Anticholinergic drug use and risk of mortality for people with dementia in Northern Ireland.

OBJECTIVE: Anticholinergic burden refers to the cumulative effect of medications which contain anticholinergic properties. We assessed how anticholinergic burden and different types of anticholinergic medications influence mortality rates among people with dementia in Northern Ireland. Our secondary aim was to determine what demographic characteristics predict the anticholinergic burden of people with dementia. METHODS: Data were extracted from the Enhanced Prescribing database for 25,418 people who were prescribed at least one dementia management medication between 2010 and 2016. Information was also extracted on the number of times each available anticholinergic drug was prescribed between 2010 and 2016, allowing the calculation of an overall anticholinergic burden. Cox proportional hazard models were used to determine how anticholinergic burden influenced mortality whilst multilevel model regression determined what demographic characteristics influence overall anticholinergic burden. RESULTS: Of the 25,418 people with dementia, only 15% (n = 3880) had no anticholinergic burden. Diazepam (42%) and risperidone (18%) were the two most commonly prescribed drugs. Unadjusted Cox proportional hazard models indicated that higher anticholinergic burden was associated with significantly higher mortality rates in comparison to people with dementia who had no anticholinergic burden (HR = 1.59: 95% CI = 1.07-2.36). In particular, urological (HR = 1.20: 95% CI = 1.05-1.38) and respiratory (HR = 1.17: 95% CI = 1.08-1.27) drugs significantly increased mortality rates. People with dementia living in areas with low levels of deprivation had significantly lower anticholinergic burden (HR=-.39: 95% CI=-.47:-30). CONCLUSIONS: Reducing anticholinergic burden is essential for people with dementia. Further research should address the unfavourable prognosis of people living with dementia in highly deprived areas.

Pseudofolliculitis barbae: understanding the condition and the role of facial grooming.

Pseudofolliculitis barbae (PFB) is an inflammatory condition of the beard area, with a high prevalence in men of subequatorial African ancestry and, to a much lesser extent, Indo-Europeans. But it can affect both men and women of all ethnicities. Invariably reported as being associated with shaving, recent evidence suggests a strong genetic component in patients with persistent PFB. There is a lack of robust clinical evidence to support recommendations to avoid or curtail shaving or to shave with a single-blade razor. There is recent clinical evidence that PFB is not exacerbated by daily shaving with a multiblade razor as part of a regimen. Further, there is preliminary evidence that a daily shaving regimen, which includes pre-shave hydration and post-shave moisturization, may be beneficial. To develop evidence-based initial management strategies for PFB, there is a requirement for more randomized blinded clinical trials comparing the use of multi- and single-edge razors, different shaving techniques, shaving frequencies and pre- and post-shaving cosmetic products.

Climate change, food systems and population health risks in their eco-social context.

The establishment of ecological public health as crucial to modern public health is overdue. While the basic concepts have been gestating for decades, receptivity within broader public health has been limited. This position is changing, not least as the population-level impacts of climate change and, more broadly, of limits to growth are emerging from theory and forecasting into daily reality. This paper describes several key elements of ecological public health thinking. These include the 'environmental' risks to human health (often systemic and disruptive, rather than local and toxic) posed by climate change and other forms of adverse global environmental change. Closer recognition of the links between social and environmental factors has been urged--an 'eco-social' approach--and, relatedly, for greater co-operation between social and natural sciences. The authors revisit critics of capitalism who foresaw the global capture and transformation of ecosystems for material human ends, and their resultant despoliation. The perennial call within public health to reduce vulnerability by lessening poverty is more important than ever, given the multifactored threat to the health of the poor which is anticipated, assuming no radical strategies to alleviate these pressures. But enhanced health security for the poor requires more than the reconfiguring of social determinants; it also requires, as the overarching frame, ecological public health.

Early-life hygiene-related factors affect risk of central nervous system demyelination and asthma differentially.

The increasing prevalence of immune-related diseases, including multiple sclerosis, may be partly explained by reduced microbial burden during childhood. Within a multi-centre case-control study population, we examined: (i) the co-morbid immune diseases profile of adults with a first clinical diagnosis of central nervous system demyelination (FCD) and (ii) sibship structure in relation to an autoimmune (FCD) and an allergic (asthma) disease. FCD cases (n = 282) were aged 18-59 years; controls (n = 558) were matched on age, sex and region. Measures include: history of doctor-diagnosed asthma; sibling profile (number; dates of birth); and regular childcare attendance. FCD cases did not differ from controls with regard to personal or family history of allergy, but had a greater likelihood of chronic fatigue syndrome [odds ratio (OR) = 3·11; 95% confidence interval (CI) 1·11, 8·71]. Having any younger siblings showed reduced odds of FCD (OR = 0·68; 95% CI: 0·49, 0·95) but not asthma (OR = 1·47; 95% CI: 0·91, 2·38). In contrast, an increasing number of older siblings was associated with reduced risk of asthma (P trend = 0·04) but not FCD (P trend = 0·66). Allergies were not over-represented among people presenting with FCD. Sibship characteristics influence both FCD and asthma risk but the underlying mechanisms differ, possibly due to the timing of the putative 'sibling effect'.

Occupational exposure and risk of central nervous system demyelination.

Inconsistent evidence exists regarding the association between work-related factors and risk of multiple sclerosis (MS). We examined the association between occupational exposures and risk of a first clinical diagnosis of central nervous system demyelination (FCD), which is strongly associated with progression to MS, in a matched case-control study of 276 FCD cases and 538 controls conducted in Australia (2003-2006). Using a personal residence and work calendar, information on occupational history and exposure to chemicals and animals was collected through face-to-face interviews. Few case-control differences were noted. Fewer cases had worked as professionals (≥6 years) than controls (adjusted odds ratio (AOR) = 0.60, 95% confidence interval (CI): 0.37, 0.96). After further adjustment for number of children, cases were more likely to have ever been exposed to livestock than controls (AOR = 1.54, 95% CI: 1.03, 2.29). Among women, there was an increase in FCD risk associated with 10 or more years of exposure to livestock (AOR = 2.78, 95% CI: 1.22, 6.33) or 6 or more years of farming (AOR = 2.00, 95% CI: 1.23, 3.25; also adjusted for number of children). Similar findings were not evident among men. Thus, farming and exposure to livestock may be important factors in the development of FCD among women, with this finding further revealed after the confounding effect of parity or number of children is considered.

The AusD Study: a population-based study of the determinants of serum 25-hydroxyvitamin D concentration across a broad latitude range.

Observational studies suggest that people with a high serum 25-hydroxyvitamin D (25(OH)D) concentration may have reduced risk of chronic diseases such as osteoporosis, multiple sclerosis, type 1 diabetes, cardiovascular disease, and some cancers. The AusD Study (A Quantitative Assessment of Solar UV Exposure for Vitamin D Synthesis in Australian Adults) was conducted to clarify the relationships between ultraviolet (UV) radiation exposure, dietary intake of vitamin D, and serum 25(OH)D concentration among Australian adults residing in Townsville (19.3°S), Brisbane (27.5°S), Canberra (35.3°S), and Hobart (42.8°S). Participants aged 18-75 years were recruited from the Australian Electoral Roll between 2009 and 2010. Measurements were made of height, weight, waist:hip ratio, skin, hair, and eye color, blood pressure, and grip strength. Participants completed a questionnaire on sun exposure and vitamin D intake, together with 10 days of personal UV dosimetry and an associated sun-exposure and physical-activity diary that was temporally linked to a blood test for measurement of 25(OH)D concentration. Ambient solar UV radiation was also monitored at all study sites. We collected comprehensive, high-quality data from 1,002 participants (459 males, 543 females) assessed simultaneously across a range of latitudes and through all seasons. Here we describe the scientific and methodological issues considered in designing the AusD Study.

Offspring number, pregnancy, and risk of a first clinical demyelinating event: the AusImmune Study.

OBJECTIVE: To examine the association between past pregnancy, offspring number, and first clinical demyelination risk. METHODS: Cases (n = 282) were aged 18-59 years with a first clinical diagnosis of CNS demyelination (first clinical demyelinating event [FCD]) and resident within 1 of 4 Australian centers (from latitudes 27° south to 43° south) from 2003 to 2006. Controls (n = 542) were matched to cases on age, sex, and study region, without first clinical diagnosis of CNS demyelination. RESULTS: Higher offspring number was associated with FCD risk among women (p < 0.001) but not men (p = 0.71); difference in effect; p = 0.001. Among women, higher parity was associated with reduced risk of FCD (adjusted odds ratio 0.51 [95% confidence interval 0.36, 0.72] per birth) with a similar magnitude of effect observed among classic first demyelinating events (adjusted odds ratio 0.47 [95% confidence interval 0.29, 0.74]). The apparent beneficial effect of higher parity was also evident among parous women only (p < 0.001). Among cases, a clear female excess was evident for those with low but not high (4 or more) offspring number. Factors such as human leukocyte antigen DR15 genotype did not appear to modify the association between higher parity and a reduced FCD risk among women. CONCLUSIONS: These findings are consistent with a cumulative beneficial effect of pregnancy. Temporal changes toward an older maternal age of parturition and reduced offspring number may partly underlie the increasing female excess among MS cases over time.

Current and past Epstein-Barr virus infection in risk of initial CNS demyelination.

OBJECTIVES: To assess risk of a first clinical diagnosis of CNS demyelination (FCD) in relation to measures of Epstein-Barr virus (EBV) infection within the context of other known risk factors. METHODS: This was a multicenter incident case-control study. FCD cases (n = 282) aged 18-59 years and controls (n = 558, matched on age, sex, and region) were recruited from 4 Australian centers between November 1, 2003, and December 31, 2006. A nested study (n = 215 cases, n = 216 controls) included measurement of whole blood quantitative EBV DNA load and serum EBV-specific antibodies. Conditional logistic regression was used to analyze case-control differences. RESULTS: There were no significant case-control differences in the proportion with detectable EBV DNA (55.8% vs 50.5%, respectively, p = 0.28), or in quantitative EBV DNA load (p = 0.33). Consistent with previous work, higher anti-EBV-specific immunoglobulin G (IgG) titers and a history of infectious mononucleosis were associated with increased FCD risk and there was an additive interaction with HLA-DRB1*1501 status. We found additional interactions between high anti-EBNA IgG titer and SNPs in HLA-A (adjusted odds ratios [AOR] = 19.84 [95% confidence interval (CI) 5.95 to 66.21] for both factors compared to neither) and CTLA-4 genes (AOR = 0.31 [95% CI 0.13 to 0.76] for neither factor compared to both). EBV DNA load was lower at higher serum 25-hydroxyvitamin D concentrations in controls (r = -0.17, p = 0.01). An adverse effect of higher EBV DNA load on FCD risk was increased with higher 25-hydroxyvitamin D concentration (p[interaction] = 0.02). CONCLUSION: Past infection with EBV, but not current EBV DNA load in whole blood, is significantly associated with increased FCD risk. These associations appear to be modified by immune-related gene variants.

Climate change: present and future risks to health, and necessary responses.

Recent observed changes in Earth's climate, to which humans have contributed substantially, are affecting various health outcomes. These include altered distributions of some infectious disease vectors (ticks at high latitudes, malaria mosquitoes at high altitudes), and an uptrend in extreme weather events and associated deaths, injuries and other health outcomes. Future climate change, if unchecked, will have increasing, mostly adverse, health impacts - both direct and indirect. Climate change will amplify health problems in vulnerable regions, influence infectious disease emergence, affect food yields and nutrition, increase risks of climate-related disasters and impair mental health. The health sector should assist society understand the risks to health and the needed responses.

Sun exposure and vitamin D are independent risk factors for CNS demyelination.

OBJECTIVES: To examine whether past and recent sun exposure and vitamin D status (serum 25-hydroxyvitamin D [25(OH)D] levels) are associated with risk of first demyelinating events (FDEs) and to evaluate the contribution of these factors to the latitudinal gradient in FDE incidence in Australia. METHODS: This was a multicenter incident case-control study. Cases (n = 216) were aged 18-59 years with a FDE and resident within one of 4 Australian centers (from latitudes 27°S to 43°S), from November 1, 2003, to December 31, 2006. Controls (n = 395) were matched to cases on age, sex, and study region, without CNS demyelination. Exposures measured included self-reported sun exposure by life stage, objective measures of skin phenotype and actinic damage, and vitamin D status. RESULTS: Higher levels of past, recent, and accumulated leisure-time sun exposure were each associated with reduced risk of FDE, e.g., accumulated leisure-time sun exposure (age 6 years to current), adjusted odds ratio (AOR) = 0.70 (95% confidence interval [CI] 0.53-0.94) for each ultraviolet (UV) dose increment of 1,000 kJ/m(2) (range 508-6,397 kJ/m(2)). Higher actinic skin damage (AOR = 0.39 [95% CI 0.17-0.92], highest grade vs the lowest) and higher serum vitamin D status (AOR = 0.93 [95% CI 0.86-1.00] per 10 nmol/L increase in 25(OH)D) were independently associated with decreased FDE risk. Differences in leisure-time sun exposure, serum 25(OH)D level, and skin type additively accounted for a 32.4% increase in FDE incidence from the low to high latitude regions. CONCLUSIONS: Sun exposure and vitamin D status may have independent roles in the risk of CNS demyelination. Both will need to be evaluated in clinical trials for multiple sclerosis prevention.

Promoting global population health while constraining the environmental footprint.

Populations today face increasing health risks from human-induced regional and global environmental changes and resultant ecological nonsustainability. Localized environmental degradation that has long accompanied population growth, industrialization, and rising consumerism has now acquired a global and often systemic dimension (e.g., climate change, disrupted nitrogen cycling, biodiversity loss). Thus, the economic intensification and technological advances that previously contributed to health gains have now expanded such that humanity's environmental (and ecological) footprint jeopardizes global population health. International data show, in general, a positive correlation of a population's health with level of affluence and size of per-person footprint. Yet, beyond a modest threshold, larger footprints afford negligible health gain and may impair health (e.g., via the rise of obesity). Furthermore, some lower-income countries have attained high levels of health. Many changes now needed to promote ecological (and social) sustainability will benefit local health. Continued improvement of global health could thus coexist with an equitably shared global environmental footprint.

Climate change, noncommunicable diseases, and development: the relationships and common policy opportunities.

The rapid growth in noncommunicable diseases (NCDs), including injury and poor mental health, in low- and middle-income countries and the widening social gradients in NCDs within most countries worldwide pose major challenges to health and social systems and to development more generally. As Earth's surface temperature rises, a consequence of human-induced climate change, incidences of severe heat waves, droughts, storms, and floods will increase and become more severe. These changes will bring heightened risks to human survival and will likely exacerbate the incidence of some NCDs, including cardiovascular disease, some cancers, respiratory health, mental disorders, injuries, and malnutrition. These two great and urgent contemporary human challenges-to improve global health, especially the control of NCDs, and to protect people from the effects of climate change-would benefit from alignment of their policy agendas, offering synergistic opportunities to improve population and planetary health. Well-designed climate change policy can reduce the incidence of major NCDs in local populations.

Functional analysis of dendritic cell-T cell interaction in sarcoidosis.

The primary cause of the intense immune response in sarcoidosis is unclear. Potentially, a functional abnormality in dendritic cells (DCs) could cause a reduction in clearance of antigen and downstream persistence in immune activity. In this study, we investigate the interaction between monocyte-derived dendritic cells and T cells in patients with sarcoidosis compared to normal controls (n = 8 each) by examining the kinetics of autologous and allogeneic mixed leucocyte reactions over 9-10 days. We found markedly depressed proliferation kinetics in autologous DC-peripheral blood mononuclear cell (PBMC) co-cultures from sarcoid patients compared to normal subjects. In allogeneic experiments PBMCs from patients showed a reduced response to allogeneic DCs from a single donor, but no difference was observed in the ability of patients and control DCs to stimulate proliferation of allogeneic PBMC from a single donor. We conclude that there is a markedly impaired autologous mixed leucocyte reaction (MLR) in sarcoidosis patients. In allogeneic MLR, monocyte-derived DCs in sarcoidosis were able to stimulate T cells normally, but PBMCs responses were reduced. This contradicts recent published studies on ex vivo isolated myeloid DCs from sarcoidosis patients although, potentially, an in vivo conditioning factor, which reduces DC function in sarcoidosis, could be a unifying explanation for the contrasting findings.

Observational analytic studies in multiple sclerosis: controlling bias through study design and conduct. The Australian Multicentre Study of Environment and Immune Function.

Rising multiple sclerosis incidence over the last 50 years and geographic patterns of occurrence suggest an environmental role in the causation of this multifactorial disease. Design options for epidemiological studies of environmental causes of multiple sclerosis are limited by the low incidence of the disease, possible diagnostic delay and budgetary constraints. We describe scientific and methodological issues considered in the development of the Australian Multicentre Study of Environment and Immune Function (the Ausimmune Study), which seeks, in particular, to better understand the causes of the well-known MS positive latitudinal gradient. A multicentre, case-control design down the eastern seaboard of Australia allows the recruitment of sufficient cases for adequate study power and provides data on environmental exposures that vary by latitude. Cases are persons with an incident first demyelinating event (rather than prevalent multiple sclerosis), sourced from a population base using a two tier notification system. Controls, matched on sex, age (within two years) and region of residence, are recruited from the general population. Biases common in case-control studies, eg, prevalence-incidence bias, admission-rate bias, non-respondent bias, observer bias and recall bias, as well as confounding have been carefully considered in the study design and conduct of the Ausimmune Study.