Item reduction of the patient-rated wrist evaluation using decision tree modelling

Background: The aim of this study is to assess the viability of a decision tree version of an often used questionnaire to measure wrist pain and disability, the Patient Rated Wrist Evaluation. Methods: Patient Rated Wrist Evaluation scores were collected from a cohort of 10394 patients who are part of a routine outcome measurement system. A decision tree version of the Patient Rated Wrist Evaluation (PRWE) was created. The intraclass correlation was used to evaluate the inter-version reliability between the original PRWE and the decision tree version. Results: The decision tree reduced the number of questions from 5 to 3 for the pain subscale, and from 10 to 3 for the disability subscale. The intraclass correlation between the original PRWE and the decision tree version was 0.97. The mean difference between the Patient Rated Wrist Evaluation and the decision tree Patient Rated Wrist Evaluation total sumscore was 0.35 (95% CI 9.92–10.62). Conclusions: We found that the decision tree was successful at reducing the items of the Patient Rated Wrist Evaluation from fifteen to only six questions with very high similarity to the scores of the full questionnaire

Better patients’ treatment experiences are associated with better postoperative results in Dupuytren’s disease

This prospective study investigates the extent to which a better experience with healthcare delivery is associated with better postoperative treatment outcomes after surgery for Dupuytren’s contracture. Patients undergoing limited fasciectomy or percutaneous needle fasciotomy for Dupuytren’s contractures completed the Michigan Hand Outcomes Questionnaire before and 3 months after surgery, together with a patient reported experience measu

Response to Conservative Treatment for Thumb Carpometacarpal Osteoarthritis Is Associated With Conversion to Surgery: A Prospective Cohort Study

Background. The current guidelines for treatment of carpometacarpal osteoarthritis recommend starting with conservative treatment before a surgical procedure is considered. Objective. The objective was to investigate how response to conservative treatment, in terms of pain and hand function, influences the hazard that patients convert to surgical treatment. Design. This was a multicenter, prospective cohort study. Methods. Participants comprised 701 patients who received 3 months of hand therapy and an orthosis. Pain and function were measured with the Michigan Hand Questionnaire (MHQ) at baseline and at 6 weeks and 3 months follow-up. Conversion to surgical treatment was recorded from clinical records. Joint modeling (a statistical method of combining prediction models) was used to perform the analysis and to calculate hazard ratios (HRs). Results. The joint analytical model showed that both MHQ pain score at a certain point (HR = 0.93; 95% confidence interval [CI] = 0.92–0.94) and change in MHQ pain score (HR = 1.07; 95% CI = 1.06–1.09) during conservative treatment was significantly associated with conversion to surgical treatment. The joint analytical model between functional outcome and conversion to surgical treatment showed only a significant association between MHQ function at a certain point (HR = 0.97; 95% CI = 0.95–0.99), and no significant association between the change in MHQ score for function (HR = 1.0; 95% CI = 1.0–1.0) and conversion to surgical treatment. Limitations. Missing data might have resulted in biased estimates. Conclusions. Self-reported pain and function, as well as change in self-reported pain during treatment, were associated with the hazard of conversion to surgical treatment, whereas change in self-reported functioning was not associated with conversion. Because a reduction in pain during conservative treatment appears to decrease the rate of conversion to surgical treatment, it is advised to structurally monitor pain levels during treatment

Positive experience with treatment is associated with better surgical outcome in trapeziometacarpal osteoarthritis

The aim of this study was to investigate the association between patients’ experiences with trapeziometacarpal arthroplasty and treatment outcomes in terms of patient-reported outcome measures, grip and pinch strength. We included 233 patients who received a Weilby procedure for trapeziometacarpal osteoarthritis. Before surgery and 12 months after surgery, patients completed the Michigan Hand Outcomes Questionnaire, and their pinch and grip strengths were measured. At 3 months after surgery, a patient-reported experience measure was completed. Using regression analysis, significantly positive associations were found between the Michigan Hand questionnaire and the patient-reported experience measure, with the strongest significant associations being for patients’ experiences with information provision. No significant associations were found between the patients’ experience and strength outcomes. The results highlight the potential importance of positive experience with the treatment process to improve treatment outcomes in patients undergoing surgery for trapeziometacarpal osteoarthritis. Level of evidence: IV

Randomness Increases Order in Biological Evolution

n this text, we revisit part of the analysis of anti-entropy in Bailly and Longo (2009} and develop further theoretical reflections. In particular, we analyze how randomness, an essential component of biological variability, is associated to the growth of biological organization, both in ontogenesis and in evolution. This approach, in particular, focuses on the role of global entropy production and provides a tool for a mathematical understanding of some fundamental observations by Gould on the increasing phenotypic complexity along evolution. Lastly, we analyze the situation in terms of theoretical symmetries, in order to further specify the biological meaning of anti-entropy as well as its strong link with randomness

Autosomal genetic variation is associated with DNA methylation in regions variably escaping X-chromosome inactivation

X-chromosome inactivation (XCI), i.e., the inactivation of one of the female X chromosomes, restores equal expression of X-chromosomal genes between females and males. However, ~10% of genes show variable degrees of escape from XCI between females, although little is known about the causes of variable XCI. Using a discovery data-set of 1867 females and 1398 males and a replication sample of 3351 females, we show that genetic variation at three autosomal loci is associated with female-specific changes in X-chromosome methylation. Through cis-eQTL expression analysis, we map these loci to the genes SMCHD1/METTL4, TRIM6/HBG2, and ZSCAN9. Low-expression alleles of the loci are predominantly associated with mild hypomethylation of CpG islands near genes known to variably escape XCI, implicating the autosomal genes in variable XCI. Together, these results suggest a genetic basis for variable escape from XCI and highlight the potential of a population genomics approach to identify genes involved in XCI

Skewed X-inactivation is common in the general female population

X-inactivation is a well-established dosage compensation mechanism ensuring that X-chromosomal genes are expressed at comparable levels in males and females. Skewed X-inactivation is often explained by negative selection of one of the alleles. We demonstrate that imbalanced expression of the paternal and maternal X-chromosomes is common in the general population and that the random nature of the X-inactivation mechanism can be sufficient to explain the imbalance. To this end, we analyzed blood-derived RNA and whole-genome sequencing data from 79 female children and their parents from the Genome of the Netherlands project. We calculated the median ratio of the paternal over total counts at all X-chromosomal heterozygous single-nucleotide variants with coverage ≥10. We identified two individuals where the same X-chromosome was inactivated in all cells. Imbalanced expression of the two X-chromosomes (ratios ≤0.35 or ≥0.65) was observed in nearly 50% of the population. The empirically observed skewing is explained by a theoretical model where X-inactivation takes place in an embryonic stage in which eight cells give rise to the hematopoietic compartment. Genes escaping X-inactivation are expressed from both alleles and therefore demonstrate less skewing than inactivated genes. Using this characteristic, we identified three novel escapee genes (SSR4, REPS2, and SEPT6), but did not find support for many previously reported escapee genes in blood. Our collective data suggest that skewed X-inactivation is common in the general population. This may contribute to manifestation of symptoms in carriers of recessive X-linked disorders. We recommend that X-inactivation results should not be used lightly in the interpretation of X-linked variants

Patient Mindset and the Success of Carpal Tunnel Release

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Heparin and heparinoids prevent the binding of immune complexes containing nucleosomal antigens to the GBM and delay nephritis in MRL/lpr mice

Heparin and heparinoids prevent the binding of immune complexes containing nucleosomal antigens to the GBM and delay nephritis in MRL/lpr mice. Monoclonal anti-nucleosome antibodies (mAbs) complexed to nucleosomal antigens can bind to DNA and to heparan sulfate (HS) in ELISA and to the GBM in vivo in a rat renal perfusion system, whereas non-complexed mAbs do not bind [1]. In this study, we analyzed whether heparin (HEP) or N-desulfated/acetylated heparins (DSA-HEP), structurally and functionally strongly related to HS, are able to prevent the binding of these complexed mAbs to DNA and to HS in vitro and to rat GBM in vivo. In ELISA the binding of nucleosome complexed anti-nucleosome antibodies to DNA and HS was inhibited dose-dependently by HEP, DSA-HEP and low molecular weight (LMW) DSA-HEP. Intravenous injection of nucleosome/anti-nucleosome immune complexes without heparin/heparinoids in BALB/c mice led to GBM binding, while simultaneous injection of heparin/heparinoids with complexed antibodies or pretreatment with heparin subcutaneously prior to injection of complexes prevented this binding. Subsequently, we tested the preventive effect of HEP, DSA-HEP and LMW-DSA-HEP on progression of renal disease in MRL/lpr mice. Treatment was started at an age of eight weeks in a dose of 50 µg daily. With all three drugs albuminuria was significantly delayed compared to PBS treated controls (cumulative incidence of proteinuria at 20 weeks in controls 60% vs. 13%, 14% and 6% respectively for HEP, DSA-HEP and LMW-DSA-HEP; P < 0.05). At week 21 the glomerulonephritis was histologically less severe in heparin/heparinoid treated animals (P = 0.02). In immunofluorescence the amount of immunoglobulin and C3 deposits in the glomerular capillary wall tended to be less in heparin/heparinoid treated mice compared to PBS treated controls (P = 0.07). Furthermore, at 20 weeks anti-HS levels in plasma of heparin/heparinoid treated mice were significantly lower (P < 0.05). We conclude that interaction of heparin or heparin analogs with HS reactive immune complexes containing nucleosomal antigens prevents the binding of these immune complexes to the GBM and delays nephritis in MRL/lpr mice