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Background Variation in mitochondrial DNA (mtDNA) identified by genotyping microarrays or by sequencing only the hypervariable regions of the genome may be insufficient to reliably assign mitochondrial genomes to phylogenetic lineages or haplogroups. This lack of resolution can limit functional and clinical interpretation of a substantial body of existing mtDNA data. To address this limitation, we developed and evaluated a large, curated reference alignment of complete mtDNA sequences as part of a pipeline for imputing missing mtDNA single nucleotide variants (mtSNVs). We call our reference alignment and pipeline MitoImpute. Results We aligned the sequences of 36,960 complete human mitochondrial genomes downloaded from GenBank, filtered and controlled for quality. These sequences were reformatted for use in imputation software, IMPUTE2. We assessed the imputation accuracy of MitoImpute by measuring haplogroup and genotype concordance in data from the 1000 Genomes Project and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The mean improvement of haplogroup assignment in the 1000 Genomes samples was 42.7% (Matthew’s correlation coefficient = 0.64). In the ADNI cohort, we imputed missing single nucleotide variants. Conclusion These results show that our reference alignment and panel can be used to impute missing mtSNVs in existing data obtained from using microarrays, thereby broadening the scope of functional and clinical investigation of mtDNA. This improvement may be particularly useful in studies where participants have been recruited over time and mtDNA data obtained using different methods, enabling better integration of early data collected using less accurate methods with more recent sequence data.

Preseason functional tests have been previously associated with noncontact time-loss lower extremity injuries in a variety of athletic populations. This study aimed to determine the effectiveness of one or more functional tests to discriminate injury risk in a cohort of female collegiate volleyball players in the United States.Prospective cohort study.National Collegiate Athletic Association Division IIIII, National Association of Intercollegiate Athletics female volleyball players; PARTICIPANTS: 130 female volleyball players (mean age: 19.31 ± 1.1 years).Lower extremity functional test, single limb hop for distance, standing long jump, previous injury history, lower quarter Y-balance test, and limb symmetry index were measured prior to the season beginning. Noncontact time-loss lower quarter injuries were tracked during the season.Athletes with suboptimal scores on the single limb hop test (70% of height) and standing long jump (80% of height), combined with a previous history of injury, were three times more likely to sustain an injury during the season (OR = 3.0; 95% CI: 1.09 to 8.30). Individual functional tests did not discriminate injury risk.A battery of preseason functional tests and injury history discriminates injury risk in female collegiate volleyball players.

Contains fulltext : 235277.pdf (Publisher’s version ) (Closed access) BACKGROUND: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. METHODS: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. FINDINGS: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models. INTERPRETATION: The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted. FUNDING: British Heart Foundation and Stroke Association.

Previously, variation in retinal vascular caliber has been reported in association with chronic kidney disease (CKD) but findings remain inconsistent. To help clarify this we conducted individual participant data meta-analysis and aggregate data meta-analysis on summary estimates to evaluate cross-sectional associations between retinal vascular caliber and CKD. A systematic review was performed using Medline and EMBASE for articles published until October 2018. The aggregate analysis used a two-stage approach combining summary estimates from eleven studies (44,803 patients) while the individual participant analysis used a one-stage approach combining raw data from nine studies (33,222 patients). CKD stages 3-5 was defined as an estimated glomerular filtration rate under 60 mL/min/1.73m2. Retinal arteriolar and venular caliber (central retinal arteriolar and venular equivalent) were assessed from retinal photographs using computer-assisted methods. Logistic regression estimated relative risk of CKD stages 3-5 associated with a 20 μm decrease (approximately one standard deviation) in central retinal arteriolar and venular equivalent. Prevalence of CKD stages 3-5 was 11.2% of 33,222 and 11.3% of 44,803 patients in the individual participant and aggregate data analysis, respectively. No significant associations were detected in adjusted analyses between central retinal arteriolar and venular equivalent and CKD stages 3-5 in the aggregate analysis for central retinal arteriolar relative risk (0.98, 95% confidence interval 0.94-1.03); venular equivalent (0.99, 0.95-1.04) or individual participant central retinal arteriolar (0.99, 0.95-1.04) or venular equivalent (1.01, 0.97-1.05). Thus, meta-analysis provided little evidence to suggest that cross sectional direct measurements of retinal vascular caliber was associated with CKD stages 3-5 in the general population. Hence, meta-analyses of longitudinal studies evaluating the association between retinal parameters and CKD stages 3-5 may be warranted.

OBJECTIVE: Diabetes summer camps provide children and adolescents with type 1 diabetes opportunities to learn about the disease and its management in a supportive environment to help improve glycaemic control, self-reliance and quality of life. The objective of this quantitative review was to assess the advantages of attending summer camps and study any adverse psychological effects.METHODS: Studies with a pre/post study design in children and adolescents attending summer camp were systematically reviewed. Five bibliographic databases were searched and relevant data extracted. Random effects meta-analyses were used to combine the individual study results to derive pooled estimates and meta-regression was used to explore between-study heterogeneity.RESULTS: Studies in the literature report short-term improvements in the glycaemic control, diabetes knowledge (DK), quality of life (QOL) anxiety, diabetes self-management and self-esteem. Thirty-three studies were identified, and those outcomes reported in five or more studies were included in meta-analyses. There were significant benefits with a pooled mean change for glycated haemoglobin (95%CI) of -0.59(-0.95,-0.23)% (-6.4(-10.4,-2.5)mmol/mol), and for standardised DK score of 1.99(1.28,2.70) but corresponding changes for QOL 0.17(-0.06,0.39) and for anxiety -0.32(-0.70,0.06) were not significant. However, all outcomes showed considerable between-study heterogeneity little of which was explained by study characteristics.CONCLUSION: The findings suggests short-term benefits of camp on metabolic control, DK, QOL and anxiety in T1D children and adolescents, although the latter two were not statistically significant. Further research is warranted with more methodological rigor and longer-term follow-up to determine if there are long-term benefits associated with camp attendance. This article is protected by copyright. All rights reserved.

Background The main underlying risk factors associated with coronary heart disease (CHD) are modifiable and oxidative injury and systemic inflammatory damage represent key aetiological factors associated with the development and progression of CHD and premature mortality. Objective To examine associations of plasma antioxidant status with all-cause mortality and fatal or non-fatal cardiovascular events. Design The PRIME study prospectively evaluated 9709 men aged 50–59 years between 1991 and 1993 in Northern Ireland and France who were free of CHD at recruitment and followed annually for deaths and cardiovascular events for 10 years. Serum concentrations of vitamin C, retinol, two forms of vitamin E (α- and γ-tocopherol) and six carotenoids were quantified by high-performance liquid chromatography. Baseline conventional risk factors were considered, as well as socioeconomic differences and lifestyle behaviours including diet, smoking habit, physical activity, and alcohol consumption through Cox regression analyses. Results At 10 years, there were 538 deaths from any cause and 440 fatal or non-fatal cardiovascular events. After adjustment for country, age, systolic blood pressure, diabetes, body mass index, cholesterol, high density lipoprotein cholesterol, triglycerides, height, total physical activity, alcohol consumption and smoking habit, higher levels of all antioxidants were associated with significantly lower risk of all-cause mortality, with the exception of γ-tocopherol. Only retinol was significantly associated with decreased risk of cardiovascular events in a fully adjusted model. Conclusions Low antioxidant levels contribute to the gradient of all-cause mortality and cardiovascular incidence independent of lifestyle behaviours and traditional cardiovascular and socioeconomic risk factors.

Objective The objective of this study is to describe agreement between administrative and self-report data on the number and type of chronic conditions (CCs) and determine whether associations between CC count and health service use differ by data source. Study Design and Setting We linked Canadian Community Health Survey and administrative data for a cohort of adults aged 45+ years in Ontario and identified 12 CCs from both data sources. Agreement was described by count and constituent CCs. We estimated associations between CC count (self-report and administrative data) and health service use (administrative data only) over 1 year. Results Among 71,317 adults, 26.9% showed agreement on both count and constituent CCs but agreement declined with increasing CCs. Health service use increased with CC count but the association was stronger when CCs were measured with administrative data. For example, when measured with administrative data, the odds of a general practitioner visit for 5+ CCs vs. none was 20.3 (95% CI 20.0–20.5) but when using self-report data, the estimate was 8.0 (95% CI 7.8–8.2). Conclusion Agreement on the number of CCs was low and resulted in different estimates on the association with health service use, illustrating the challenges in CC measurement and the ability to interpret the effects on outcomes.

To critically synthesize the literature that describes men's help-seeking and engagement with general practice.Integrative literature review.CINAHL plus, Medline and APA PsycInfo were searched for papers published between 1999 and March 2021.After screening titles and abstracts, full-text papers were screened against inclusion / exclusion criteria. All included papers were assessed for methodological quality. Findings were extracted, critically examined and synthesized into themes.Twenty studies met the inclusion criteria. Thematic analysis revealed four themes related to; (1) structural barriers, (2) internal barriers, (3) men's understanding of the role of general practice, and (4) self-care and help-seeking. The findings indicate that men can find general practice unwelcoming and unaccommodating. Men can also experience psychological barriers that impact engagement and help-seeking. Men predominantly view general practice as a source of acute health care and do not appreciate the role of general practice in preventive health care and advice.This review has provided insight into the issues around the barriers to health care engagement, men's understanding of the role of general practice and their associated help-seeking. Seeking to further understand these issues could assist in the development of strategies to promote engagement of men with general practice health care.This review highlights research about men's engagement with general practice and the missed opportunities in receiving preventive health care and education. Enhancing men's engagement with general practice has the potential to reduce the impact of their health on quality of life and improve health outcomes.

Background There are limited data on performance of biomarkers to predict pre-eclampsia (PE) in high-risk women. This study investigated the ability of FABP4, PAPP-A, PlGF, sFlt-1 and sEng to predict PE in a high-risk group. Methods Non-fasting samples were analysed at 11 + 0–13 + 6 (V1) and 19 + 0–21 + 6 weeks (V2) ( n = 195). Logistic regression models were determined. Area under (AUC) the receiver operating characteristic (ROC) curve analysis was performed. The added value of biomarkers to clinical characteristics for PE prediction was quantified using integrated discrimination improvement (IDI) and net reclassification improvement (NRI) indices. Results Prevalence of PE was 12%. Lower concentrations of sFlt-1:PlGF (V1) and PlGF and PlGF:sEng (V2) were seen in women who developed PE. Controlling for baseline characteristics (V1), a doubling of sFlt-1 (pg/mL) (median 896.0, IQR 725.5–1097.0) and sFlt-1:PlGF (median 21.2, IQR 14.7–32.3) was associated with reduction in odds of PE (OR 0.20, 95% CI 0.06–0.65, P = 0.007 and OR 0.48, 95% CI 0.25–0.92, P = 0.04). Addition of sFlt-1 and sFlt-1:PlGF to baseline characteristics non-significantly improved AUC (0.74) (AUC 0.77, P = 0.40 and 0.76, P = 0.39). NRI and IDI analyses confirmed added clinical utility of sFlt-1 (NRI = 0.539, P = 0.01 and IDI = 0.052, P = 0.03). In V2, doubling of PlGF:sEng (median 71.9, IQR 47.0–102.8) was associated with reduction in the risk of PE (OR 0.56, 95% CI 0.35–0.98, P = 0.04). The addition of PlGF:sEng to baseline characteristics non-significantly improved AUC from 0.78 to 0.82 ( P = 0.25) and improved reclassification of cases (NRI = 0.682, P = 0.002). Conclusions Screening tests incorporating first trimester sFlt-1 and second trimester PlGF:sEng have potential to aid PE prediction in high-risk pregnancies.

AIM The aim was to investigate the role of systemic inflammation in the relationship between periodontitis, edentulism, and all-cause mortality in a group of men in Northern Ireland aged 58-72 years. MATERIALS AND METHODS A representative sample of 1558 men had a detailed dental examination between 2001 and 2003. The primary end point was death from any cause. Cox's proportional hazards model was used to assess the longitudinal relationship between periodontitis, edentulism, and all-cause mortality. Accelerated failure time modelling was performed to investigate the mediating role of systemic inflammation. RESULTS Mean age of the men at baseline was 64.3 (standard deviation 2.9) years. During a median follow-up of 17 years, 500 (32.1%) men died. After adjustment for confounding variables, compared to men with no/mild periodontitis, edentulous men had a hazard ratio for all-cause mortality of 1.52 (95% confidence interval [CI] 1.16-1.99) p

ObjectiveTo evaluate the pattern of frailty across several of social stratifiers associated with health inequalities.Design, setting and participantsCross-sectional baseline data on 51 338 community-living women and men aged 45–85 years from the population-based Canadian Longitudinal Study on Aging (collected from September 2011 to May 2015) were used in this study.Primary outcomes and measuresA Frailty Index (FI) was constructed using self-reported chronic conditions, psychological function and cognitive status and physical functioning variables. Social stratifiers were chosen based on the Pan-Canadian Health Inequalities Reporting Initiative, reflecting key health inequalities in Canada. Unadjusted and adjusted FIs and domain-specific FIs (based on chronic conditions, physical function, psychological/cognitive deficits) were examined across population strata.ResultsThe overall mean FI was 0.13±0.08. It increased with age and was higher in women than men. Higher mean FIs were found among study participants with low income (0.20±0.10), who did not complete secondary education (0.17±0.09) or had low perceived social standing (0.18±0.10). Values did not differ by Canadian province of residence or urban/rural status. After simultaneously adjusting for population characteristics and other covariates, income explained the most heterogeneity in frailty, especially in younger age groups; similar patterns were found for men and women. The average frailty for people aged 45–54 in the lowest income group was greater than that for those aged 75–85 years. The heterogeneity in the FI among income groups was greatest for the psychological/cognitive domain.ConclusionsOur results suggest that especially in the younger age groups, psychological/cognitive deficits are most highly associated with both overall frailty levels and the gradient in frailty associated with income. If this is predictive of later increases in the other two domains (and overall frailty), it raises the question whether targeting mental health factors earlier in life might be an effective approach to mitigating frailty.

The prevalence of patellar tendinopathy has been reported to be as high as 50% in elite male volleyball (VB) players; however, the rate of injury in female collegiate VB athletes is unknown. The purpose of this study was to 1) identify the prevalence of ultrasonographic evidence of patellar tendon abnormality at the start of the preseason in female collegiate VB players; 2) report the incidence of tendinopathy during the season; and 3) determine if the preseason presence of tendon abnormality is associated with onset of disease. One hundred and six female collegiate VB players had both patellar tendons imaged. Incidence of patellar tendinopathy was tracked during the course of the 4-month season. Twenty-two athletes presented with ultrasonographic evidence of patellar tendon abnormality in at least one knee at the start of the preseason. The incidence of time-loss patellar tendinopathy was 0.26 (95% CI: 0.04, 0.85) per 1000 athletic exposures. This study was unable to determine if preseason presence of tendon abnormality was associated with a greater risk of tendinopathy due to power. The prevalence of tendon abnormality in the preseason and the incidence of patellar tendinopathy in female collegiate VB players are lower than that observed in other populations.

Background Most studies that examine comorbidity and its impact on health service utilization focus on a single index-condition and are published in disease-specific journals, which limit opportunities to identify patterns across conditions/disciplines. These comparisons are further complicated by the impact of using different study designs, multimorbidity definitions and data sources. The aim of this paper is to share insights on multimorbidity and associated health services use and costs by reflecting on the common patterns across 3 parallel studies in distinct disease cohorts (diabetes, dementia, and stroke) that used the same study design and were conducted in the same health jurisdiction over the same time period. Methods We present findings that lend to broader Insights regarding multimorbidity based on the relationship between comorbidity and health service use and costs seen across three distinct disease cohorts. These cohorts were originally created using multiple linked administrative databases to identify community-dwelling residents of Ontario, Canada with one of diabetes, dementia, or stroke in 2008 and each was followed for health service use and associated costs. Results We identified 376,434 indviduals wtih diabetes, 95,399 wtih dementia, and 29,671 with stroke. Four broad insights were identified from considering the similarity in comorbidity, utilization and cost patterns across the three cohorts: 1) the most prevalent comorbidity types were hypertension and arthritis, which accounted for over 75% of comorbidity in each cohort; 2) overall utilization increased consistently with the number of comorbidities, with the vast majority of services attributed to comorbidity rather than the index conditions; 3) the biggest driver of costs for those with lower levels of comorbidity was community-based care, e.g., home care, GP visits, but at higher levels of comorbidity the driver was acute care services; 4) service-specific comorbidity and age patterns were consistent across the three cohorts. Conclusions Despite the differences in population demographics and prevalence of the three index conditions, there are common patterns with respect to comorbidity, utilization, and costs. These common patterns may illustrate underlying needs of people with multimorbidity that are often obscured in literature that is still single disease-focused. Electronic supplementary material The online version of this article (10.1186/s12913-019-4149-3) contains supplementary material, which is available to authorized users.

Les outils cliniques employes dans les etablissements de soins peuvent fournir des informations pronostiques importantes aux professionnels de la sante. Dans cette etude observationnelle prospective d'un an, nous avons examine l'association entre les scores au Short Performance Physical Battery (SPPB), d'une part, et les consultations a l'urgence et les hospitalisations au cours de l'etude, d'autre part. Au total, 191 patients ayant ete nouvellement referes a une clinique geriatrique externe de Hamilton (Ontario) ont ete contactes, et parmi eux, 120 pris part a l'etude. Le SPPB et d'autres evaluations ont ete realises dans le cadre de consultations de routine. Les dossiers medicaux electroniques ont ete examines pour determiner le nombre de consultations a l'urgence et d'hospitalisations dans l'annee qui a suivi l'evaluation de base. Des analyses de regression logistique ont ete utilisees pour identifier des predicteurs des consultations a l'urgence et des hospitalisations. Le score moyen au SPPB dans la cohorte etudiee (moyenne d'âge = 80,6 ans, ecart-type = 6,3 ans ; 53 % de femmes) etait de 6,3 (ecart-type = 3,2). Au cours de cette periode d'un an, le score au SPPB etait associe au nombre de consultations a l'urgence [RR = 0,90 (0,78-1,03)] et d'hospitalisations [RR = 0,84 (0,72-0,97)], apres ajustement pour l'âge, le sexe et les comorbidites. Tools applied at the point of care can provide valuable prognostic information for practitioners. In this one-year, prospective observational study, we examined the association of the short performance physical battery (SPPB) and one-year emergency department (ED) visits and hospitalizations. Overall, 191 new referrals attending an outpatient geriatric clinic in Hamilton, Ontario, were approached, and 120 were enrolled. SPPB and other assessments were completed during the routine clinical visit. ED visits and hospitalizations within one year of the baseline assessment were abstracted from electronic medical records. Logistic regression analyses were used to determine ED visits and hospitalization predictors. The mean SPPB score in the study cohort (mean age 80.6, SD 6.3 years; 53% female) was 6.3 (SD 3.2). SPPB score was associated with a one-year ED visit (OR = 0.90 [0.78–1.03]) and hospitalization (OR = 0.84 [0.72–0.97]) after adjusting for age, sex, and co-morbidities.

Four key articles published in 2018 have been selected to represent clinical situations where recent evidence may prompt changes in practice relevant to the nursing home population. There is no evidence of benefit for levothyroxine replacement in mild subclinical hypothyroidism. Duloxetine may be considered as an option for the treatment of pain and stiffness in osteoarthritis of the knees. Supplemental oxygen in the absence of hypoxemia is unnecessary and potentially harmful. Methylphenidate has modest benefit in treating apathy in dementia. For each subject, a brief review of the pertinent article is followed by a “bottom line” recommendation.

OBJECTIVE To investigate whether there was an association between chronic periodontitis (CP) and reduced respiratory function. METHODS A group of dentate 58- to 72-year-old men in Northern Ireland had a comprehensive periodontal examination. Parallel to the periodontal examination, participants completed questionnaires gathering information on their medical history, social circumstances, demographic background and tobacco use. A physical examination assessed anthropometric measures. Fasting blood samples were obtained and analysed for high-sensitivity C-reactive protein (hs-CRP). Spirometry measures were performed using a wedge bellows spirometer (Vitalograph S Model). The primary outcome variable of interest was the percentage predicted forced expiratory volume in one-second (% predicted FEV1 ). Analysis included multiple linear regression with adjustment for various confounders and a regression-based mediation analysis. RESULTS A total of 1,380 men were included in the analysis. The mean age was 63.7 years (SD 3.0). Multiple linear regression analysis showed that a doubling in mean clinical attachment loss (CAL) equated to a -3.33% (95% CI: -4.80, -1.86), p

Background Researchers often use survey data to study the effect of health and social variables on physician use, but how self-reported physician use compares to administrative data, the gold standard, in particular within the context of multimorbidity and functional limitations remains unclear. We examine whether multimorbidity and functional limitations are related to agreement between self-reported and administrative data for physician use. Methods Cross-sectional data from 52,854 Ontario participants of the Canadian Community Health Survey linked to administrative data were used to assess agreement on physician use. The number of general practitioner (GP) and specialist visits in the previous year was assessed using both data sources; multimorbidity and functional limitation were from self-report. Results Fewer participants self-reported GP visits (84.8%) compared to administrative data (89.1%), but more self-reported specialist visits (69.2% vs. 64.9%). Sensitivity was higher for GP visits (≥90% for all multimorbidity levels) compared to specialist visits (approximately 75% for 0 to 90% for 4+ chronic conditions). Specificity started higher for GP than specialist visits but decreased more swiftly with multimorbidity level; in both cases, specificity levels fell below 50%. Functional limitations, age and sex did not impact the patterns of sensitivity and specificity seen across level of multimorbidity. Conclusions Countries around the world collect health surveys to inform health policy and planning, but the extent to which these are linked with administrative, or similar, data are limited. Our study illustrates the potential for misclassification of physician use in self-report data and the need for sensitivity analyses or other corrections.

Weakness of the hip extensors and lumbar spine extensors has been proposed to contribute to greater demands on the lumbar spine during lifting. The purpose of the current study was to examine the associations among strength of the hip and lumbar spine extensors, lumbar spine extensor moments and lumbar paraspinal muscle activation during a squat lift task. Twenty-seven healthy females participated. Strength of the hip and lumbar spine extensors was measured using a dynamometer. Lumbar spine moments and lumbar paraspinal muscle activity were quantified during the concentric phase of the squat lifting task. There was a significant positive association between lumbar extensor strength and average lumbar extensor moment during lifting (r=0.498, p=0.008). Similarly, hip extensor strength was positively associated with the average lumbar extension moment (r=0.382, p=0.049). Hip extensor strength was negatively associated with activation of the lumbar paraspinal muscles during lifting ( ρ =-0.382, p=0.049). Stronger individuals are more likely to use their hip extensors and lumbar spine extensors to perform a squat lift task. In contrast, those with lower strength employ subtle biomechanical changes to reduce lumbar spine demand.

Delirium is a serious and common condition that leads to significant adverse health outcomes for hospitalised older adults. It occurs in 30%–55% of patients with hip fractures and is one of the most common postoperative complications in older adults undergoing orthopaedic surgery. Multicomponent, non-pharmacological interventions can reduce delirium incidence by up to 30% but are often challenging to implement as part of routine care. We identified a gap in the delivery of non-pharmacological interventions on an orthopaedic unit. This project aimed to implement a bedside sign on an orthopaedic unit to reduce the occurrence of delirium by prompting staff to use multicomponent evidence-based delirium prevention strategies for at-risk older adults. Quality improvement methods were used to integrate and optimise the use of a bedside ‘delirium prevention’ sign on an orthopaedic unit.The sign was implemented in four target rooms and sign completion rates increased from 47% to 83% (95% CI 71.7% to 94.9%; p

OBJECTIVE: To investigate periodontitis as a risk factor for prevalent and incident coronary heart disease (CHD) in a group of middle-aged men from Northern Ireland.METHODS: A representative sample of 1400 dentate men had a comprehensive periodontal examination between 2001 and 2003. Prevalent and incident CHD events were validated by independent cardiologists. Logistic regression was used to assess the cross-sectional relationship between periodontitis and prevalent CHD and Cox's proportional hazards analysis to assess the longitudinal relationship between periodontitis and incident CHD.RESULTS: The mean age of the men at baseline was 63.7 (SD 3.0) years. Of the 1400 men examined, 126 (9%) had prevalent CHD. After adjusting for confounding variables, men with highest mean CAL (Q4) had an odds ratio of 2.15 (95% CI 1.15-4.02), p = 0.02 for prevalent CHD in comparison to men with the lowest CAL (Q1). During a median follow-up of 12.7 years, 137 (10.8%) of the 1274 men free of CHD at baseline had an incident CHD event. After adjusting for confounding variables, the hazard ratio for incident CHD in men in Q4 versus Q1 CAL categories was 1.36 (95% CI 0.81-2.29), p = 0.24.CONCLUSIONS: In this group of dentate men, periodontitis was associated with prevalent CHD. However, there was no association with incident CHD.

Increased fruit and vegetable (FV) intake is associated with reduced blood pressure. However, it is not clear whether the effect of FV on blood pressure depends on the type of FV consumed. Furthermore, there is limited research regarding the comparative effect of juices or whole FV on blood pressure. Baseline data from a prospective cohort study examined the cross-sectional association between total FV intake, but also specific types of FV and blood pressure in France and Northern Ireland. A total of 10660 men aged 50-59 years were recruited from 1991 to 1994. Blood pressure was measured in a clinic setting, and dietary intake was assessed by food-frequency questionnaire (FFQ). After adjusting for potential confounders, both systolic (SBP) and diastolic blood pressure (DBP) were significantly inversely associated with total fruit, vegetable and fruit juice intake however when results were examined according to the sub-type of fruit or vegetable (citrus fruit, other fruit, fruit juices, cooked vegetables and raw vegetables), only the other fruit and raw vegetable categories were consistently associated with reduced SBP and DBP. In relation to the risk of hypertension based on systolic blood pressure >140 mmHg, the odds ratio for total fruit, vegetable and fruit juice intake (per fourth) was 0.95 (95 % CI 0.91, 1.00), with the same estimates being 0.98 (CI % 0.94, 1.02) for citrus fruit intake (per fourth), 1.02 (CI % 0.98, 1.06) for fruit juice intake (per fourth), 0.93 (CI % 0.89, 0.98) for other fruit intake (per fourth), 1.05 (CI % 0.99, 1.10) for cooked vegetable intake (per fourth) and 0.86 (CI % 0.80, 0.91) for raw vegetable intake (per fourth). Similar results were obtained for DBP. In conclusion, a high overall intake of fruit, vegetables and fruit juice was inversely associated with SBP and DBP and risk of hypertension, but that this association differs by FV sub-type, suggesting that the strength of the association between these FV sub-types and blood pressure might be related to the type consumed, or to processing or cooking-related factors.

Aims/hypothesis Data on type 1 diabetes incidence and prevalence are limited, particularly for adults. This study aims to estimate global numbers of incident and prevalent cases of type 1 diabetes in 2017 for all age groups, by country and areas defined by income and region. Methods Incidence rates of type 1 diabetes in children (available from 94 countries) from the IDF Atlas were used and extrapolated to countries without data. Age-specific incidence rates in adults (only known across full age range for fewer than ten countries) were obtained by applying scaling ratios for each adult age group relative to the incidence rate in children. Age-specific incidence rates were applied to population estimates to obtain incident case numbers. Duration of diabetes was estimated from available data and adjusted using differences in childhood mortality rate between countries from United Nations demographic data. Prevalent case numbers were derived by modelling the relationship between prevalence, incidence and disease duration. Sensitivity analyses were performed to quantify the impact of alternative assumptions and model inputs. Results Global numbers of incident and prevalent cases of type 1 diabetes were estimated to be 234,710 and 9,004,610, respectively, in 2017. High-income countries, with 17% of the global population, accounted for 49% of global incident cases and 52% of prevalent cases. Asia, which has the largest proportion of the world’s population (60%), had the largest number of incident (32%) and prevalent (31%) cases of type 1 diabetes. Globally, 6%, 35%, 43% and 16% of prevalent cases were in the age groups 0–14, 15–39, 40–64 and 65+ years, respectively. Based on sensitivity analyses, the estimates could deviate by ±15%. Conclusions/interpretation Globally, type 1 diabetes represents about 2% of the estimated total cases of diabetes, ranging from less than 1% in certain Pacific countries to more than 15% in Northern European populations in 2017. This study provides information for the development of healthcare and policy approaches to manage type 1 diabetes. The estimates need further validation due to limitations and assumptions related to data availability and estimation methods. Graphical abstract

OBJECTIVE The re-emergence of iodine deficiency in the UK has recently been reported in a large cohort of teenage girls including from Northern Ireland (NI) using the gold standard spot urinary iodine concentration. We wished to explore and confirm this by analysing neonatal thyroid-stimulating hormone (nTSH) levels in the NI population. DESIGN We analysed the nTSH heel prick tests results from the NI national screening database between 2003 and 2014. The WHO proposes a definition for population iodine sufficiency at 5 mIU/L. METHODS Anonymized results from 288 491 nTSH tests were retrieved, and prevalence rates of results at increasing cut-offs including >2 mIU/L and >5 mIU/L calculated. We also assessed for possible seasonal variation in nTSH results. RESULTS An overall population prevalence of 0.49% with TSH >5 mIU/L was found, indicating population iodine sufficiency with no year attaining a prevalence >3%. The prevalence of nTSH >2 mIU/L decreased to 4.1% in 2007 and subsequently increased to 9.8% in 2014. Modest seasonal variation was also detected, with higher levels among April/May births. CONCLUSIONS The neonatal TSH database suggests iodine sufficiency in the NI population. However, the rising frequency of results >2 mIU/L may indicate an emerging mild iodine deficiency. This is one of the largest and longest studies of its kind in the UK and the first carried out in NI. The summer months may be a time of increased risk of iodine deficiency in our pregnant women whose requirements are increased and who are not currently targeted by any iodine fortification programme in the UK.

Objective: To assess ability of first and second trimester Placental Vascularization Indices (PVIs) to predict pre-eclampsia (PE) in high-risk pregnancies. Method: PVIs derived from 3-Dimensional power Doppler imaging were measured at 11+0–13 + 6 (n = 194) and 19+0–21 + 6 weeks (n = 195). Logistic regression (LR) models used PE as the outcome. To quantify added value of PVIs to baseline characteristics in predicting PE, integrated discrimination improvement (IDI) and net reclassification improvement (NRI) indices were calculated. Results: Overall rate of PE was 12% (n = 26). Lower first trimester PVIs were seen in women with PE (mean, SD); Vascularization Index (VI,%): 10.0 (6.2) v 14.7 (7.6), P = 0.005, Flow Index (FI): 37.7 (9.1) v 42.9 (10.4), P = 0.03, Vascularization Flow Index (VFI): 3.8 (2.5) v 6.6 (4.0), P Conclusion: First trimester placental vascularization indices (VI, FI and VFI) have the potential to predict PE in high-risk pregnancies, with FI remaining predictive in the second trimester.

ObjectivesAfter 20 years of data collection, pregnancy registers have informed prescribing practice. Various populations show trends for a reduction in valproate prescribing, which is associated with an increased risk of anatomical teratogenesis and neurodevelopmental effects in those exposed in utero. Our aim was to determine if any shifts in prescribing trends have occurred in the UK and Ireland Epilepsy and Pregnancy Register cohort and to assess if there had been any change in the overall major congenital malformation (MCM) rate over time.MethodsThe UK and Ireland Epilepsy and Pregnancy Register, a prospective, observational, registration and follow-up study established in 1996, was used to determine the changes in antiepileptic drugs (AEDs) utilised during pregnancy and the MCM rate between 1996 and 2016. Linear regression analysis was used to assess changes in AED utilisation, and Poisson regression was used for the analysis of trends in the MCM rates.ResultsOutcome data for 9247 pregnancies showed a stable percentage of monotherapy to polytherapy prescribing habits over time. After Bonferroni correction, statistically significant (pConclusionSignificant changes are seen in the prescribing habits in this cohort over 20 years, but a statistically significant change in the MCM rate was not detected. This work should be replicated on a larger scale to determine if significant changes are occurring in the MCM rate, which would allow a robust economic estimate of the benefits of improvements in prescribing practice and the personal effect of such changes.

Aims/hypothesis: The incidence of pre-eclampsia, a multisystem disorder of pregnancy, is fourfold higher in type 1 diabetic than non-diabetic women; it is also increased in women with features of the metabolic syndrome and insulin resistance. In a prospective study of pregnant women with type 1 diabetes, we measured plasma levels of adipokines known to be associated with insulin resistance: leptin, fatty acid binding protein 4 (FABP4), adiponectin (total and high molecular weight [HMW]; also known as high molecular mass), retinol binding protein 4 (RBP4) and resistin and evaluated associations with the subsequent development of pre-eclampsia. Methods: From an established prospective cohort of pregnant type 1 diabetic women, we studied 23 who developed pre-eclampsia and 24 who remained normotensive; for reference values we included 19 healthy non-diabetic normotensive pregnant women. Plasma adipokines were measured (by ELISA) in stored samples from three study visits (Visit 1– Visit 3) at different gestational ages (mean ± SD): Visit 1, 12.4 ± 1.8 weeks; Visit 2, 21.7 ± 1.4 weeks; and Visit 3, 31.4 ± 1.5 weeks. All the women were free of microalbuminuria and hypertension at enrolment. All study visits preceded the clinical onset of pre-eclampsia. Results: In all groups, leptin, the ratio of leptin to total or HMW adiponectin, FABP4 concentration, ratio of FABP4 to total or HMW adiponectin and resistin level increased, while total and HMW adiponectin decreased, with gestational age. At Visit 1: (1) in diabetic women with vs without subsequent pre-eclampsia, leptin, ratio of leptin to total or HMW adiponectin, and ratio of FABP4 to total or HMW adiponectin, were increased (p 1c, insulin kg−1 day−1 and gestational age), the best predictive models for pre-eclampsia were as follows: Visit 1, doubling of leptin, OR 9.0 (p

Background In North America, heart failure (HF) is the leading cause for hospital readmission. Supportive technology, such as computers and tablets, could potentially assist patients with self-care to manage their condition after hospital discharge; however, older individuals have difficulties in adopting technology to manage their condition. Method This study used a mixed methods design to identify barriers to technology use in HF self-care. In the qualitative phase, semi-structured interviews were conducted with 18 HF patients and 10 informal caregivers or care partners (CP). In the quantitative phase, five questionnaires were administered to 15 patients and 8 CP: Montreal Cognitive Assessment; Short Literacy Survey and Subjective Numeracy Scale; Self-Care of HF Index; Knowledge Assessment Questionnaire; and Patient Activation Measure. Results In the qualitative phase, five themes emerged regarding engagement in self care and technology use: knowledge level of HF; level of willingness to ask questions related to HF; confidence level in making health-related decisions individually; level of technology usage in daily activities; and self-recording of health measurements. Quantitative analysis found that most HF patients had mild cognitive impairment (MCI), adequate health numeracy levels to understand and manage their health condition, high confidence levels in managing their condition and willingness to engage in self-care. There was variation in willingness to adopt technology. Conclusion Patients were willing to engage in HF self-care however they relied on CPs who were more willing to ask questions about HF. Technology tools may assist in HF self-care, but they must be tailored for use among older individuals.

Aims Diabetes puts many individuals at risk for developing diabetic retinopathy (DR). Non-mydriatic (NM) retinal photography without pharmacological pupil dilation can be used to detect DR, however, its value in a general clinical setting has not been established. The objective of this review is to evaluate the validity of NM retinal photos, as compared to the reference standard of seven standard stereoscopic 30 degree field photographs (7SF), for their use of detecting DR in community-dwelling adults. Methods English articles were identified through MEDLINE (1992–2016), EMBASE (1992–2016), Center for Disease Control and Prevention, Food and Drug Administration, Health Canada, and Google Scholar (1992–2016). Only studies that examined the validity of NM retinal photos, without pharmacological pupil dilation, as compared to 7SF, used in a community-dwelling adult population were included. Risk of bias was assessed using the QUADAS-2. Results Of the 368 articles identified in the search, 6 articles met eligibility requirements. Sensitivities ranged from 64 to 97.9% and specificities ranged from 65.6 to 98%. Studies that used multiple field images to detect DR in a younger population generally produced higher quality photos and more valid results. Conclusions The strongest validity indicators were reported in studies capturing multiple field images.

Fruit and vegetable (FV) intake is associated with reduced risk of a number of non-communicable diseases. Research tends to focus on antioxidants, flavonoids and polyphenols contained in FV as the main beneficial components to health; however, increasing FV may also alter overall diet profile. Extra FV may be substituted for foods thought to be less healthy, therefore altering the overall macronutrient and/or micronutrient content in the diet. This analysis merged dietary data from four intervention studies in participants with varying health conditions and examined the effect of increased FV consumption on diet profile. Dietary intake was assessed by either diet diaries or diet histories used in four FV randomised intervention studies. All food and drink intake recorded was analysed using WISP version 3.0, and FV portions were manually counted using household measures. Regression analysis revealed significant increases in intakes of energy (172 kJ (+41 kcal)), carbohydrate (+3·9 g/4184 kJ (1000 kcal)), total sugars (+6·0 g/4184 kJ (1000 kcal)) and fibre (+0·8 g/4184 kJ (1000 kcal)) and significant decreases in intakes of total fat (−1·4 g/4184 kJ (1000 kcal)), SFA (−0·6 g/4184 kJ (1000 kcal)), MUFA (−0·6 g/4184 kJ (1000 kcal)), PUFA (−0·1 g/4184 kJ (1000 kcal)) and starch (−2·1 g/4184 kJ (1000 kcal)) per one portion increase in FV. Significant percentage increases were also observed in vitamin C (+24 %) and -carotene (+20 %) intake, per one portion increase in FV. In conclusion, pooled analysis of four FV intervention studies, that used similar approaches to achieving dietary change, in participants with varying health conditions, demonstrated an increase in energy, total carbohydrate, sugars and fibre intake, and a decrease in fat intake alongside an expected increase in micronutrient intake.

Aims The diagnosis of gestational diabetes mellitus (GDM) during pregnancy can lead to anxiety. This study evaluated the impact of an innovative patient-centred educational DVD on anxiety and glycaemic control in women newly diagnosed with GDM. Methods 150 multi-ethnic women, aged 19-44 years, from three UK hospitals were randomised to either usual care plus DVD (DVD group, n=77) or usual care alone (control group, n=73) at GDM diagnosis. Primary outcomes were anxiety (State-Trait Anxiety Inventory) and mean 1-hour postprandial capillary self-monitored blood glucose for all meals, on day prior to follow-up. Results No significant difference between the DVD and control group were reported, for anxiety (37.7±11.7 vs 36.2±10.9; mean difference after adjustment for covariates (95%CI) 2.5 (-0.8, 5.9) or for mean 1-hour postprandial glucose for all meals (6.9±0.9 vs 7.0±1.2 mmol/L; -0.2 (-0.5, 0.2). However, the DVD group had significantly lower postprandial breakfast glucose compared to the control group (6.8±1.2 vs 7.4±1.9 mmol/L; -0.5 (-1.1, - Conclusions The results in this trial did not highlight any differences between those who received the intervention and those who received usual care. It is possible that women already felt supported by their frequent attendance at specialist clinics for monitoring and advice. Healthcare professional and family support are key elements to empowering women with GDM and require further consideration in future interventions. Nonetheless, educational resources such as this will be beneficial to help support women given the current resource and time implications of the year on year rises in the incidence of gestational diabetes.

Objectives The aim of this study was to investigate periodontitis as a risk factor for incident type 2 diabetes mellitus (T2DM) in a group of men aged 58–72 years. Methods One thousand three hundred and thirty-one dentate, diabetes-free men in Northern Ireland underwent a detailed periodontal examination during 2001–2003. Follow-up was by bi-annual questionnaire and for those reporting diabetes their general medical practitioner was contacted to validate diabetes type, treatment and diagnosis date. Cox's proportional hazard models were used to estimate the effect of periodontitis on incident diabetes. Multivariable analysis included adjustment for various known confounders. Results The mean age of the men was 63.7 (SD 3.0) years. There were 80 cases (6.0%) of incident T2DM. Follow-up was for a median period of 7.8 years (IQR 6.7–8.3). After adjusting for confounding variables, the hazard ratio (HR) for incident T2DM in men with moderate/severe periodontitis versus those with no/mild periodontitis was 1.69 (95% CI 1.06–2.69), p = 0.03. Conclusion There was evidence in this homogenous group of dentate men, that those with moderate to severe periodontitis had a significantly increased risk of incident T2DM.

EFHC1 variants are the most common mutations in inherited myoclonic and grand mal clonic-tonic-clonic (CTC) convulsions of juvenile myoclonic epilepsy (JME). We reanalyzed 54 EFHC1 variants associated with epilepsy from 17 cohorts based on National Human Genome Research Institute (NHGRI) and American College of Medical Genetics and Genomics (ACMG) guidelines for interpretation of sequence variants. We calculated Bayesian LOD scores for variants in coinheritance, unconditional exact tests and odds ratios (OR) in case–control associations, allele frequencies in genome databases, and predictions for conservation/pathogenicity. We reviewed whether variants damage EFHC1 functions, whether efhc1−/− KO mice recapitulate CTC convulsions and “microdysgenesis” neuropathology, and whether supernumerary synaptic and dendritic phenotypes can be rescued in the fly model when EFHC1 is overexpressed. We rated strengths of evidence and applied ACMG combinatorial criteria for classifying variants. Nine variants were classified as “pathogenic,” 14 as “likely pathogenic,” 9 as “benign,” and 2 as “likely benign.” Twenty variants of unknown significance had an insufficient number of ancestry-matched controls, but ORs exceeded 5 when compared with racial/ethnic-matched Exome Aggregation Consortium (ExAC) controls. NHGRI gene-level evidence and variant-level evidence establish EFHC1 as the first non–ion channel microtubule–associated protein whose mutations disturb R-type VDCC and TRPM2 calcium currents in overgrown synapses and dendrites within abnormally migrated dislocated neurons, thus explaining CTC convulsions and “microdysgenesis” neuropathology of JME. Genet Med 19 2, 144–156.

Aim To evaluate the effect of regional implementation of a preconception counselling resource into routine diabetes care on pregnancy planning indicators. Methods A preconception counselling DVD was distributed to women by diabetes care teams and general practices. Subsequently, in a prospective population-based study, pregnancy planning indicators were evaluated. The post-DVD cohort (n = 135), including a viewed-DVD subgroup (n = 58), were compared with an historical cohort (pre-DVD, n = 114). Primary outcome was HbA1c at first diabetes-antenatal visit. Secondary outcomes included preconception folic acid consumption, planned pregnancy and HbA1c recorded in the 6 months preconception. Results Mean first visit HbA1c was lower post-DVD vs. pre-DVD: 7.5% vs. 7.8% [58.4 vs. 61.8 mmol/mol]; p = 0.12), although not statistically significant. 53% and 20% of women with type 1 and 2 diabetes, respectively, viewed the DVD. The viewed-DVD subgroup were significantly more likely to have lower first visit HbA1c: 6.9% vs. 7.8% [52.1 vs. 61.8 mmol/mol], P < 0.001; planned pregnancy (88% vs. 59%, P < 0.001); taken folic acid preconception (81% vs. 43%, P = 0.001); and had HbA1c recorded preconception (88% vs. 53%, P < 0.001) than the pre-DVD cohort. Conclusions Implementation of a preconception counselling resource was associated with improved pregnancy planning indicators. Women with type 2 diabetes are difficult to reach. Greater awareness within primary care of the importance of preconception counselling among this population is needed.

Objective: Few interventions have tested the effects of different alcohol types on cardiovascular risk biomarkers. The aim of this study was to investigate the effects of red wine versus vodka on i...

BACKGROUND: Caesarean section (CS) has been associated with an increased risk of type 1 diabetes (T1D). The lack of exposure to maternal vaginal and anal microbiome and bypassing the labor process often observed in elective CS may affect neonatal immune system development. This study aims to summarize the effects of elective and non-elective CS on T1D risk in the offspring.METHODS: A systematic literature search was conducted online for publications providing data on elective and non-elective CS with T1D diagnosis in children and young adults, followed by a meta-analysis from selected studies. Newcastle-Ottawa Scale and GRADEpro tool were applied for quality analysis.RESULTS: Nine observational studies comprising over 5 million individuals fulfilled the inclusion criteria. Crude OR estimates showed a 12% increased T1D risk from elective CS compared to vaginal delivery with significant heterogeneity. Adjusted ORs from seven studies did not show T1D risk differences from either CS category, and heterogeneity was detected between studies. Separate analysis of cohort and case-control studies reduced the heterogeneity and revealed a slight increase in T1D risk associated with elective CS in cohort studies (adjusted OR = 1.12 (1.01-1.24)), and a higher increased risk associated with non-elective CS in case-control studies (adjusted OR = 1.19 (1.06-1.34)).CONCLUSION: Summarized crude risk estimates showed a small increased T1D risk in children and young adults born through elective CS compared to vaginal delivery, but with significant heterogeneity. Adjusted risk estimates by study design indicated a slightly increased T1D risks associated with elective or non-elective CS.

AIMS: This article describes the methods, results and limitations of the International Diabetes Federation (IDF) Diabetes Atlas 9th edition estimates of worldwide numbers of cases of type 1 diabetes in children and adolescents.METHODS: Most information in the published literature is in the form of incidence rates derived from registers of newly-diagnosed cases. After systematic review of the published literature and recent conference abstracts, identified studies were quality graded. If no study was available, extrapolation was used to assign a country the rate from an adjacent country with similar characteristics. Estimates of incident cases were obtained by applying incidence rates to United Nations 2019 population estimates. Estimates of prevalent cases were derived from incidence rates after making allowance for higher mortality rates in less-developed countries.RESULTS: Incidence rates were available for 45% of countries (ranging from 6% in the sub-Saharan Africa region to 77% in the European region). Worldwide annual incidence estimates were 98,200 (128,900) new cases in the under 15 year (under 20 year) age-groups. Corresponding prevalence estimates were 600,900 (1,110,100) existing cases. Compared with estimates in earlier Atlas editions, numbers have increased in most IDF regions, reflecting incidence rate increases, but prevalence estimates have decreased in sub-Saharan Africa because allowance has been made for increased mortality in those with diabetes.CONCLUSIONS: Worldwide estimates of numbers of children and adolescents with type 1 diabetes continue to increase.

Objective: Mild iodine deficiency has re-emerged among school girls in the UK. We wished to study a contemporaneous pregnant population because a relationship between maternal iodine deficiency and offspring cognitive scores has recently been reported. The WHO has set a median population urinary iodine concentration (UIC) of ≥100 and ≥150 µg/L to define adequacy outside of and during pregnancy, respectively. Iodine creatinine ratio (ICR) is also used to correct for dilution effects (sufficiency ≥150 µg/g creatinine in pregnancy). Design and methods: A total of 241 women were followed across trimesters (T) into the postpartum period (PPP) along with 80 offspring with spot urine sampling and food frequency questionnaires. Results: Median UIC was 73 µg/L in the 1st T (ICR 102 µg/g creatinine) despite 55% taking iodine-containing supplements. Median UICs were 94, 117 and 90 µg/L in the 2nd T, 3rd T and PPP, respectively. Corresponding ICRs were 120, 126 and 60 µg/g creatinine. ICR was associated with volume of milk consumed throughout pregnancy. Median UIC among the offspring was 148 µg/L, with no difference between the breast- and formula-fed babies. Conclusions: Pregnant women living in Northern Ireland may be at risk of iodine deficiency across pregnancy and into the PPP while the offspring are iodine sufficient. This is the first study of its kind in the UK with data for pregnant women and their offspring. The UK does not provide an iodine fortification programme nor offer routine iodine dietary advice in pregnancy and this requires consideration by public health agencies.

OBJECTIVES: To explore how different frameworks and categories of chronic conditions impact multimorbidity (defined as two or more chronic conditions) prevalence estimates and associations with patient-important functional outcomes. DESIGN: Baseline data from a population-based cohort study. SETTING: National sample of Canadians. PARTICIPANTS: A total of 51 338 community-living adults, aged 45 to 85 years. MAIN OUTCOME MEASURES: Chronic conditions from three commonly recognized frameworks were categorized as: (1) diseases, (2) risk factors, or (3) symptoms. Estimates of multimorbidity prevalence were compared among frameworks by age and sex. Separate weighted logistic regression models were used to explore the impact of the different frameworks and categories of chronic conditions on odds ratios (ORs) for multimorbidity for four patient-important functional outcomes: disability, social participation restriction, and self-rated physical and mental health. RESULTS: One framework included diseases and risk factors, and two frameworks included diseases, risk factors, and symptoms. The prevalence of multimorbidity differed among the frameworks, ranging from 33.5% to 60.6% having two or more chronic conditions. Including risk factors in frameworks increased prevalence estimates, while including symptoms increased prevalence estimates and associations with most patient-important outcomes. The two frameworks that included symptoms had the largest ORs for associations with disability, social participation restriction, and self-rated physical health but not self-rated mental health. Similar results were found when we compared ORs for patient-important outcome for multimorbidity based on three subframeworks: one including diseases only, one including diseases and risk factors, and one including diseases, risk factors, and symptoms. CONCLUSIONS: Including risk factors appeared to increase only the prevalence of multimorbidity without significantly altering relationships to outcomes. The inclusion of symptoms increased prevalence and associations with patient-important outcomes. These findings underscore the importance of considering not only the number, but also the category, of conditions included in multimorbidity frameworks, as simply counting the number of diagnoses may reduce sensitivity to outcomes that are important to individuals. J Am Geriatr Soc 67:1632-1640, 2019. ispartof: JOURNAL OF THE AMERICAN GERIATRICS SOCIETY vol:67 issue:8 pages:1632-1640 ispartof: location:United States status: published

Contains fulltext : 208975.pdf (Publisher’s version ) (Open Access) BACKGROUND: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. METHODS: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. FINDINGS: Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1.34 years [IQR 0.19-2.44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1.35 (95% CI 1.20-1.50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2.45 (1.82-3.29) for intracranial haemorrhage and 1.23 (1.08-1.40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4.55 [95% CI 3.08-6.72] for intracranial haemorrhage vs 1.47 [1.19-1.80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5.52 [3.36-9.05] vs 1.43 [1.07-1.91]; and for >/=20 cerebral microbleeds, aHR 8.61 [4.69-15.81] vs 1.86 [1.23-1.82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95% CI 48-84] per 1000 patient-years vs 27 intracranial haemorrhages [17-41] per 1000 patient-years; and for >/=20 cerebral microbleeds, 73 ischaemic strokes [46-108] per 1000 patient-years vs 39 intracranial haemorrhages [21-67] per 1000 patient-years). INTERPRETATION: In patients with recent ischaemic stroke or transient ischaemic attack, cerebral microbleeds are associated with a greater relative hazard (aHR) for subsequent intracranial haemorrhage than for ischaemic stroke, but the absolute risk of ischaemic stroke is higher than that of intracranial haemorrhage, regardless of cerebral microbleed presence, antomical distribution, or burden. FUNDING: British Heart Foundation and UK Stroke Association.

Objective The objective of the study was to compare multimorbidity prevalence using self-reported and administrative data and identify factors associated with agreement between data sources. Study Design and Setting Self-reported cross-sectional data from four Canadian Community Health Survey waves were linked to administrative data in Ontario, Canada. Multimorbidity prevalence was examined using two definitions, 2+ and 3+ chronic conditions (CCs). Agreement between data sources was assessed using Kappa and Phi statistics. Logistic regression was used to estimate associations between agreement and sociodemographic, health behavior, and health status variables for each multimorbidity definition. Results Regardless of multimorbidity definition, prevalence was higher using administrative data (2+ CCs: 55.5% vs. 47.1%; 3+ CCs: 30.0% vs. 24.2%). Agreement between data sources was moderate (2+ CCs K = 0.482; 3+ CCs K = 0.442), and while associated with sociodemographic, health behavior, and health status factors, the magnitude and sometimes direction of association differed by multimorbidity definition. Conclusion A better understanding is needed of what factors influence individuals’ reporting of CCs and how they align with what is in administrative data as policy makers need a solid evidence base on which to make decisions for health planning. Our results suggest that data sources may need to be triangulated to provide accurate estimates of multimorbidity for health services planning and policy.

We examined the associations between mitochondrial DNA haplogroups (MT-hg) and their interactions with a polygenic risk score based on nuclear-encoded mitochondrial genes (nMT-PRS) with risk of dementia and age of onset of dementia (AOO). Logistic regression was used to determine the effect of MT-hgs and nMT-PRS on dementia at baseline (332 controls / 204 cases). Cox proportional hazards models were used to model dementia AOO (n=1047; 433 incident cases). Additionally, we tested for interactions between MT-hg and nMT-PRS in the logistic and Cox models. MT-hg K and a one SD larger nMT-PRS were associated with elevated odds of dementia. Significant antagonistic interactions between the nMT-PRS and MT-hg K and T were observed. Individual MT-hg were not associated with AOO; however, a significant antagonistic interactions was observed between the nMT-PRS and MT-hg T and a synergistic interaction between the nMT-PRS and MT-hg V. These results suggest that MT-hgs influence dementia risk, and that variants in the nuclear and mitochondrial genome interact to influence the age of onset of dementia.HighlightsMitochondrial dysfunction has been proposed to influence dementia riskMT-hg K and T interacted with a genetic risk score to reduce dementia riskMT-hg T and V interacted with a genetic risk score to influence dementia age of onset

BACKGROUND: Investigating participant engagement and nonusage attrition can help identify the likely active ingredients of electronic health interventions. Research on engagement can identify which intervention components predict health outcomes. Research on nonusage attrition is important to make recommendations for retaining participants in future studies. OBJECTIVE: This study aimed to investigate engagement and nonusage attrition in the Physical Activity Loyalty (PAL) scheme, a 6-month complex physical activity intervention in workplaces in Northern Ireland. The intervention included financial incentives with reward redemption and self-regulation techniques. Specific objectives were (1) to determine whether engagement in specific intervention components predicted physical activity at 6 months, (2) to determine whether engagement in specific intervention components predicted targeted mediators at 6 months, and (3) to investigate predictors of nonusage attrition for participants recording daily activity via the PAL scheme physical activity monitoring system and logging onto the website. METHODS: Physical activity was assessed at baseline and 6 months using pedometers (Yamax Digiwalker CW-701, Japan). Markers of engagement and website use, monitoring system use, and reward redemption were collected throughout the scheme. Random-effects generalized least-squares regressions determined whether engagement with specific intervention components predicted 6-month physical activity and mediators. Cox proportional hazards regressions were used to investigate predictors of nonusage attrition (days until first 2-week lapse). RESULTS: A multivariable generalized least-squares regression model (n=230) showed that the frequency of hits on the website's monitoring and feedback component (regression coefficient [b]=50.2; SE=24.5; P=.04) and the percentage of earned points redeemed for financial incentives (b=9.1; SE=3.3; P=.005) were positively related to 6-month pedometer steps per day. The frequency of hits on the discussion forum (b=-69.3; SE=26.6; P=.009) was negatively related to 6-month pedometer steps per day. Reward redemption was not related to levels of more internal forms of motivation. Multivariable Cox proportional hazards regression models identified several baseline predictors associated with nonusage attrition. These included identified regulation (hazard ratio [HR] 0.88, 95% CI 0.81-0.97), recovery self-efficacy (HR 0.88, 95% CI 0.80-0.98), and perceived workplace environment safety (HR 1.07, 95% CI 1.02-1.11) for using the physical activity monitoring system. The EuroQoL health index (HR 0.33, 95% CI 0.12-0.91), financial motivation (HR 0.93, 95% CI 0.87-0.99), and perceived availability of physical activity opportunities in the workplace environment (HR 0.96, 95% CI 0.93-0.99) were associated with website nonusage attrition. CONCLUSIONS: Our results provide evidence opposing one of the main hypotheses of self-determination theory by showing that financial rewards are not necessarily associated with decreases in more internal forms of motivation when offered as part of a complex multicomponent intervention. Identifying baseline predictors of nonusage attrition can help researchers to develop strategies to ensure maximum intervention adherence. TRIAL REGISTRATION: ISRCTN Registry ISRCTN17975376; http://www.isrctn.com/ISRCTN17975376 (Archived by WebCite at http://www.webcitation.org/76VGZsZug).

AIMS/HYPOTHESIS: Against a background of a near-universally increasing incidence of childhood type 1 diabetes, recent reports from some countries suggest a slowing in this increase. Occasional reports also describe cyclical variations in incidence, with periodicities of between 4 and 6 years.METHODS: Age/sex-standardised incidence rates for the 0- to 14-year-old age group are reported for 26 European centres (representing 22 countries) that have registered newly diagnosed individuals in geographically defined regions for up to 25 years during the period 1989-2013. Poisson regression was used to estimate rates of increase and test for cyclical patterns. Joinpoint regression software was used to fit segmented log-linear relationships to incidence trends.RESULTS: Significant increases in incidence were noted in all but two small centres, with a maximum rate of increase of 6.6% per annum in a Polish centre. Several centres in high-incidence countries showed reducing rates of increase in more recent years. Despite this, a pooled analysis across all centres revealed a 3.4% (95% CI 2.8%, 3.9%) per annum increase in incidence rate, although there was some suggestion of a reduced rate of increase in the 2004-2008 period. Rates of increase were similar in boys and girls in the 0- to 4-year-old age group (3.7% and 3.7% per annum, respectively) and in the 5- to 9-year-old age group (3.4% and 3.7% per annum, respectively), but were higher in boys than girls in the 10- to 14-year-old age group (3.3% and 2.6% per annum, respectively). Significant 4 year periodicity was detected in four centres, with three centres showing that the most recent peak in fitted rates occurred in 2012.CONCLUSIONS/INTERPRETATION: Despite reductions in the rate of increase in some high-risk countries, the pooled estimate across centres continues to show a 3.4% increase per annum in incidence rate, suggesting a doubling in incidence rate within approximately 20 years in Europe. Although four centres showed support for a cyclical pattern of incidence with a 4 year periodicity, no plausible explanation for this can be given.

The association between dietary patterns (DP) and prevalence of hearing loss in men enrolled in the Caerphilly Prospective Study was investigated. During 1979–1983, the study recruited 2512 men aged 45–59 years. At baseline, dietary data were collected using a semi-quantitative FFQ, and a 7-d weighed food intake (WI) in a 30 % subsample. Five years later, pure-tone unaided audiometric threshold was assessed at 0·5, 1, 2 and 4 kHz. Principal component analysis (PCA) identified three DP and multiple logistic and ordinal logistic regression models examined the association with hearing loss (defined as pure-tone average of frequencies 0·5, 1, 2 and 4 kHz >25 dB). Traditional, healthy and high-sugar/low-alcohol DP were found with both FFQ and WI data. With the FFQ data, fully adjusted models demonstrated significant inverse association between the healthy DP and hearing loss both as a dichotomous variable (OR=0·83; 95 % CI 0·77, 0·90; PPPP=0·02) and as an ordinal variable (OR=1·17; 95 % CI 1·03, 1·33; P=0·02). A healthy DP was significantly and inversely associated with hearing loss in older men. The role of diet in age-related hearing loss warrants further investigation.

Aim To examine, in a proof-of-concept study, the ability of visceral adipose tissue depth and subcutaneous fat depth measured in early pregnancy to predict subsequent gestational diabetes, and to assess the performance of these measures as screening tests for gestational diabetes compared with use of the current UK criteria. Methods A total of 100 women in early pregnancy were recruited from a maternity hospital in Belfast, UK. Visceral adipose tissue depth and subcutaneous fat depth were measured, and each participant underwent a 75-g oral glucose tolerance test at 28 weeks' gestation for the diagnosis of gestational diabetes using WHO 2013 criteria. Results Eighty women completed the study, of whom 15 (19%) developed gestational diabetes. Increasing visceral adipose tissue depth, but not subcutaneous fat depth, was associated with greater gestational diabetes risk after adjusting for confounding factors (odds ratio for a 1-sd rise 2.09, 95% CI 1.06-4.12; P=0.03). Visceral adipose tissue depth ≥4.27 cm had greater sensitivity compared with current National Institute of Health and Care Excellence criteria (87% vs 40%, respectively; P=0.02) and similar specificity (62% vs 74%, respectively; P=0.15) for identifying gestational diabetes. Conclusions Ultrasonography-measured visceral adipose tissue in early pregnancy is a potential clinical tool for improving sensitivity of selective screening for gestational diabetes, which, compared with universal oral glucose tolerance testing, is likely to reduce by half the numbers requiring this test. Further larger studies are now required for confirmation, including investigation into impact on clinical outcomes.

Objective: To characterize comorbid chronic conditions, describe health services use, and estimate health care costs among community-dwelling older adults with prior stroke. Methods: This is a retrospective cohort study using administrative data from Ontario, Canada. We identified all community-dwelling individuals aged 66 and over on April 1, 2008 (baseline), who had experienced a stroke at least 6 months prior. We estimated the prevalence of 14 comorbid conditions at baseline; we captured all physician visits, emergency department visits, hospital admissions, home care contacts, and associated costs over 5 years stratifying by number of comorbid conditions. Where possible, we distinguished between health services use for stroke- and non-stroke-related reasons. Results: A total of 29,673 individuals met our criteria. Only 1% had no comorbid conditions, while 74.9% had 3 or more. The most common conditions were hypertension (89.8%) and arthritis (65.8%); 5 other conditions had a prevalence of 20% or more (ischemic heart disease, diabetes, chronic obstructive pulmonary disease, inflammatory bowel disease, and dementia). Use of all health services doubled with increasing comorbidity and was largely attributed to non-stroke-related reasons. Total and per-patient costs increased with comorbidity. Main cost drivers shifted from physician and home care visits to hospital admissions with greater comorbidity. Conclusions: Our findings demonstrate the importance of community-based patient-centered care strategies for stroke survivors that address their range of health needs and prevent more costly acute care use.

Background Patients with dementia have increased healthcare utilization and often have comorbid chronic conditions. It is not clear if the increase in utilization is driven by dementia, the comorbidities or both. The objective of this study was to describe the number and types of comorbid conditions in a population-based cohort of older adults with dementia and how the level of comorbidity impacts dementia-related and non-dementia-related health service utilization. Methods This study is a retrospective cohort study using multiple linked administrative databases to examine health service utilization and costs of 100,630 community-living older adults living with pre-existing dementia in Ontario, Canada. Comorbid conditions and health service utilization were measured using administrative data (physician visits, emergency department visits, hospitalizations, and homecare contacts). Results Nearly all, 96.3 %, had at least one comorbid condition, while 18.4 % had five or more comorbid conditions. The most common comorbid conditions were hypertension (77.8 %), and arthritis (66.2 %). All types of utilization increased consistently with the number of comorbid conditions. The average number of dementia-related services tended to be similar across all levels of comorbidity while the average number of non-dementia related visits tended to increase with the level of comorbidity. Conclusions Comorbidities in community-living older adults with dementia are common and account for a substantial proportion of health service use and costs in this population. Our results suggest that comprehensive programs that take a holistic view to identify the needs of patients in the context of other comorbidities are required for persons with dementia living in the community. Electronic supplementary material The online version of this article (doi:10.1186/s12877-016-0351-x) contains supplementary material, which is available to authorized users.

Aims Epidemiological evidence suggests that adipokines may be associated with the onset of type 2 diabetes, but the evidence to date is limited and inconclusive. This study examined the association between adiponectin and leptin and the subsequent diagnosis of type 2 diabetes in a UK population based cohort of non-diabetic middle-aged men. Methods Baseline serum levels of leptin and adiponectin were measured in 1839 non-diabetic men aged 50–60 years who were participating in the prospective population-based PRIME study. Over a mean follow-up of 14.7 years, new cases of type 2 diabetes were determined from self-reported clinical information with subsequent validation by general practitioners. Results 151 Participants developed type 2 diabetes during follow-up. In Cox regression models adjusted for age, men in the top third of the leptin distribution were at increased risk (hazard ratio (HR) 4.27, 95% CI 2.67–6.83) and men in the top third of the adiponectin distribution at reduced risk (HR 0.24, 95% CI 0.14–0.42) relative to men in the bottom third. However, significance was lost for leptin after additional adjustment for BMI, waist to hip ratio, lifestyle factors and biological risk factors, including C-reactive protein (CRP). Further adjustment for HOMA-IR also resulted in loss of significance for adiponectin. Conclusions This study provides evidence that adipokines are associated with men’s future type 2 diabetes risk but not independently of other risk factors.

SummaryContext In observational studies, low serum 25-hydroxyvitamin D (25-OHD) concentration is associated with an increased risk of type 2 diabetes mellitus (DM). Increasing serum 25-OHD may have beneficial effects on insulin resistance or beta-cell function. Cross-sectional studies utilizing suboptimal methods for assessment of insulin sensitivity and serum 25-OHD concentration provide conflicting results. Objective This study examined the relationship between serum 25-OHD concentration and insulin resistance in healthy overweight individuals at increased risk of cardiovascular disease, using optimal assessment techniques. Methods A total of 92 subjects (mean age 56·0, SD 6·0 years), who were healthy but overweight (mean body mass index 30·9, SD 2·3 kg/m2), underwent assessments of insulin sensitivity (two-step euglycaemic hyperinsulinaemic clamp, HOMA2-IR), beta-cell function (HOMA2%B), serum 25-OHD concentration and body composition (DEXA). Results Mean total 25-OHD concentration was 32·2, range 21·8–46·6 nmol/l. No association was demonstrated between serum 25-OHD concentration and insulin resistance. Conclusions In this study using optimal assessment techniques to measure 25-OHD concentration, insulin sensitivity and body composition, there was no association between serum 25-OHD concentration and insulin resistance in healthy, overweight individuals at high risk of developing cardiovascular disease. This study suggests the documented inverse association between serum 25-OHD concentration and risk of type 2 DM is not mediated by a relationship between serum 25-OHD concentration and insulin resistance.