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In a national sample of Medicare nursing home residents with dementia treated with bisphosphonates, 20% had bisphosphonates deprescribed. Residents with clinical characteristics representing decreased likelihood for long-term benefit were more likely to have bisphosphonates deprescribed. Future studies are needed to evaluate outcomes of deprescribing bisphosphonates in this population. To determine incidence of deprescribing bisphosphonates among nursing home (NH) residents with dementia and identify factors associated with deprescribing. 2015–2016 Medicare claims, Part D prescriptions, Minimum Data Set (MDS) 3.0, and Nursing Home Compare for non-skilled NH residents aged 65 + with dementia and prescriptions for oral bisphosphonates overlapping the first 14 days of the stay. Our primary definition for deprescribing was a 90-day gap in medication supply; we also explored the reliability of different deprescribing definitions (30-, 90-, 180-day gaps). We estimated associations of NH, provider, and resident characteristics with deprescribing bisphosphonates using competing risks regression models. Most NH residents with dementia treated with bisphosphonates (n = 5312) were ≥ 80 years old (72%), white (81%), and female (90%); about half were dependent for transfers (50%) or mobility (45%). Using a 90-day gap in supply, the 180-day cumulative incidence of deprescribing bisphosphonates was 14.8%. This increased to 32.1% using a 30-day gap and decreased to 11.7% using a 180-day gap. Factors associated with increased likelihood for bisphosphonate deprescribing were age ≥ 90 years, newly admitted (vs. prevalent stay), dependent for mobility, swallowing difficulty, > 1 hospitalization in the prior year, CCRC facility, and nurse practitioner primary provider (vs. physician). Cancer and western geographic region were associated with reduced likelihood for deprescribing. In a national sample of NH residents with dementia, bisphosphonate deprescribing was uncommon, and associated with clinical characteristics signifying poor prognosis and decreased likelihood for long-term benefit. Future studies should evaluate clinical outcomes of deprescribing bisphosphonates in this population.

Accurate safety information in published clinical trials guides the assessment of risk-benefit, as well as the design of future clinical trials. Comprehensive reporting of adverse events, toxicity, and discontinuations from acute spinal cord injury clinical trials is an essential step in this process. Here, we sought to assess the degree of "satisfactoriness" of reporting in past clinical trials in spinal cord injury. A review of citations from MEDLINE and EMBASE identified eligible clinical trials in acute (within 30 days) spinal cord injury. English language studies, published between 1980 and 2020, with sensory, motor, or autonomic neurological assessments as the primary outcome measure were eligible for inclusion. Criteria were then established to qualify the safety reporting as satisfactory (i.e., distinguished severe/life-threatening events), partially satisfactory, or unsatisfactory (i.e., only mentioned in general statements, or reported but without distinguishing severe events). A total of 40 trials were included. Satisfactory reporting for clinical adverse events was observed in 30% of trials; partially satisfactory was achieved by 10% of the trials, and the remaining 60% were unsatisfactory. The majority of trials were determined to be unsatisfactory for the reporting of laboratory-defined toxicity (82.5%); only 17.5% were satisfactory. Discontinuations were satisfactorily reported for the majority of trials (80%), with the remaining partially satisfactory (5%) or unsatisfactory (15%). Reporting of safety in clinical trials for acute spinal cord injury is suboptimal. Due to the complexities of acute spinal cord injury (e.g., polytrauma, multiple systems affected), tailored and specific standards for tracking adverse events and safety reporting should be established.

[BACKGROUND & AIMS] Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intra-hepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. [METHODS] We combined new and existing genotype data for 10, 516 cases and 20, 772 controls from five European and two East Asian cohorts. [RESULTS] We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57th genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, each having key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, Jak-STAT signalling, and differentiation of TH1 and TH17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some well-established in the treatment of other autoimmune disorders. [CONCLUSIONS] This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. [Lay summary] Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10, 516 people with PBC and 20, 772 healthy individuals recruited in Canada, China, Italy, Japan, UK, or USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these ‘candidate genes’ to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC., 原発性胆汁性胆管炎のゲノムワイド関連解析 --国際メタ解析による新規疾患感受性遺伝子と治療薬候補の同定--. 京都大学プレスリリース. 2021-06-28.

Aims: This systematic review examines the available evidence on the use of medical stretching devices to treat knee arthrofibrosis, it suggests a focus for future studies addressing limitations in current research and identifies gaps in the published literature to facilitate future works. Materials and methods: Articles were identified using the Cochrane Library, MEDLINE, PubMed and SCOPUS databases. Articles from peer reviewed journals investigating the effectiveness of medical stretching devices to increase range of movement when treating arthrofibrosis of the knee were included. Results: A total of 13 studies (558 participants) met the inclusion criteria with the devices falling into the following categories; CPM, load control or displacement control stretching devices. A statistically significant increase in range of movement was demonstrated in CPM, load-control and displacement-control studies (p ​

Clinical trials are complicated, time-consuming and costly. From the initial screening, informed consent and recruitment of the participants’ to study completion, the sponsor must undertake a wide array of complex and closely monitored operations, complying with international standards for human subject research and local requirements. Conducting these studies in an underdeveloped country, with limited resources, infrastructure, and experience with regulated clinical trials adds to this complexity. The initial site selection, set up and preparatory activities for the clinical trial are crucial to minimizing the risks to both participants and to successful completion during the subsequent study execution. In this paper, we describe the experience and lessons learned of building clinical trial site capacity in terms of infrastructure and human resource development for a Phase III vaccine clinical trial. We believe that sharing the experience of setting up a clinical trial in a resource-limited country will enable other entities contemplating clinical research in these countries, to prepare and plan ahead, to minimize the impact of barriers, and to contribute to bringing more studies to the countries where people live with the burden of vaccine-preventable, poverty-associated diseases.

Thyrotoxicosis is a common condition resulting from excess of circulating thyroid hormones in the blood. The most frequent cause of thyrotoxicosis is Graves' disease and the clinical features include goitre and eye disease. The treatment strategies of Graves' disease involve anti-thyroid drugs, radioiodine and thyroidectomy. Thyroiditis (inflammation of the thyroid) is caused by release of stored thyroid hormones and may also result in thyrotoxicosis. The aetiology, pathogenesis, diagnosis, investigation and management of conditions causing thyrotoxicosis and thyroiditis are reviewed in this article. Rare causes of thyrotoxicosis are highlighted.

BackgroundLimited data exist regarding tenofovir disoproxil fumarate (TDF) safety and effectiveness in chronic hepatitis B virus-infected (CHB) patients with renal impairment (RI).AimsTo compare real-world data on renal safety and effectiveness of TDF vs entecavir (ETV) in CHB patients with moderate-to-severe RI.MethodsRetrospective, non-interventional, cohort study analysing medical records for TDF/ETV-treated CHB patients (54 European centres). Included patients experienced moderate-to-severe RI (creatinine clearance 20-60 mL/min [Cockcroft-Gault]) either before TDF/ETV initiation ('before' subgroup [baseline = treatment initiation]) or after TDF/ETV initiation ('after' subgroup [baseline = first RI occurrence]). The primary objective was TDF safety, particularly renal-related adverse events of special interest (AESI). TDF and ETV safety and effectiveness were compared and multivariate analyses were performed using inverse probability treatment weighting.Results'Before' subgroup included 107 TDF- and 91 ETV-treated patients; 'after' subgroup included 212 TDF- and 77 ETV-treated patients. Mean baseline creatinine clearance was higher for TDF- vs ETV-treated patients (both subgroups). Median follow-up was 3.1 years (both treatments). AESI were more frequent with TDF vs ETV ('before': 18.7% vs 8.8%; 'after': 9.9% vs 3.9%); however, differences were not significant by multivariate analysis. Only TDF-treated patients experienced renal tubular dysfunction (6.5% 'before'; 1.9% 'after') as well as renal adverse events leading to treatment discontinuation (8.4% 'before'; 7.1% 'after'). Effectiveness was similar between treatments.ConclusionsOverall safety was similar for TDF vs ETV (both subgroups). Given that renal tubular dysfunction occurred with TDF and not with ETV, renal safety concerns may be greater with TDF in CHB patients with RI.

BACKGROUND/OBJECTIVES Geriatric guidelines recommend against statin use in older adults with limited life expectancy (LLE) or advanced dementia (AD). This study examined resident and facility factors predicting statin discontinuation after nursing home (NH) admission in veterans with LLE/AD taking statins for secondary prevention. DESIGN Retrospective cohort study of Veterans Affairs (VA) bar code medication administration records, Minimum Data Set (MDS) assessments, and utilization records linked to Medicare claims. SETTING VA NHs, known as community living centers (CLCs). PARTICIPANTS Veterans aged 65 and older with coronary artery disease, stroke, or diabetes mellitus, type II, admitted in fiscal years 2009 to 2015, who met criteria for LLE/AD on their admission MDS and received statins in the week after admission (n = 13,110). MEASUREMENTS Residents were followed until statin discontinuation (ie, gap in statin use ≥14 days), death, or censoring due to discharge, day 91 of the stay, or end of the study period. Competing risk models assessed cumulative incidence and predictors of discontinuation, stratified by whether the resident had their end-of-life (EOL) status designated or used hospice at admission. RESULTS Overall cumulative incidence of statin discontinuation was 31% (95% confidence interval [CI] = 30%-32%) by day 91, and it was markedly higher in those with (52%; 95% CI = 50%-55%) vs without (25%; 95% CI = 24%-26%) EOL designation/hospice. In patients with EOL designation/hospice (n = 2,374), obesity, congestive heart failure, and admission from nonhospital settings predicted decreased likelihood of discontinuation; AD, dependency in activities of daily living, greater number of medications, and geographic region predicted increased likelihood of discontinuation. In patients without EOL designation/hospice (n = 10,736), older age and several specific markers of poor prognosis predicted greater discontinuation, whereas obesity/overweight predicted decreased discontinuation. CONCLUSION Most veterans with LLE/AD taking statins for secondary prevention do not discontinue statins following CLC admission. Designating residents as EOL status, hospice use, and individual clinical factors indicating poor prognosis may prompt deprescribing.

Calcitonin-negative medullary thyroid carcinoma is a rare, poorly understood primary neuroendocrine carcinoma of the thyroid characterised by classic medullary thyroid carcinoma morphology without raised serum calcitonin. A 24-year-old woman presented with a slow-growing, right-sided neck swelling. She underwent an ultrasound scan, cytopathological and histopathological examination, and tests for alternative diagnoses. The ultrasound showed a heterogeneous, hyperechoic nodule in the right thyroid lobe. Serum calcitonin was normal. Cytopathology and histopathology showed typical medullary thyroid carcinoma morphology but without calcitonin upon immunostaining and mRNA in situ hybridisation. A ‘triple-negative’ calcitonin-negative medullary thyroid carcinoma was diagnosed. A completion thyroidectomy with bilateral central lymph node dissection was performed. The patient remains well three-years post-surgery. When cytopathology suggests a medullary thyroid carcinoma, serum calcitonin, pro-calcitonin, carcinoembryonic antigen and calcitonin-gene-related peptide should be measured to identify cases of calcitonin-negative medullary thyroid carcinoma. They should also be measured post-treatment for monitoring purposes. This will aid future calcitonin-negative medullary thyroid carcinoma diagnoses and will inform prognostic stratification and influence treatment decisions.

BACKGROUND & AIMS: It is thought that alcohol intake and BMI interact supra-additively to modulate the risk of cirrhosis; but evidence for this phenomenon is limited. We investigated the interrelationship between alcohol and BMI on the incidence of cirrhosis morbidity for participants of the United Kingdom Biobank study (UKB) study.APPROACH & RESULTS: The primary outcome was the cumulative incidence of cirrhosis morbidity, defined as a first-time hospital admission for cirrhosis (with non-cirrhosis mortality incorporated as a competing risk). All UKB participants without a previous hospital admission for cirrhosis were included in the analysis. We determined the ratio of the 10-year cumulative incidence in harmful drinkers versus safe drinkers according to BMI. We also calculated the excess cumulative incidence at 10 years for individuals with obesity and/or harmful alcohol compared to safe drinkers with a healthy BMI of 20-25.0 kg/m2 . 489,285 UK Biobank participants were included, with mean of 10.7 person-years follow-up. 2070 participants developed the primary outcome, equating to a crude cumulative incidence of 0.36% at 10years (95% CI:0.34-0.38). The 10-year cumulative incidence was 8.6 times higher for harmful (1.38%) versus safe drinkers (0.16%) if BMI was healthy. Conversely, it was only 3.6 times higher for obese participants (1.99% Vs 0.56%). Excess cumulative incidence was 1.22% (95% CI:0.89-1.55) for harmful drinkers with a healthy BMI, 0.40% (95% CI:0.34-0.46) for obese individuals drinking at safe levels, and 1.83% (95% CI:1.46-2.20) for obese harmful drinkers (all compared to safe drinkers with a healthy BMI).CONCLUSIONS: Alcohol intake and obesity are independent risk factors for cirrhosis morbidity, but they do not interact supra-additively to modulate the cumulative incidence of this outcome.

Background The Hepatitis B virus (HBV) affects over 250 million people worldwide and can lead to cirrhosis and hepatocellular carcinoma. HBV surface antigen (HBsAg) quantification is increasingly used to predict disease activity and treatment response. As there is no virologic cure, clinicians are seeking a “functional cure”, or HBsAg loss, as a guide to safely stopping nucleos(t)ide analogue therapy. Tenofovir Disoproxil Fumarate (TDF) and Entecavir (ETV) are first line therapy but require prolonged treatment to achieve HBsAg clearance. Aims To assess the association between nucleos(t)ide therapy and decline in quantitative HBsAg (qHBsAg) in patients with HBV from Calgary, Alberta. Methods A retrospective review of adult patients with chronic HBV, followed at the University of Calgary Liver Clinic, was conducted between January 2012 and October 2020. Patients were excluded if treatment was discontinued or changed, only had a single qHBsAg measurement, or were co-infected with hepatitis C virus, hepatitis delta virus, or HIV. Patients were stratified according to therapy with TDF, ETV, or no treatment. To identify associations between mean changes in qHBsAg by medication exposure, one-way ANOVAs and t-tests were performed. Results were reported as means and 95% confidence intervals (CI). The median time from initial qHBsAg to most-recent was calculated. Results 187 patients were included in the final analysis (Table 1). 77 were excluded for being on more than one medication over the study period, 10 were excluded due to discontinuation of treatment, and 195 were excluded for single qHBsAg measurements. The mean qHBsAg decline was -750.04 IU/mL (95% CI -1311.58, -188.50) in the TDF group (n=45) and -309.20 IU/mL (95% CI -600.90, -17.50) in the ETV group (n=35) (p=0.20). In the no treatment group (n=107), the mean qHBsAg increased by 711.29 IU/mL (95% CI -600.78, 2023.80)(Figure 1). The median time from initial qHBsAg to most-recent was 980 days. Conclusions Quantitative HBsAg levels declined in patients on TDF and ETV, but increased in untreated patients. Although HBsAg levels showed a trend for greater decline in TDF-treated patients, results failed to reach statistical significance, and may be affected by overall treatment duration. Future studies will explore medication use as a time-varying covariate to identify how change in treatment influences changes in HBsAg over time. Funding Agencies None

PurposeTo examine the reporting rates of adverse drug events (ADEs) with apixaban and empagliflozin as reports move up to the next level of spontaneous reporting.MethodsThis was a retrospective cohort study of outpatients who discontinued apixaban or empagliflozin within 3 years of Food and Drug Administration (FDA) approval. We enriched the sample using an active surveillance strategy to identify subsets of patients with International Classification of Diseases (ICD) codes possibly associated with an ADE. Stratified random samples of charts were reviewed to determine if patients discontinued the medication due to an ADE. If so, we ascertained whether these were uploaded into the Veterans Administration (VA) electronic health record reporting system (Adverse Reaction Tracking System [ARTS]), VA national Web-based system (VA Adverse Drug Event Reporting System [VA ADERS]), and FDA MedWatch.ResultsFrom the cohort of 2,973 patients who discontinued apixaban, 321 patients (10.8%) were randomly sampled for chart review (including 61 patients with relevant ICD codes). During chart review, 88 ADEs were identified, with 40/61 (65.6%) from the subset with ICD codes. Of the total of 88 ADEs, 18.2%, 10.2%, and 6.8% were reported in ARTS, VA ADERS, and MedWatch, respectively. Of the 1,555 patients who discontinued empagliflozin, 179 patients (11.5%) were randomly sampled for chart review (40 patients with relevant ICD codes). During chart review, 78 ADEs were identified, with 19/40 (47.5%) from the subset with ICD codes. Of the 78 ADEs, 28.2%, 19.2%, and 7.7% were reported in ARTS, VA ADERS, and MedWatch, respectively.ConclusionWe found substantial underreporting of apixaban and empagliflozin ADEs that became worse at each higher level of spontaneous reporting.

Purpose Many medications that were marketed prior to 1962 but lack Food and Drug Administration (FDA) approval are prescribed in the United States. Usage patterns of these “unapproved medications” are poorly elucidated, which is concerning due to potential lack of data on safety and efficacy. The purpose of this project was to characterize purchases of unapproved medications within the Veterans Health Administration (VHA) by type, frequency, and cost. Methods VHA purchasing databases were used to create a list of all products with National Drug Codes (NDCs) purchased nationwide in fiscal year 2016 (FY16). This list was compared to FDA databases to identify unapproved prescription medications. For each identified combination of active pharmaceutical ingredient (API) and route of administration (“API/route combination”), numbers of packages purchased and associated costs were added. Results VHA pharmacy purchasing records contained 3,299 unapproved products with NDCs in FY16. After excluding equipment, nutrition products, compounding ingredients, nonmedication products, and duplicate NDCs, there were 600 unique NDCs associated with 130 distinct API/route combinations. The most commonly acquired product was prescription sodium fluoride dental paste (350,775 packages). The greatest pharmaceutical expenditure was for sodium hyaluronate injection ($24.5 million). Unapproved products accounted for less than 1% of overall VHA pharmacy purchasing in FY16. Conclusion VHA purchased many unapproved prescription products in FY16 but is taking action to address use of such products in consideration of safety and efficacy data and available alternatives.

Categorize data to investigate the surgeon volume outcome relationship in thyroidectomies. Determine the evidence base for recommending a minimum number of thyroidectomies performed per year to maintain surgical competency.Data on thyroid operations in the United Kingdom Registry of Endocrine and Thyroid Surgery (UKRETS) from 01/09/2010 to 31/08/2016 was analysed. The primary outcome measure was permanent hypoparathyroidism (PH). Recurrent laryngeal nerve palsy (RLN) and post-operative haematoma were also examined. Exclusion criteria included patient age 85 or 18 years, and surgeons contributing10 operations. Data analysis was performed using general additive models and mixed effect logistic regression for PH and binary logistic regression for others.For PH 10313 bilateral thyroid operations were analysed. The Annual rate (AR, p = 0.012) and nodal dissection (P 10Surgeon annual operative volume is a factor in determining outcome from thyroid surgery. Results are limited by a high proportion of missing data, which could potentially bias the outcome, but tentatively suggests the minimum recommended number of thyroid operations / year should be 50 cases.

Background and aims: the health, financial and societal arguments for public health action to prevent lifestyle related liver disease are clear. Primary care has frequently been suggested as a key location for prevention strategies. Evidence on the most appropriate cut-offs for liver biochemistry and indirect fibrosis markers, which may be used for screening before more definitive assessment, has predominantly been gathered in patients with existing liver disease. These thresholds may not be suitable in community settings. For the first time liver function tests, from a sample representative of the general population in England, are available. We explored the distribution of risk factors for liver disease, liver function test results and liver fibrosis scores in the Health Survey for England (HSE) 2016. Method: cross-sectional survey with interview, examination and blood tests. Multi-stage, stratified, random probability sample designed to be representative of the population living in private households in England. Participants: 7,826 adults aged 18 years and over, of whom 3,791 had a blood test. Exposures and markers: Risk factors were alcohol consumption >14 units/wk, body mass index ≥25 and diabetes. Liver function tests were Alanine aminotransferase (ALT) and Aspartate Aminotransferase (AST). Liver fibrosis scores calculated were FIB-4 score (high>2.67), APRI score (high≥1.0), AST:ALT ratio (high>0.8), BARD score (high≥2).Results: 85.5% (84.4 to 86.7%,n=5670) of the population representative sample have at least one risk factor for liver disease. 25.9% (24.4 to 27.5%,n=4685) have two or more risk factors. 2.5% (2.0 to 3.1%,n=3388) had a high FIB-4; 11.5% (10.3 to 12.8%,n=3607) had a raised ALT; 86.0% (84.5 to 87.3%,n=3424) had a high AST:ALT ratio. Only 5.1% (4.3 to 6.0%,n=4031) of those with at least one risk factor and 7.9% (6.1 to 10.1%,n=3749) of those with two or more risk factors had been told by a health professional that they were at risk of liver disease. 12.9% (11.8 to 14.1%, n=4722) of the sample and 17.7% (10.9 to 27.3%, n=85) of those with a high FIB-4 score report ever being tested for liver disease. Conclusion: this is the first analysis of liver biochemistry and indirect fibrosis markers in a sample representative of the general population of England. Modifiable lifestyle risk factors for liver disease are present in more than 85% of participants. Multiple risk factors are common and may be synergistic. Commonly used liver function tests and fibrosis scores showed large variation in positivity. Awareness of risk and testing for liver disease was low, even in those with multiple risk factors. The best approach to achieve detection of liver disease in primary care remains unclear.

This report presents further evidence on the escalating alcohol consumption in the UK and the burden of liver disease associated with this major risk factor, as well as the effects on hospital and primary care. We reiterate the need for fiscal regulation by the UK Government if overall alcohol consumption is to be reduced sufficiently to improve health outcomes. We also draw attention to the effects of drastic cuts in public services for alcohol treatment, the repeated failures of voluntary agreements with the drinks industry, and the influence of the industry through its lobbying activities. We continue to press for reintroduction of the alcohol duty escalator, which was highly effective during the 5 years it was in place, and the introduction of minimum unit pricing in England, targeted at the heaviest drinkers. Results from the introduction of minimum unit pricing in Scotland, with results from Wales to follow, are likely to seriously expose the weakness of England's position. The increasing prevalence of obesity-related liver disease, the rising number of people diagnosed with type 2 diabetes and its complications, and increasing number of cases of end-stage liver disease and primary liver cancers from non-alcoholic fatty liver disease make apparent the need for an obesity strategy for adults. We also discuss the important effects of obesity and alcohol on disease progression, and the increased risk of the ten most common cancers (including breast and colon cancers). A new in-depth analysis of the UK National Health Service (NHS) and total societal costs shows the extraordinarily large expenditures that could be saved or redeployed elsewhere in the NHS. Excellent results have been reported for new antiviral drugs for hepatitis C virus infection, making elimination of chronic infection a real possibility ahead of the WHO 2030 target. However, the extent of unidentified cases remains a problem, and will also apply when new curative drugs for hepatitis B virus become available. We also describe efforts to improve standards of hospital care for liver disease with better understanding of current service deficiencies and a new accreditation process for hospitals providing liver services. New commissioning arrangements for primary and community care represent progress, in terms of effective screening of high-risk subjects and the early detection of liver disease.

Background Non-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular risk irrespective of conventional risk factors. The role of gut-liver interaction is implicated in its development. We investigated the effects of VSL#3® probiotic supplementation on biomarkers of cardiovascular risk and liver injury in patients with NAFLD. Methods A randomised, double-blinded, placebo-controlled, proof-of-concept study was undertaken. Patients with NAFLD were randomly allocated to take 2 sachets VSL#3® probiotic or placebo twice daily for 10 weeks. Measurements of endothelial function (digital photoplethysmography, sVCAM-1 and cGMP), oxidative stress (glutathione ratio and LHP), inflammation (hsCRP), insulin resistance (HOMA-IR) and liver injury [transaminases, fibrosis risk score and acoustic structure quantification (ASQ)] were undertaken before and after intervention. Difference in baseline characteristics between the treatment groups was analysed using independent t-test or Mann Whitney U test for non-parametric data. Independent t-test was used to compare the outcomes at the end of the study between the two treatment groups. Wilcoxon Signed Rank test was used to determine the difference in fibrosis risk scores before and after treatment. Spearman’s correlation was used to determine any association between cardiovascular and hepatic markers at baseline. Results Thirty-five patients completed the study (28 males and 7 females) with a mean age of 57 ± 8 years, body mass index of 32.6 ± 5.0 kg/m2 and a relatively short duration of NAFLD (median duration 0.3 IQR 2.0 years). No significant difference was observed in biomarkers of cardiovascular risk and liver injury following VSL#3® supplementation. Significant correlations were noted between sVCAM-1 and hsCRP (rho = 0.392, p = 0.01), and HOMA-IR and AST (rho = 0.489, p Conclusions This is the first study to evaluate the effect of VSL#3® on ASQ in patients with NAFLD. VSL#3® did not significantly improve markers of cardiovascular risk and liver injury in patients with NAFLD. However, the study supports an association between endothelial dysfunction and inflammation in patients with NAFLD and suggests that NAFLD is linked with insulin resistance. Trial registration: ISRCTN05474560 (https://doi.org/10.1186/ISRCTN05474560) Registered 9 August 2012 (retrospectively registered).

Infection and increased systemic inflammation cause organ dysfunction and death in patients with decompensated cirrhosis. Preclinical studies provide support for an antiinflammatory role of albumin, but confirmatory large-scale clinical trials are lacking. Whether targeting a serum albumin level of 30 g per liter or greater in these patients with repeated daily infusions of 20% human albumin solution, as compared with standard care, would reduce the incidences of infection, kidney dysfunction, and death is unknown.We conducted a randomized, multicenter, open-label, parallel-group trial involving hospitalized patients with decompensated cirrhosis who had a serum albumin level of less than 30 g per liter at enrollment. Patients were randomly assigned to receive either targeted 20% human albumin solution for up to 14 days or until discharge, whichever came first, or standard care. Treatment commenced within 3 days after admission. The composite primary end point was new infection, kidney dysfunction, or death between days 3 and 15 after the initiation of treatment.A total of 777 patients underwent randomization, and alcohol was reported to be a cause of cirrhosis in most of these patients. A median total infusion of albumin of 200 g (interquartile range, 140 to 280) per patient was administered to the targeted albumin group (increasing the albumin level to ≥30 g per liter), as compared with a median of 20 g (interquartile range, 0 to 120) per patient administered to the standard-care group (adjusted mean difference, 143 g; 95% confidence interval [CI], 127 to 158.2). The percentage of patients with a primary end-point event did not differ significantly between the targeted albumin group (113 of 380 patients [29.7%]) and the standard-care group (120 of 397 patients [30.2%]) (adjusted odds ratio, 0.98; 95% CI, 0.71 to 1.33; P = 0.87). A time-to-event analysis in which data were censored at the time of discharge or at day 15 also showed no significant between-group difference (hazard ratio, 1.04; 95% CI, 0.81 to 1.35). More severe or life-threatening serious adverse events occurred in the albumin group than in the standard-care group.In patients hospitalized with decompensated cirrhosis, albumin infusions to increase the albumin level to a target of 30 g per liter or more was not more beneficial than the current standard care in the United Kingdom. (Funded by the Health Innovation Challenge Fund; ATTIRE EudraCT number, 2014-002300-24; ISRCT number, N14174793.).

Illnesses transmitted by food and water cause a major disease burden in the United States despite advancements in food safety, water treatment, and sanitation. We report estimates from a structured expert judgment study using 48 experts who applied Cooke's classical model of the proportion of disease attributable to 5 major transmission pathways (foodborne, waterborne, person-to-person, animal contact, and environmental) and 6 subpathways (food handler-related, under foodborne; recreational, drinking, and nonrecreational/nondrinking, under waterborne; and presumed person-to-person-associated and presumed animal contact-associated, under environmental). Estimates for 33 pathogens were elicited, including bacteria such as Salmonella enterica, Campylobacter spp., Legionella spp., and Pseudomonas spp.; protozoa such as Acanthamoeba spp., Cyclospora cayetanensis, and Naegleria fowleri; and viruses such as norovirus, rotavirus, and hepatitis A virus. The results highlight the importance of multiple pathways in the transmission of the included pathogens and can be used to guide prioritization of public health interventions.

Clinicians struggle with whether to prescribe osteoporosis medications for fracture prevention for older nursing home (NH) residents with dementia, given the lack of evidence in this population. To better understand real-world clinical practice, we conducted a retrospective cohort study examining patterns of fracture prevention medication use for older NH residents with dementia and high fracture risk. Data sources included 2015-16 Medicare claims, Part D prescriptions, and Minimum Data Set (MDS) assessments. Among NH residents aged 65+ with dementia and prior fracture or high fracture risk based on the MDS FRAiL (Fracture Risk Assessment in Long-term care), we assessed medications for fracture prevention using prescription data from 1 year prior through 90 days after the first MDS assessment. Multivariable logistic regression was used to evaluate factors associated with receiving treatment. Most of the sample (n = 72,639) was80 years (78%), female (82%), and white (88%); 63% had moderate/severe dementia and 60% had an osteoporosis diagnosis. Only 11.6% received fracture prevention medications. In adjusted analyses, treated residents were more likely to be female, Hispanic or other non-black minority,90 years old, and newly admitted to the NH. Other associated factors included osteoporosis diagnosis, walker or wheelchair use, bone disorders (eg, Paget disease),5 medications, steroid or proton pump inhibitor use, and regions outside of the Northeast. Resident characteristics suggestive of comorbidity burden and worsening dementia were associated with reduced likelihood of treatment. Low use of fracture prevention medications for NH residents with dementia may reflect an attempt by prescribers reconcile medication use with changing goals of care, or inappropriate underuse in patients who still have high fracture risk. Additional research is needed to help clinicians better evaluate when to use these medications in this heterogeneous and vulnerable population.

Aims This study aims to evaluate a new home medical stretching device called the Self Treatment Assisted Knee (STAK) tool to treat knee arthrofibrosis. Methods 35 patients post-major knee surgery with arthrofibrosis and mean range of movement (ROM) of 68° were recruited. Both the STAK intervention and control group received standard physiotherapy for eight weeks, with the intervention group additionally using the STAK at home. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Oxford Knee Scores (OKS) were collected at all timepoints. An acceptability and home exercise questionnaire capturing adherence was recorded after each of the interventions. Results Compared to the control group, the STAK intervention group made significant gains in mean ROM (30° versus 8°, p < 0.0005), WOMAC (19 points versus 3, p < 0.0005), and OKS (8 points versus 3, p < 0.0005). The improvements in the STAK group were maintained at long-term follow-up. No patients suffered any complications relating to the STAK, and 96% of patients found the STAK tool ‘perfectly acceptable’. Conclusion The STAK tool is effective in increasing ROM and reducing pain and stiffness. Patients find it acceptable and adherence to treatment was high. This study indicates that the STAK tool would be of benefit in clinical practice and may offer a new, cost-effective treatment for arthrofibrosis. Cite this article: Bone Joint Open 2020;1-8:465–473.

Background The United Kingdom Registry of Endocrine and Thyroid Surgeons is a national database holding details on > 28,000 parathyroidectomies. Methods An extract (2004–2017) of the database was analysed to investigate the reported efficacy, safety and use of intra-operative surgical adjuncts in targeted parathyroidectomy (tPTx) and bilateral neck exploration (BNE) for adult, first-time primary hyperparathyroidism (PHPT). Results 50.9% of 21,738 cases underwent tPTx. Excellent short-term (median follow-up 35 days) post-operative normocalcaemia rates were reported overall (tPTx 96.6%, BNE 94.5%, p p p p p p p > 0.05), nor any difference in VC dysfunction when formally examined (4.9% vs 4.1%, p > 0.05). Conclusions In image-positive, first time, adult PHPT cases, tPTx is as safe and effective as BNE, with both achieving excellent short-term results with minimal complications.

This Review, in addressing the unacceptably high mortality of patients with liver disease admitted to acute hospitals, reinforces the need for integrated clinical services. The masterplan described is based on regional, geographically sited liver centres, each linked to four to six surrounding district general hospitals-a pattern of care similar to that successfully introduced for stroke services. The plan includes the establishment of a lead and deputy lead clinician in each acute hospital, preferably a hepatologist or gastroenterologist with a special interest in liver disease, who will have prime responsibility for organising the care of admitted patients with liver disease on a 24/7 basis. Essential for the plan is greater access to intensive care units and high-dependency units, in line with the reconfiguration of emergency care due to the COVID-19 pandemic. This Review strongly recommends full implementation of alcohol care teams in hospitals and improved working links with acute medical services. We also endorse recommendations from paediatric liver services to improve overall survival figures by diagnosing biliary atresia earlier based on stool colour charts and better caring for patients with impaired cognitive ability and developmental mental health problems. Pilot studies of earlier diagnosis have shown encouraging progress, with 5-6% of previously undiagnosed cases of severe fibrosis or cirrhosis identified through use of a portable FibroScan in primary care. Similar approaches to the detection of early asymptomatic disease are described in accounts from the devolved nations, and the potential of digital technology in improving the value of clinical consultation and screening programmes in primary care is highlighted. The striking contribution of comorbidities, particularly obesity and diabetes (with excess alcohol consumption known to be a major factor in obesity), to mortality in COVID-19 reinforces the need for fiscal and other long delayed regulatory measures to reduce the prevalence of obesity. These measures include the food sugar levy and the introduction of the minimum unit price policy to reduce alcohol consumption. Improving public health, this Review emphasises, will not only mitigate the severity of further waves of COVID-19, but is crucial to reducing the unacceptable burden from liver disease in the UK.

Background The study aim was to systematically review literature evaluating surgeon volume-outcome relationships for thyroid and parathyroid operations in order to inform surgical quality improvement initiatives. Current literature suggests surgeons who perform a high volume of thyroid and/or parathyroid operations have better outcomes than low volume surgeons, though specific volume definition are not standardized. Methods Eligible studies were selected through a literature search focused on the effect of surgeon volume on thyroid and parathyroid surgery patient outcomes. The literature search was conducted in accordance with the PRISMA guidelines. Publication dates extended from January 1998 to February 2021, and were limited to articles published in English. Results A total of 33 studies were included: 25 studies evaluating thyroid surgery outcomes, 4 studies evaluating parathyroid surgery outcomes, and 4 studies evaluating both thyroid and parathyroid (mixed) surgery outcomes. Higher volume thyroid and parathyroid surgeons were found to be associated with fewer surgical and medical complications, shorter length of hospital stay, and reduced total cost when compared to lower volume surgeons. This volume-outcome relationship was also found to specifically affect the complication and recurrence rates for thyroid cancer patients undergoing surgery, especially for individuals with advanced stage disease. Conclusion The heterogeneity in cut-offs used for characterizing surgeons as high versus low volume, and also in subsequent patient outcome measures, limited direct study comparisons. The trend of improved patient outcomes with higher surgeon volume for both thyroid and parathyroid surgeries was consistently present in all studies reviewed.

The objective of this study was to evaluate the association between fluoroquinolone (FQ) use and the occurrence of aortic aneurysm/dissection (AA/AD), acute myocardial infarction (AMI), ventricular arrhythmias (VenA), and all‐cause mortality vs other commonly used antibiotics. We conducted a self‐controlled case series analysis of patients who experienced the outcomes of AA/AD, AMI, and VenA, based on diagnosis codes from emergency department visits and hospitalizations within Veterans Health Administration, and death in FY2014‐FY2018. These Veterans also received outpatient prescriptions for FQs. Conditional Poisson regression models were used to estimate the association between FQs and each of the outcomes vs antibiotics of interest (ie amoxicillin or amoxicillin/clavulanate, azithromycin, doxycycline, cefuroxime or cephalexin, or sulfamethoxazole‐trimethoprim), adjusted for time‐varying covariates. Using a 30‐day risk period after each antibiotic prescription, adjusted incidence rate ratios (aIRRs) for FQs vs each comparator antibiotic were not statistically different for outcomes of VenA or AMI. For AA/AD, incidence was higher during FQ risk periods vs amoxicillin [aIRR 1.50 (95% CI 1.01, 2.25)] and azithromycin [aIRR 2.15 (95% CI 1.27, 3.64)] risk periods. A significantly increased risk of mortality was observed with FQs vs each antibiotic of interest. FQs were associated with an increased risk of AA/AD vs amoxicillin and azithromycin and an increased risk of all‐cause mortality vs multiple antibiotics commonly used for outpatient infections. Although the differences in event rates are small, FQ use should be limited to serious infections without appropriate alternatives.

Little is known about genetic factors that affect development of alcohol-related cirrhosis. We performed a genome-wide association study (GWAS) of samples from the United Kingdom Biobank (UKB) to identify polymorphisms associated with risk of alcohol-related liver disease., info:eu-repo/semantics/published

Purpose The delivery of surgical care in England has seen a momentum towards centralisation within larger volume hospitals and surgical teams. The aim of this study was to investigate outcomes in England in relationship to hospital and surgeon annual volumes for total thyroidectomy. Methods Data were extracted from the Hospital Episodes Statistics (HES) database for England. A 6-year period (April 2012–March 2018 inclusive) for all adult admissions for thyroidectomy was used in the analysis. The primary outcome measure used was a length of hospital stay greater than 2 days or an emergency readmission within 30 days following surgery. This was used as a proxy for surgical complications. A multilevel modelling strategy was used to adjust for hierarchy and potentially confounding. Results Data for 22,823 total thyroidectomies across 144 hospital trusts were used for analysis. For total thyroidectomy, larger volume surgeons had reduced levels of post-surgical complications; length of stay > 2 and > 4 days; emergency readmission at 30 days; and hypoparathyroidism, vocal cord palsy, stridor, and tracheostomy at 1-year post-surgery. Larger hospital volume was associated with lower levels of emergency readmission at 30 days and hypoparathyroidism at 1 year. Conclusions There is significant correlation between surgeon volume and clinical outcome for total thyroidectomy. The relationship was approximately linear, and a low-volume threshold could not be defined. Supplementary Information The online version contains supplementary material available at 10.1007/s00423-021-02223-8.

Objective: To develop an outcomes instrument that assesses observations that can be reliably reported by caregivers and can be used to assess health of infants with a cleft lip or cleft lip and cleft palate (CL±P) and impacts of treatments. Design: Cross-sectional, mixed methods study. Setting: Caregivers and health-care providers were recruited from 3 academic craniofacial centers and national advertisements. Most interviews were conducted by telephone, and surveys were completed online. Participants: Caregivers had a child less than 3 years of age with CL±P and spoke either English or Spanish. Health-care providers were members of a cleft team. Caregivers (n = 492) and health-care professionals (n = 75) participated in at least one component of this study. Main Outcome Measure(s): Caregivers and health-care providers participated in tasks related to instrument development: concept elicitation for items within relevant health domains, prioritization of items, and item review. Results: We identified 295 observations of infant well-being across 9 health areas. Research staff and specialists evaluated items for clarity, specificity to CL±P, and responsiveness to treatment. Caregivers and health-care providers rated the resulting list of 104 observations and developed the final instrument of 65 items. Conclusions: In this phase of development of the Infant with Clefts Observation Outcomes (iCOO) instrument, items were developed to collect caregiver observations about indicators of children’s health and well-being across multiple domains allowing for psychometric testing, sensitivity to changes associated with treatment, and documentation of the effects of treatment.

ObjectiveNon-alcoholic fatty liver disease (NAFLD) affects approximately one in four adults of the general population, with an important minority of cases at high risk of developing cirrhosis. We evaluated the utility of a primary care NAFLD pathway incorporating a specialist nurse-led NAFLD clinic and a two-step testing approach for advanced liver fibrosis.Design/MethodWe performed a retrospective evaluation of prospectively collected demographic and clinical data on all patients diagnosed with NAFLD and intermediate NAFLD fibrosis score seen in our nurse-led NAFLD clinic between 1 May 2014 and 30 April 2017. Patients were assessed using a specific clerking pro forma and transient elastography (TE). Discharge to primary care with lifestyle advice was considered where TEResults904 patients were identified, 114 (12.6%) of whom did not meet NAFLD criteria. Among the NAFLD population (n=790 (87.4%)), TEConclusionAn integrated primary/secondary care NAFLD pathway, including a specialist nurse-led clinic may be a useful way of managing increasing demand on secondary care hepatology services.

Background Chronic liver disease (CLD) is frequently diagnosed at a late stage when prognosis is poor. We aimed to determine the patient factors associated with a late CLD diagnosis and its subsequent impact on survival to support early diagnosis initiatives. Methods We identified participants of UK biobank (UKB) study who developed first-time advanced CLD within 5 years. We identified the factors associated with late diagnosis via logistic regression and used survival analysis to measure the association between late CLD diagnosis and mortality risk. Results A total of 725 UKB participants developed first-time advanced CLD event within 5 years. In total, 83% of cases were diagnosed late. Late diagnosis was associated with aetiology; the odds of late diagnosis were 12 times higher for an individual with alcohol-related liver disease (ArLD) vs viral hepatitis (aOR:12.01; P Cumulative mortality 5 years after incident advanced CLD was 43.4% (95% CI:39.6–47.0). Late diagnosis was associated with a higher risk of postadvanced CLD mortality for patients with non-alcoholic fatty liver disease (aHR:2.18; 95% CI:0.86–5.51; P = 0.10), but not for other aetiologies. Conclusions Late CLD diagnosis varies according to aetiology and is highest for patients with ArLD and non-alcoholic fatty liver disease. The association between late diagnosis and postadvanced CLD mortality may also vary by aetiology.

These guidelines on transjugular intrahepatic portosystemic stent-shunt (TIPSS) in the management of portal hypertension have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the Liver Section of the BSG. The guidelines are new and have been produced in collaboration with the British Society of Interventional Radiology (BSIR) and British Association of the Study of the Liver (BASL). The guidelines development group comprises elected members of the BSG Liver Section, representation from BASL, a nursing representative and two patient representatives. The quality of evidence and grading of recommendations was appraised using the GRADE system. These guidelines are aimed at healthcare professionals considering referring a patient for a TIPSS. They comprise the following subheadings: indications; patient selection; procedural details; complications; and research agenda. They are not designed to address: the management of the underlying liver disease; the role of TIPSS in children; or complex technical and procedural aspects of TIPSS.

INTRODUCTION We evaluated the impact of deprescribing acetylcholinesterase inhibitors (AChEIs) on aggressive behaviors and incident antipsychotic use in nursing home (NH) residents with severe dementia. METHODS We conducted a retrospective study of Medicare claims, Part D, Minimum Data Set for NH residents aged 65+ with severe dementia receiving AChEIs in 2016. Aggressive behaviors were measured using the aggressive behavior scale (ABS; n = 30,788). Incident antipsychotic prescriptions were evaluated among antipsychotic non-users (n = 25,188). Marginal structural models and inverse probability of treatment weights were used to evaluate associations of AChEI deprescribing and outcomes. RESULTS The severity of aggressive behaviors was low at baseline (mean ABS = 0.5) and was not associated with deprescribing AChEIs (0.002 increase in ABS, P = .90). Incident antipsychotic prescribing occurred in 5.1% of residents and was less likely with AChEI deprescribing (adjusted odds ratio = 0.52 [0.40-0.68], P

The Bethesda system for cytopathology (TBSRTC) is a 6-tier diagnostic framework developed to standardize thyroid cytopathology reporting. The aim of this study was to determine the risk of malignancy (ROM) for each Bethesda category. Thyroidectomy-related data from 314 facilities in 22 countries were entered into the following outcome registries: CESQIP (North America), Eurocrine (Europe), SQRTPA (Sweden) and UKRETS (UK). Demographic, cytological, pathologic and extent of surgery data were mapped into one dataset and analyzed. Out of 41,294 thyroidectomy patient entries from January 1, 2015, to June 30, 2017, 21,746 patients underwent both thyroid FNA and surgery. A comparison of cytology and surgical pathology data demonstrated a ROM for Bethesda categories 1 to 6 of 19.2%, 12.7%, 31.9%, 31.4%, 77.8% and 96.0%, respectively. Male patients had a higher rate of malignancy for every Bethesda category. Secondary analysis demonstrated a high ROM in male patients with Bethesda 3 category aged 31–35 years (52.1%, 95% confidence interval (CI) 37.9–66.2%), aged 36–40 years (55.9%, 95% CI 39.2–72.6%) and aged 41–45 years (46.9%, 95% CI 33–60.9%). Patients with Bethesda 5 and 6 scores were more likely to undergo total thyroidectomy (65.9% and 84.6%); for patients with Bethesda scores 2 and 3, a higher percentage of females underwent total thyroidectomy compared to males in spite of a higher ROM for males. These data demonstrate that Bethesda categories 1–4 are associated with a higher ROM compared to the first edition of TBSRTC, especially in male patients, and validate findings from the second edition of TBSRTC.

Although aerobic capacity has been identified as an important predictor of mortality in Cystic Fibrosis (CF) individuals, many remain insufficiently active. As a ‘lack of time’ is a commonly cited barrier to exercise, reduced-exertion high-intensity interval training (REHIT) may provide a truly time-effective method to increase aerobic capacity. Six-weeks of REHIT in a CF individual was assessed by a cardiopulmonary exercise test (CPET) and individual perceptions described using a self-report narrative. Peak oxygen uptake (V˙ O2peak) increased by 6% whilst pulmonary function remained unchanged. Qualitative data indicated social support and low-time commitment positively influenced adherence with fatigue and lack of enjoyment noted as a significant barriers. REHIT was demonstrated as a viable, manageable option for a CF individual with moderate-severe pulmonary limitation. Further research is needed to determine the efficacy of REHIT in a large representative sample to ascertain whether it represents an alternative treatment strategy., Highlights • REHIT is a viable option for individuals with moderate-severe pulmonary limitation. • Small, intense bouts of exercise can increase aerobic capacity in a CF individual. • REHIT had no effect on pulmonary function. • Social support and low-time commitment positively influenced adherence. • Lack of enjoyment during REHIT was a significant barrier to exercise.

Ultrasound localisation of parathyroid glands correlates with gland weight. We hypothesise that gland identification is also dependent on anatomical location. Perrier et al. have described a uniform and reliable nomenclature for parathyroid locations. We aimed to correlate surgeon-performed ultrasound (SUS) with intra-operative Perrier classification and gland weight.Review of a prospectively maintained single operator SUS database of 194 patients referred with non-familial primary hyperparathyroidism (PHPT) at a tertiary centre between 2010 and 2015. Patients underwent MIBI localisation as well as on table SUS. Intra-operative pathological gland locations were classified according to the Perrier nomenclature.Mean weight of pathological glands found and missed by SUS was 1.07 ± 0.1 g and 0.48 ± 0.08 g respectively (p = 0.0001, unpaired t test). The weight of glands identified was greater than that of missed glands for each of the Perrier locations (p 0.001, Mann-Whitney). The proportion of pathological glands found at each Perrier location varied significantly (p 0.0001, Chi Square); so we find proportionally more B-, D-, E- and F-type glands and miss more A- and C-type glands. The median weight of glands missed on SUS varied significantly across the Perrier groups (Kruskal-Wallis, p = 0.0034) and suggests that SUS can miss quite large glands ( 0.5 g) in locations B, C and F; whereas missed glands in locations A, D and E were all small ( 0.5 g).Whilst gland identification correlates well with gland weight, anatomical location has a significant impact on failure of localisation irrespective of gland weight. For the surgeon operating on PHPT patients with negative US localisation, particular attention should be paid to locations C, D and A as these are the sites where pathological glands are most often missed on pre-operative US.

Objectives To examine the association between central nervous system (CNS) medication dosage burden and risk of serious falls, including hip fractures, in individuals with a history of a recent fall. Design Nested case–control study. Setting Veterans Health Administration (VHA) Community Living Centers (CLCs). Participants CLC residents aged 65 and older with a history of a fall or hip fracture in the year before a CLC admission between July 1, 2005, and June 30, 2009. Each case (n = 316) was matched to four controls (n = 1264) on age, sex, and length of stay. Measurements Outcomes were serious falls identified using International Classification of Diseases, Ninth Revision (ACD‐9) or Current Procedural Terminology (CPT) E codes, diagnosis codes, or procedure codes associated with a VHA emergency department visit or hospitalization during the CLC stay. Bar code medication administration data were used to calculate CNS standardized daily doses (SDDs) for opioid and benzodiazepine receptor agonists, some antidepressants, antiepileptics, and antipsychotics received in the 6 days before the outcome date by dividing residents' actual CNS daily doses by the minimum effective geriatric daily doses and adding the results. Multivariable conditional logistic regression models were used to evaluate the association between total CNS medication dosage burden, categorized as 0, 1 to 2, and 3 or more SDDs, and the outcome of recurrent serious falls. Results More cases (44.3%) than controls (35.8%) received 3.0 or more CNS SDDs (p = .02). Risk of serious falls was greater in residents with 3.0 or more SDDs than in those with 0 (adjusted odds ratio (aOR)=1.49, 95% confidence interval (CI)=1.03–2.14). Those with 1.0 to 2.9 SDDs had a risk similar to that of those with 0 SDDs (aOR=1.03, 95%CI=0.72–1.48). Conclusion Nursing home residents with a history of a fall or hip fracture receiving 3.0 or more CNS SDDs were more likely to have a recurrent serious fall than those taking no CNS medications. Interventions targeting this vulnerable population may help reduce serious falls. J Am Geriatr Soc 67:74–80, 2019.

Background & Aims The advent of direct-acting antivirals (DAAs) has led to ambitious targets for hepatitis C virus (HCV) elimination. However, in the context of alcohol use disorder the ability of DAAs to achieve these targets may be compromised. The aim of this study was to evaluate the contribution of alcohol use disorder to HCV-related decompensated cirrhosis in three settings. Methods HCV notifications from British Columbia, Canada; New South Wales, Australia, and Scotland (1995–2011/2012/2013, respectively) were linked to hospital admissions (2001–2012/2013/2014, respectively). Alcohol use disorder was defined as non-liver-related hospitalisation due to alcohol use. Age-standardised decompensated cirrhosis incidence rates were plotted, associated factors were assessed using Cox regression, and alcohol use disorder-associated population attributable fractions (PAFs) were computed. Results Among 58,487, 84,529, and 31,924 people with HCV in British Columbia, New South Wales, and Scotland, 2,689 (4.6%), 3,169 (3.7%), and 1,375 (4.3%) had a decompensated cirrhosis diagnosis, and 28%, 32%, and 50% of those with decompensated cirrhosis had an alcohol use disorder, respectively. Age-standardised decompensated cirrhosis incidence rates were considerably higher in people with alcohol use disorder in New South Wales and Scotland. Decompensated cirrhosis was independently associated with alcohol use disorder in British Columbia (aHR 1.92; 95% CI 1.76–2.10), New South Wales (aHR 3.68; 95% CI 3.38–4.00) and Scotland (aHR 3.88; 95% CI 3.42–4.40). The PAFs of decompensated cirrhosis-related to alcohol use disorder were 13%, 25%, and 40% in British Columbia, New South Wales and Scotland, respectively. Conclusions Alcohol use disorder was a major contributor to HCV liver disease burden in all settings, more distinctly in Scotland. The extent to which alcohol use would compromise the individual and population-level benefits of DAA therapy needs to be closely monitored. Countries, where appropriate, must develop strategies combining promotion of DAA treatment uptake with management of alcohol use disorders, if World Health Organization 2030 HCV mortality reduction targets are going to be achieved. Lay summary The burden of liver disease has been rising among people with hepatitis C globally. The recent introduction of highly effective medicines against hepatitis C (called direct-acting antivirals or DAAs) has brought renewed optimism to the sector. DAA scale-up could eliminate hepatitis C as a public health threat in the coming decades. However, our findings show heavy alcohol use is a major risk factor for liver disease among people with hepatitis C. If continued, heavy alcohol use could compromise the benefits of new antiviral treatments at the individual- and population-level. To tackle hepatitis C as a public health threat, where needed, DAA therapy should be combined with management of heavy alcohol use.

Objectives The World Health Organization (WHO) developed a European Regional Action Plan (EAP) to fast-track action towards the goal of eliminating viral hepatitis. Robust monitoring is essential to assess national programme performance. The purpose of this study was to assess the availability of selected monitoring data sources in European Union/European Economic Area (EU/EEA) Member States (MS). Methods Availability of data sources at EU/EEA level was assessed using two surveys distributed to 31 EU/EEA MS in 2016. The two surveys covered (A) availability of policy documents on testing; testing practices and monitoring; monitoring of diagnosis and treatment initiation, and; (B) availability of data on mortality attributable to chronic viral hepatitis. Results Just over two-thirds of EU/EEA MS responded to the surveys. 86% (18/21) reported national testing guidance covering HBV, and 81% (17/21) covering HCV; while 33% (7/21) and 38% (8/21) of countries, respectively, monitored the number of tests performed. 71% (15/21) of countries monitored the number of chronic HBV cases diagnosed and 33% (7/21) the number of people treated. Corresponding figures for HCV were 48% (10/21) and 57% (12/21). 27% (6/22) of countries reported availability of data on mortality attributable to chronic viral hepatitis. Conclusions The results of this study suggest that sources of information in EU/EEA Member States to monitor the progress towards the EAP milestones and targets related to viral hepatitis diagnosis, cascade of care and attributable mortality are limited. Our analysis should raise awareness among EU/EEA policy makers and stimulate higher prioritisation of efforts to improve the monitoring of national viral hepatitis programmes.

Background & aims To describe the burden on inpatient hospital resources over time from patients diagnosed with hepatitis C virus (HCV) infection and who have reached the decompensated stage of cirrhosis (DC), as existing estimates of hospital stay in these patients are limited. Methods A retrospective longitudinal dataset was formed via record-linkage between the national HCV diagnosis database and inpatient/daycase hospitalisation and death registers in Scotland. The study population consisted of HCV-diagnosed patients with a first DC admission in 1996-2013, with follow-up available until 31 May 2014. We investigated and quantified the mean cumulative length of hospital stay, distributions over discharge diagnosis categories, and trends in admission rates. Results Among our study population (n = 1543), we identified 10 179 admissions with any diagnosis post-first DC admission. Between 1996 and 2013 there was a 16-fold rise in annual total admissions (from 112 to 1791) and an 11-fold rise in hospital stay (719-8045). When restricting minimum possible follow-up to 2 years, DC patients (n = 1312) had an overall admission rate of 7.3 per person-year, and spent on average 43 days (26 days during first 6 months) in hospital; for all liver-related, liver-related other than HCC/DC, and non-liver related only admissions, this was 39, 14, and 5 days respectively. Conclusions HCV-infected DC patients impose a considerable inpatient hospital burden, mostly from DC- and other liver-related admissions, but also from admissions associated with non-liver comorbidities. Estimates will be useful for monitoring the impact of prevention and treatment, and for computing the cost-effectiveness of new therapies.

Introduction Hypoxic stress is a feature of rapidly growing thyroid tumours. Cancer progression is thought to be driven by a small population of tumour cells possessing stem cell properties. Hypoxia-inducible factors (HIFs) are important mediators of hypoxia. Both HIF-1alpha and HIF-2alpha have been reported to be expressed in thyroid cancers. There is growing evidence that the HIF pathway plays a significant role in the maintenance of thyroid cancer stem cells (CSC). Methodology We have isolated thyroid CSC from a papillary thyroid cancer-derived cell line (BCPAP) and an anaplastic thyroid cancer-derived cell line (SW1736) as side population (SP) cells (a putative stem cell population) and treated them with cobalt chloride (II) to induce hypoxia. Results and discussion We observed an increase in the SP of cells within the thyroid cancer cell lines following induction of hypoxia.

First Place Award Submission - CA147Category: Clinical ApplicationManagement of obesity after spinal cord injury: a systematic reviewMir Hatef Shojaei1, Mohammad Alavinia1, B. Catharine Craven1,21N...

Chikungunya virus (CHIKV) was until recently perceived only as a tropical disease. Since the first report of a case in Saint Martin Island in 2013, it has spread to South, Central, and North America. The first local transmission in the continental United States was reported in Florida in July 2014. CHIV infection is known to cause debilitating rheumatologic disease. Older adults are particularly susceptible to severe and chronic infection. Without an effective vaccine and antiviral therapy to prevent and control CHIKV, U.S. geriatricians could soon be confronted with major clinical, functional, and therapeutic challenges. After a general overview of CHIKV infection, this review will examine reasons why it has become such a threat to the United States and consider factors that contribute to the greater burden and effect of this disease in elderly adults. Consideration will be given to how aging and immunosenescence may contribute to CHIKV's atypical and more-severe clinical features in older adults. This review concludes with possible therapeutic approaches that best fit the unique needs of older adults, especially with regard to multimorbidity and polypharmacy.