in Oak Bay or Saanich or the Highlands\" is ludicrous. I have been a Saanich police telecommunications operator for the past 14 years and, over the past year, have taken daily reports from Saanich and Oak Bay residents on various problems with the homeless in our communities.

Surface acoustic wave (SAW) sensors can rapidly detect Ebola antigens at the point-of-care without the need for added reagents, sample processing, or specialized personnel. This preliminary study demonstrates SAW biosensor detection of the Ebola virus in a concentration-dependent manner. The detection limit with this methodology is below the average level of viremia detected on the first day of symptoms by PCR. We observe a log-linear sensor response for highly fragmented Ebola viral particles, with a detection limit corresponding to 1.9 × 104 PFU/mL prior to virus inactivation. We predict greatly improved sensitivity for intact, infectious Ebola virus. This point-of-care methodology has the potential to detect Ebola viremia prior to symptom onset, greatly enabling infection control and rapid treatment. This biosensor platform is powered by disposable AA batteries and can be rapidly adapted to detect other emerging diseases in austere conditions.

Anna Andersson, Tanja Gruber, James Downing and colleagues report a genomic analysis of infant acute lymphoblastic leukemias with MLL rearrangements. They identify recurrent activating mutations in tyrosine kinase, phosphatidylinositol 3-kinase and RAS pathway genes but find that these mutations were often present in minor subclones and lost at the time of relapse. Infant acute lymphoblastic leukemia (ALL) with MLL rearrangements ( MLL -R) represents a distinct leukemia with a poor prognosis. To define its mutational landscape, we performed whole-genome, exome, RNA and targeted DNA sequencing on 65 infants (47 MLL -R and 18 non– MLL -R cases) and 20 older children ( MLL -R cases) with leukemia. Our data show that infant MLL -R ALL has one of the lowest frequencies of somatic mutations of any sequenced cancer, with the predominant leukemic clone carrying a mean of 1.3 non-silent mutations. Despite this paucity of mutations, we detected activating mutations in kinase-PI3K-RAS signaling pathway components in 47% of cases. Surprisingly, these mutations were often subclonal and were frequently lost at relapse. In contrast to infant cases, MLL -R leukemia in older children had more somatic mutations (mean of 6.5 mutations/case versus 1.3 mutations/case, P = 7.15 × 10 −5 ) and had frequent mutations (45%) in epigenetic regulators, a category of genes that, with the exception of MLL , was rarely mutated in infant MLL -R ALL.

The broadnose sevengill shark, Notorynchus cepedianus, a common coastal species in the eastern North Pacific, was sampled during routine capture and tagging operations conducted from 2005-2012. One hundred and thirty three biopsy samples were taken during these research operations in Willapa Bay, Washington and in San Francisco Bay, California. Genotypic data from seven polymorphic microsatellites (derived from the related sixgill shark, Hexanchus griseus) were used to describe N. cepedianus genetic diversity, population structure and relatedness. Diversity within N. cepedianus was found to be low to moderate with an average observed heterozygosity of 0.41, expected heterozygosity of 0.53, and an average of 5.1 alleles per microsatellite locus. There was no evidence of a recent population bottleneck based on genetic data. Analyses of genetic differences between the two sampled estuaries suggest two distinct populations with some genetic mixing of sharks sampled during 2005-2006. Relatedness within sampled populations was high, with percent relatedness among sharks caught in the same area indicating 42.30% first-order relative relationships (full or half siblings). Estuary-specific familial relationships suggest that management of N. cepedianus on the U.S. West Coast should incorporate stock-specific management goals to conserve this ecologically important predator.

Primary open angle glaucoma (POAG) is a complex disease and is one of the major leading causes of blindness worldwide. Genome-wide association studies have successfully identified several common variants associated with glaucoma; however, most of these variants only explain a small proportion of the genetic risk. Apart from the standard approach to identify main effects of variants across the genome, it is believed that gene-gene interactions can help elucidate part of the missing heritability by allowing for the test of interactions between genetic variants to mimic the complex nature of biology. To explain the etiology of glaucoma, we first performed a genome-wide association study (GWAS) on glaucoma case-control samples obtained from electronic medical records (EMR) to establish the utility of EMR data in detecting non-spurious and relevant associations; this analysis was aimed at confirming already known associations with glaucoma and validating the EMR derived glaucoma phenotype. Our findings from GWAS suggest consistent evidence of several known associations in POAG. We then performed an interaction analysis for variants found to be marginally associated with glaucoma (SNPs with main effect p-value <0.01) and observed interesting findings in the electronic MEdical Records and GEnomics Network (eMERGE) network dataset. Genes from the top epistatic interactions from eMERGE data (Likelihood Ratio Test i.e. LRT p-value <1e-05) were then tested for replication in the NEIGHBOR consortium dataset. To replicate our findings, we performed a gene-based SNP-SNP interaction analysis in NEIGHBOR and observed significant gene-gene interactions (p-value <0.001) among the top 17 gene-gene models identified in the discovery phase. Variants from gene-gene interaction analysis that we found to be associated with POAG explain 3.5% of additional genetic variance in eMERGE dataset above what is explained by the SNPs in genes that are replicated from previous GWAS studies (which was only 2.1% variance explained in eMERGE dataset); in the NEIGHBOR dataset, adding replicated SNPs from gene-gene interaction analysis explain 3.4% of total variance whereas GWAS SNPs alone explain only 2.8% of variance. Exploring gene-gene interactions may provide additional insights into many complex traits when explored in properly designed and powered association studies.

Background Chronic medical diseases require regular and longitudinal care and self-management for effective treatment. When chronic diseases include substance use disorders, care and treatment of both the medical and addiction disorders may affect access to care and the ability to focus on both conditions. The objective of this paper is to evaluate the association between the presence of chronic medical disease and recent addiction treatment utilization among adults with substance dependence. Methods Cross-sectional secondary data analysis of self-reported baseline data from alcohol and/or drug-dependent adults enrolled in a randomized clinical trial of a disease management program for substance dependence in primary care. The main independent variable was chronic medical disease status, categorized using the Katz Comorbidity Score as none, single condition of lower severity, or higher severity (multiple conditions or single higher severity condition), based on comorbidity scores determined from self-report. Asthma was also examined in secondary analyses. The primary outcome was any self-reported addiction treatment utilization (excluding detoxification) in the 3 months prior to study entry, including receipt of any addiction-focused counseling or addiction medication from any healthcare provider. Logistic regression models were adjusted for sociodemographics, type of substance dependence, recruitment site, current smoking, and recent anxiety severity. Results Of 563 subjects, 184 (33%) reported any chronic disease (20% low severity; 13% higher severity) and 111 (20%) reported asthma; 157 (28%) reported any addiction treatment utilization in the past 3 months. In multivariate regression analyses, no significant effect was detected for chronic disease on addiction treatment utilization (adjusted odds ratio [AOR] 0.88 lower severity vs. none, 95% confidence interval (CI): 0.60, 1.28; AOR 1.29 higher severity vs. none, 95% CI: 0.89, 1.88) nor for asthma. Conclusions In this cohort of alcohol and drug dependent persons, there was no significant effect of chronic medical disease on recent addiction treatment utilization. Chronic disease may not hinder or facilitate connection to addiction treatment.