Vitamin D did not reduce multiple sclerosis disease activity after a clinically isolated syndrome.

Low serum levels of 25-hydroxyvitamin D [25(OH)D] and low sunlight exposure are known risk factors for the development of multiple sclerosis. Add-on vitamin D supplementation trials in established multiple sclerosis have been inconclusive. The effects of vitamin D supplementation to prevent multiple sclerosis is unknown. We aimed to test the hypothesis that oral vitamin D3 supplementation in high-risk clinically isolated syndrome (abnormal MRI, at least three T2 brain and/or spinal cord lesions), delays time to conversion to definite multiple sclerosis, that the therapeutic effect is dose-dependent, and that all doses are safe and well tolerated. We conducted a double-blind trial in Australia and New Zealand. Eligible participants were randomized 1:1:1:1 to placebo, 1000, 5000 or 10 000 international units (IU) of oral vitamin D3 daily within each study centre (n = 23) and followed for up to 48 weeks. Between 2013 and 2021, we enrolled 204 participants. Brain MRI scans were performed at baseline, 24 and 48 weeks. The main study outcome was conversion to clinically definite multiple sclerosis based on the 2010 McDonald criteria defined as either a clinical relapse or new brain MRI T2 lesion development. We included 199 cases in the intention-to-treat analysis based on assigned dose. Of these, 116 converted to multiple sclerosis by 48 weeks (58%). Compared to placebo, the hazard ratios (95% confidence interval) for conversion were 1000 IU 0.87 (0.50, 1.50); 5000 IU 1.37 (0.82, 2.29); and 10 000 IU 1.28 (0.76, 2.14). In an adjusted model including age, sex, latitude, study centre and baseline symptom number, clinically isolated syndrome onset site, presence of infratentorial lesions and use of steroids, the hazard ratios (versus placebo) were 1000 IU 0.80 (0.45, 1.44); 5000 IU 1.36 (0.78, 2.38); and 10 000 IU 1.07 (0.62, 1.85). Vitamin D3 supplementation was safe and well tolerated. We did not demonstrate reduction in multiple sclerosis disease activity by vitamin D3 supplementation after a high-risk clinically isolated syndrome.

Risk of a first clinical diagnosis of central nervous system demyelination in relation to human herpesviruses in the context of Epstein-Barr virus.

BACKGROUND AND PURPOSE: Epstein-Barr virus (EBV) is implicated in multiple sclerosis (MS) risk; evidence for other herpesviruses is inconsistent. Here, we test blood markers of infection with human herpesvirus 6 (HHV-6), varicella zoster virus (VZV), and cytomegalovirus (CMV) as risk factors for a first clinical diagnosis of central nervous system demyelination (FCD) in the context of markers of EBV infection. METHODS: In the Ausimmune case-control study, cases had an FCD, and population controls were matched on age, sex, and study region. We quantified HHV-6- and VZV-DNA load in whole blood and HHV-6, VZV, and CMV antibodies in serum. Conditional logistic regression tested associations with FCD risk, adjusting for Epstein-Barr nuclear antigen (EBNA) IgG, EBV-DNA load, and other covariates. RESULTS: In 204 FCD cases and 215 matched controls, only HHV-6-DNA load (positive vs. negative) was associated with FCD risk (adjusted odds ratio = 2.20, 95% confidence interval = 1.08-4.46, p = 0.03). Only EBNA IgG and HHV-6-DNA positivity were retained in a predictive model of FCD risk; the combination had a stronger association than either alone. CMV-specific IgG concentration modified the association between an MS risk-related human leucocyte antigen gene and FCD risk. Six cases and one control had very high HHV-6-DNA load (>1.0 × 106 copies/mL). CONCLUSIONS: HHV-6-DNA positivity and high load (possibly due to inherited HHV-6 chromosomal integration) were associated with increased FCD risk, particularly in association with markers of EBV infection. With growing interest in prevention/management of MS through EBV-related pathways, there should be additional consideration of the role of HHV-6 infection.

The burden of occupational injury attributable to high temperatures in Australia, 2014-19: a retrospective observational study.

OBJECTIVES: To assess the population health impact of high temperatures on workplace health and safety by estimating the burden of heat-attributable occupational injury in Australia. STUDY DESIGN, SETTING: Retrospective observational study; estimation of burden of occupational injury in Australia attributable to high temperatures during 2014-19, based on Safe Work Australia (work-related traumatic injury fatalities and workers' compensation databases) and Australian Institute of Health and Welfare data (Australian Burden of Disease Study and National Hospital Morbidity databases), and a meta-analysis of climate zone-specific risk data. MAIN OUTCOME MEASURE: Burden of heat-attributable occupational injuries as disability-adjusted life years (DALYs), comprising the numbers of years of life lived with disability (YLDs) and years of life lost (YLLs), nationally, by Köppen-Geiger climate zone, and by state and territory. RESULTS: During 2014-19, an estimated 42 884 years of healthy life were lost to occupational injury, comprising 39 485 YLLs (92.1%) and 3399 YLDs (7.9%), at a rate of 0.80 DALYs per 1000 workers per year. A total of 967 occupational injury-related DALYs were attributable to heat (2.3% of occupational injury-related DALYs), comprising 890 YLLs (92%) and 77 YLDs (8%). By climate zone, the heat-attributable proportion was largest in the tropical Am (12 DALYs; 3.5%) and Aw zones (34 DALYs; 3.5%); by state and territory, the proportion was largest in New South Wales and Queensland (each 2.9%), which also included the largest numbers of heat-attributable occupational injury-related DALYs (NSW: 379 DALYs, 39% of national total; Queensland: 308 DALYs; 32%). CONCLUSION: An estimated 2.3% of the occupational injury burden in Australia is attributable to high ambient temperatures. To prevent this burden increasing with global warming, adaptive measures and industry-based policies are needed to safeguard workplace health and safety, particularly in heat-exposed industries, such as agriculture, transport, and construction.

Current and projected heatwave-attributable occupational injuries, illnesses, and associated economic burden in Australia.

INTRODUCTION: The costs of global warming are substantial. These include expenses from occupational illnesses and injuries (OIIs), which have been associated with increases during heatwaves. This study estimated retrospective and projected future heatwave-attributable OIIs and their costs in Australia. MATERIALS AND METHODS: Climate and workers' compensation claims data were extracted from seven Australian capital cities representing OIIs from July 2005 to June 2018. Heatwaves were defined using the Excess Heat Factor. OIIs and associated costs were estimated separately per city and pooled to derive national estimates. Results were projected to 2030 (2016-2045) and 2050 (2036-2065). RESULTS: The risk of OIIs and associated costs increased during heatwaves, with the risk increasing during severe and particularly extreme heatwaves. Of all OIIs, 0.13% (95% empirical confidence interval [eCI]: 0.11-0.16%) were heatwave-attributable, equivalent to 120 (95%eCI:70-181) OIIs annually. 0.25% of costs were heatwave-attributable (95%eCI: 0.18-0.34%), equal to $AU4.3 (95%eCI: 1.4-7.4) million annually. Estimates of heatwave-attributable OIIs by 2050, under Representative Concentration Pathway [RCP]4.5 and RCP8.5, were 0.17% (95%eCI: 0.10-0.27%) and 0.23% (95%eCI: 0.13-0.37%), respectively. National costs estimates for 2030 under RCP4.5 and RCP8.5 were 0.13% (95%eCI: 0.27-0.46%) and 0.04% (95%eCI: 0.66-0.60), respectively. These estimates for extreme heatwaves were 0.04% (95%eCI: 0.02-0.06%) and 0.04% (95%eCI: 0.01-0.07), respectively. Cost-AFs in 2050 were, under RCP4.5, 0.127% (95%eCI: 0.27-0.46) for all heatwaves and 0.04% (95%eCI: 0.01-0.09%) for extreme heatwaves. Attributable fractions were approximately similar to baseline when assuming theoretical climate adaptation. DISCUSSION: Heatwaves represent notable and preventable portions of preventable OIIs and economic burden. OIIs are likely to increase in the future, and costs during extreme heatwaves in 2030. Workplace and public health policies aimed at heat adaptation can reduce heat-attributable morbidity and costs.

Changes in Australian food anaphylaxis admission rates following introduction of updated allergy prevention guidelines.

BACKGROUND: Food anaphylaxis admission rates have increased steadily in recent decades. Global food allergy prevention guidelines recommending early introduction of allergenic foods were introduced in 2015-2016. Australian guidelines to not delay the introduction of allergenic foods were introduced in 2007-2008. OBJECTIVE: Our aim was to examine whether introduction of Australian guidelines (2007-2008) and global allergy prevention guidelines (2015-2016) were associated with reductions in food anaphylaxis admission rates. METHODS: We compared food anaphylaxis admission rates across 3 periods: 1998-1999 to 2006-2007, 2007-2008 to 2014-2015, and 2015-2016 to 2018-2019. RESULTS: Annual food anaphylaxis admission rates increased 9-fold between 1998-1999 and 2018-2019, from 2.0 per 105 population to 18.2 per 105 population; the highest absolute rates were in those younger than 1 year. When year-on-year rates of change were examined across the 3 time periods, the annual rate of increase slowed after 2007-2008 in those aged 1 to 4 years (17.6%, 6.2%, and 3.9% per year, respectively) and those aged 5 to 9 years (22%, 13.9%, and -2.4%, respectively), and after 2015-2016, in those aged 10 to 14 years (17.5%, 18.0%, and 10.8%, respectively). By contrast, the year-on-year rate of increase accelerated in those younger than 1 year (5.2%, 8.0%, and 18.0%, respectively) and in all age groups older than 15 years. CONCLUSIONS: Although food anaphylaxis continues to increase overall, there is preliminary evidence indicating a slowing in the year-on-year rate of increase among those aged 1 to 4, 5 to 9, and 10 to 14 years, coinciding with introduction of updated infant feeding and allergy prevention guidelines in 2007-2008 and 2015-2016. Changes to the guidelines may have contributed to an attenuated rate of increase in food anaphylaxis in these age groups, as well as to increased rates in those younger than 1 year.

Understanding current and projected emergency department presentations and associated healthcare costs in a changing thermal climate in Adelaide, South Australia.

BACKGROUND: Exposure to extreme temperatures is associated with increased emergency department (ED) presentations. The resulting burden on health service costs and the potential impact of climate change is largely unknown. This study examines the temperature-EDs/cost relationships in Adelaide, South Australia and how this may be impacted by increasing temperatures. METHODS: A time series analysis using a distributed lag nonlinear model was used to explore the exposure-response relationships. The net-attributable, cold-attributable and heat-attributable ED presentations for temperature-related diseases and costs were calculated for the baseline (2014-2017) and future periods (2034-2037 and 2054-2057) under three climate representative concentration pathways (RCPs). RESULTS: The baseline heat-attributable ED presentations were estimated to be 3600 (95% empirical CI (eCI) 700 to 6500) with associated cost of $A4.7 million (95% eCI 1.8 to 7.5). Heat-attributable ED presentations and costs were projected to increase during 2030s and 2050s with no change in the cold-attributable burden. Under RCP8.5 and population growth, the increase in heat-attributable burden would be 1.9% (95% eCI 0.8% to 3.0%) for ED presentations and 2.5% (95% eCI 1.3% to 3.7%) for ED costs during 2030s. Under the same conditions, the heat effect is expected to increase by 3.7% (95% eCI 1.7% to 5.6%) for ED presentations and 5.0% (95% eCI 2.6% to 7.1%) for ED costs during 2050s. CONCLUSIONS: Projected climate change is likely to increase heat-attributable emergency presentations and the associated costs in Adelaide. Planning health service resources to meet these changes will be necessary as part of broader risk mitigation strategies and public health adaptation actions.

Occupational heat stress and economic burden: A review of global evidence.

BACKGROUND: The adverse effects of heat on workers' health and work productivity are well documented. However, the resultant economic consequences and productivity loss are less understood. This review aims to summarize the retrospective and potential future economic burden of workplace heat exposure in the context of climate change. METHODS: Literature was searched from database inception to October 2020 using Embase, PubMed, and Scopus. Articles were limited to original human studies investigating costs from occupational heat stress in English. RESULTS: Twenty studies met criteria for inclusion. Eighteen studies estimated costs secondary to heat-induced labor productivity loss. Predicted global costs from lost worktime, in US$, were 280 billion in 1995, 311 billion in 2010 (≈0.5% of GDP), 2.4-2.5 trillion in 2030 (>1% of GDP) and up to 4.0% of GDP by 2100. Three studies estimated heat-related healthcare expenses from occupational injuries with averaged annual costs (US$) exceeding 1 million in Spain, 1 million in Guangzhou, China and 250,000 in Adelaide, Australia. Low- and middle-income countries and countries with warmer climates had greater losses as a proportion of GDP. Greater costs per worker were observed in outdoor industries, medium-sized businesses, amongst males, and workers aged 25-44 years. CONCLUSIONS: The estimated global economic burden of occupational heat stress is substantial. Climate change adaptation and mitigation strategies should be implemented to likely minimize future costs. Further research exploring the relationship between occupational heat stress and related expenses from lost productivity, decreased work efficiency and healthcare, and costs stratified by demographic factors, is warranted. Key messages. The estimated retrospective and future economic burden from occupational heat stress is large. Responding to climate change is crucial to minimize this burden. Analyzing heat-attributable occupational costs may guide the development of workplace heat management policies and practices as part of global warming strategies.

Estimation of annual probabilities of changing disability levels in Australians with relapsing-remitting multiple sclerosis.

BACKGROUND: Transition probabilities are the engine within many health economics decision models. However, the probabilities of progression of disability due to multiple sclerosis (MS) have not previously been estimated in Australia. OBJECTIVES: To estimate annual probabilities of changing disability levels in Australians with relapsing-remitting MS (RRMS). METHODS: Combining data from Ausimmune/Ausimmune Longitudinal (2003-2011) and Tasmanian MS Longitudinal (2002-2005) studies (n = 330), annual transition probabilities were obtained between no/mild (Expanded Disability Status Scale (EDSS) levels 0-3.5), moderate (EDSS 4-6.0) and severe (EDSS 6.5-9.5) disability. RESULTS: From no/mild disability, 6.4% (95% confidence interval (CI): 4.7-8.4) and 0.1% (0.0-0.2) progressed to moderate and severe disability annually, respectively. From moderate disability, 6.9% (1.0-11.4) improved (to no/mild state) and 2.6% (1.1-4.5) worsened. From severe disability, 0.0% improved to moderate and no/mild disability. Male sex, age at onset, longer disease duration, not using immunotherapies greater than 3 months and a history of relapse were related to higher probabilities of worsening. CONCLUSION: We have estimated probabilities of changing disability levels in Australians with RRMS. Probabilities differed between various subgroups, but due to small sample sizes, results should be interpreted with caution. Our findings will be helpful in predicting long-term disease outcomes and in health economic evaluations of MS.

Gastrostomies Preserve But Do Not Increase Quality of Life for Patients and Caregivers.

BACKGROUND & AIMS: Gastrostomies are widely used to provide long-term enteral nutrition to patients with neurologic conditions that affect swallowing (eg, following a cerebrovascular accident or for patients with motor neuron disease) or with oropharyngeal malignancies. The benefits derived from this intervention are uncertain for patients and caregivers. We conducted a prospective, multicenter cohort study to determine how gastrostomies affect health-related quality of life (HRQoL) in recipients and caregivers. METHODS: We performed a study of 100 patients who received gastrostomies (55% percutaneous endoscopic gastrostomy, 45% radiologically inserted) at 5 centers in the United Kingdom, 100 caregivers, and 200 population control subjects. We used the EuroQol-5D (comprising a questionnaire, index, visual analogue scale) to assess HRQoL for patients and caregivers before the gastrostomy insertion and then 3 months afterward; findings were compared with those from control subjects. Ten patients and 10 caregivers were also interviewed after the procedure to explore quantitative findings. Findings from the EuroQol-5D and semi-structured interviews were integrated using a mixed-methods matrix. RESULTS: Six patients died before the 3-month HRQoL reassessments. We observed no significant longitudinal changes in mean EuroQol-5D index scores for patients (0.70 before vs 0.710 after; P = .83) or caregivers (0.95 before vs 0.95 after; P = .32) following gastrostomy insertion. The semi-structured interviews revealed problems in managing gastrostomy tubes, social isolation, and psychological and emotional consequences that reduced HRQoL. CONCLUSIONS: We performed a mixed-methods prospective study of the effects of gastrostomy feeding on HRQoL. HRQoL did not significantly improve after gastrostomy insertion for patients or caregivers. The lack of significant decrease in HRQoL after the procedure indicates that gastrostomies may help maintain HRQoL. Findings have relevance to those involved in gastrostomy insertion decisions and indicate the importance of carefully selecting patients for this intervention, despite the relative ease of insertion.

Incidence and prevalence of NMOSD in Australia and New Zealand.

OBJECTIVES: We have undertaken a clinic-based survey of neuromyelitis optica spectrum disorders (NMOSDs) in Australia and New Zealand to establish incidence and prevalence across the region and in populations of differing ancestry. BACKGROUND: NMOSD is a recently defined demyelinating disease of the central nervous system (CNS). The incidence and prevalence of NMOSD in Australia and New Zealand has not been established. METHODS: Centres managing patients with demyelinating disease of the CNS across Australia and New Zealand reported patients with clinical and laboratory features that were suspicious for NMOSD. Testing for aquaporin 4 antibodies was undertaken in all suspected cases. From this group, cases were identified who fulfilled the 2015 Wingerchuk diagnostic criteria for NMOSD. A capture-recapture methodology was used to estimate incidence and prevalence, based on additional laboratory identified cases. RESULTS: NMOSD was confirmed in 81/170 (48%) cases referred. Capture-recapture analysis gave an adjusted incidence estimate of 0.37 (95% CI 0.35 to 0.39) per million per year and a prevalence estimate for NMOSD of 0.70 (95% CI 0.61 to 0.78) per 100 000. NMOSD was three times more common in the Asian population (1.57 (95% CI 1.15 to 1.98) per 100 000) compared with the remainder of the population (0.57 (95% CI 0.50 to 0.65) per 100 000). The latitudinal gradient evident in multiple sclerosis was not seen in NMOSD. CONCLUSIONS: NMOSD incidence and prevalence in Australia and New Zealand are comparable with figures from other populations of largely European ancestry. We found NMOSD to be more common in the population with Asian ancestry.

Records of medical malpractice litigation: a potential indicator of health-care quality in China.

OBJECTIVE: To assess the characteristics and incidence of medical litigation in China and the potential usefulness of the records of such litigation as an indicator of health-care quality. METHODS: We investigated 13 620 cases of medical malpractice litigation that ended between 2010 and 2015 and were reported to China's Supreme Court. We categorized each case according to location of the court, the year the litigation ended, the medical specialization involved, the severity of the reported injury, the type of allegation raised by the plaintiff - including any alleged shortcomings in the health care received - and the outcome of the litigation. FINDINGS: The annual incidence of medical malpractice litigation increased from 75 in 2010 to 6947 in 2014. Most cases related to general surgery (1350 litigations), internal medicine (3500 litigations), obstetrics and gynaecology (1251 litigations) and orthopaedics (1283 litigations). Most of the reported injuries were either minor (1358 injuries) or fatal (4111 deaths). The most frequent allegation was of lack of consent or notification (1356 litigations), followed by misdiagnosis (1172 litigations), delay in treatment (1145 litigations) and alteration or forgery of medical records (975 litigations). Of the 11 014 plaintiffs with known litigation outcomes, 7482 (67.9%) received monetary compensation. CONCLUSION: Over our study period, the incidence of litigation over potential medical malpractice increased in China. As many of the cases related to alleged inadequacies in the quality of health care, records of medical malpractice litigation in China may be worth exploring as an indicator of health-care quality.

Risk factors for deaths during the 2009 heat wave in Adelaide, Australia: a matched case-control study.

The extreme heat wave in Australia in 2009 resulted in significantly increased number of daily deaths. The circumstances that lead to deaths during extreme heat have not been explored before in Australia. This study aims to identify the individual and community risk factors for deaths during this extreme heat wave in Adelaide. A matched case-control study was conducted. Cases were those who died in the Adelaide metropolitan area during the heat wave period. For each case, two community controls were randomly selected, matched by age and gender. Face-to-face or telephone interviews were conducted to collect data of demographic information, living environment, social support, health status and behavioural changes during the heat wave. Descriptive analysis, as well as simple and multiple conditional logistic regressions were performed. In total, 82 deaths and 164 matched community controls were included in the analysis, with a median age of 77.5 (range 26.6-100.7). The multiple logistic regression model indicated that, compared with controls, the risk of death during the heat wave was significantly increased for people living alone (AOR = 42.31, 95 % CI 2.3, 792.8) or having existing chronic heart disease (AOR = 22.4, 95 % CI 1.7, 303.0). In addition, having air conditioning in bedrooms (AOR = 0.004, 95 % CI 0.00006, 0.28) and participating in social activities more than once a week (AOR = 0.011, 95 % CI 0.0004, 0.29) indicated significant protective effects. We have identified factors that could significantly impact on the likelihood of deaths during heat waves. Our findings could assist in the development of future intervention programs and policies to reduce mortality associated with a warmer climate.

Challenges and Opportunities for Urban Environmental Health and Sustainability: the HEALTHY-POLIS initiative.

Cities around the world face many environmental health challenges including contamination of air, water and soil, traffic congestion and noise, and poor housing conditions exacerbated by unsustainable urban development and climate change. Integrated assessment of these risks offers opportunities for holistic, low carbon solutions in the urban environment that can bring multiple benefits for public health. The Healthy-Polis consortium aims to protect and promote urban health through multi-disciplinary, policy-relevant research on urban environmental health and sustainability. We are doing this by promoting improved methods of health risk assessment, facilitating international collaboration, contributing to the training of research scientists and students, and engaging with key stakeholders in government, local authorities, international organisations, industry and academia. A major focus of the consortium is to promote and support international research projects coordinated between two or more countries. The disciplinary areas represented in the consortium are many and varied, including environmental epidemiology, modelling and exposure assessment, system dynamics, health impact assessment, multi-criteria decision analysis, and other quantitative and qualitative approaches. This Healthy-Polis special issue presents a range of case studies and reviews that illustrate the need for a systems-based understanding of the urban environment.

Investigating the patterns and determinants of seasonal variation in vitamin D status in Australian adults: the Seasonal D Cohort Study.

BACKGROUND: Vitamin D status generally varies seasonally with changing solar UVB radiation, time in the sun, amount of skin exposed, and, possibly, diet. The Seasonal D Study was designed to quantify the amplitude and phase of seasonal variation in the serum concentration of 25-hydroxyvitamin D, (25OH)D)) and identify the determinants of the amplitude and phase and those of inter-individual variability in seasonal pattern. METHODS: The Seasonal D Study collected data 2-monthly for 12 months, including demographics, personal sun exposure using a diary and polysulphone dosimeters over 7 days, and blood for serum 25(OH)D concentration. The study recruited 333 adults aged 18-79 years living in Canberra (35°S, n = 168) and Brisbane (27°South, n = 165), Australia. DISCUSSION: We report the study design and cohort description for the Seasonal D Study. The study has collected a wealth of data to examine inter- and intra-individual seasonal variation in vitamin D status and serum 25(OH)D levels in Australian adults.

Time trends in Australian hospital anaphylaxis admissions in 1998-1999 to 2011-2012.

BACKGROUND: Studies from the United Kingdom, the United States, and Australia have reported increased childhood food allergy and anaphylaxis prevalence in the 15 years after 1990. OBJECTIVE: We sought to examine whether childhood food allergy/anaphylaxis prevalence has increased further since 2004-2005. METHODS: We examined hospital anaphylaxis admission rates between 2005-2006 and 2011-2012 and compared findings with those from 1998-1999 to 2004-2005. RESULTS: Overall population food-related anaphylaxis admission rates (per 10(5) population per year) increased from 5.6 in 2005-2006 to 8.2 in 2011-2012 (a 1.5-fold increase over 7 years). The highest rates occurred in children aged 0 to 4 years (21.7 in 2005-2006 and 30.3 in 2011-2012, a 1.4-fold increase), but the greatest proportionate increase occurred in those aged 5 to 14 years (5.8-12.1/10(5) population/y, respectively, a 2.1-fold increase) compared with those aged 15 to 29 years and 30 years or older (a 1.5- and 1.3-fold increase, respectively). Not only did absolute food-related anaphylaxis admissions increase, but the modeled year-on-year rate of increase in overall food-related anaphylaxis admissions also increased over time from an additional 0.35 per 10(5) population/y in 1998-1999 (all ages) to 0.49 in 2004-2005 and 0.63 in 2011-2012 (P < .001). CONCLUSIONS: Food-related anaphylaxis has increased further in all age groups since 2004-2005. Although the major burden falls on those aged 0 to 4 years, there is preliminary evidence for a recent acceleration in incidence rates in those aged 5 to 14 years. This contrasts with the previous decade in which the greatest proportionate increase was in those aged 0 to 4 years. These findings suggest a possible increasing burden of disease among adolescents and adults who carry the highest risk for fatal anaphylaxis.

Keyhole limpet haemocyanin - a model antigen for human immunotoxicological studies.

Immunization with a T-cell dependent antigen has been promoted as a reliable and sensitive tool for assessing the influence of putative immunotoxic exposures or agents on immune function. Keyhole limpet haemocyanin (KLH) is a very large, copper-containing protein molecule derived from the haemolymph of the inedible mollusc, Megathura crenulata. KLH is a highly immunogenic T-cell dependent antigen that is used increasingly in immunotoxicological studies, particularly in those involving animals. This report systematically reviews the human clinical studies that have used trans-cutaneous KLH immunization for assessment of the influence of various physiological and disease states and exposures on immune function over the last 20 years (1994-2013). These studies varied in their immunization protocols, formulation of KLH, dose, site and route of administration and immunoassay platforms developed to assess KLH-specific responses. KLH immunization has been well tolerated with only mild to moderate adverse effects reported. Though very promising as a model antigen candidate in immunotoxicology research, more work on standardizing immunization and immunoassay protocols is required.

The association between temperature and mortality in tropical middle income Thailand from 1999 to 2008.

We have investigated the association between tropical weather condition and age-sex adjusted death rates (ADR) in Thailand over a 10-year period from 1999 to 2008. Population, mortality, weather and air pollution data were obtained from four national databases. Alternating multivariable fractional polynomial (MFP) regression and stepwise multivariable linear regression analysis were used to sequentially build models of the associations between temperature variable and deaths, adjusted for the effects and interactions of age, sex, weather (6 variables), and air pollution (10 variables). The associations are explored and compared among three seasons (cold, hot and wet months) and four weather zones of Thailand (the North, Northeast, Central, and South regions). We found statistically significant associations between temperature and mortality in Thailand. The maximum temperature is the most important variable in predicting mortality. Overall, the association is nonlinear U-shape and 31 °C is the minimum-mortality temperature in Thailand. The death rates increase when maximum temperature increase with the highest rates in the North and Central during hot months. The final equation used in this study allowed estimation of the impact of a 4 °C increase in temperature as projected for Thailand by 2100; this analysis revealed that the heat-related deaths will increase more than the cold-related deaths avoided in the hot and wet months, and overall the net increase in expected mortality by region ranges from 5 to 13 % unless preventive measures were adopted. Overall, these results are useful for health impact assessment for the present situation and future public health implication of global climate change for tropical Thailand.

Quantifying the health impacts of air pollution under a changing climate-a review of approaches and methodology.

Climate change has been predicted to affect future air quality, with inevitable consequences for health. Quantifying the health effects of air pollution under a changing climate is crucial to provide evidence for actions to safeguard future populations. In this paper, we review published methods for quantifying health impacts to identify optimal approaches and ways in which existing challenges facing this line of research can be addressed. Most studies have employed a simplified methodology, while only a few have reported sensitivity analyses to assess sources of uncertainty. The limited investigations that do exist suggest that examining the health risk estimates should particularly take into account the uncertainty associated with future air pollution emissions scenarios, concentration-response functions, and future population growth and age structures. Knowledge gaps identified for future research include future health impacts from extreme air pollution events, interactions between temperature and air pollution effects on public health under a changing climate, and how population adaptation and behavioural changes in a warmer climate may modify exposure to air pollution and health consequences.

Shifts in the seasonal distribution of deaths in Australia, 1968-2007.

Studies in temperate countries have shown that both hot weather in summer and cold weather in winter increase short-term (daily) mortality. The gradual warming, decade on decade, that Australia has experienced since the 1960s, might therefore be expected to have differentially affected mortality in the two seasons, and thus indicate an early impact of climate change on human health. Failure to detect such a signal would challenge the widespread assumption that the effect of weather on mortality implies a similar effect of a change from the present to projected future climate. We examine the ratio of summer to winter deaths against a background of rising average annual temperatures over four decades: the ratio has increased from 0.71 to 0.86 since 1968. The same trend, albeit of varying strength, is evident in all states of Australia, in four age groups (aged 55 years and above) and in both sexes. Analysis of cause-specific mortality suggests that the change has so far been driven more by reduced winter mortality than by increased summer mortality. Furthermore, comparisons of this seasonal mortality ratio calculated in the warmest subsets of seasons in each decade, with that calculated in the coldest seasons, show that particularly warm annual conditions, which mimic the expected temperatures of future climate change, increase the likelihood of higher ratios (approaching 1:1). Overall, our results indicate that gradual climate change, as well as short-term weather variations, affect patterns of mortality.

Can an educational video improve the adequacy of bowel preparation for patients undergoing their first colonoscopy? Results of the EBOPS RCT.

Background and study aims The aim of this study was to assess the effect of an educational video on the quality of bowel preparation of patients from a UK population attending for their first colonoscopy. Patients and methods A prospective, endoscopist-blinded trial with 1:1 allocation was performed. Patients referred for their first colonoscopy were recruited between February 2019 and December 2019. All participants were prescribed Moviprep and received the trial site's standard written bowel preparation instructions, with the intervention group also receiving a bespoke educational video. Adequacy of bowel preparation (defined as a Boston Bowel Preparation Scale of ≥2 in each segment of the bowel) and polyp detection rates (PDRs) were compared. Fisher's chi squared test was utilized with P <0.05 as the threshold for significance. Results A total of 509 participants completed the trial from six centers; 251 were randomized to the intervention group. The mean age was 57 years and 52.3% were female. The primary endpoint was met with an adequacy rate of 216 of 251 (86.1%) in the intervention group, compared with 205 of 259 (79.1%) in the control group ( P <0.05, odds ratio [OR] 1.626, 95% CI 1.017-2.614). The PDR was significantly higher in the intervention group (39% vs 30%, OR 1.51, 95% CI 1.04-2.19, P <0.05). Conclusions An educational video leads to improved bowel preparation for patients attending for their first colonoscopy, and is also associated with greater detection of polyps. Widespread adoption of an educational video incurs minimal investment, but would reduce the number of inadequate procedures, missed pathology, and the cost that both these incur.