Effect of two behavioural 'nudging' interventions on management decisions for low back pain: A randomised vignette-based study in general practitioners

Objective €Nudges' are subtle cognitive cues thought to influence behaviour. We investigated whether embedding nudges in a general practitioner (GP) clinical decision support display can reduce low-value management decisions. Methods Australian GPs completed four clinical vignettes of patients with low back pain. Participants chose from three guideline-concordant and three guideline-discordant (low-value) management options for each vignette, on a computer screen. A 2×2 factorial design randomised participants to two possible nudge interventions: €partition display' nudge (low-value options presented horizontally, high-value options listed vertically) or €default option' nudge (high-value options presented as the default, low-value options presented only after clicking for more). The primary outcome was the proportion of scenarios where practitioners chose at least one of the low-value care options. Results 120 GPs (72% male, 28% female) completed the trial (n=480 vignettes). Participants using a conventional menu display without nudges chose at least one low-value care option in 42% of scenarios. Participants exposed to the default option nudge were 44% less likely to choose at least one low-value care option (OR 0.56, 95%CI 0.37 to 0.85; p=0.006) compared with those not exposed. The partition display nudge had no effect on choice of low-value care (OR 1.08, 95%CI 0.72 to 1.64; p=0.7). There was no interaction between the nudges (OR 0.94, 95% CI 0.41 to 2.15; p=0.89). Interpretation A default option nudge reduced the odds of choosing low-value options for low back pain in clinical vignettes. Embedding high value options as defaults in clinical decision support tools could improve quality of care. More research is needed into how nudges impact clinical decision-making in different contexts

The Modern Universal Total Knee Arthroplasty: Maximized Value, Streamlined Efficiency

A universal total knee arthroplasty system able to accurately resurface either left or right knees of all shapes and sizes is compelling as there is an increased need for improved efficiency and value. With a modern universal total knee system, a single instrument tray can be utilized for more than 90% of cases and doesn’t require any specific customization or disposable instruments. This streamlined workflow is accomplished with unique instrumentation that features a symmetrical femoral and tibial implant for all patients. Symmetrical tibial implants have been shown to have equivalent outcomes and low complications compared to asymmetric tibial trays. The universal symmetrical femoral implant, with its deepened trochlear groove, allows for optimal patellar tracking and recent studies have demonstrated this symmetrical femoral implant to have comparable femoral rollback and axial rotation to native knees. This efficient instrumentation reduces overall inventory, decreases turnover times, and exposes fewer instruments that may otherwise be susceptible to contamination. All without detriment to the patient outcome or surgeon workflow. Studies have shown clinical scores of the modern universal total knee arthroplasty system are a great value not only to the surgeon but also to the healthcare system as a whole—a necessity in modern healthcare

Reconceptualizing the English Lounge with Maker Duty

資料・研究ノー

Behavioral and psychological symptoms of dementia: The effects of physical activity at adult day service centers

Adult day services (ADS) are an increasingly popular option for caregivers of people with dementia, but there is little research on the effects of activities on the behavior and mood of the client. This study examines participation by 94 individuals in different types of adult day-care activities and their association with changes in behavior and psychological symptoms of dementia (BPSD) for the client during a three-month span. Three domains of BPSD were examined: restless behaviors, mood behaviors, and positive behaviors. Using growth curve modeling, results show that the restless and mood behavior domains, on average, were stable over three months, whereas positive behaviors increased. For all three behavior domains there were individual differences in average level of BPSD. Average rate of change for individuals also varied from the mean for restless and mood behaviors. Physical activities, social activities, engaging activities, and watching and listening activities, along with a day-care dosage variable, were used as covariates to explain these individual differences in change. Engaging activities explained some of the individual variance for restless behaviors; as individuals increased one increment in engaging activities, they had fewer restless behavior problems over time. These results suggest that some features of programming may be related to improvements in restless behavior

Tumor immune infiltration estimated from gene expression profiles predicts colorectal cancer relapse

A substantial fraction of patients with stage I-III colorectal adenocarcinoma (CRC) experience disease relapse after surgery with curative intent. However, biomarkers for predicting the likelihood of CRC relapse have not been fully explored. Therefore, we assessed the association between tumor infiltration by a broad array of innate and adaptive immune cell types and CRC relapse risk. We implemented a discovery-validation design including a discovery dataset from Moffitt Cancer Center (MCC; Tampa, FL) and three independent validation datasets: (1) GSE41258 (2) the Molecular Epidemiology of Colorectal Cancer (MECC) study, and (3) GSE39582. Infiltration by 22 immune cell types was inferred from tumor gene expression data, and the association between immune infiltration by each cell type and relapse-free survival was assessed using Cox proportional hazards regression. Within each of the four independent cohorts, CD4+ memory activated T cell (HR: 0.93, 95% CI: 0.90-0.96; FDR = 0.0001) infiltration was associated with longer time to disease relapse, independent of stage, microsatellite instability, and adjuvant therapy. Based on our meta-analysis across the four datasets, 10 innate and adaptive immune cell types associated with disease relapse of which 2 were internally validated using multiplex immunofluorescence. Moreover, immune cell type infiltration was a better predictors of disease relapse than Consensus Molecular Subtype (CMS) and other expression-based biomarkers (Immune-AICMCC:238.1-238.9; CMS-AICMCC: 241.0). These data suggest that transcriptome-derived immune profiles are prognostic indicators of CRC relapse and quantification of both innate and adaptive immune cell types may serve as candidate biomarkers for predicting prognosis and guiding frequency and modality of disease surveillance

Upfront Biology-Guided Therapy in Diffuse Intrinsic Pontine Glioma: Therapeutic, Molecular, and Biomarker Outcomes from PNOC003

PURPOSE PNOC003 is a multicenter precision medicine trial for children and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG). PATIENTS AND METHODS Patients (3-25 years) were enrolled on the basis of imaging consistent with DIPG. Biopsy tissue was collected for whole-exome and mRNA sequencing. After radiotherapy (RT), patients were assigned up to four FDA-approved drugs based on molecular tumor board recommendations. H3K27M-mutant circulating tumor DNA (ctDNA) was longitudinally measured. Tumor tissue and matched primary cell lines were characterized using whole-genome sequencing and DNA methylation profiling. When applicable, results were verified in an independent cohort from the Children's Brain Tumor Network (CBTN). RESULTS Of 38 patients enrolled, 28 patients (median 6 years, 10 females) were reviewed by the molecular tumor board. Of those, 19 followed treatment recommendations. Median overall survival (OS) was 13.1 months [95% confidence interval (CI), 11.2-18.4] with no difference between patients who followed recommendations and those who did not. H3K27M-mutant ctDNA was detected at baseline in 60% of cases tested and associated with response to RT and survival. Eleven cell lines were established, showing 100% fidelity of key somatic driver gene alterations in the primary tumor. In H3K27-altered DIPGs, TP53 mutations were associated with worse OS (TP53mut 11.1 mo; 95% CI, 8.7-14; TP53wt 13.3 mo; 95% CI, 11.8-NA; P = 3.4e-2), genome instability (P = 3.1e-3), and RT resistance (P = 6.4e-4). The CBTN cohort confirmed an association between TP53 mutation status, genome instability, and clinical outcome. CONCLUSIONS Upfront treatment-naïve biopsy provides insight into clinically relevant molecular alterations and prognostic biomarkers for H3K27-altered DIPGs

Stigma in the health clinic and implications for PrEP access and use by adolescent girls and young women : conflicting perspectives in South Africa

DATA AVAILABILITY : Data and materials are available on request from Dr. Wendee Wechsberg at [email protected] : Globally, an urgent need exists to expand access to HIV prevention among adolescent girls and young women (AGYW), but the need is particularly acute in sub-Saharan Africa. Oral pre-exposure prophylaxis (PrEP) offers an effective HIV prevention method. In many countries, however, accessing PrEP necessitates that AGYW visit their local health clinic, where they may face access challenges. Some countries have implemented youth-friendly services to reduce certain challenges in local health clinics, but barriers to access persist, including clinic stigma. However, evidence of clinic stigma toward AGYW, particularly with respect to PrEP service delivery, is still limited. This mixed methods study explores stigma toward AGYW seeking clinic services, in particular PrEP, from the perspective of both clinic staff (clinical and nonclinical) and AGYW who seek services at clinic sites in Tshwane province, South Africa. METHODS : Six focus group discussions were conducted with AGYW (43 total participants) and four with clinic staff (42 total participants) and triangulated with survey data with AGYW (n = 449) and clinic staff (n = 130). Thematic analysis was applied to the qualitative data and descriptive statistics were conducted with the survey data. RESULTS : Four common themes emerged across the qualitative and quantitative data and with both AGYW and clinic staff, although with varying degrees of resonance between these two groups. These themes included (1) clinic manifestations of stigma toward AGYW, (2) concerns about providing PrEP services for AGYW, (3) healthcare providers’ identity as mothers, and (4) privacy and breaches of confidentiality. An additional theme identified mainly in the AGYW data pertained to stigma and access to healthcare. CONCLUSION : Evidence is needed to inform strategies for addressing clinic stigma toward AGYW, with the goal of removing barriers to PrEP services for this group. While awareness has increased and progress has been achieved around the provision of comprehensive, youth-friendly sexual and reproductive health services, these programs need to be adapted for the specific concerns of young people seeking PrEP services. Our findings point to the four key areas noted above where programs seeking to address stigma toward AGYW in clinics can tailor their programming.The Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health.http://www.biomedcentral.com/bmcpublichealtham2023Medical Microbiolog

TCEAL1 Loss-of-Function Results in an X-Linked Dominant Neurodevelopmental Syndrome and Drives the Neurological Disease Trait in Xq222 Deletions

An Xq22.2 region upstream of PLP1 has been proposed to underly a neurological disease trait when deleted in 46,XX females. Deletion mapping revealed that heterozygous deletions encompassing the smallest region of overlap (SRO) spanning six Xq22.2 genes (BEX3, RAB40A, TCEAL4, TCEAL3, TCEAL1, and MORF4L2) associate with an early-onset neurological disease trait (EONDT) consisting of hypotonia, intellectual disability, neurobehavioral abnormalities, and dysmorphic facial features. None of the genes within the SRO have been associated with monogenic disease in OMIM. Through local and international collaborations facilitated by GeneMatcher and Matchmaker Exchange, we have identified and herein report seven de novo variants involving TCEAL1 in seven unrelated families: three hemizygous truncating alleles; one hemizygous missense allele; one heterozygous TCEAL1 full gene deletion; one heterozygous contiguous deletion of TCEAL1, TCEAL3, and TCEAL4; and one heterozygous frameshift variant allele. Variants were identified through exome or genome sequencing with trio analysis or through chromosomal microarray. Comparison with previously reported Xq22 deletions encompassing TCEAL1 identified a more-defined syndrome consisting of hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features include strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies. An additional maternally inherited hemizygous missense allele of uncertain significance was identified in a male with hypertonia and spasticity without syndromic features. These data provide evidence that TCEAL1 loss of function causes a neurological rare disease trait involving significant neurological impairment with features overlapping the EONDT phenotype in females with the Xq22 deletion