The effect of increased fruit and vegetable consumption on blood pressure and lipids: a pooled analysis of six randomised controlled fruit and vegetable intervention trials.

BACKGROUND: Increasing fruit and vegetable (FV) consumption is associated with reduced cardiovascular disease risk in observational studies but with little evidence from randomised controlled trials (RCTs). The impact of concurrent pharmacological therapy is unknown. OBJECTIVE: To pool data from six RCTs to examine the effect of increasing FV intake on blood pressure (BP) and lipid profile, also exploring whether effects differed by medication use. DESIGN: Across trials, dietary intake was assessed by diet diaries or histories, lipids by routine biochemical methods and BP by automated monitors. Linear regression provided an estimate of the change in lipid profile or BP associated with a one portion increase in self-reported daily FV intake, with interaction terms fitted for medication use. RESULTS: The pooled sample included a total of 554 participants (308 males and 246 females). Meta-analysis of regression coefficients revealed no significant change in either systolic or diastolic BP per portion FV increase, although there was significant heterogeneity across trials for systolic BP (I2 = 73%). Neither adjusting for change in body mass index, nor analysis according to use of anti-hypertensive medication altered the relationship. There was no significant change in lipid profile per portion FV increase, although there was a significant reduction in total cholesterol among those not on lipid-lowering therapy (P < 0.05 after Bonferroni correction). CONCLUSION: Pooled analysis of six individual FV trials showed no impact of increasing intake on BP or lipids, but there was a total cholesterol-lowering effect in those not on lipid-lowering therapy.

Association of low plasma antioxidant levels with all-cause mortality and coronary events in healthy middle-aged men from France and Northern Ireland in the PRIME study.

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.

Effect of Moderate Red Wine versus Vodka Consumption on Inflammatory Markers Related to Cardiovascular Disease Risk: A Randomized Crossover Study.

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 inflammatory and vascular health-related biomarkers.Methods: In a crossover study, participants were randomized to receive either red wine or vodka (3 units/day) for 2 weeks. Following a 2-week washout period, participants then consumed the alternate alcoholic drink for 2 weeks. Fasting blood samples were collected just prior to and at the end of each 2-week period. A total of 13 inflammatory and vascular health biomarkers were assessed.Results: A total of 77 of 85 recruited healthy men completed the study. Leptin levels were significantly raised after each intervention (p ≤ 0.01). APO A1 significantly increased following vodka, but not red wine, intervention (p ≤ 0.01). A significant difference between the interventions was noted for adiponectin only (p ≤ 0.01), although neither of the within-group changes were statistically significant (p > 0.01).Conclusions: The current study found significantly increased levels of leptin following both red wine and vodka consumption, increased levels of APO A1 following vodka consumption, and significant difference between both interventions for adiponectin only. Further studies are needed to investigate the effects of longer-term alcohol consumption on inflammatory and vascular health biomarkers.

Dietary patterns and hearing loss in older men enrolled in the Caerphilly Study.

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; P<0·001) and as an ordinal variable (OR=0·87; 95 % CI 0·81, 0·94; P<0·001). With the WI data, fully adjusted models showed a significant and inverse association between the healthy DP and hearing loss (OR=0·85; 95 % CI 0·73, 0·99; P<0·03), and a significant association between the traditional DP (per fifth increase) and hearing loss both as a dichotomous variable (OR=1·18; 95 % CI 1·02, 1·35; P=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.

Changing antiepilepsy drug-prescribing trends in women with epilepsy in the UK and Ireland and the impact on major congenital malformations.

OBJECTIVES: After 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. METHODS: The 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. RESULTS: Outcome data for 9247 pregnancies showed a stable percentage of monotherapy to polytherapy prescribing habits over time. After Bonferroni correction, statistically significant (p<0.003) changes were found in monotherapy prescribing with increases in lamotrigine and levetiracetam and decreases in valproate and carbamazepine use. Between 1996 and 2016, the total MCM rate showed a 2.1% reduction per year (incidence risk ratio 0.979 (95% CIs 0.956 to 1.002) but Poisson regression analysis showed that this was not statistically significant p=0.08). CONCLUSION: Significant 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.

Maternal vitamin D and neonatal anthropometrics and markers of neonatal glycaemia: Belfast Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study.

Vitamin D deficiency is a common occurrence globally, and particularly so in pregnancy. There is conflicting evidence regarding the role of vitamin D during pregnancy in non-skeletal health outcomes for both the mother and the neonate. The aim of this study was to investigate the associations of maternal total 25-hydroxy vitamin D (25OHD) with neonatal anthropometrics and markers of neonatal glycaemia in the Belfast centre of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. Serological samples (n 1585) were obtained from pregnant women in the Royal Jubilee Maternity Hospital, Belfast, Northern Ireland, between 24 and 32 weeks' gestation as part of the HAPO study. 25OHD concentrations were measured by liquid chromatography tandem-MS. Cord blood and neonatal anthropometric measurements were obtained within 72 h of birth. Statistical analysis was performed. After adjustment for confounders, birth weight standard deviation scores (SDS) and birth length SDS were significantly associated with maternal total 25OHD. A doubling of maternal 25OHD at 28 weeks' gestation was associated with mean birth weight SDS and mean birth length SDS higher by 0·05 and 0·07, respectively (both, P=0·03). There were no significant associations with maternal 25OHD and other measures of neonatal anthropometrics or markers of neonatal glycaemia. In conclusion, maternal total 25OHD during pregnancy was independently associated with several neonatal anthropometric measurements; however, this association was relatively weak.

The effect of increased fruit and vegetable consumption on selected macronutrient and micronutrient intakes in four randomised-controlled trials.

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.

Vaccinations and childhood type 1 diabetes mellitus: a meta-analysis of observational studies.

AIMS/HYPOTHESIS: The aim of this study was to investigate the association between routine vaccinations and the risk of childhood type 1 diabetes mellitus by systematically reviewing the published literature and performing meta-analyses where possible. METHODS: A comprehensive literature search was performed of MEDLINE and EMBASE to identify all studies that compared vaccination rates in children who subsequently developed type 1 diabetes mellitus and in control children. ORs and 95% CIs were obtained from published reports or derived from individual patient data and then combined using a random effects meta-analysis. RESULTS: In total, 23 studies investigating 16 vaccinations met the inclusion criteria. Eleven of these contributed to meta-analyses which included data from between 359 and 11,828 childhood diabetes cases. Overall, there was no evidence to suggest an association between any of the childhood vaccinations investigated and type 1 diabetes mellitus. The pooled ORs ranged from 0.58 (95% CI 0.24, 1.40) for the measles, mumps and rubella (MMR) vaccination in five studies up to 1.04 (95% CI 0.94, 1.14) for the haemophilus influenza B (HiB) vaccination in 11 studies. Significant heterogeneity was present in most of the pooled analyses, but was markedly reduced when analyses were restricted to study reports with high methodology quality scores. Neither this restriction by quality nor the original authors' adjustments for potential confounding made a substantial difference to the pooled ORs. CONCLUSIONS/INTERPRETATION: This study provides no evidence of an association between routine vaccinations and childhood type 1 diabetes.

Comorbidity in severe asthma requiring systemic corticosteroid therapy: cross-sectional data from the Optimum Patient Care Research Database and the British Thoracic Difficult Asthma Registry.

OBJECTIVE: To determine the prevalence of systemic corticosteroid-induced morbidity in severe asthma. DESIGN: Cross-sectional observational study. SETTING: The primary care Optimum Patient Care Research Database and the British Thoracic Society Difficult Asthma Registry. PARTICIPANTS: Optimum Patient Care Research Database (7195 subjects in three age- and gender-matched groups)-severe asthma (Global Initiative for Asthma (GINA) treatment step 5 with four or more prescriptions/year of oral corticosteroids, n=808), mild/moderate asthma (GINA treatment step 2/3, n=3975) and non-asthma controls (n=2412). 770 subjects with severe asthma from the British Thoracic Society Difficult Asthma Registry (442 receiving daily oral corticosteroids to maintain disease control). MAIN OUTCOME MEASURES: Prevalence rates of morbidities associated with systemic steroid exposure were evaluated and reported separately for each group. RESULTS: 748/808 (93%) subjects with severe asthma had one or more condition linked to systemic corticosteroid exposure (mild/moderate asthma 3109/3975 (78%), non-asthma controls 1548/2412 (64%); p<0.001 for severe asthma versus non-asthma controls). Compared with mild/moderate asthma, morbidity rates for severe asthma were significantly higher for conditions associated with systemic steroid exposure (type II diabetes 10% vs 7%, OR=1.46 (95% CI 1.11 to 1.91), p<0.01; osteoporosis 16% vs 4%, OR=5.23, (95% CI 3.97 to 6.89), p<0.001; dyspeptic disorders (including gastric/duodenal ulceration) 65% vs 34%, OR=3.99, (95% CI 3.37 to 4.72), p<0.001; cataracts 9% vs 5%, OR=1.89, (95% CI 1.39 to 2.56), p<0.001). In the British Thoracic Society Difficult Asthma Registry similar prevalence rates were found, although, additionally, high rates of osteopenia (35%) and obstructive sleep apnoea (11%) were identified. CONCLUSIONS: Oral corticosteroid-related adverse events are common in severe asthma. New treatments which reduce exposure to oral corticosteroids may reduce the prevalence of these conditions and this should be considered in cost-effectiveness analyses of these new treatments.

The cost of treating severe refractory asthma in the UK: an economic analysis from the British Thoracic Society Difficult Asthma Registry.

Severe refractory asthma poses a substantial burden in terms of healthcare costs but relatively little is known about the factors which drive these costs. This study uses data from the British Thoracic Society Difficult Asthma Registry (n=596) to estimate direct healthcare treatment costs from an National Health Service perspective and examines factors that explain variations in costs. Annual mean treatment costs among severe refractory asthma patients were £2912 (SD £2212) to £4217 (SD £2449). Significant predictors of costs were FEV1% predicted, location of care, maintenance oral corticosteroid treatment and body mass index. Treating individuals with severe refractory asthma presents a substantial cost to the health service.

Impaired lung function and health status in adult survivors of bronchopulmonary dysplasia.

More infants with bronchopulmonary dysplasia (BPD) now survive to adulthood, but little is known regarding persisting respiratory impairment. We report respiratory symptoms, lung function and health-related quality of life (HRQoL) in adult BPD survivors compared with preterm (non-BPD) and full-term controls. Respiratory symptoms (European Community Respiratory Health Survey) and HRQoL (EuroQol (EQ)-5D) were measured in 72 adult BPD survivors (mean ± sd study age 24.1 ± 4.0 years; mean ± sd gestational age 27.1 ± 2.1 weeks; and mean ± sd birth weight 955 ± 256 g) cared for in the regional neonatal intensive care unit, Royal Maternity Hospital, Belfast, UK (between 1978 and 1993). These were compared with 57 non-BPD controls (mean ± sd study age 25.3 ± 4.0 years; mean ± sd gestational age 31.0 ± 2.5 weeks; and mean ± sd birth weight 1238 ± 222 g) and 78 full-term controls (mean ± sd study age 25.7 ± 3.8 years; mean ± sd gestational age 39.7 ± 1.4 weeks; and mean ± sd birth weight 3514 ± 456 g) cared for at the same hospital. Spirometry was performed on 56 BPD, 40 non-BPD and 55 full-term participants. BPD subjects were twice as likely to report wheeze and three times more likely to use asthma medication than controls. BPD adults had significantly lower forced expiratory volume in 1 s and forced expiratory flow at 25-75% of forced vital capacity than both the preterm non-BPD and full-term controls (all p<0.01). Mean EQ-5D was 6 points lower in BPD adults compared to full-term controls (p<0.05). BPD survivors have significant respiratory and quality of life impairment persisting into adulthood.

Inappropriate prescribing of combination inhalers in Northern Ireland: retrospective cross-sectional cohort study of prescribing practice in primary care.

BACKGROUND: Asthma management guidelines advocate a stepwise approach to asthma therapy, including the addition of a long-acting bronchodilator to inhaled steroid therapy at step 3. This is almost exclusively prescribed as inhaled combination therapy. AIMS: To examine whether asthma prescribing practice for inhaled combination therapy (inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA)) in primary care in Northern Ireland is in line with national asthma management guidelines. METHODS: Using data from the Northern Ireland Enhanced Prescribing Database, we examined initiation of ICS/LABA in subjects aged 5-35 years in 2010. RESULTS: A total of 2,640 subjects (67%) had no inhaled corticosteroid monotherapy (ICS) in the study year or six months of the preceding year (lead-in period) and, extending this to a 12-month lead-in period, 52% had no prior ICS. 41% of first prescriptions for ICS/LABA were dispensed in January to March. Prior to ICS/LABA prescription, in the previous six months only 17% had a short-acting ß2-agonist (SABA) dispensed, 5% received oral steroids, and 17% received an antibiotic. CONCLUSIONS: ICS/LABA therapy was initiated in the majority of young subjects with asthma without prior inhaled steroid therapy. Most prescriptions were initiated in the January to March period. However, the prescribing of ICS/LABA did not appear to be driven by asthma symptoms (17% received SABA in the previous 6 months) or severe asthma exacerbation (only 5% received oral steroids). Significant reductions in ICS/LABA, with associated cost savings, would occur if the asthma prescribing guidelines were followed in primary care.

The influence of diet and physical activity on bone density of children aged 5-7 years: The Belfast HAPO family study.

OBJECTIVE: Osteoporosis is a global health issue, and modifiable behavioural factors need to be identified in childhood to reduce the risk of osteoporosis in later life. The aim of this study was to investigate the influence of diet and physical activity on bone density of children aged 5-7 years participating in the Belfast Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) Family study. DESIGN AND METHODS: Pregnant women were recruited to the Belfast centre of the HAPO study at 24-32 weeks gestation. Offspring were followed up at 5-7 years as part of the Belfast HAPO Family Study. Heel bone mineral density (BMD) and bone mineral apparent density (BMAD) were measured and calculated, respectively. Physical activity in the offspring was measured by accelerometery and dietary intakes were measured using a 4-day food diary. RESULTS: Results from 793 offspring were analysed. Mean age of the offspring ± standard deviation was 6.4 ± 0.5 years. A mean of 48.3 ± 22.4 min each day was spent in moderate to vigorous physical activity (MVPA). Median (interquartile range) dietary calcium and vitamin D intakes were 844 (662-1073) mg/day and 1.7 (1.1-2.5) µg/day, respectively. Neither dietary vitamin D nor calcium intakes were significantly associated with offspring heel BMD or BMAD in multiple regression. However, controlling for confounders, a 30-min greater MVPA was associated with significantly larger heel BMD (0.018 g/cm2 in boys and 0.010 g/cm2 in girls) and BMAD (0.005 g/cm3 in boys and 0.003 g/cm3 in girls). CONCLUSION: Physical activity was associated with better BMD and BMAD in 5-7-year-old children. Dietary calcium and vitamin D were not predictive of BMD and BMAD.

A pragmatic lifestyle intervention for overweight and obese women with gestational diabetes mellitus (PAIGE2): A parallel arm, multicenter randomized controlled trial study protocol.

Background: The global epidemic of type 2 diabetes (T2D) and obesity has been translated into pregnancy, with approximately 18% of women being diagnosed worldwide with Gestational Diabetes Mellitus (GDM). Whilst preventive strategies have proven effective in the non-pregnant context, attrition rates are high and there is an urgent need to develop a customized, pragmatic lifestyle intervention for women both during and after pregnancy. Diet and exercise modification, behavioral support, and Commercial Weight Management Organizations have been strongly recommended to aid postpartum weight reduction for mothers with previous GDM, subsequently reducing their risk of developing obesity and T2D. This study, informed by a previous pilot study, aims to determine the effectiveness of a pragmatic pregnancy and postpartum lifestyle modification program for overweight women with previous GDM (PAIGE2) to reduce body weight at 12 months postpartum. Methods/design: This paper summarizes the protocol for the PAIGE2 study, which has been developed based on results from a pilot study (PAIGE). A six center, two parallel arm, 12-month, randomized controlled trial will be conducted across Northern Ireland and the Republic of Ireland (3 centers each), involving 340 women with GDM and body mass index ≥25 kg/m2 recruited during pregnancy. The lifestyle intervention involves a one-hour virtual educational program (to take place at 32-36 weeks gestation). Postpartum, the intervention will include monthly phone calls, weekly motivational text messages, weekly step counts, and referral for three months to a Commercial Weight Management Organization (Slimming World). The control arm will receive usual care as offered by the local maternity hospital. The primary outcome is weight loss at 12 months postpartum. Study visits for anthropometric and clinical measurements, fasting blood samples, questionnaires pertaining to health, wellbeing and physical activity will take place at 6 weeks, 6- and 12-months postpartum. Focus groups will be conducted with intervention mothers' post-intervention to determine the acceptability of the study design including utility of a Commercial Weight Management Organization, feasibility of remote patient contact, family involvement and patient satisfaction. Discussion: The PAIGE2 study will address the gaps in previously conducted research and, if positive, has the potential to have major public health implications for the prevention of future GDM and subsequent T2D. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04579016?term=NCT04579016&draw=2&rank=1, identifier NCT04579016.

Clinical management and outcome of refractory asthma in the UK from the British Thoracic Society Difficult Asthma Registry.

Refractory asthma represents a significant unmet clinical need. Data from a national online registry audited clinical outcome in 349 adults with refractory asthma from four UK specialist centres in the British Thoracic Society Difficult Asthma Network. At follow-up, lung function improved, with a reduction in important healthcare outcomes, specifically hospital admission, unscheduled healthcare visits and rescue courses of oral steroids. The most frequent therapeutic intervention was maintenance oral corticosteroids and most steroid sparing agents (apart from omalizumab) demonstrated minimal steroid sparing benefit. A significant unmet clinical need remains in this group, specifically a requirement for therapies which reduce systemic steroid exposure.

Effect of fruit and vegetable intake on oxidative stress and inflammation in COPD: a randomised controlled trial.

Epidemiological evidence supports a positive relationship between fruit and vegetable (FV) intake, lung function and chronic obstructive pulmonary disease (COPD). Increasing FV intake may attenuate the oxidative stress and inflammation associated with COPD. An exploratory randomised controlled trial to examine the effect of increased consumption of FV on oxidative stress and inflammation in moderate-to-severe COPD was conducted. 81 symptomatically stable patients with a habitually low FV intake (two or fewer portions of FV per day) were randomised to the intervention group (five or more portions of FV per day) or the control group (two or fewer portions of FV per day). Each participant received self-selected weekly home deliveries of FV for 12 weeks. 75 participants completed the intervention. There was a significant between-group change in self-reported FV intake and biomarkers of FV intake (zeaxanthin (p = 0.034) and ß-cryptoxanthin (p = 0.015)), indicating good compliance; post-intervention intakes in intervention and control groups were 6.1 and 1.9 portions of FV per day, respectively. There were no significant changes in biomarkers of airway inflammation (interleukin-8 and myeloperoxidase) and systemic inflammation (C-reactive protein) or airway and systemic oxidative stress (8-isoprostane). This exploratory study demonstrated that patients with moderate-to-severe COPD were able to comply with an intervention to increase FV intake; however, this had no significant effect on airway or systemic oxidative stress and inflammation.

All-cause mortality and periodontitis in 60-70-year-old men: a prospective cohort study.

OBJECTIVE: To investigate the association between periodontitis and mortality from all causes in a prospective study in a homogenous group of 60- to 70-year-old West European men. METHODOLOGY: A representative sample of 1400 dentate men, (mean age 63.8, SD 3.0 years), drawn from the population of Northern Ireland, had a comprehensive periodontal examination between 2001 and 2003. Men were divided into thirds on the basis of their mean periodontal attachment loss (PAL). The primary endpoint, death from any cause, was analysed using Kaplan-Meier survival plots and Cox's proportional hazards model. RESULTS: In total, 152 (10.9%) of the men died during a mean follow-up of 8.9 (SD 0.7) years; 37 (7.9%) men in the third with the lowest PAL (<1.8 mm) died compared with 73 (15.7%) in the third with the highest PAL (>2.6 mm). The unadjusted hazard ratio (HR) for death in the men with the highest level of PAL compared with those with the lowest PAL was 2.11 (95% CI 1.42-3.14), p < 0.0001. After adjustment for confounding variables (age, smoking, hypertension, BMI, diabetes, cholesterol, education, marital status and previous history of a cardiovascular event) the HR was 1.57 (1.04-2.36), p = 0.03. CONCLUSION: The European men in this prospective cohort study with the most severe loss of periodontal attachment were at an increased risk of death compared with those with the lowest loss of periodontal attachment.

Global estimates of incidence of type 1 diabetes in children and adolescents: Results from the International Diabetes Federation Atlas, 10th edition.

BACKGROUND: Type 1 diabetes (T1D) incidence in children and adolescents varies widely, and is increasing in many nations. The 10th edition of the International Diabetes Federation Atlas estimated incident cases in 2021 for 215 countries/territories ("countries"). METHODS: Studies on T1D incidence for young people aged 0-19 years were sourced and graded using previously described methods. For countries without studies, data were extrapolated from similar nearby countries. RESULTS: An estimated 108,300 children under 15 years will be diagnosed in 2021, a number rising to 149,500 when the age range extends to under 20 years. The ratio of incidence in 15-19 years compared to those aged 0-14 years was particularly high in some countries in sub-Saharan Africa, North Africa/Middle East, and in Mexico. Only 97 countries have their own incidence data, with extrapolation required for some very populous nations. Most data published were not recent, with 27 countries (28%) having data in which the last study year was 2015 or afterwards, and 26 (27%) having no data after 1999. CONCLUSIONS: Many countries have recent data but there are large gaps globally. Such data are critical for allocation of resources, teaching, training, and advocacy. All countries are encouraged to collect and publish current data.

Evidence of association of APOE with age-related macular degeneration: a pooled analysis of 15 studies.

Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status has been reported. We present a pooled analysis (n = 21,160) demonstrating associations between late AMD and APOε4 (odds ratio [OR] = 0.72 per haplotype; confidence interval [CI]: 0.65-0.74; P = 4.41×10(-11) ) and APOε2 (OR = 1.83 for homozygote carriers; CI: 1.04-3.23; P = 0.04), following adjustment for age group and sex within each study and smoking status. No evidence of interaction between APOE and sex or smoking was found. Ever smokers had significant increased risk relative to never smokers for both neovascular (OR = 1.54; CI: 1.38-1.72; P = 2.8×10(-15) ) and atrophic (OR = 1.38; CI: 1.18-1.61; P = 3.37×10(-5) ) AMD but not early AMD (OR = 0.94; CI: 0.86-1.03; P = 0.16), implicating smoking as a major contributing factor to disease progression from early signs to the visually disabling late forms. Extended haplotype analysis incorporating rs405509 did not identify additional risks beyond ε2 and ε4 haplotypes. Our expanded analysis substantially improves our understanding of the association between the APOE locus and AMD. It further provides evidence supporting the role of cholesterol modulation, and low-density cholesterol specifically, in AMD disease etiology.

Variations in apolipoprotein E frequency with age in a pooled analysis of a large group of older people.

Variation in the apolipoprotein E gene (APOE) has been reported to be associated with longevity in humans. The authors assessed the allelic distribution of APOE isoforms ε2, ε3, and ε4 among 10,623 participants from 15 case-control and cohort studies of age-related macular degeneration (AMD) in populations of European ancestry (study dates ranged from 1990 to 2009). The authors included only the 10,623 control subjects from these studies who were classified as having no evidence of AMD, since variation within the APOE gene has previously been associated with AMD. In an analysis stratified by study center, gender, and smoking status, there was a decreasing frequency of the APOE ε4 isoform with increasing age (χ(2) for trend = 14.9 (1 df); P = 0.0001), with a concomitant increase in the ε3 isoform (χ(2) for trend = 11.3 (1 df); P = 0.001). The association with age was strongest in ε4 homozygotes; the frequency of ε4 homozygosity decreased from 2.7% for participants aged 60 years or less to 0.8% for those over age 85 years, while the proportion of participants with the ε3/ε4 genotype decreased from 26.8% to 17.5% across the same age range. Gender had no significant effect on the isoform frequencies. This study provides strong support for an association of the APOE gene with human longevity.