Estimating health state utilities in Duchenne muscular dystrophy using the health utilities index and EQ-5D-5L.

BACKGROUND: The progression of Duchenne muscular dystrophy (DMD) is characterized by loss of ambulation, respiratory insufficiency, cardiomyopathy, and early mortality. DMD profoundly impacts health-related quality-of-life (HRQoL). However, few health state utility data exist; published utilities tend to be derived from small samples for a limited number of health states and are often based on caregiver-reported patient health status. This study estimated utility values for varied clinical and functional health states in DMD, based on patient-reported health status. METHODS: Individuals with DMD in the US aged 12-40 years completed the EQ-5D (5-level) and Health Utilities Index (HUI) preference-based instruments. Based on responses to a clinical questionnaire, participants self-classified into functional health states according to level of lower and upper limb function, use of respiratory support, and presence of cardiomyopathy. Mean [standard deviation (SD)] utility and EQ-5D visual analogue scale (VAS) scores were estimated according to health state; and median (interquartile range) attribute levels calculated to understand which domains of health are most severely affected in DMD. RESULTS: Of 63 males with DMD, mean (SD) age was 19.8 (6.1) years and 11 (17.5%) were ambulatory. Mean (SD) utility values were 0.92 (0.08; HUI2), 0.84 (0.20; HUI3), and 0.84 (0.13; EQ-5D) for ambulatory patients without cardiomyopathy (n = 10). For non-ambulatory patients with moderately impaired upper limb function, night and daytime ventilation without cardiomyopathy, mean (SD) utilities were 0.49 (0.07) for the HUI2, 0.16 (0.15) for the HUI3 and 025 (0.14) for the EQ-5D. Mean (SD) VAS scores for the same health states were 91 (9) and 83 (21), respectively. In addition to impairments in mobility/ambulation, and self-care, attributes like usual activities and pain also showed notable effects of DMD. CONCLUSIONS: In DMD, although a relationship between disease progression and HRQoL is observed, there is large variability in utility within functional health states, and across instruments. Utility values for less severe non-ambulatory health states described by level of upper limb function are novel. These utility values, derived based on direct patient feedback rather than from caregiver report, are relevant to individuals of varying functional statuses and augment scarce DMD-specific utility data.

Health State Utility Mapping of Rimegepant for the Preventive Treatment of Migraine: Double-Blind Treatment Phase and Open Label Extension (BHV3000-305).

INTRODUCTION: The objectives of this study were to (1) report long-term health-related quality of life (HRQoL) outcomes among patients using rimegepant preventatively in BHV3000-305 (NCT03732638) open-label extension (OLE) and (2) map Migraine-Specific Quality of Life questionnaire version 2.1 (MSQv2) to EQ-5D-3L utility values over the double-blind treatment (DBT; 0-12 weeks) and the OLE (13-64 weeks) to assess the influence of treatment on these values. METHODS: This was a post hoc analysis using data from a rimegepant study for the prevention of migraine (BHV3000-305). Adult patients with migraine took either rimegepant 75 mg or placebo every other day (EOD) during the DBT phase. All patients received rimegepant during the OLE. MSQv2 was measured at baseline, weeks 12, 24, and 64. A validated algorithm was used to map MSQv2 scores to EQ-5D utilities. RESULTS: Baseline data were available for 347 patients treated with placebo and 348 treated with rimegepant in the DBT period, who continued to the OLE. Baseline EQ-5D utilities were similar between trial arms: 0.598 for placebo and 0.614 for rimegepant. EQ-5D improved from baseline to week 12 and utilities increased by + 0.09 for placebo and + 0.10 for rimegepant (p value = 0.011). By 24 weeks, at which point patients who were originally randomized to placebo had received rimegepant 75 mg EOD for 12 weeks, HRQoL measures (MSQv2 and EQ-5D) were similar across groups, demonstrating rapid onset of treatment effect. This HRQoL improvement was durable out to 64 weeks. CONCLUSION: Compared to placebo, treatment with rimegepant 75 mg was associated with greater improvement in EQ-5D utilities during the 12-week DBT phase. Patients originally randomized to placebo experienced a similar improvement in EQ-5D utilities after switching to rimegepant during the OLE, demonstrating that benefits are realized within 12 weeks of active treatment. This preventive effect was durable out to 64 weeks and was associated with an additional increase in HRQoL over time. TRIAL REGISTRATION: NCT03732638.

People who make frequent emergency department visits based on persistence of frequent use in Ontario and Alberta: a retrospective cohort study.

BACKGROUND: The factors that underlie persistent frequent visits to the emergency department are poorly understood. This study aimed to characterize people who visit emergency departments frequently in Ontario and Alberta, by number of years of frequent use. METHODS: This was a retrospective cohort study aimed at capturing information about patients visiting emergency departments in Ontario and Alberta, Canada, from Apr. 1, 2011, to Mar. 31, 2016. We identified people 18 years or older with frequent emergency department use (top 10% of emergency department use) in fiscal year 2015/16, using the Dynamic Cohort from the Canadian Institute of Health Information. We then organized them into subgroups based on the number of years (1 to 5) in which they met the threshold for frequent use over the study period. We characterized subgroups using linked emergency department, hospitalization and mental health-related hospitalization data. RESULTS: We identified 252 737 people in Ontario and 63 238 people in Alberta who made frequent visits to the emergency department. In Ontario and Alberta, 44.3% and 44.7%, respectively, met the threshold for frequent use in only 1 year and made 37.9% and 38.5% of visits; 6.8% and 8.2% met the threshold for frequent use over 5 years and made 11.9% and 13.2% of visits. Many characteristics followed gradients based on persistence of frequent use: as years of frequent visits increased (1 to 5 years), people had more comorbidities, homelessness, rural residence, annual emergency department visits, alcohol- and substance use-related presentations, mental health hospitalizations and instances of leaving hospital against medical advice. INTERPRETATION: Higher levels of comorbidities, mental health issues, substance use and rural residence were seen with increasing years of frequent emergency department use. Interventions upstream and in the emergency department must address unmet needs, including services for substance use and social supports.

Subgroups of people who make frequent emergency department visits in Ontario and Alberta: a retrospective cohort study.

BACKGROUND: The population that visits emergency departments frequently is heterogeneous and at high risk for mortality. This study aimed to characterize these patients in Ontario and Alberta, compare them with controls who do not visit emergency departments frequently, and identify subgroups. METHODS: This was a retrospective cohort study that captured patients in Ontario or Alberta from fiscal years 2011/12 to 2015/16 in the Dynamic Cohort from the Canadian Institute for Health Information, which defined people with frequent visits to the emergency department in the top 10% of annual visits and randomly selected controls from the bottom 90%. We included patients 18 years of age or older and linked to emergency department, hospitalization, continuing care, home care and mental health-related hospitalization data. We characterized people who made frequent visits to the emergency department over time, compared them with controls and identified subgroups using cluster analysis. We examined emergency department visit acuity using the Canadian Triage and Acuity Scale. RESULTS: The number of patients who made frequent visits to the emergency department ranged from 435 334 to 477 647 each year in Ontario (≥ 4 visits per year), and from 98 840 to 105 047 in Alberta (≥ 5 visits per year). The acuity of these visits increased over time. Those who made frequent visits to the emergency department were older and used more health care services than controls. We identified 4 subgroups of those who made frequent visits: "short duration" (frequent, regularly spaced visits), "older patients" (median ages 69 and 64 years in Ontario and Alberta, respectively; more comorbidities; and more admissions), "young mental health" (median ages 45 and 40 years in Ontario and Alberta, respectively; and common mental health-related and alcohol-related visits) and "injury" (increased prevalence of injury-related visits). INTERPRETATION: From 2011/12 to 2015/16, people who visited emergency departments frequently had increasing visit acuity, had higher health care use than controls, and comprised distinct subgroups. Emergency departments should codevelop interventions with the identified subgroups to address patient needs.

The CCEDRRN COVID-19 Mortality Score to predict death among nonpalliative patients with COVID-19 presenting to emergency departments: a derivation and validation study.

BACKGROUND: Predicting mortality from COVID-19 using information available when patients present to the emergency department can inform goals-of-care decisions and assist with ethical allocation of critical care resources. The study objective was to develop and validate a clinical score to predict emergency department and in-hospital mortality among consecutive nonpalliative patients with COVID-19; in this study, we define palliative patients as those who do not want resuscitative measures, such as intubation, intensive care unit care or cardiopulmonary resuscitation. METHODS: This derivation and validation study used observational cohort data recruited from 46 hospitals in 8 Canadian provinces participating in the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN). We included adult (age ≥ 18 yr) nonpalliative patients with confirmed COVID-19 who presented to the emergency department of a participating site between Mar. 1, 2020, and Jan. 31, 2021. We randomly assigned hospitals to derivation or validation, and prespecified clinical variables as candidate predictors. We used logistic regression to develop the score in a derivation cohort and examined its performance in predicting emergency department and in-hospital mortality in a validation cohort. RESULTS: Of 8761 eligible patients, 618 (7.0%) died. The CCEDRRN COVID-19 Mortality Score included age, sex, type of residence, arrival mode, chest pain, severe liver disease, respiratory rate and level of respiratory support. The area under the curve was 0.92 (95% confidence interval [CI] 0.90-0.93) in derivation and 0.92 (95% CI 0.90-0.93) in validation. The score had excellent calibration. These results suggest that scores of 6 or less would categorize patients as being at low risk for in-hospital death, with a negative predictive value of 99.9%. Patients in the low-risk group had an in-hospital mortality rate of 0.1%. Patients with a score of 15 or higher had an observed mortality rate of 81.0%. INTERPRETATION: The CCEDRRN COVID-19 Mortality Score is a simple score that can be used for level-of-care discussions with patients and in situations of critical care resource constraints to accurately predict death using variables available on emergency department arrival. The score was derived and validated mostly in unvaccinated patients, and before variants of concern were circulating widely and newer treatment regimens implemented in Canada. STUDY REGISTRATION: ClinicalTrials.gov, no. NCT04702945.

Characteristics of frequent emergency department users in British Columbia, Canada: a retrospective analysis.

BACKGROUND: Frequent emergency department users disproportionately account for rising health care costs. We aimed to characterize frequent emergency department users in British Columbia, Canada. METHODS: We performed a retrospective analysis using health administrative databases. We included patients aged 18 years or more with at least 1 emergency department visit from 2012/13 to 2015/16, linked to hospital, physician billing, prescription and mortality data. We used annual emergency department visits made by the top 10% of patients to define frequent users (≥ 3 visits/year). RESULTS: Over the study period, 13.8%-15.3% of patients seen in emergency departments were frequent users. We identified 205 136 frequent users among 1 196 353 emergency department visitors. Frequent users made 40.3% of total visits in 2015/16. From 2012/13 to 2015/16, their visit rates per 100 000 BC population showed a relative increase of 21.8%, versus 13.1% among all emergency department patients. Only 1.8% were frequent users in all study years. Mental illness accounted for 8.2% of visits among those less than 60 years of age, and circulatory or respiratory diagnoses for 13.3% of visits among those aged 60 or more. In 2015/16, frequent users were older and had lower household incomes than nonfrequent users; the sex distribution was similar. Frequent users had more prescriptions (median 9, interquartile range [IQR] 5-14 v. 1, IQR 1-3), primary care visits (median 15, IQR 9-27 v. 7, IQR 4-12) and hospital admissions (median 2, IQR 1-3 v. 1, IQR 1-1), and higher 1-year mortality (10.2% v. 3.5%) than nonfrequent users. INTERPRETATION: Emergency department use by frequent users increased in BC between 2012/13 and 2015/16; these patients were heterogenous, had high mortality and rarely remained frequent users over multiple years. Our results suggest that interventions must account for heterogeneity and address triggers of frequent use episodes.

Identifying subgroups and risk among frequent emergency department users in British Columbia.

Objective: Frequent emergency department (ED) users are heterogeneous. We aimed to identify subgroups and assess their mortality. Methods: We identified patients ≥18 years with ≥1 ED visit in British Columbia from April 1, 2012 to March 31, 2015, and linked to hospitalization, physician billing, prescription, and mortality data. Frequent users were the top 10% of patients by ED visits. We employed cluster analysis to identify frequent user subgroups. We assessed 365-day mortality using Kaplan-Meier curves and conducted Cox regressions to assess mortality risk factors within subgroups. Results: We identified 4 subgroups. Subgroup 1 ("Elderly") had median age 77 years (interquartile range [IQR]: 66-85), 5 visits/year (IQR: 4-6), median 8 prescription medications (IQR: 5-11), and 24.7% mortality. Subgroup 2 ("Mental Health and Alcohol Use") had median age 48 years (IQR: 34-61), 13 visits/year (IQR: 10-16), and 12.3% mortality. They made a median 31 general practitioner visits (IQR: 19-51); however, only 23.7% received a majority of services from 1 primary care physician. Subgroup 3 ("Young Mental Health") had median age 39 years (IQR: 28-51), 5 visits/year (IQR: 4-6), and 2.2% mortality. Subgroup 4 ("Short-term") had median age 50 years (IQR: 34-65), 4 visits/year (IQR: 4-5) regularly spaced over a short term, and 1.4% mortality. Male sex (all subgroups), long-term care ("Mental Health and Alcohol Use;" "Young Mental Health"), and rural residence ("Elderly" in long-term care; "Young Mental Health") were associated with increased mortality. Conclusions: Our results identify frequent user subgroups with varying mortality. Future research should explore subgroups' unmet needs and tailor interventions toward them.

Short communication: Systematic review on effectiveness of micro-induction approaches to buprenorphine initiation.

BACKGROUND/OBJECTIVES: Micro-induction is a novel buprenorphine induction approach that seeks to avoid withdrawal and minimize precipitated withdrawal, both barriers to standard inductions. We aimed to synthesize evidence on micro-induction effectiveness, and regimens described. METHODS: We searched scientific databases and grey literature for studies including adolescents or adults with opioid use disorder who received buprenorphine micro-induction. Study selection, data extraction and quality assessments occurred in duplicate. We narratively synthesized results. RESULTS: We screened 4,752 citations and included 19 case studies/series and one feasibility study (n = 57 patients; mean age 38 years [SD 12.0]; 57.9% male [33/57]). Studies described 26 regimens; starting and maintenance doses ranged from 0.03 to 1.0 mg, and 8 to 32 mg, respectively. We calculated rate of increase to 8 mg. All patients achieved the desired maintenance dose. Among 54 patients in whom precipitated withdrawal was not reported, mean increases were 1.36 mg/day (SD 0.41). For three patients in whom precipitated withdrawal was specifically reported, mean increase was 1.17 mg/day (SD 0.11). All studies were low quality. DISCUSSION: Described regimens are highly variable. Inconsistent reporting, selection bias, and poor quality evidence limit conclusions regarding optimal dosing, and patient characteristics and clinical settings in which micro-induction is likely beneficial. CONCLUSIONS: This systematic review provides the most up-to-date synthesis on buprenorphine micro-induction regimens. Rigorous studies evaluating effectiveness and safety of micro-induction, and patient and clinical factors influencing its success, are needed.

Horticulture in Queensland Australia, COVID-19 Response. It Hasn't All Been Bad on Reflection.

Australia and with that Queensland have been extremely fortunate with the impact of COVID-19. Queensland has only had 1,067 cases as of June 30, 2020, of which 78% have been overseas acquired. Australia and Queensland acted early to address COVID-19 by putting in place a range of strategies including travel bans (international and domestic), isolation measures, testing regimes, advice to business, economic support, and research funding. Agriculture was designated an essential business and as such has continued operating throughout the pandemic. They have however had to develop and implement COVID plans to keep workers safe. To help agricultural business establish plans information was developed by Safe Work Australia, National Farmers Federation and the Queensland Department of Workplace Health and Safety. Workforce issues were identified early, particularly seasonal workers (those who travel from their usual place of residence to another place to work). The Queensland Government enacted a directive about how seasonal workers were to be managed and also developed a guide specifically for horticulture to help manage their COVID-19 response. We provide two case studies demonstrating how agriculture has responded to COVID-19. Agriculture has successfully, in Queensland, adapted quickly to the changing work conditions due to COVID-19. This is due to all levels of government coming together with industry to find solutions. Some changes have had wider benefits such as improved sanitation, better communication and a greater recognition of seasonal worker needs. Being prepared and resilient has enabled agriculture to alleviate the impact on their businesses ensuring the health of all.

Effectiveness of micro-induction approaches to buprenorphine initiation: A systematic review protocol.

BACKGROUND: Buprenorphine is first-line opioid agonist therapy for opioid use disorder. Standard regimens require that patients be in opioid withdrawal prior to induction, which is a barrier for many. Micro-induction is a novel induction approach that does not require patients to be in withdrawal. Our primary objective is to synthesize available evidence on the effectiveness of micro-inductions on patient and clinical outcomes compared to standard dosing or other approaches, or evaluated without a comparator group. Secondary objectives are to synthesize evidence on clinical factors that influence micro-induction effectiveness, and to summarize micro-induction regimens described in the literature. METHODS: We will search MEDLINE, Embase, CINAHL, Psycinfo, Science Citation Index, and the grey literature for studies that include adolescents or adults with opioid use disorder who received a buprenorphine micro-induction regimen. We will consider any patient or clinical outcomes defined by study authors. We will include controlled and non-controlled interventional studies, observational studies, case reports/series and reports from relevant organizations or guidelines pertinent to our third objective. We will select studies, extract data and assess study quality (using the Downs and Black, and Cochrane Risk of Bias tools) in duplicate. We will narratively synthesize our results, and will meta-analyze outcome measures if multiple studies report common outcomes with acceptably low heterogeneity. DISCUSSION: Our review will include the most up-to-date available data on buprenorphine micro-inductions. We anticipate limitations relating to study heterogeneity and quality. We will disseminate study results widely to inform updated guidelines for opioid agonist therapy prescribers.

Naloxone dosing in the era of ultra-potent opioid overdoses: a systematic review.

OBJECTIVES: Evaluate the relationship between naloxone dose (initial and cumulative) and opioid toxicity reversal and adverse events in undifferentiated and presumed fentanyl/ultra-potent opioid overdoses. METHODS: We searched Embase, MEDLINE, Cochrane Central Register of Controlled Trials, DARE, CINAHL, Science Citation Index, reference lists, toxicology websites, and conference proceedings (1972 to 2018). We included interventional, observational, and case studies/series reporting on naloxone dose and opioid toxicity reversal or adverse events in people >12 years old. RESULTS: A total of 174 studies (110 case reports/series, 57 observational, 7 interventional) with 26,660 subjects (median age 35 years; 74% male). Heterogeneity precluded meta-analysis. Where reported, we abstracted naloxone dose and proportion of patients with toxicity reversal. Among patients with presumed exposure to fentanyl/ultra-potent opioids, 56.9% (617/1,085) responded to an initial naloxone dose ≤0.4 mg compared with 80.2% (170/212) of heroin users, and 30.4% (7/23) responded to an initial naloxone dose >0.4 mg compared with 59.1% (1,434/2,428) of heroin users. Among patients who responded, median cumulative naloxone doses were higher for presumed fentanyl/ultra-potent opioids than heroin overdoses in North America, both before 2015 (fentanyl/ultra-potent opioids: 1.8 mg [interquartile interval {IQI}, 1.0, 4.0]; heroin: 0.8 mg [IQI, 0.4, 0.8]) and after 2015 (fentanyl/ultra-potent opioids: 3.4 mg [IQI, 3.0, 4.1]); heroin: 2 mg [IQI, 1.4, 2.0]). Where adverse events were reported, 11% (490/4,414) of subjects experienced withdrawal. Variable reporting, heterogeneity and poor-quality studies limit conclusions. CONCLUSIONS: Practitioners have used higher initial doses, and in some cases higher cumulative naloxone doses to reverse toxicity due to presumed fentanyl/ultra-potent opioid exposure compared with other opioids. High-quality comparative naloxone dosing studies assessing effectiveness and safety are needed.

Sunshine is an Important Determinant of Vitamin D Status Even Among High-dose Supplement Users: Secondary Analysis of a Randomized Controlled Trial in Crohn's Disease Patients.

Sunshine is considered to be the most important source of vitamin D. Due to an increased risk of skin cancer, sun avoidance is advised, but this directly contributes to the high prevalence of vitamin D deficiency. The simple solution is to advise vitamin D supplementation. The aim of this study was to examine the absolute and relative contribution of sunshine and supplementation to vitamin status. This study was a secondary analysis of an RCT of 92 Crohn's disease patients in remission (49% female, median age = 44). Participants were randomized to 2000 IU day-1 of vitamin D3 or placebo for 1 year, with 25-hydroxyvitamin D (25(OH)D) being measured at baseline and every 4 months. Based on participant's place of residence, daily ambient UVB dose at wavelengths that can induce vitamin D synthesis (D-UVB) was obtained. Cumulative and weighted ambient D-UVB (cw-D-UVB) exposure prior to each blood draw was calculated for each participant. Linear regression analysis and multilevel modeling were used to examine the association between UVB exposure, supplementation and 25(OH)D concentration. There was considerable annual variation in D-UVB, cw-D-UVB and 25(OH)D. Both supplementation and cw-D-UVB were found to be strongly associated with 25(OH)D: in multilevel model, an increase of approximately 6 nmol L-1 for every 100 kJ m-2 in cw-D-UVB was found, among those receiving placebo and supplementation (P < 0.0001). Treatment was associated with increase of 23 nmol L-1 (P < 0.0001). Sunshine is an important determinant of 25(OH)D concentration, even in those who are taking high-dose vitamin D supplements and reside at a higher mid-latitude location.

Annual Ambient UVB at Wavelengths that Induce Vitamin D Synthesis is Associated with Reduced Esophageal and Gastric Cancer Risk: A Nested Case-Control Study.

Vitamin D has been shown to be beneficial at reducing the risk of cancer; however, studies examining esophageal and gastric cancer have been scarce and findings inconsistent. The UK Biobank cohort was used for this nested case-control study (N = 3732). Primary, incident esophageal and gastric cancer cases diagnosed after recruitment were identified via linkage to National Cancer Registries. Tropospheric Emissions Monitoring Internet Service database was used to calculate ambient annual UVB dose (D-UVB). Conditional logistic regression was used to investigate the relationship between annual ambient D-UVB and risk of esophageal and gastric cancer, and odds ratios (ORs) are reported. In total, 373 esophageal and 249 gastric cancer cases and 3110 age- and gender-matched controls were included in the study. We found a strong inverse association between annual ambient D-UVB and odds of developing esophageal or gastric cancer: Compared to the lowest tertile, OR for the highest tertile was 0.64 (95%CI:0.51-0.79) in adjusted analysis. The association was strengthened when restricted to esophageal cancer (OR = 0.60; 95%CI:0.45-0.80) and esophageal adenocarcinoma cases (OR = 0.48; 95%CI: 0.34-0.68). Similar results were found in unadjusted and stratified analysis. In conclusion, ambient UVB radiation is inversely associated with the development of esophageal and gastric cancer, even in a high-latitude country.

Ambient UVB Dose and Sun Enjoyment Are Important Predictors of Vitamin D Status in an Older Population.

Background: UVB-induced skin synthesis is considered the key source of vitamin D, yet exposure to UVB is poorly accounted for in epidemiological studies.Objectives: The aim of this study was to examine the association of serum 25-hydroxyvitamin D [25(OH)D] concentration with accurately measured ambient UVB dose, sun enjoyment, supplements, and other factors.Methods: An all-Irish cohort of community-dwelling participants aged >60 y [median age: 73; 67% female; median 25(OH)D: 54.5 nmol/L] was used. Participants from this large, cross-sectional study completed a questionnaire to provide information on demographic factors and lifestyle (including supplement use and sun enjoyment). The Tropospheric Emission Monitoring Internet Service database was used to extract the daily ambient UVB dose at wavelengths that could induce vitamin D synthesis (D-UVB) over Ireland (latitude: 51°N-55°N). Blood sampling occurred throughout the year. Ambient exposure at the place of residence was calculated for each participant individually. Associations between determinants and serum 25(OH)D concentration were examined in a multivariate model. Random forest analysis was used to establish prediction models of vitamin D deficiency, and area under the curve (AUC) is shown.Results: In total, 5138 individuals were included. Median D-UVB was 63 mJ/cm2, which varied between seasons and latitudes, despite the small latitude differential. Vitamin D supplementation (ß = 27.7; P < 10 × 10-10), D-UVB (ß = 1.58 per 1000 mJ/cm2; P < 10 × 10-10), and sun enjoyment (ß = 6.6; P < 0.001) were strongly positively associated with serum 25(OH)D. Those who avoided sunshine were largely at risk of deficiency (<40 nmol/L), whereas those who enjoyed sunshine tended to be vitamin D sufficient (≥50 nmol/L). D-UVB and sun enjoyment improved prediction of deficiency in non-supplement-taking individuals; the overall AUC improved by 3.5%.Conclusion: D-UVB and sun enjoyment are important predictors of vitamin D status, even in this elderly population at northern latitudes. Accurate estimation of ambient UVB can help to further clarify the role of other determinants of vitamin D status and inform sunshine recommendation guidelines.

Markers of Vitamin D Exposure and Esophageal Cancer Risk: A Systematic Review and Meta-analysis.

Vitamin D has been associated with reduced risk of many cancers, but evidence for esophageal cancer is mixed. To clarify the role of vitamin D, we performed a systematic review and meta-analysis to evaluate the association of vitamin D exposures and esophageal neoplasia, including adenocarcinoma, squamous cell carcinoma (SCC), Barrett's esophagus, and squamous dysplasia. Ovid MEDLINE, EMBASE, and Web of Science were searched from inception to September 2015. Fifteen publications in relation to circulating 25-hydroxyvitamin D [25(OH)D; n = 3], vitamin D intake (n = 4), UVB exposure (n = 1), and genetic factors (n = 7) were retrieved. Higher [25(OH)D] was associated with increased risk of cancer [adenocarcinoma or SCC, OR = 1.39; 95% confidence interval (CI), 1.04-1.74], with the majority of participants coming from China. No association was observed between vitamin D intake and risk of cancer overall (OR, 1.03; 0.65-1.42); however, a nonsignificantly increased risk for adenocarcinoma (OR, 1.45; 0.65-2.24) and nonsignificantly decreased risk for SCC (OR, 0.80; 0.48-1.12) were observed. One study reported a decreased risk of adenocarcinoma with higher UVB exposure. A decreased risk was found for VDR haplotype rs2238135(G)/rs1989969(T) carriers (OR, 0.45; 0.00-0.91), and a suggestive association was observed for rs2107301. In conclusion, no consistent associations were observed between vitamin D exposures and occurrence of esophageal lesions. Further adequately powered, well-designed studies are needed before conclusions can be made. Cancer Epidemiol Biomarkers Prev; 25(6); 877-86. ©2016 AACR.

The international forum of ophthalmic simulation: developing a virtual reality training curriculum for ophthalmology.

BACKGROUND: To investigate the effect of a structured, supervised, cataract simulation programme on ophthalmic surgeons in their first year of training, and to evaluate the level of skill transfer. METHODS: Trainees with minimal intraocular and simulator experience in their first year of ophthalmology undertook a structured, sequential, customised, virtual reality (VR) cataract training programme developed through the International Forum of Ophthalmic Simulation. A set of one-handed, bimanual, static and dynamic tasks were evaluated before and after the course and scores obtained. Statistical significance was evaluated with the Wilcoxon sign-rank test. RESULTS: The median precourse score of 101.50/400 (IQR 58.75-145.75) was significantly improved after completing the training programme ((postcourse score: 302/400, range: 266.25-343), p<0.001). While improvement was evident and found to be statistically significant in all parameters, greatest improvements were found for capsulorhexis and antitremor training ((Capsulorhexis: precourse score=0/100, range 0-4.5; postcourse score=81/100, range 13-87.75; p=0.002), (antitremor training: precourse score=0/100, range 0-0; postcourse score=80/100, range 60.25-91.50; p=0.001)). CONCLUSIONS: Structured and supervised VR training can offer a significant level of skills transfer to novice ophthalmic surgeons. VR training at the earliest stage of ophthalmic surgical training may, therefore, be of benefit.

Imprinted expression of the canine IGF2R, in the absence of an anti-sense transcript or promoter methylation.

Imprinted genes are epigenetically modified in a parent of origin-dependent manner, and as a consequence, are differentially expressed. Although the evolution of genomic imprinting is a subject of intense debate, imprinted genes have been studied primarily in mice and humans and in a small number of marsupial mammals. Comparative studies involving rodents and primates are of limited value, as they belong to the same superordinal group of eutherian mammals (Euarchontoglires). On the other hand, comparisons involving marsupials may not be informative, due to phylogenetic distance. Canis familiaris belongs to Laurasiatheria, a sister-group of Euarchontoglires, and should prove useful in comparative studies of imprinted genes. Using RT-PCR we demonstrate monoallelic expression of the canine IGF2R in several tissues, including uterus and umbilical cord. In the case of umbilical cord, we identify the expressed allele as maternally derived. The canine IGF2R is thus an imprinted gene. Using bisulfite sequencing, we show that the canine IGF2R resembles the imprinted mouse Igf2r in having a CpG island in intron 2 that is hemi-methylated. However, it differs from the mouse gene in that maintenance of the monoallelic expression of canine IGF2R does not require expression of an anti-sense transcript from the paternally derived allele, or methylation of the repressed IGF2R promoter. In these two important features, the imprinted canine gene resembles the imprinted opossum IGF2R. Our data suggest that these features were properties of the ancestral imprinted IGF2R and that the anti-sense transcript (Air) and promoter methylation observed in mouse are derived features of the mouse Igf2r locus.

Results of the betaxolol versus placebo treatment trial in ocular hypertension.

PURPOSE: To determine whether treatment with betaxolol can delay or prevent the conversion from ocular hypertension to early glaucoma on the basis of visual field criteria, by means of a prospective, randomised, placebo-controlled trial. METHODS: Three hundred and fifty-six ocular hypertensives were randomized to treatment with either betaxolol drops or placebo drops during the period 1992-1996. Each patient was followed prospectively with 4-monthly visits. Examination at each visit included visual field testing, intra-ocular pressure (IOP) measurement and optic disc imaging. Conversion to early glaucoma was defined on the basis of visual field change by AGIS criteria. An intent-to-treat analysis compared visual field conversion after 3 years in the treatment and placebo arms. Normal visual field survival analysis was also performed. The IOP characteristics of the two treatment groups were compared. RESULTS: Two hundred and fifty-five patients completed the study, which ended in 1998, with a range of follow-up of 2-6 years. Sixteen (13.2%) of 121 patients in the placebo group converted to glaucoma, compared with 12 (9.0%) of 134 patients in the betaxolol group. The intent-to-treat analysis demonstrated no evidence of any difference in conversion rates between the betaxolol and placebo groups after 3 years. Visual field survival analysis demonstrated no significant difference between the betaxolol and placebo groups. The betaxolol-treated group had significantly lower post-treatment IOP values. Converters had significantly higher pre- and post-treatment IOP values than non-converters. CONCLUSIONS: Betaxolol significantly lowered the IOP level compared with placebo. Conversion to glaucoma was found to be related to both the baseline and post-treatment IOP levels. However the intent-to-treat analysis did not demonstrate a statistically significant reduction in the conversion rate in the betaxolol-treated group.