Human health impacts of exposure to phthalate plasticizers: An overview of reviews.

In this review of reviews, we overview the current global body of available evidence from structured reviews of epidemiological studies that explore human health outcomes associated with exposure to phthalates (chemical plasticisers commonly found in plastics). We found robust evidence for an association with lower semen quality, neurodevelopment and risk of childhood asthma, and moderate to robust evidence for impact on anogenital distance in boys. We identified moderate evidence for an association between phthalates/metabolites and low birthweight, endometriosis, decreased testosterone, ADHD, Type 2 diabetes and breast/uterine cancer. There was some evidence for other outcomes including anofourchette distance, fetal sex hormones, pre-term birth, lower antral follicle count, reduced oestrodiol, autism, obesity, thyroid function and hearing disorders. We found no reviews of epidemiological human studies on the impact of phthalates from recycled plastics on human health. We recommend that future research should use urine samples as exposure measures, consider confounders in analyses and measure impacts on female reproductive systems. Our findings align with emerging research indicating that health risks can occur at exposure levels below the "safe dose" levels set out by regulators, and are of particular concern given potential additive or synergistic "cocktail effects" of chemicals. This raises important policy and regulatory issues for identifying and controlling plastics and health related impacts and highlights a need for more research into substances of concern entering plastics waste streams via recycling.

Disconnect between standardized field-based testing and mannitol challenge in Scottish elite swimmers.

BACKGROUND: Elite swimmers have high rates of rhinoconjunctivitis and exercise-induced bronchoconstriction. Moreover, exposure to chlorine and chlorine metabolites is known to induce bronchial hyper-reactivity. OBJECTIVE: To assess the early and late effects of chlorine and exercise on the unified airway of elite swimmers, and to compare the response to mannitol and field-based exercise challenge. METHODS: The Scottish national squad underwent exhaled tidal (FE(NO)) and nasal (N(NO)) nitric oxide measurement, peak nasal inspiratory flow (PNIF), and forced expiratory volume in 1 s before, immediately after, and 4-6 h post-swimming. A sport-specific exercise test was carried out during an intensive lactate set (8 min at >/=80% maximum hear rate). All swimmers underwent mannitol challenge, and completed a health questionnaire. RESULTS: N=61 swimmers were assessed: 8/59 (14%) of swimmers had a positive mannitol challenge. Nine out of 57 (16%) of swimmers had a positive exercise test. Only one swimmer was positive to both. Swimmers with a positive mannitol had a significantly higher baseline FE(NO) (37.3 vs. 18.0 p.p.b., P=0.03) than those with a positive exercise challenge. A significant decrease in FE(NO) was observed pre vs. immediate and delayed post-chlorine exposure: mean (95% CI) 18.7 (15.9-22.0) p.p.b. vs. 15.9 (13.3-19.1) p.p.b. (P<0.01), and 13.9 (11.5-16.7) p.p.b. (P<0.01), respectively. There were no significant differences in N(NO.) Mean PNIF increased from 142.4 L/min (5.8) at baseline to 162.6 L/min (6.3) immediately post-exposure (P<0.01). Delayed post-exposure PNIF was not significantly different from pre-exposure. CONCLUSIONS: No association was found between mannitol and standardized field-based testing in elite swimmers. Mannitol was associated with a high baseline FE(NO); however, exercise/chlorine challenge was not. Thus, mannitol may identify swimmers with a 'traditional' inflammatory asthmatic phenotype, while field-based exercise/chlorine challenge may identify a swimmer-specific bronchoconstrictor response. A sustained fall in FE(NO) following chlorine exposure suggests that a non-cellular, perhaps neurogenic, response may be involved in this group of athletes.

Differential anti-inflammatory effects of large and small particle size inhaled corticosteroids in asthma.

BACKGROUND: Extra-fine particle formulations of hydrofluoroalkane-134a beclometasone dipropionate (HFA-BDP) exhibit clinical effects comparable with conventional particle formulations of chlorofluorocarbon beclometasone dipropionate (CFC-BDP) at half the dose. There is little data comparing their effects on inflammation. We have evaluated the effects of HFA-BDP and CFC-BDP on pulmonary and systemic markers of asthmatic inflammation. METHODS: A double-blind randomized crossover trial was undertaken comparing the anti-inflammatory effects of HFA-BDP (100 and 400 microg/day) and CFC-BDP (200 and 800 microg/day). Treatment with montelukast was evaluated as add-on to the higher dose of BDP. RESULTS: Compared with baseline after withdrawal of usual asthma therapy, 100 microg of HFA-BDP significantly attenuated serum eosinophilic cationic protein levels (0.61-fold change, 95% CI 0.49-0.77; a 39% reduction, P < 0.001), but 200 microg of CFC-BDP did not (0.87-fold change, 95% CI 0.63-1.23; P = 1). A dose of 800 microg of CFC-BDP and 400 microg of HFA-BDP led to reductions in exhaled nitric oxide (0.57-fold change, 95% CI 0.44-0.73; a 43% reduction, P < 0.001 and 0.65-fold change, 95% CI 0.47-0.91; a 35% reduction, P = 0.008, respectively); and peripheral eosinophils (-74 cells/microl, 95% CI -146 to -2; P = 0.020 and -77 cells/microl, 95% CI -140 to -14; P = 0.012, respectively). Montelukast further reduced exhaled nitric oxide (0.81-fold change, 95% CI 0.66-0.98; P = 0.028) with 400 microg HFA-BDP and eosinophils (-44 cells/microl, 95% CI -80 to -8; P = 0.012) with 800 microg CFC-BDP, but not vice versa. CONCLUSION: Chlorofluorocarbon beclometasone dipropionate and HFA-BDP have differential effects on pulmonary and systemic inflammation, which dictate the additive effects of montelukast.

A proof-of-concept study to assess the putative dose response to topical corticosteroid in persistent allergic rhinitis using adenosine monophosphate challenge.

INTRODUCTION: The aim of this proof-of-concept study was to assess whether nasal adenosine monophosphate (AMP) challenge may be used to quantify dose response to topical fluticasone propionate (FP) in persistent allergic rhinitis (PER). METHODS: Eligible subjects with PER entered a randomized double-blind crossover study of 2 weeks of intranasal FP at 100 microg or 400 microg daily, with a 2-week placebo washout period before each randomized treatment. Measurements after each washout or treatment comprised: peak nasal inspiratory flow (PNIF) response to nasal AMP (the primary outcome), domiciliary PNIF, the mini rhinoconjunctivitis quality of life questionnaire (miniRQLQ), symptom scores, nasal nitric oxide levels and overnight urinary cortisol:creatinine ratios. RESULTS: Thirteen patients completed per protocol. Maximal PNIF response to AMP was attenuated 0.9% (95% confidence interval -7.1 to 9.0, P=NS) by FP 100 microg, and 12.9% (4.8-20.9, P=0.009) by FP 400 microg. The 400-100 microg difference was 12.0% U (2.6-21.3, P=0.049). None of the other outcomes were responsive enough to detect any significant treatment effects. The standardized response means to FP 400 microg were 81% for AMP challenge, 54% for domiciliary PNIF, 53% for miniRQLQ, 24% for symptom scores and 18% for nasal nitric oxide. No adrenal suppression was detected at either dose. CONCLUSION: FP exhibited dose-related suppression of nasal airway hyperresponsiveness to AMP challenge, but without associated detectable adrenal suppression at the higher dose. Moreover, the AMP response demonstrated the highest signal to noise ratio compared with other outcome measures in PER.

Evaluating the performance of the Framingham risk equations in a population with diabetes.

AIMS: The Framingham risk equations are widely used to estimate risk of coronary heart disease (CHD). The purpose of this study was to evaluate the reliability of these equations in predicting CHD risk in people with diabetes and the reliability of using imputed mean HDL-cholesterol values. METHODS: Data describing the baseline characteristics of recognized CHD risk factors for 938 people aged 30-74 years were extracted from the Cardiff Diabetes Database. Data describing CHD events were available for up to 4 years following the baseline year (1996). Several mathematical techniques were used to assess the reliability of predictions provided by the Framingham equations in this population. RESULTS: Thirty-four percent of males and 25% of females who experienced CHD events had a predicted 10-year CHD risk >/= 30%. Seventy-five percent of males and 58% of females had a predicted 10-year CHD risk >/= 20%. Using imputed HDL-cholesterol values, 26% of males and 6% of females who later developed CHD events had a 10-year CHD risk >/= 30%. Using imputed HDL-cholesterol values, the CHD risk predicted by the Framingham equations consistently underestimated the actual risk of CHD events. However, refitting the Framingham risk equations to the Cardiff data resulted in only marginal improvements in discriminatory capabilities. CONCLUSIONS: The Framingham risk equations can be unreliable when applied to the diabetic population, tending to underestimate an individual's probability of progressing to CHD; the equations perform marginally better in women than in men. The use of imputed mean HDL-cholesterol values improved the reliability of the estimates of risk.

The projected health care burden of Type 2 diabetes in the UK from 2000 to 2060.

AIMS/HYPOTHESIS: To predict the incidence and prevalence of Type 2 diabetes in the UK, the trends in the levels of diabetes-related complications, and the associated health care costs for the period 2000-60. METHODS: An established epidemiological and economic model of the long-term complications and health care costs of Type 2 diabetes was applied to UK population projections from 2000 to 2060. The model was used to calculate the incidence and prevalence of Type 2 diabetes, the caseloads and population burden for diabetes-related complications, and annual NHS health care costs for Type 2 diabetes over this time period. RESULTS: The total UK population will not increase by more than 3% at any time in the next 60 years. However, the population over 30 will increase by a maximum of 11% by 2030. Due to population ageing, in 2036 there will be approximately 20% more cases of Type 2 diabetes than in 2000. Cases of diabetes-related complications will increase rapidly to peak 20-30% above present levels between 2035 and 2045, before showing a modest decline. The cost of health care for patients with Type 2 diabetes rises by up to 25% during this period, but because of reductions in the economically active age groups, the relative economic burden of the disease can be expected to increase by 40-50%. CONCLUSION/INTERPRETATION: In the next 30 years Type 2 diabetes will present a serious clinical and financial challenge to the UK NHS.

Impact of long-term complications on quality of life in patients with type 2 diabetes not using insulin.

OBJECTIVES: The complications of diabetes have the potential to greatly impact the health-related quality of life (HRQOL) of patients with type 2 diabetes. The effect of diabetic complications on HRQOL was assessed in 1233 patients with type 2 diabetes who were not using insulin. METHODS AND DATA: Patients were aged 35 and older and had stable fasting serum glucose (FSG) after washout of antidiabetic therapy. Patients who required insulin or suffered from severe cardiovascular or hepatic disease, neuropathy, or retinopathy were excluded. Patients completed the SF-36 generic quality of life questionnaire. Demographic data, including body mass index (BMI), blood glucose hemoglobin A1c (HbA1c), FSG, and the presence and severity of eight specified diabetic complications were also collected. A linear regression analysis was performed for each of the SF-36 domains and for the physical and mental health summary scales. RESULTS: The most prevalent diabetic complications were hypertension (46% of patients), peripheral sensory neuropathy (PSN; 12%), coronary artery disease (CAD; 8%), retinopathy (8%), and peripheral vascular disease (PVD; 7%). Most (73%) of the complications were assessed to be mild. PSN was associated with significantly lower scores (i.e., worse quality of life) in the mental health scale; CAD was associated with significant reductions of all but role-emotional and mental health scales of the SF-36; and PVD was associated with significantly lower physical and social functioning scales. Hypertension did not have an independent effect on HRQOL. CONCLUSIONS: The presence of even mild diabetic complications has a significant impact on patients' quality of life. Early diagnosis and treatment is essential to help prevent deterioration of HRQOL in these patients.

An economic model of the long-term health care burden of Type II diabetes.

AIMS/HYPOTHESIS: To develop a long-term economic model of health care for Type II diabetes initially for the United Kingdom; characterize experiences of diabetes-related morbidities and the use of health care resources among a typical Type II diabetes cohort; to estimate lifetime differences in expected health outcomes and costs attributable to Type II diabetes; and to facilitate evaluation of policies or interventions in treating Type II diabetes from the funder's perspective. METHODS: A compact spreadsheet structure of interconnected Markov chain modules was developed to facilitate rapid estimation of costs and outcomes for whole populations. Recent clinical findings from the United Kingdom Prospective Diabetes Study and other sources were incorporated and a detailed costing module developed from United Kingdom observational data. RESULTS: The model allows the assessment of costs and long-term complications experienced by people suffering from Type II diabetes, including direct health care costs associated with the main diabetic complications and second-order effects on other health services required by such patients. Initial results suggest that the lifetime cost of health care for patients from the diagnosis of diabetes is more than double that for an equivalent non-diabetic population. CONCLUSION/INTERPRETATION: The model is intended for use by health care policy makers and payers to assess the long-term budgetary impact of trends in a variety of demographic and epidemiological factors on future services, and is also useful to physicians when considering the impact of new treatment strategies or programmes to modify risk factors for diabetic complications.

An evaluation of the cost effectiveness of adding lamivudine to zidovudine-containing regimens in HIV infection. Canadian perspective.

BACKGROUND: A prospective cost-effectiveness analysis undertaken as part of the CAESAR (Canada, Australia, Europe, South Africa) placebo-controlled clinical trial showed that the addition of lamivudine to zidovudine-containing regimens for 1 year reduced progression of HIV infection to AIDS or death, as well as significantly reducing the number of hospitalisations, outpatient visits and the requirement for medications for HIV-related illness and adverse events. Data from all 1840 patients included in the 'intent-to-treat' population of the CAESAR trial were used for the present analysis. A Canadian third-party payer perspective was adopted, and all costs were adjusted to 1997 prices. RESULTS: The savings associated with reduced healthcare resource use in the CAESAR study were estimated to be 1123 Canadian dollars ($Can) per patient, over the year. These savings partly offset the cost of lamivudine. The analysis showed that the addition of lamivudine to zidovudine-containing regimens resulted in an incremental cost-effectiveness ratio of $Can 14,225 [95% confidence interval (CI): $Can4383 to $Can29,577] for progression to AIDS/death avoided and of $Can5631 (95%CI: $Can2010 to $Can12,929) for HIV-related illness avoided. CONCLUSIONS: Our findings indicate that treatments that slow the progression of HIV infection to AIDS or death have the potential to facilitate healthcare savings, which partly offset the drug acquisition costs. The results also demonstrate that it is possible to undertake economic evaluations in parallel with a major clinical end-point study.

Occupational stress and community mental health nursing: what CPNs really said.

The Claybury Nursing Stress Study assessed the levels of occupational stress experienced by both ward-based and community nurses. This paper presents the results obtained from a qualitative analysis of statements made by community psychiatric nurses during a questionnaire based interview. Key areas identified by CPNs as relevant to stress and coping are reported and suggestions for further, qualitative research in this area are made.

Comparison of Department of Veterans Affairs pharmacy services in 1992 and 1994 with strategic-planning goals.

Data were collected from Department of Veterans Affairs (VA) medical center pharmacies in 1992 and 1994 to measure progress toward implementation of the VA 1990 strategic plan. A questionnaire was pretested and mailed to pharmacy chiefs at all 173 VA medical centers (VAMCs) with pharmacies in 1992. The same questionnaire, with slight modifications consistent with revision of the strategic plan, was mailed in 1994. Usable responses were received from more than 80% of VAMCs in both years. The number and types of activities, services, and staffing at VAMC pharmacies varied with respect to automation, procurement, drug accountability, image, participation in professional organizations, professional role, pharmaceutical care activities, technicians, and research and education. Compared with the 1992 results, the 1994 results indicated greater pharmacist involvement in patient-education activities, expanded roles for pharmacists in monitoring anticoagulation therapy and in pharmacokinetic services, and less use of pharmacists for distributive functions. In 1994, more facilities reported having an open pharmacy concept in place to encourage direct patient care initiatives. VAMCs reported greater involvement in pharmacy education in 1994 than in 1992, with more VAMCs having affiliations with pharmacy schools and clerkship and residency training programs. Responses indicated considerable variation among VAMC pharmacies in the number and types of services provided.