A novel approach to accurately measuring the burden of hospitalisations for cardiovascular disease in people with diabetes: A pilot study.

AIM: To determine the reliability of hospital discharge codes for heart failure (HF), acute myocardial infarction (AMI) and stroke compared with adjudicated diagnosis, and to pilot a scalable approach to adjudicate records on a population-based sample. METHODS: A population-based sample of 685 people with diabetes admitted (1274 admissions) to one of three Australian hospitals during 2018-2020 were randomly selected for this study. All medical records were reviewed and adjudicated. RESULTS: Cardiovascular diseases were the most common primary reason for hospitalisation in people with diabetes, accounting for ~17% (215/1274) of all hospitalisations, with HF as the leading cause. ICD-10 codes substantially underestimated HF prevalence and had the lowest agreement with the adjudicated diagnosis of HF (Kappa = 0.81), compared with AMI and stroke (Kappa ≥ 0.91). While ICD-10 codes provided suboptimal sensitivity (72%) for HF, the performance was better for AMI (sensitivity 84%; specificity 100%) and stroke (sensitivity 85%; specificity 100%). A novel approach to screen possible HF cases only required adjudicating 8% (105/1274) of records, correctly identified 78/81 of HF admissions and yielded 96% sensitivity and 98% specificity. CONCLUSIONS: While ICD-10 codes appear reliable for AMI or stroke, a more complex diagnosis such as HF benefits from a two-stage process to screen for suspected HF cases that need adjudicating. The next step is to validate this novel approach on large multi-centre studies in diabetes.

Associations of early life and childhood risk factors with obstructive sleep apnoea in middle-age.

BACKGROUND AND OBJECTIVE: Early-life risk factors for obstructive sleep apnoea (OSA) are poorly described, yet this knowledge may be critical to inform preventive strategies. We conducted the first study to investigate the association between early-life risk factors and OSA in middle-aged adults. METHODS: Data were from population-based Tasmanian Longitudinal Health Study cohort (n = 3550) followed from 1st to 6th decades of life. Potentially relevant childhood exposures were available from a parent-completed survey at age 7-years, along with previously characterized risk factor profiles. Information on the primary outcome, probable OSA (based on a STOP-Bang questionnaire cut-off ≥5), were collected when participants were 53 years old. Associations were examined using logistic regression adjusting for potential confounders. Analyses were repeated using the Berlin questionnaire. RESULTS: Maternal asthma (OR = 1.5; 95% CI 1.1-2.0), maternal smoking (OR = 1.2; 1.05, 1.5), childhood pleurisy/pneumonia (OR = 1.3; 1.04, 1.7) and frequent bronchitis (OR = 1.2; 1.01, 1.5) were associated with probable OSA. The risk-factor profiles of 'parental smoking' and 'frequent asthma and bronchitis' were also associated with probable OSA (OR = 1.3; 1.01, 1.6 and OR = 1.3; 1.01-1.9, respectively). Similar associations were found for Berlin questionnaire-defined OSA. CONCLUSIONS: We found novel temporal associations of maternal asthma, parental smoking and frequent lower respiratory tract infections before the age of 7 years with adult OSA. While determination of their pathophysiological and any causal pathways require further research, these may be useful to flag the risk of OSA within clinical practice and create awareness and vigilance among at-risk groups.

Long Chain Fatty Acids Mediate Hepatic Metabolic Flux in Preruminating Dairy Calves Fed Flaxseed Oil, High Oleic Soybean Oil, or Milk Fat.

Nutrition and physiological state affect hepatic metabolism. Our objective was to determine if feeding flaxseed oil (∼50% C18:3n-3 cis), high oleic soybean oil (∼70% C18:1 cis-9), or milk fat (∼50% C16:0) alters hepatic expression of PC, PCK1, and PCK2 and the flow of carbons from propionate and pyruvate into the TCA cycle in preruminating calves. Male Holstein calves (n = 40) were assigned to a diet of skim milk with either: 3% milk fat (MF; n = 8), 3% flaxseed oil (Flax; n = 8), 3% high oleic soybean oil (HOSO; n = 8), 1.5% MF + 1.5% high oleic soybean oil (MF-HOSO; n = 8), or 1.5% MF + 1.5% flaxseed oil (MF-Flax; n = 8) from d 14 to d 21 postnatal. At d 21 postnatal, a liver biopsy was taken for gene expression and metabolic flux analysis. Liver explants were incubated in [U-13C] propionate and [U-13C] pyruvate to trace carbon flux through TCA cycle intermediates or with [U-14C] lactate, [1-14C] palmitic acid, or [2-14C] propionate to quantify substrate oxidation to CO2 and acid soluble products. Compared with other treatments, plasma C18:3n-3 cis was 10 times higher and C18:1 cis-9 was 3 times lower in both flax (Flax and MF-Flax) treatments. PC, PCK1, and PCK2 expression and flux of [U-13C] pyruvate as well as [U-13C] propionate were not different between treatments. PC expression was negatively correlated with the enrichment of citrate M+5 and malate M+3, and PCK2 was negatively correlated with citrate M+5, suggesting that when expression of these enzymes is increased, carbon from pyruvate enters the TCA cycle via PC mediated carboxylation, and then OAA is converted to phosphoenolpyruvate via PCK2. Acid soluble product formation and PC expression were reduced in HOSO (MF-HOSO and HOSO) treatments compared with flax (MF-Flax and Flax), indicating that fatty acids regulate PC expression and carbon flux, but that fatty acid flux control points are not connected to PC, PCK1, or PCK2. In conclusion, fatty acids regulate hepatic expression of PC, PCK1, and PCK2, and carbon flux, but the point of control is distinct.

Clinical and pathological findings in five dogs with nodular histiocytic iritis in the United Kingdom: A case series.

PURPOSE: The aim of this study was to describe the clinical presentation, histopathology, management, and outcome of nodular histiocytic iritis, an intraocular variant of nodular granulomatous episcleritis (NGE). METHODS: A retrospective review of the medical records of five dogs with intraocular NGE-type inflammation as diagnosed by histopathology. RESULTS: Four Border Collies and one crossbreed dog, aged 1.5-3.4 years (mean age 2.38 years). The clinical presentation was an extensive, raised, pale iris lesion of variable location. All cases were unilateral. The physical examination was normal. Complete blood count/serum biochemistry (n = 1) and thoracic radiography (n = 1) were normal. Ocular ultrasound (n = 2) was normal apart from increased iris thickness. Enucleation (n = 4) or excisional biopsy (iridectomy, n = 1) was performed because of suspected neoplasia. Following enucleation, the remaining, contralateral eye did not develop additional lesions (9 days-3.7 years follow-up). There was no recurrence following sector iridectomy with 5 months topical 1% prednisolone acetate (3.9 years follow-up). The histopathologic findings in all five cases indicated a focal histiocytic and lymphoplasmacytic anterior uveitis (iritis), similar to that seen in cases of NGE. CONCLUSION: Nodular histiocytic iritis presents as unilateral iris thickening in isolation and young Collies appear to be predisposed. The histopathological findings are similar to NGE. Although the clinical presentation resembles intraocular neoplasia, an inflammatory process should be considered, which may be amenable to medical management. Definitive diagnosis may be obtained by iris sampling.

Longitudinal population-based study of progression rates for borderline thyroid-stimulating hormone abnormalities.

BACKGROUND: Current guidelines recommend thyroid-stimulating hormone (TSH) for initial biochemical evaluation of thyroid function, with borderline TSH abnormalities a common finding. The likelihood of a borderline TSH progressing to overt abnormality is not well characterised at the population level. AIMS: To determine risk factors and likelihood for progression of borderline TSH to overt abnormality. METHODS: Population-based retrospective longitudinal data-linkage study for TSH tests performed in Tasmania (1996-2013). Kaplan-Meier methodology was used to summarise conversion time for overt TSH elevation (≥10 mU/L) and overt suppression (≤0.1 mU/L) in patients whose initial TSH was borderline elevated (BeTSH; 4.0-9.99 mU/L) and borderline suppressed (BsTSH; 0.10-0.39 mU/L) respectively. Main outcome measures are the progression from borderline to overt TSH abnormality. RESULTS: A total of 1 296 060 TSH tests was performed on 367 917 patients. Of these, 14 507 (3.9%) patients had BeTSH on initial assessment; mean age 51.4 ± 21.8 years and median TSH of 5.0 mU/L (interquartile range (IQR) 4.4, 5.2). Patients aged ≥80 years were most likely to progress (hazard ratio (HR) = 2.09 compared with age <20 years reference group (95% confidence interval (CI): 1.64, 2.68)). Patients aged 20-39 years had the second-highest rate of progression (HR = 1.49 (95% CI: 1.18, 1.88)). Seven thousand, eight hundred and eighty-three (2.14%) patients had BsTSH; mean age 50.7 ± 22.1 years and median TSH 0.30 mU/L (IQR 0.22, 0.35). Patients aged 60-79 years had the highest rate of progression to overt TSH suppression (HR = 2.47 compared with age <20 years reference group (95% CI: 1.88, 3.22)). CONCLUSIONS: Follow-up intervals for patients with borderline TSH abnormalities should take into account patient age as a progression risk factor.

Revised FDI criteria for evaluating direct and indirect dental restorations-recommendations for its clinical use, interpretation, and reporting.

OBJECTIVES: The FDI criteria for the evaluation of direct and indirect dental restorations were first published in 2007 and updated in 2010. Meanwhile, their scientific use increased steadily, but several questions from users justified some clarification and improvement of the living document. MATERIALS AND METHODS: An expert panel (N = 10) initiated the revision and consensus process that included a kick-off workshop and multiple online meetings by using the Delphi method. During and after each round of discussion, all opinions were collected, and the aggregated summary was presented to the experts aiming to adjust the wording of the criteria as precisely as possible. Finally, the expert panel agreed on the revision. RESULTS: Some categories were redefined, ambiguities were cleared, and the descriptions of all scores were harmonized to cross-link different clinical situations with possible management strategies: reviewing/monitoring (score 1-4), refurbishment/reseal (score 3), repair (score 4), and replacement (score 5). Functional properties (domain F: fracture of material and retention, marginal adaptation, proximal contact, form and contour, occlusion and wear) were now placed at the beginning followed by biological (domain B: caries at restoration margin, hard tissue defects, postoperative hypersensitivity) and aesthetic characteristics (domain A: surface luster and texture, marginal staining, color match). CONCLUSION: The most frequently used eleven categories of the FDI criteria set were revised for better understanding and handling. CLINICAL RELEVANCE: The improved description and structuring of the criteria may help to standardize the evaluation of direct and indirect restorations and may enhance their acceptance by researchers, teachers, and dental practitioners.

Evaluation of direct restorations using the revised FDI criteria: results from a reliability study.

OBJECTIVES: The purpose of this in vitro reliability study was to determine the intra- and inter-examiner agreement of the revised FDI criteria including the categories "fracture of material and retention" (F1) and "caries at restoration margin" (B1). MATERIALS AND METHODS: Forty-nine photographs of direct tooth-coloured posterior (n = 25) and anterior (n = 24) restorations with common deficiencies were included. Ten dental experts repeated the assessment in three blinded rounds. Later, the experts re-evaluated together all photographs and agreed on a reference standard. Statistical analysis included the calculation of Cohen's (Cκ), Fleiss' (Fκ), and weighted Kappa (wκ), the development of a logistic regression with a backward elimination model and Bland/Altman plots. RESULTS: Intra- and inter-examiner reliability exhibited mostly moderate to substantial Cκ, Fκ, and wκ values for posterior restorations (e.g. Intra: F1 Cκ = 0.57, wκ = 0.74; B1 Cκ = 0.57, wκ = 0.73/Inter F1 Fκ = 0.32, wκ = 0.53; B1 Fκ = 0.41, wκ = 0.64) and anterior restorations (e.g. Intra F1 Cκ = 0.63, wκ = 0.76; B1 Cκ = 0.48, wκ = 0.68/Inter F1 Fκ = 0.42, wκ = 0.57; B1 Fκ = 0.40, wκ = 0.51). Logistic regression analyses revealed significant differences between the evaluation rounds, examiners, categories, and tooth type. Both the intra- and inter-examiner reliability increased along with the evaluation rounds. The overall agreement was higher for anterior restorations compared to posterior restorations. CONCLUSIONS: The overall reliability of the revised FDI criteria set was found to be moderate to substantial. CLINICAL RELEVANCE: If properly trained, the revised FDI criteria set are a valid tool to evaluate direct and indirect restorations in a standardized way. However, training and calibration are needed to ensure reliable application.

Incremental healthcare expenditure attributable to diabetes mellitus: A cost of illness study in Tasmania, Australia.

AIMS: To quantify the incremental direct medical costs in people with diabetes from the healthcare system perspective; and to identify trends in the incremental costs. METHODS: This was a matched retrospective cohort study based on a linked data set developed for investigating chronic kidney disease in Tasmania, Australia. Using propensity score matching, 51,324 people with diabetes were matched on age, sex and residential area with 102,648 people without diabetes. Direct medical costs (Australian dollars 2020-2021) due to hospitalisation, Emergency Department visits and pathology tests were included. The incremental costs and cost ratios between mean annual costs of people with diabetes and their controls were calculated. RESULTS: On average, people with diabetes had healthcare costs that were almost double their controls ($2427 [95% CI 2322-2543]; ratio 1.87 [95% CI 1.85-1.91]; pooled from 2007-2017). While in the first year of follow-up, the costs of a person with diabetes were $1643 (95% CI 1489-1806); ratio 1.83 (95% CI 1.76-1.92) more than their control, this increased to $2480 (95% CI 2265-2680); ratio 1.69 (95% CI 1.62-1.77) in the final year. Although the incremental costs were higher in older age groups (e.g., ≥70: $2498 [95% CI 2265-2754]; 40-49: $2117 [95% CI 1887-2384]), the cost ratios were higher in younger age groups (≥70: 1.52 [95% CI 1.48-1.56]; 40-49: 2.37 [95% CI 2.25-2.61]). CONCLUSIONS: Given the increasing burden that diabetes imposes, our findings will support policymakers in future planning for diabetes and enable targeting sub-groups with higher long-term costs for possible cost savings for the Tasmanian healthcare system.

Analysis of Citrus Bioflavonoid Content and Dipeptidyl Peptidase-4 Inhibitory Potential of Commercially Available Supplements.

Citrus bioflavonoids are polyphenolic plant-derived pigments found in high levels in oranges, lemons, grapefruits and other citrus fruits. The three most abundant types of citrus bioflavonoids are hesperidin, naringenin and eriocitrin. Citrus bioflavonoids have long been known to possess powerful free radical-scavenging properties and cardioprotective effects. The study involved the analysis of 10 commercially available citrus bioflavonoid supplements from three different countries: Australia, the United States and Canada. The supplements were tested for their citrus bioflavonoid content which varied from 0.8 to 33.3% w/w. The daily bioflavonoid dose varied from 19 mg to 560 mg. Hesperidin was the major citrus bioflavonoid in nine out of ten supplements. One supplement was found to contain less than 10% of the quantity of rutin claimed to have been added. The DPP-4 inhibitory potential, compared through an estimation of rutin equivalence, ranged from 1.9 mg to 400 mg per day. This data highlights the variability between the supplements in their potential to inhibit DPP-4 for subsequent health benefits.

Exposure to household air pollution over 10†years is related to asthma and lung function decline.

INTRODUCTION: We investigated if long-term household air pollution (HAP) is associated with asthma and lung function decline in middle-aged adults, and whether these associations were modified by glutathione S-transferase (GST) gene variants, ventilation and atopy. MATERIALS AND METHODS: Prospective data on HAP (heating, cooking, mould and smoking) and asthma were collected in the Tasmanian Longitudinal Health Study (TAHS) at mean ages 43 and 53 years (n=3314). Subsamples had data on lung function (n=897) and GST gene polymorphisms (n=928). Latent class analysis was used to characterise longitudinal patterns of exposure. Regression models assessed associations and interactions. RESULTS: We identified seven longitudinal HAP profiles. Of these, three were associated with persistent asthma, greater lung function decline and % reversibility by age 53 years compared with the "Least exposed" reference profile for those who used reverse-cycle air conditioning, electric cooking and no smoking. The "All gas" (OR 2.64, 95% CI 1.22-5.70), "Wood heating/smoking" (OR 2.71, 95% CI 1.21-6.05) and "Wood heating/gas cooking" (OR 2.60, 95% CI 1.11-6.11) profiles were associated with persistent asthma, as well as greater lung function decline and % reversibility. Participants with the GSTP1 Ile/Ile genotype were at a higher risk of asthma or greater lung function decline when exposed compared with other genotypes. Exhaust fan use and opening windows frequently may reduce the adverse effects of HAP produced by combustion heating and cooking on current asthma, presumably through increasing ventilation. CONCLUSIONS: Exposures to wood heating, gas cooking and heating, and tobacco smoke over 10 years increased the risks of persistent asthma, lung function decline and % reversibility, with evidence of interaction by GST genes and ventilation.

Childhood vaccination and allergy: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: As the rise in prevalence of allergic diseases worldwide corresponds in time with increasing infant vaccination, it has been hypothesized that childhood vaccination may increase the risk of allergic disease. We aimed to synthesize the literature on the association between childhood vaccination and allergy. DESIGN: We searched the electronic databases PubMed and EMBASE (January 1946-January 2018) using vaccination and allergy terms. METHODS: Two authors selected papers according to the inclusion criteria. Pooled effects across studies were estimated using random-effects meta-analysis. Due to inadequate number of homogeneous publications on newer and underused vaccines, meta-analysis was limited to allergic outcomes following administration of (Bacillus Calmette-Guérin) BCG, measles or pertussis vaccination. The review was prospectively registered in the PROSPERO systematic review registry (NO: CRD42017071009). RESULTS: A total of 35 publications based on cohort studies and 7 publications based on randomized controlled trials (RCTs) met the inclusion criteria. RCTs: From 2 studies, early vaccination with BCG vaccine was associated with a reduced risk of eczema (RR = 0.83; 95% CI = 0.73-0.93; I2  = 0%) but not food allergy or asthma. No association was found between pertussis vaccine and any allergic outcome based on a single RCT. COHORT STUDIES: Childhood measles vaccination was associated with a reduced risk of eczema (RR = 0.65; 95% CI = 0.47-0.90, I2  = 0.0%), asthma (RR = 0.78; 95% CI = 0.62-0.98, I2  = 93.9%) and, with a similar, statistically non-significant reduction in sensitization (RR = 0.78; 95% CI = 0.61-1.01, I2  = 19.4%). CONCLUSIONS: We found no evidence that childhood vaccination with commonly administered vaccines was associated with increased risk of later allergic disease. Our results from pooled analysis of both RCTs and cohort studies suggest that vaccination with BCG and measles vaccines were associated with a reduced risk of eczema.

In vitro inhibition of demineralization from bioglass-containing adhesive and composite.

PURPOSE: To measure and compare the area of inhibition around a bioglass-containing adhesive and resin-based composite following an in vitro artificial caries model in human extracted teeth. METHODS: Preparations were made at the CEJ of extracted human molars (40, n=10/material) and restored with combinations of a bioglass-containing adhesive (BA, Regen), a reference adhesive which served as a negative control (RA), a bioglass-containing composite (BC, Regen), and a reference composite which served as a negative control (RC): BABC, RABC, BARC, RARC. All materials were light-cured and then finished with a polishing disc. Teeth were incubated (37°C) for 24 hours in water. A demineralization solution composed of 0.1 M lactic acid, 3 mM Ca3(PO4)2, 0.1% thymol, and NaOH (to adjust pH= 4.5) and a remineralization solution composed of 1.5 mM Ca, 0.9 mM P, and 20 mM Tris(hydroxymethil)-aminomethane (pH= 7.0) were prepared. Specimens were placed in the demineralization solution for 4 hours followed by a remineralization solution for 20 hours and cycled daily for 30 days. The specimens were embedded, sectioned into 100 µm sections, and the interface between the adhesive/composite and root dentin margin was viewed with polarized light. A line was drawn parallel with the zone of demineralization for each tooth. The area of "inhibition" (defined as the area external to the line) or "wall lesion" (defined as the area internal to the line) was traced with internal image evaluation software and measured. Areas of inhibition were measured as positive values and areas of wall lesions were measured as negative values. RESULTS: A one-way ANOVA found significant differences between materials for "inhibition/wall lesion" areas in root dentin (P< 0.001). Tukey post-hoc analysis ranked materials (µm2, mean± SD): BABC (3590± 2847)a RABC (1903± 1025)a, BARC (-792± 850)b, RARC (-2544± 1760)b. CLINICAL SIGNIFICANCE: The use of bioglass-containing resin-based composite with or without a bioglass-containing adhesive demonstrated inhibition of demineralization at the restoration margin.

The clinical expression and impact of multiple endocrine neoplasia 1 during pregnancy.

CONTEXT: Multiple endocrine neoplasia type 1 (MEN 1) is characterized by multisystem neoplasia including primary hyperparathyroidism and pituitary adenoma. Despite the adolescent onset of endocrinopathies, information regarding the impact of maternal MEN 1 on pregnancy is limited to case reports. OBJECTIVE: To explore pregnancy outcomes in MEN 1 positive women. METHODS: Retrospective case series of maternofoetal outcomes MEN 1 positive mothers managed at the Royal Hobart Hospital between 1967 and 2018. Data were retrieved from medical records and Australian averages calculated based on the Australian Institute of Health and Welfare data. RESULTS: Twenty-six women with MEN 1 were identified accounting for 96 pregnancies and 76 live born infants. Hyperparathyroidism was evident in 16 pregnancies. A significant increase in serum calcium in the second trimester (ß = 0.14, P < .001) occurred that was not mediated by parathyroid hormone. Hypercalcaemia was mild-moderate with parathyroidectomy or medical management required in one and four pregnancies, respectively. Compared to the Australian average, women with MEN 1 were more likely to develop gestational diabetes (56% vs 8.9%, P = .001), hypertensive disorders (25.9% vs 7.6, P = .018), have shorter gestations (38.1 vs 38.7 weeks, P = .015) and have low birthweight infants (30.1% vs 6.5%, P = .001). However, emergency caesarean deliveries (63.2% vs 52.3%) and miscarriage rate (20.8% vs 20%) were not significantly different. CONCLUSION: Maternal MEN 1 is associated with an increased risk of gestational diabetes, hypertensive disorders and low neonatal birthweight, but not with an increased miscarriage rate. Whilst hypercalcaemia worsens during the second trimester, most pregnancies progressed without overt complications or requirement for intervention.

Non-pharmacological management of adult asthma in Australia: cross-sectional analysis of a population-based cohort study.

Aim: To identify the level of non-pharmacological care received by middle-aged adults with current asthma in Australia and to identify its association with clinical measures. Methods: The Tasmanian Longitudinal Health Study (TAHS) is a population-based cohort first studied in 1968 (n = 8583). In 2010, when participants were aged 49 years, a stratified sample enriched for asthma and bronchitis underwent clinical assessments including respiratory questionnaires and lung function testing (n = 836). Current asthma was defined as self-reported asthma symptoms and/or healthcare utilization in the last 12 months. Multivariable linear regression and log-binomial models were used to assess the relevant associations. Results: Of the entire TAHS cohort, 15.6% (95% CI 13.4-18.2%) had current asthma. Of these, 37.9% (95% CI 30.5-45.9%) had seen a general practitioner for their asthma and 16.5% (95% CI 11.5-23.1%) had discussed their asthma with a pharmacist in the last 12 months. Written asthma action plans (AAPs) were reported by 17.9% (95% CI 12.9-23.2%), verbal AAPs by 53.8% (95% CI 45.9-61.6%) and doctor-assessments of inhaler technique by 42.7% (95% CI 35.2-50.5%). Adults with asthma of greater severity were more likely to have received verbal AAPs (p-trend =0.02). In contrast, adults with lower spirometry were more likely to have received verbal AAPs (p = 0.04), written AAPs (p = 0.001) and education on inhaler technique (p = 0.04). Conclusion: Despite an established evidence base and recommendations in local and international guidelines, non-pharmacological asthma management remains sub-optimal in the middle-aged adult asthma population.

Early menarche is associated with lower adult lung function: A longitudinal cohort study from the first to sixth decade of life.

BACKGROUND AND OBJECTIVE: Early menarche is increasing in prevalence worldwide, prompting clinical and public health interest on its links with pulmonary function. We aimed to investigate the relationship between early menarche and lung function in middle age. METHODS: The population-based Tasmanian Longitudinal Health Study (born 1961; n = 8583), was initiated in 1968. The 5th Decade follow-up data (mean age: 45 years) included age at menarche and complex lung function testing. The 6th Decade follow-up (age: 53 years) repeated spirometry and gas transfer factor. Multiple linear regression and mediation analyses were performed to determine the association between age at menarche and adult lung function and investigate biological pathways, including the proportion mediated by adult-attained height. RESULTS: Girls reporting an early menarche (<12 years) were measured to be taller with greater lung function at age 7 years compared with those reporting menarche ≥12 years. By 45 years of age, they were shorter and had lower post-bronchodilator (BD) forced expiratory volume in 1 s (adjusted mean difference: -133 mL; 95% CI: -233, -33), forced vital capacity (-183 mL; 95% CI: -300, -65) and functional residual capacity (-168 mL; 95% CI: -315, -21). Magnitudes of spirometric deficits were similar at age 53 years. Forty percent of these total effects were mediated through adult-attained height. CONCLUSION: Early menarche was associated with reduced adult lung function. This is the first study to investigate post-BD outcomes and quantify the partial role of adult height in this association.

Thiazolidinedione use is associated with reduced risk of Parkinson's disease in patients with diabetes: a meta-analysis of real-world evidence.

BACKGROUND: The thiazolidinedione (TZD) class of oral antidiabetic agents are used to treat type 2 diabetes mellitus (DM). This meta-analysis aimed to understand the protective effect of TZD on Parkinson's disease (PD) in people with diabetes. METHOD: A literature search was performed in PubMed, Embase, and Cochrane central from inception to until 30 September 2019. We included all real-world evidence studies assessing the use of TZD class of drugs and the risk of PD in people with diabetes. Quality of the studies was evaluated using the Newcastle-Ottawa scale. The primary outcome was the pooled hazard ratio (HR) of PD among type 2 DM TZD users as compared with TZD non-users in people with diabetes. The secondary outcome was the HR of PD among type 2 DM TZD users as compared with non-users (include both diabetic and nondiabetic population). Meta-analysis was performed using RevMan software. RESULTS: Out of five studies selected for inclusion, four studies fulfilled the criteria for primary outcomes. The participants' mean age and follow-up duration were 66.23 ± 9.59 years and 5.25 years (2.97-7.9 years), respectively. There was a significant reduction in the risk of PD (pooled adjusted HR of 0.81 [95% CI 0.70-0.93, p = 0.004]) in TZD users compared with non-TZD users in people with diabetes. A significant protective effect of TZD was observed in Caucasian population (3 studies) (HR 0.78 (95% CI 0.66-0.92), p = 0.003). CONCLUSION: This meta-analysis demonstrates a potential neuroprotective effect of TZD for PD risk in the population with DM.

Minimal effects of reduced teaching hours on undergraduate medical student learning outcomes and course evaluations.

Introduction: Various pressures exist for curricular change, including economic forces, burgeoning knowledge, broadening learning outcomes, and improving quality and outcomes of learning experiences. In an Australian 5-year undergraduate medical course, staff were asked to reduce teaching hours by 20% to alleviate perceived overcrowded preclinical curriculum, achieve operating efficiencies and liberate time for students' self-directed learning.Methods: A case study design with mixed methods was used to evaluate outcomes.Results: Teaching hours were reduced by 198 hours (14%) overall, lectures by 153 hours (19%) and other learning activities by 45 hours (7%). Summative assessment scores did not change significantly after the reductions: 0.4% increase, 1.5% decrease and 1.7% increase in Years 1, 2 and 3, respectively. The percentage of students successfully completing their academic year did not change significantly: 94.4% before and 93.3% after the reductions. Student evaluations from eVALUate surveys changed little, except workload was perceived to be more reasonable.Conclusions: Teaching hours, particularly lectures, can be moderately reduced with little impact on student learning outcomes or satisfaction with an undergraduate medical course.

Occupational exposure to solvents and lung function decline: A population based study.

RATIONALE: While cross-sectional studies have shown associations between certain occupational exposures and lower levels of lung function, there was little evidence from population-based studies with repeated lung function measurements. OBJECTIVES: We aimed to investigate the associations between occupational exposures and longitudinal lung function decline in the population-based Tasmanian Longitudinal Health Study. METHODS: Lung function decline between ages 45 years and 50 years was assessed using data from 767 participants. Using lifetime work history calendars completed at age 45 years, exposures were assigned according to the ALOHA plus Job Exposure Matrix. Occupational exposures were defined as ever exposed and cumulative exposure -unit- years. We investigated effect modification by sex, smoking and asthma status. RESULTS: Compared with those without exposure, ever exposures to aromatic solvents and metals were associated with a greater decline in FEV1 (aromatic solvents 15.5 mL/year (95% CI -24.8 to 6.3); metals 11.3 mL/year (95% CI -21.9 to - 0.7)) and FVC (aromatic solvents 14.1 mL/year 95% CI -28.8 to - 0.7; metals 17.5 mL/year (95% CI -34.3 to - 0.8)). Cumulative exposure (unit years) to aromatic solvents was also associated with greater decline in FEV1 and FVC. Women had lower cumulative exposure years to aromatic solvents than men (mean (SD) 9.6 (15.5) vs 16.6 (14.6)), but greater lung function decline than men. We also found association between ever exposures to gases/fumes or mineral dust and greater decline in lung function. CONCLUSIONS: Exposures to aromatic solvents and metals were associated with greater lung function decline. The effect of aromatic solvents was strongest in women. Preventive strategies should be implemented to reduce these exposures in the workplace.

Age at introduction to complementary solid food and food allergy and sensitization: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: An infant's age at introduction of complementary solids may contribute to food allergy. We aimed to synthesize the literature on the association between age at introduction of complementary solids, excluding milk products, and food allergy and sensitization. DESIGN: We searched the electronic databases PubMed and EMBASE (January 1946-February 2017) using solid food, allergy and sensitization terms. METHODS: Two authors selected papers according to inclusion criteria, identifying 16 cohort studies, 1 case-control study and 8 randomized controlled trials (RCTs). Pooled effects across studies were estimated using random-effects meta-analysis. RESULTS: Cohort studies-Introducing complementary solids at age ≥ 4 months vs <4 months was not associated with food allergy (OR 1.22; 95% CI, 0.76-1.96) but was associated with food sensitization (OR 1.93; 95% CI 1.57-2.38). First exposure from age 4 to 6 months vs <4 months was not associated with food allergy (OR 1.01; 95% CI, 0.64-1.60) but was associated with food sensitization (OR 2.46; 95% CI 1.55-3.86). Randomized controlled trials-Egg exposure from age 4 months was associated with reduced egg allergy (OR 0.63, 95% CI, 0.44-0.90) and sensitization (OR 0.76, 95% CI, 0.51-0.95). Peanut exposure from age 4 months compared to delayed exposure was associated with reduced peanut allergy (OR 0.28, 95% CI 0.14-0.57). CONCLUSIONS: We found no evidence from observational studies that introducing solids before 4 months protected against food allergy, but there was evidence for protection against food sensitization. From RCTs, introducing egg from 4 to 6 months and peanut from 4 to 11 months reduced the risk of egg allergy, peanut allergy and egg sensitization. PROSPERO systematic review registry (CRD42016033473).

Early-life exposure to sibling modifies the relationship between CD14 polymorphisms and allergic sensitization.

BACKGROUND: Markers of microbial exposure are thought to be associated with risk of allergic sensitization; however, the associations are inconsistent and may be related to gene-environment interactions. OBJECTIVE: To examine the relationship between polymorphisms in the CD14 gene and allergic sensitization and whether sibling exposure, as a marker of microbial exposure, modified this relationship. METHODS: We used data from the Tasmanian Longitudinal Health Study and the Melbourne Atopy Cohort Study. Two CD14 polymorphisms were genotyped. Allergic sensitization was defined by a positive response to a skin prick test. Sibling exposure was measured as cumulative exposure to siblings before age 6 months, 2 and 4 years. Logistic regression and multi-level mixed-effects logistic regression were used to examine the associations. Effect estimates across the cohorts were pooled using random-effects meta-analysis. RESULTS: CD14 SNPs were not individually associated with allergic sensitization in either cohort. In TAHS, cumulative sibling exposure before age 6 months, 2 and 4 years was each associated with a reduced risk of allergic sensitization at age 45 years. A similar effect was observed in MACS. Meta-analysis across the two cohorts showed consistent evidence of an interaction between cumulative sibling exposure before 6 months and the rs5744455-SNP (P = 0.001) but not with the rs2569190-SNP (P = 0.60). The pooled meta-analysis showed that the odds of sensitization with increasing cumulative exposure to sibling before 6 months of age was 20.9% smaller in those with the rs5744455-C-allele than the T-allele (OR = 0.83 vs 1.05, respectively). CONCLUSION AND CLINICAL RELEVANCE: Cumulative sibling exposure reduced the risk of sensitization from childhood to middle age in genetically susceptible individuals.