Takshan/R1 huggingface dataset:
Associations between the Drug Burden Index, Potentially Inappropriate Medications and Quality of Life in Residential Aged Care.

BACKGROUND: Inappropriate polypharmacy may negatively impact the quality of life of residents in aged care facilities, but it remains unclear which medications may influence this reduced quality of life. OBJECTIVE: The objective of this study was to examine whether the Drug Burden Index and potentially inappropriate medications were associated with quality of life in older adults living in residential care with a high prevalence of cognitive impairment and dementia. METHODS: We conducted cross-sectional analyses of 541 individuals recruited from 17 residential aged care facilities in Australia in the Investigating Services Provided in the Residential Environment for Dementia (INSPIRED) study. Quality of life was measured using the EuroQol Five Dimensions Questionnaire (a measure of generic quality of life) and the Dementia Quality of Life Questionnaire completed by the participant or a proxy. RESULTS: In the 100 days prior to recruitment, 83.1% of the participants received at least one anticholinergic or sedative medication included in the Drug Burden Index and 73.0% received at least one potentially inappropriate medication according to the Beers Criteria. Multi-level linear models showed there was a significant association between a higher Drug Burden Index and lower quality of life according to the EuroQol Five Dimensions Questionnaire [β (standard error): - 0.034 (0.012), p = 0.006] after adjustment for potential confounding factors. Increasing numbers of potentially inappropriate medications were also associated with lower EuroQol Five Dimensions Questionnaire scores [- 0.030 (0.010), p = 0.003] and Dementia Quality of Life Questionnaire-Self-Report-Utility scores [- 0.020 (0.009), p = 0.029]. Exposure to both Drug Burden Index-associated medications and potentially inappropriate medications was associated with lower Dementia Quality of Life Questionnaire-Self-Report-Utility scores [- 0.034 (0.017), p = 0.049]. CONCLUSION: Exposure to anticholinergic and sedative medications and potentially inappropriate medications occurred in over three-quarters of a population of older adults in residential care and was associated with a lower quality of life.
Cost-effectiveness of an internet-based perioperative care programme to enhance postoperative recovery in gynaecological patients: economic evaluation alongside a stepped-wedge cluster-randomised trial.

OBJECTIVES: To evaluate the cost-effectiveness and cost-utility of an internet-based perioperative care programme compared with usual care for gynaecological patients. DESIGN: Economic evaluation from a societal perspective alongside a stepped-wedge cluster-randomised controlled trial with 12 months of follow-up. SETTING: Secondary care, nine hospitals in the Netherlands, 2011-2014. PARTICIPANTS: 433 employed women aged 18-65 years scheduled for a hysterectomy and/or laparoscopic adnexal surgery. INTERVENTION: The intervention comprised an internet-based care programme aimed at improving convalescence and preventing delayed return to work (RTW) following gynaecological surgery and was sequentially rolled out. Depending on the implementation phase of their hospital, patients were allocated to usual care (n=206) or to the intervention (n=227). MAIN OUTCOME MEASURES: The primary outcome was duration until full sustainable RTW. Secondary outcomes were quality-adjusted life years (QALYs), health-related quality of life and recovery. RESULTS: At 12 months, there were no statistically significant differences in total societal costs (€-647; 95% CI €-2116 to €753) and duration until RTW (-4.1; 95% CI -10.8 to 2.6) between groups. The incremental cost-effectiveness ratio (ICER) for RTW was 56; each day earlier RTW in the intervention group was associated with cost savings of €56 compared with usual care. The probability of the intervention being cost-effective was 0.79 at a willingness-to-pay (WTP) of €0 per day earlier RTW, which increased to 0.97 at a WTP of €76 per day earlier RTW. The difference in QALYs gained over 12 months between the groups was clinically irrelevant resulting in a low probability of cost-effectiveness for QALYs. CONCLUSIONS: Considering that on average the costs of a day of sickness absence are €230, the care programme is considered cost-effective in comparison with usual care for duration until sustainable RTW after gynaecological surgery for benign disease. Future research should indicate whether widespread implementation of this care programme has the potential to reduce societal costs associated with gynaecological surgery. TRIAL REGISTRATION NUMBER: NTR2933; Results.
Quality indicators for in-hospital geriatric co-management programmes: a systematic literature review and international Delphi study.

OBJECTIVE: To find consensus on appropriate and feasible structure, process and outcome indicators for the evaluation of in-hospital geriatric co-management programmes. DESIGN: An international two-round Delphi study based on a systematic literature review (searching databases, reference lists, prospective citations and trial registers). SETTING: Western Europe and the USA. PARTICIPANTS: Thirty-three people with at least 2 years of clinical experience in geriatric co-management were recruited. Twenty-eight experts (16 from the USA and 12 from Europe) participated in both Delphi rounds (85% response rate). MEASURES: Participants rated the indicators on a nine-point scale for their (1) appropriateness and (2) feasibility to use the indicator for the evaluation of geriatric co-management programmes. Indicators were considered appropriate and feasible based on a median score of seven or higher. Consensus was based on the level of agreement using the RAND/UCLA Appropriateness Method. RESULTS: In the first round containing 37 indicators, there was consensus on 14 indicators. In the second round containing 44 indicators, there was consensus on 31 indicators (structure=8, process=7, outcome=16). Experts indicated that co-management should start within 24 hours of hospital admission using defined criteria for selecting appropriate patients. Programmes should focus on the prevention and management of geriatric syndromes and complications. Key areas for comprehensive geriatric assessment included cognition/delirium, functionality/mobility, falls, pain, medication and pressure ulcers. Key outcomes for evaluating the programme included length of stay, time to surgery and the incidence of complications. CONCLUSION: The indicators can be used to assess the performance of geriatric co-management programmes and identify areas for improvement. Furthermore, the indicators can be used to monitor the implementation and effect of these programmes.
Impact of geriatric consultation teams on clinical outcome in acute hospitals: a systematic review and meta-analysis.

BACKGROUND: Comprehensive geriatric assessment for older patients admitted to dedicated wards has proven to be beneficial, but the impact of comprehensive geriatric assessment delivered by mobile inpatient geriatric consultation teams remains unclear. This review and meta-analysis aims to determine the impact of inpatient geriatric consultation teams on clinical outcomes of interest in older adults. METHODS: An electronic search of Medline, CINAHL, EMBASE, Web of Science and Invert for English, French and Dutch articles was performed from inception to June 2012. Three independent reviewers selected prospective cohort studies assessing functional status, readmission rate, mortality or length of stay in adults aged 60 years or older. Twelve studies evaluating 4,546 participants in six countries were identified. Methodological quality of the included studies was assessed with the Methodological Index for Non-Randomized Studies. RESULTS: The individual studies show that an inpatient geriatric consultation team intervention has favorable effects on functional status, readmission and mortality rate. None of the studies found an effect on the length of the hospital stay. The meta-analysis found a beneficial effect of the intervention with regard to mortality rate at 6 months (relative risk 0.66; 95% confidence interval 0.52 to 0.85) and 8 months (relative risk 0.51; confidence interval 0.31 to 0.85) after hospital discharge. CONCLUSIONS: Inpatient geriatric consultation team interventions have a significant impact on mortality rate at 6 and 8 months postdischarge, but have no significant impact on functional status, readmission or length of stay. The reason for the lack of effect on these latter outcomes may be due to insufficient statistical power or the insensitivity of the measuring method for, for example, functional status. The questions of to whom IGCT intervention should be targeted and what can be achieved remain unanswered and require further research. TRIAL REGISTRATION: CRD42011001420 (http://www.crd.york.ac.uk/PROSPERO).
Elevated Fibroblast growth factor 21 (FGF21) in obese, insulin resistant states is normalised by the synthetic retinoid Fenretinide in mice.

Fibroblast growth factor 21 (FGF21) has emerged as an important beneficial regulator of glucose and lipid homeostasis but its levels are also abnormally increased in insulin-resistant states in rodents and humans. The synthetic retinoid Fenretinide inhibits obesity and improves glucose homeostasis in mice and has pleotropic effects on cellular pathways. To identify Fenretinide target genes, we performed unbiased RNA-seq analysis in liver from mice fed high-fat diet ± Fenretinide. Strikingly, Fgf21 was the most downregulated hepatic gene. Fenretinide normalised elevated levels of FGF21 in both high-fat diet-induced obese mice and in genetically obese-diabetic Lepr(db)mice. Moreover, Fenretinide-mediated suppression of FGF21 was independent of body weight loss or improved hepatic insulin sensitivity and importantly does not induce unhealthy metabolic complications. In mice which have substantially decreased endogenous retinoic acid biosynthesis, Fgf21 expression was increased, whereas acute pharmacological retinoid treatment decreased FGF21 levels. The repression of FGF21 levels by Fenretinide occurs by reduced binding of RARα and Pol-II at the Fgf21 promoter. We therefore establish Fgf21 as a novel gene target of Fenretinide signalling via a retinoid-dependent mechanism. These results may be of nutritional and therapeutic importance for the treatment of obesity and type-2 diabetes.
Alcohol marketing on YouTube: exploratory analysis of content adaptation to enhance user engagement in different national contexts.

BACKGROUND: We know little about how social media alcohol marketing is utilized for alcohol promotion in different national contexts. There does not appear to be any academic work on online exposure to alcohol marketing via social media in India, and most of the limited research in Australia has focused on Facebook. Hence, the present study extends previous research by investigating alcohol promotion conducted on an under-researched form of social media (YouTube) in two contrasting geographic contexts. This study examines and compares the types of strategies used by marketers on Indian and Australian alcohol brands with the greatest YouTube presence, and the extent to which users engage with these strategies. METHODS: The 10 alcohol brands per country with the greatest YouTube presence were identified based on the number of 'subscriptions'. The number of videos, views per video, and the type of content within the videos were collected for each brand. The data were analyzed using an inductive coding approach, using NVivo 10. RESULTS: The targeted brands had gathered 98,881 subscriptions (Indian brands: n = 13,868; Australian brands: n = 85,013). The type of marketing strategies utilized by brands were a mix of those that differed by country (e.g. sexually suggestive content in India and posts related to the brand's tradition or heritage in Australia) and generic approaches (e.g. encouraging time- and event-specific drinking; demonstrations of food/cocktail recipes; camaraderie; competitions and prize draws; and brand sponsorship at music, sports, and fashion events). CONCLUSIONS: This cross-national comparison demonstrates that YouTube provides alcohol marketers with an advertising platform where they utilize tailored marketing approaches to cater to specific national contexts and develop content on the cultural meanings users invoke in their interactions with these strategies. Those exposed to alcohol marketing on YouTube are likely to include those under the legal drinking age.
Bone mineral density at the hip and its relation to fat mass and lean mass in adolescents: the Tromsø Study, Fit Futures.

BACKGROUND: Positive association between body weight and bone mass is well established, and the concept of body mass index (BMI) is associated with higher areal bone mineral density (aBMD) and reduced fracture risk. BMI, that comprises both fat mass (FM) and lean mass (LM) may contribute to peak bone mass achievement in different ways. This study explored the influence of body composition in terms of total body LM and FM on hip aBMD-values in adolescence. METHODS: In 2010/2011, 93% of the region's first-year upper-secondary school students (15-17 years old) in Tromsø, Norway attended the Tromsø Study, Fit Futures. Areal BMD at femoral neck (aBMDFN) and total hip (aBMDTH) (g/cm2), total body LM and FM (g) were measured by dual energy X-ray absorptiometry (DXA). Height and weight were measured, and BMI calculated. Lifestyle variables were collected by self-administered questionnaires and interviews, including questions on time spent on leisure time physical activity. Stratified analyses of covariance and regression models included 395 girls and 363 boys. Crude results were adjusted for age, height, sexual maturation, physical activity levels, vitamin D levels, calcium intake, alcohol consumption and smoking habits. RESULTS: Unadjusted distribution indicated higher aBMD-levels at higher LM-levels in both genders (p < 0.001), but higher aBMD at higher FM-levels were found only in girls (p < 0.018). After multiple adjustments, aBMDFN-levels in girls were associated by 0.053 g/cm2 and 0.032 g/cm2 per standard deviation (SD) change in LM and FM (p < 0.001). Corresponding values in boys were 0.072 and 0.025 (p < 0.001). The high LM groups accounted for the highest aBMD-levels, while aBMD-levels at the LM/FM-combinations indicated different patterns in girls compared to boys. The adjusted odds ratio (95% CI) for low levels of aBMDFN was 6.6 (3.4,13.0) in boys, compared to 2.8 (1.6,4.9) in girls per SD lower LM. CONCLUSIONS: LM and FM should be regarded as strong predictors for bone mass and hence bone strength in adolescents. A gender specific difference indicated that high lean mass is of crucial importance prominently in boys. In adolescents with low lean mass, especially in girls, high fat mass may partially ameliorate the effect of deficient lean mass levels.
Bastion6: a bioinformatics approach for accurate prediction of type VI secreted effectors.

Motivation: Many Gram-negative bacteria use type VI secretion systems (T6SS) to export effector proteins into adjacent target cells. These secreted effectors (T6SEs) play vital roles in the competitive survival in bacterial populations, as well as pathogenesis of bacteria. Although various computational analyses have been previously applied to identify effectors secreted by certain bacterial species, there is no universal method available to accurately predict T6SS effector proteins from the growing tide of bacterial genome sequence data. Results: We extracted a wide range of features from T6SE protein sequences and comprehensively analyzed the prediction performance of these features through unsupervised and supervised learning. By integrating these features, we subsequently developed a two-layer SVM-based ensemble model with fine-grain optimized parameters, to identify potential T6SEs. We further validated the predictive model using an independent dataset, which showed that the proposed model achieved an impressive performance in terms of ACC (0.943), F-value (0.946), MCC (0.892) and AUC (0.976). To demonstrate applicability, we employed this method to correctly identify two very recently validated T6SE proteins, which represent challenging prediction targets because they significantly differed from previously known T6SEs in terms of their sequence similarity and cellular function. Furthermore, a genome-wide prediction across 12 bacterial species, involving in total 54 212 protein sequences, was carried out to distinguish 94 putative T6SE candidates. We envisage both this information and our publicly accessible web server will facilitate future discoveries of novel T6SEs. Availability and implementation: http://bastion6.erc.monash.edu/. Supplementary information: Supplementary data are available at Bioinformatics online.
Retrospective analysis of insulin responses to standard dosed oral glucose tests (OGTs) via naso-gastric tubing towards definition of an objective cut-off value.

BACKGROUND: Insulin dysregulation (ID) with basal or postprandial hyperinsulinemia is one of the key findings in horses and ponies suffering from the equine metabolic syndrome (EMS). Assessment of ID can easily be performed in clinical settings by the use of oral glucose challenge tests. Oral glucose test (OGT) performed with 1 g/kg bodyweight (BW) glucose administered via naso-gastric tube allows the exact administration of a defined glucose dosage in a short time. However, reliable cut-off values have not been available so far. Therefore, the aim of the study was to describe variations in insulin response to OGT via naso-gastric tubing and to provide a clinical useful cut-off value for ID when using the insulin quantification performed with an equine-optimized insulin enzyme-linked immunosorbent assay. RESULTS: Data visualization revealed no clear separation in the serum insulin concentration of insulin sensitive and insulin dysregulated horses during OGT. Therefore, a model based clustering method was used to circumvent the use of an arbitrary limit for categorization. This method considered all data-points for the classification, taking into account the individual insulin trajectory during the OGT. With this method two clusters were differentiated, one with low and one with high insulin responses during OGT. The cluster of individuals with low insulin response was consistently detected, independently of the initialization parameters of the algorithm. In this cluster the 97.5% quantile of insulin is 110 µLU/mL at 120 min. We suggest using this insulin concentration of 110 µLU/mL as a cut-off value for samples obtained at 120 min in OGT. CONCLUSION: OGT performed with 1 g/kg BW glucose and administration via naso-gastric tubing can easily be performed under clinical settings. Application of the cut-off value of 110 µLU/mL at 120 min allows assessment of ID in horses.
MRI-based Assessment of 3D Intrafractional Motion of Head and Neck Cancer for Radiation Therapy.

PURPOSE: To determine the 3-dimensional (3D) intrafractional motion of head and neck squamous cell carcinoma (HNSCC). METHODS AND MATERIALS: Dynamic contrast-enhanced magnetic resonance images from 56 patients with HNSCC in the treatment position were analyzed. Dynamic contrast-enhanced magnetic resonance imaging consisted of 3D images acquired every 2.9 seconds for 4 minutes 50 seconds. Intrafractional tumor motion was studied in the 3 minutes 43 seconds of images obtained after initial contrast enhancement.  To assess tumor motion, rigid registration (translations only) was performed using a region of interest (ROI) mask around the tumor. The results were compared with bulk body motion from registration to all voxels. Motion was split into systematic motion and random motion. Correlations between the tumor site and random motion were tested. The within-subject coefficient of variation was determined from 8 patients with repeated baseline measures. Random motion was also assessed at the end of the first week (38 patients) and second week (25 patients) of radiation therapy to investigate trends of motion. RESULTS: Tumors showed irregular occasional rapid motion (eg, swallowing or coughing), periodic intermediate motion (respiration), and slower systematic drifts throughout treatment.  For 95% of the patients, displacements due to systematic and random motion were <1.4 mm and <2.1 mm, respectively, 95% of the time. The motion without an ROI mask was significantly (P<.0001, Wilcoxon signed rank test) less than the motion with an ROI mask, indicating that tumors can move independently from the bony anatomy. Tumor motion was significantly (P=.005, Mann-Whitney U test) larger in the hypopharynx and larynx than in the oropharynx. The within-subject coefficient of variation for random motion was 0.33. The average random tumor motion did not increase notably during the first 2 weeks of treatment. CONCLUSIONS: The 3D intrafractional tumor motion of HNSCC is small, with systematic motion <1.4 mm and random motion <2.1 mm 95% of the time.
Applying the ROBINS-I tool to natural experiments: an example from public health.

BACKGROUND: A new tool to assess Risk of Bias In Non-randomised Studies of Interventions (ROBINS-I) was published in Autumn 2016. ROBINS-I uses the Cochrane-approved risk of bias (RoB) approach and focusses on internal validity. As such, ROBINS-I represents an important development for those conducting systematic reviews which include non-randomised studies (NRS), including public health researchers. We aimed to establish the applicability of ROBINS-I using a group of NRS which have evaluated non-clinical public health natural experiments. METHODS: Five researchers, all experienced in critical appraisal of non-randomised studies, used ROBINS-I to independently assess risk of bias in five studies which had assessed the health impacts of a domestic energy efficiency intervention. ROBINS-I assessments for each study were entered into a database and checked for consensus across the group. Group discussions were used to identify reasons underpinning lack of consensus for specific questions and bias domains. RESULTS: ROBINS-I helped to systematically articulate sources of bias in NRS. However, the lack of consensus in assessments for all seven bias domains raised questions about ROBINS-I's reliability and applicability for natural experiment studies. The two RoB domains with least consensus were selection (Domain 2) and performance (Domain 4). Underlying the lack of consensus were difficulties in applying an intention to treat or per protocol effect of interest to the studies. This was linked to difficulties in determining whether the intervention status was classified retrospectively at follow-up, i.e. post hoc. The overall risk of bias ranged from moderate to critical; this was most closely linked to the assessment of confounders. CONCLUSION: The ROBINS-I tool is a conceptually rigorous tool which focusses on risk of bias due to the counterfactual. Difficulties in applying ROBINS-I may be due to poor design and reporting of evaluations of natural experiments. While the quality of reporting may improve in the future, improved guidance on applying ROBINS-I is needed to enable existing evidence from natural experiments to be assessed appropriately and consistently. We hope future refinements to ROBINS-I will address some of the issues raised here to allow wider use of the tool.