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Background A variety of prediction models concerning COVID-19 have been proposed since onset of the pandemic, but to this date no gold standard exists. Mortality rates show a sharp increase with advancing age but with the large heterogeneity of this population in terms of comorbidities, vulnerability and disabilities, identifying risk factors is difficult. Therefore, we aimed to research the multidimensional concept of frailty, measured by the Acute Presenting Older Patient (APOP)-screener, as a risk factor for in-hospital mortality in older COVID-19 patients. Methods All consecutive patients of 70 years or older, with a PCR confirmed COVID-19 infection and a completed APOP-score, presenting at the Emergency Department (ED) of the Jeroen Bosch Hospital, the Netherlands, between February 27th 2020 and February 1st 2021 were retrospectively included. We gathered baseline characteristics and scored the CCI and CFS from patient records. The primary outcome was in-hospital mortality. Results A total of 292 patients met the inclusion criteria. Approximately half of the patients were considered frail by the APOP or CFS. 127 patients (43.5%) scored frail on the CFS, 158 (54.1%) scored high risk on the APOP-screener. 79 patients (27.1%) died during their hospital admission. The APOP-screener showed a significantly elevated risk of in-hospital mortality when patients scored both high risk of functional and evidence of cognitive impairment (OR 2.24, 95% 1.18–4.25). Significant elevation of in-hospital mortality was found for the high CCI-scores (≥ 5)(OR 1.78, 95% 1.02–3.11), but not for the highest CFS category (5–9, frail) (OR 1.35, 95% 0.75–2.47). The discriminatory performance of the APOP, CFS and CCI were comparable (AUC resp. 0.59 (0.52–0.66), 0.54 (0.46–0.62) and 0.58 (0.51–0.65)). Conclusion Although the elevated risk for in-hospital mortality found for the most frail patients as scored by the APOP, this instrument has poor discriminatory value. Additionally, the CFS did not show significance in predicting in-hospital mortality and had a poor discriminatory value as well. Therefore, treatment decisions based on frailty or comorbidities alone should be made with caution. Approaching the heterogeneity of the older population by adding frailty as assessed by the APOP-score to existing prediction models may enhance the predictive value of these models.

Objective: The objective of this study was to compare the reintervention rate of women who opted for treatment with the levonorgestrel-releasing intrauterine system (LNG-IUS) to women who opted for endometrial ablation. Furthermore, the difference in reintervention rate between women in this observational cohort and women who were randomised was compared, with the hypothesis that women who actively decide on treatment have lower reintervention rates compared to women in a RCT.Study design: An observational cohort study alongside a multicentre randomised controlled trial (RCT) was conducted between April 2012 and January 2016, with a follow-up time of 24 months, in 26 hospitals and nearby general practices in the Netherlands. Women suffering from heavy menstrual bleeding, aged 34 years and older, without intracavitary pathology and without a future fertility desire, were eligible for this trial. Women who declined randomisation were asked to participate in the observational cohort. The outcome measure was reintervention rate at 24 months of follow-up.Results: 276 women were followed in the observational cohort of which 87 women preferred an initial treatment with LNG-IUS and 189 women preferred an initial treatment with endometrial ablation. At 24 months of follow-up women in the LNG-IUS-group were more likely to receive a reintervention compared to the women in the ablation group, 28/81 (35 %) versus 25/178 (14 %) (aRR 2.42, CI 1.47-3.98, p-value 0.001). No differences in reintervention rates were found between women in the observational cohort and women in the RCT.Conclusions: Women who receive an LNG-IUS are more likely to undergo an additional intervention compared to women who receive endometrial ablation. Reintervention rates of women in the cohort and RCT population were comparable. The results of this study endorse the findings of the RCT and will contribute to shared decision making in women with heavy menstrual bleeding. (C) 2020 Elsevier B.V. All rights reserved.

Aims/hypothesis We aimed to examine associations of cardiometabolic risk factors, and (pre)diabetes, with (sensorimotor) peripheral nerve function. Methods In 2401 adults (aged 40–75 years) we previously determined fasting glucose, HbA1c, triacylglycerol, HDL- and LDL-cholesterol, inflammation, waist circumference, blood pressure, smoking, glucose metabolism status (by OGTT) and medication use. Using nerve conduction tests, we measured compound muscle action potential, sensory nerve action potential amplitudes and nerve conduction velocities (NCVs) of the peroneal, tibial and sural nerves. In addition, we measured vibration perception threshold (VPT) of the hallux and assessed neuropathic pain using the DN4 interview. We assessed cross-sectional associations of risk factors with nerve function (using linear regression) and neuropathic pain (using logistic regression). Associations were adjusted for potential confounders and for each other risk factor. Associations from linear regression were presented as standardised regression coefficients (β) and 95% CIs in order to compare the magnitudes of observed associations between all risk factors and outcomes. Results Hyperglycaemia (fasting glucose or HbA1c) was associated with worse sensorimotor nerve function for all six outcome measures, with associations of strongest magnitude for motor peroneal and tibial NCV, βfasting glucose = −0.17 SD (−0.21, −0.13) and βfasting glucose = −0.18 SD (−0.23, −0.14), respectively. Hyperglycaemia was also associated with higher VPT and neuropathic pain. Larger waist circumference was associated with worse sural nerve function and higher VPT. Triacylglycerol, HDL- and LDL-cholesterol, and blood pressure were not associated with worse nerve function; however, antihypertensive medication usage (suggestive of history of exposure to hypertension) was associated with worse peroneal compound muscle action potential amplitude and NCV. Smoking was associated with worse nerve function, higher VPT and higher risk for neuropathic pain. Inflammation was associated with worse nerve function and higher VPT, but only in those with type 2 diabetes. Type 2 diabetes and, to a lesser extent, prediabetes (impaired fasting glucose and/or impaired glucose tolerance) were associated with worse nerve function, higher VPT and neuropathic pain (p for trend Conclusions/interpretation Hyperglycaemia (including the non-diabetic range) was most consistently associated with early-stage nerve damage. Nonetheless, larger waist circumference, inflammation, history of hypertension and smoking may also independently contribute to worse nerve function.

PURPOSE: It remains unclear to what extent habitual physical activity and sedentary time are associated with visceral fat and liver fat. We studied substitution of sedentary time with time spent physically active and total body fat (TBF), visceral adipose tissue (VAT) and hepatic triglyceride content (HTGC) in middle-aged men and women. DESIGN: In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study, physical activity was assessed in 228 participants using a combined accelerometer and heart rate monitor. Total body fat was assessed by the Tanita bio-electrical impedance, VAT by MRI and HTGC by proton-MR spectroscopy. Behavioural intensity distribution was categorized as sedentary time (ST), time spent in light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA). To estimate the effect of replacing 30 minutes/day of ST with 30 minutes/day LPA or MVPA, we performed isotemporal substitution analyses, adjusted for sex, age, ethnicity, education, the Dutch Healthy Diet index, and smoking. RESULTS: Included participants (41% men) had a mean (SD) age of 56 (6) years and spent 88 (56) minutes in MVPA and 9.0 hours (2.1) of ST. Replacing 30 minutes/day of ST with 30 minutes of MVPA was associated with 1.3% less TBF (95% CI: -2.0, -0.7), 7.8 cm(2) less VAT (-11.6, -4.0) and 0.89 times HTGC (0.82, 0.97). Replacement with LPA was not associated with TBF (-0.03 %; -0.5, 0.4), VAT (-1.7 cm(2); -4.4, 0.9) or HTGC (0.98 times; 0.92, 1.04). CONCLUSIONS: Reallocation of time spent sedentary with time spent in MVPA, but not LPA, was associated with less total body fat, and visceral and liver fat. These findings contribute to the development of more specified guidelines on sedentary time and physical activity.

IntroductionPreterm birth is one of the main problems in obstetrics, and the most important cause of neonatal mortality, morbidity and neurodevelopmental impairment. Multiple gestation is an important risk factor for preterm birth, with up to 50% delivering before 37 weeks. Progesterone has a role in maintaining pregnancy and is frequently prescribed to prevent (recurrent) preterm birth and improve pregnancy outcomes in high-risk patients. However, little is known about its long-term effects in multiple gestations. The objective of this follow-up study is to assess long-term benefits and harms of prenatal exposure to progesterone treatment in multiple gestations on child development.Methods and analysisThis is a follow-up study of a multicentre, double-blind, placebo-controlled randomised trial (AMPHIA trial, ISRCTN40512715). Between 2006 and 2009 women with a multiple gestation were randomised at 16–20 weeks of gestation to weekly injections 250 mg 17α-hydroxyprogesterone caproate or placebo, until 36 weeks of gestation or delivery. The current long-term follow-up will assess all children (n=1355) born to mothers who participated in the AMPHIA trial, at 11–14 years of age, with internationally validated questionnaires, completed by themselves, their parents and their teachers.Main outcomes are child cognition and behaviourAdditional outcomes are death (perinatal and up to age 14), gender identity, educational performance and health-related problems. We will use intention-to-treat analyses comparing experimental and placebo group. To adjust for the correlation between twins, general linear mixed-effects models will be used.Ethics and disseminationAmsterdam UMC MEC provided a waiver for the Medical Research Involving Human Subjects Act (W20_234#20.268). Results will be disseminated through peer-reviewed journals and summaries shared with stakeholders, patients and participants. This protocol is published before analysis of the results.Trial registration numberNL8933.

Aims/hypotheses Our aim was to examine the independent and combined (cross-sectional) associations of sedentary time (ST), higher intensity physical activity (HPA) and cardiorespiratory fitness (CRF) with metabolic syndrome and diabetes status. Methods In 1933 adults (aged 40–75 years) ST and HPA (surrogate measure for moderate to vigorous physical activity) were measured with the activPAL3. CRF was assessed by submaximal cycle–ergometer testing. Metabolic syndrome was defined according to the Adult Treatment Panel (ATP) III guidelines. Diabetes status (normal, prediabetes [i.e. impaired glucose tolerance and/or impaired fasting glucose] or type 2 diabetes) was determined from OGTT. (Multinomial) logistic regression analyses were used to calculate likelihood for the metabolic syndrome, prediabetes and type 2 diabetes according to ST, HPA and CRF separately and combinations of ST–CRF and HPA–CRF. Results Higher ST, lower HPA and lower CRF were associated with greater odds for the metabolic syndrome and type 2 diabetes independently of each other. Compared with individuals with high CRF and high HPA (CRFhigh–HPAhigh), odds for the metabolic syndrome and type 2 diabetes were higher in groups with a lower CRF regardless of HPA. Individuals with low CRF and low HPA (CRFlow–HPAlow) had a particularly high odds for the metabolic syndrome (OR 5.73 [95% CI 3.84, 8.56]) and type 2 diabetes (OR 6.42 [95% CI 3.95, 10.45]). Similarly, compared with those with high CRF and low ST (CRFhigh–STlow), those with medium or low CRF had higher odds for the metabolic syndrome, prediabetes and type 2 diabetes, irrespective of ST. In those with high CRF, high ST was associated with significantly high odds for the metabolic syndrome (OR 2.93 [95% CI 1.72, 4.99]) and type 2 diabetes (OR 2.21 [95% CI 1.17, 4.17]). The highest odds for the metabolic syndrome and type 2 diabetes were observed in individuals with low CRF and high ST (CRFlow–SThigh) (OR [95% CI]: the metabolic syndrome, 9.22 [5.74, 14.80]; type 2 diabetes, 8.38 [4.83, 14.55]). Conclusions/interpretation These data suggest that ST, HPA and CRF should all be targeted in order to optimally reduce the risk for the metabolic syndrome and type 2 diabetes. Electronic supplementary material The online version of this article (10.1007/s00125-018-4719-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

IntroductionDistal sensorimotor polyneuropathy (DSPN) is common in people with diabetes but is also found in pre-diabetes. Peripheral nerve myelin damage, which can be assessed by reduced nerve conduction velocity (NCV), is an essential feature of DSPN. Emerging evidence indicates that the development of DSPN may involve the activation of the immune system. However, available studies have mainly investigated circulating immune mediators, whereas the role of immune cells remains unclear. Therefore, we aimed to test whether leukocyte subsets are associated with NCV.Research design and methodsThis cross-sectional study analyzed data from 850 individuals (of whom 252 and 118 had type 2 diabetes and pre-diabetes, respectively) of the Maastricht Study. NCV was measured in the peroneal and tibial motor nerves and the sural sensory nerve and summed to calculate a standardized NCV sum score. Associations between percentages of leukocyte subsets and NCV sum scores were estimated using linear regression models adjusted for demographic, lifestyle, metabolic and clinical covariates.ResultsAfter adjustment for covariates, higher percentages of basophils and CD4+ T cells were associated with lower NCV (p=0.014 and p=0.005, respectively). The percentage of CD8+ T cells was positively associated with NCV (p=0.022). These associations were not modified by glucose metabolism status (all pinteraction >0.05). No associations were found for monocytes, eosinophils, neutrophils, lymphocytes, total T cells, Treg cells and B cells.ConclusionsThe associations of basophils, CD4+ and CD8+ T cells with NCV suggest that cell types from both innate and adaptive immunity may be implicated in the development of DSPN.

Purpose Current guidelines recommend to avoid pregnancy for 12–24 months after bariatric surgery because of active weight loss and an increased risk of nutritional deficiencies. However, high-quality evidence is lacking, and only a few studies included data on gestational weight gain. We therefore evaluated pregnancy and neonatal outcomes by both surgery-to-conception interval and gestational weight gain. Materials and Methods A multicenter retrospective analysis of 196 singleton pregnancies following Roux-en-Y gastric bypass, sleeve gastrectomy, and one anastomosis gastric bypass was conducted. Pregnancies were divided into the early group (≤ 12 months), the middle group (12–24 months), and the late group (> 24 months) according to the surgery-to-conception interval. Gestational weight gain was classified as inadequate, adequate, or excessive according to the National Academy of Medicine recommendations. Results Pregnancy in the early group (23.5%) was associated with lower gestational age at delivery (267.1 ± 19.9 days vs 272.7 ± 9.2 and 273.1 ± 13.5 days, P = 0.029), lower gestational weight gain (− 0.9 ± 11.0 kg vs + 10.2 ± 5.6 and + 10.0 ± 6.4 kg, P P = 0.008) than pregnancy in the middle and late group. Inadequate gestational weight gain (40.6%) was associated with lower gestational age at delivery (266.5 ± 20.2 days vs 273.8 ± 8.4 days, P = 0.002) and lower neonatal birth weight (3061 ± 511 g vs 3217 ± 479 g, P = 0.053) compared to adequate weight gain. Preterm births were also more frequently observed in this group (15.9% vs 6.0%, P = 0.037). Conclusion Our findings support the recommendation to avoid pregnancy for 12 months after bariatric surgery. Specific attention is needed on achieving adequate gestational weight gain.

Purpose: β-Blockers (BBs) have been associated with a reduced cardiorespiratory fitness (CRF). This is possibly caused by inhibition of β2-receptors in the airways. However, there are limited data available on β-receptor selectivity and CRF. We therefore aimed to assess the association between BB use and CRF and to assess the association between β-receptor selectivity and CRF. Methods: Participants in the Maastricht Study were aged between 40 and 75 years. Exposure to BB use was determined by use of pharmacy records. General linear models were used to obtain adjusted means of 2 proxies for CRF: covered distance during the 6-minute walk test (6MWT) and estimated maximum power output adjusted for body mass ( Wmax kg−1) during the submaximal cycle ergometer test. Adjusted means were compared between current, past, and never BB users. Current users were subsequently stratified by β-receptor selectivity and dose. Results: Compared to never use, current use was associated with a lower CRF, based on the 6MWT (current use: 569.7 m; never use: 580.4 m [ P = .010]), but not based on the cycling test (current use: 2.14 W kg−1; never use: 2.13 W kg−1 [ P = .690]). There was no difference between current selective and current nonselective BB use. Conclusion: β-Blockers use was associated with CRF based on the 6MWT but not the cycling test. There was no difference between current selective and nonselective BB users, possibly due to the small number of nonselective BB users, differential underlying diseases, other pharmacological properties, and limitations related to the proxies of the outcome.

As accelerometers are commonly used for 24-h measurements of daily activity, methods for separating waking from sleeping time are necessary for correct estimations of total daily activity levels accumulated during the waking period. Therefore, an algorithm to determine wake and bed times in 24-h accelerometry data was developed and the agreement of this algorithm with self-report was examined. One hundred seventy-seven participants (aged 40-75 years) of The Maastricht Study who completed a diary and who wore the activPAL3 24 h/day, on average 6 consecutive days were included. Intraclass correlation coefficient (ICC) was calculated and the Bland-Altman method was used to examine associations between the self-reported and algorithm-calculated waking hours. Mean self-reported waking hours was 15.8 h/day, which was significantly correlated with the algorithm-calculated waking hours (15.8 h/day, ICC = 0.79, P = < 0.001). The Bland-Altman plot indicated good agreement in waking hours as the mean difference was 0.02 h (95% limits of agreement (LoA) = -1.1 to 1.2 h). The median of the absolute difference was 15.6 min (Q1-Q3 = 7.6-33.2 min), and 71% of absolute differences was less than 30 min. The newly developed automated algorithm to determine wake and bed times was highly associated with self-reported times, and can therefore be used to identify waking time in 24-h accelerometry data in large-scale epidemiological studies.

AIMS/HYPOTHESIS: The study investigated cross-sectional associations of total amount and patterns of sedentary behaviour with glucose metabolism status and the metabolic syndrome. METHODS: We included 2,497 participants (mean age 60.0 +/- 8.1 years, 52% men) from The Maastricht Study who were asked to wear an activPAL accelerometer 24 h/day for 8 consecutive days. We calculated the daily amount of sedentary time, daily number of sedentary breaks and prolonged sedentary bouts (>/=30 min), and the average duration of the sedentary bouts. To determine glucose metabolism status, participants underwent an oral glucose tolerance test. Associations of sedentary behaviour variables with glucose metabolism status and the metabolic syndrome were examined using multinomial logistic regression analyses. RESULTS: Overall, 1,395 (55.9%) participants had normal glucose metabolism, 388 (15.5%) had impaired glucose metabolism and 714 (28.6%) had type 2 diabetes. The odds ratio per additional hour of sedentary time was 1.22 (95% CI 1.13, 1.32) for type 2 diabetes and 1.39 (1.27, 1.53) for the metabolic syndrome. No significant or only weak associations were seen for the number of sedentary breaks, number of prolonged sedentary bouts or average bout duration with either glucose metabolism status or the metabolic syndrome. CONCLUSIONS/INTERPRETATION: An extra hour of sedentary time was associated with a 22% increased odds for type 2 diabetes and a 39% increased odds for the metabolic syndrome. The pattern in which sedentary time was accumulated was weakly associated with the presence of the metabolic syndrome. These results suggest that sedentary behaviour may play a significant role in the development and prevention of type 2 diabetes, although longitudinal studies are needed to confirm our findings.

Here we assess the quality and in-season development of European wheat (Triticum spp.) yield forecasts during low, medium, and high-yielding years. 440 forecasts were evaluated for 75 wheat forecast years from 1993–2013 for 25 European Union (EU) Member States. By July, years with median yields were accurately forecast with errors below ~2%. Yield forecasts in years with low yields were overestimated by ~10%, while yield forecasts in high-yielding years were underestimated by ~8%. Four-fifths of the lowest yields had a drought or hot driver, a third a wet driver, while a quarter had both. Forecast accuracy of high-yielding years improved gradually during the season, and drought-driven yield reductions were anticipated with lead times of ~2 months. Single, contrasting successive in-season, as well as spatially distant dry and wet extreme synoptic weather systems affected multiple-countries in 2003, ’06, ’07, ’11 and 12’, leading to wheat losses up to 8.1 Mt (>40% of total EU loss). In these years, June forecasts (~ 1-month lead-time) underestimated these impacts by 10.4 to 78.4%. To cope with increasingly unprecedented impacts, near-real-time information fusion needs to underpin operational crop yield forecasting to benefit from improved crop modelling, more detailed and frequent earth observations, and faster computation.

This cross-sectional study is one of the first to examine and compare the independent associations of objectively measured sedentary time, moderate to vigorous physical activity (MVPA) and fitness with cardio-metabolic risk factors. We studied 543 men and women (aged 18–49 years) from the NHANES 2003–2004 survey. Sedentary time and MVPA were measured by accelerometry. Fitness was assessed with a submaximal treadmill test. Cardio-metabolic risk factors included: waist circumference (WC), BMI, blood pressure, fasting glucose, HDL- and non HDL cholesterol, triglycerides (TG), and C-reactive protein (CRP). Sedentary time, MVPA and fitness were used as predictors for the cardio-metabolic outcomes in a multiple regression analysis. Standardized regression coefficients were computed. Results show that sedentary time was associated with HDL-cholesterol (β = −0.080, p = 0.05) and TG (β = 0.080, p = 0.03). These results became non-significant after adjustment for MVPA and fitness. MVPA was associated with WC (β = −0.226), BMI (β = −0.239), TG (β = −0.108) and HDL-cholesterol (β = 0.144) (all p &lt, 0.05). These results remained significant after adjustment for sedentary time and fitness. Fitness was associated with WC (β = −0.287), BMI (β = −0.266), systolic blood pressure (β = −0.159), TG (β = −0.092), and CRP (β = −0.130) (all p &lt, 0.05). After adjustment for sedentary time and MVPA these results remained significant. These differences in relative importance of sedentary time, MVPA and fitness on cardio-metabolic-risk are important in the design of prevention programs. In this population, the strength of the associations between MVPA and fitness with cardio-metabolic markers appeared to be similar, both MVPA and fitness showed independent associations with cardio-metabolic risk factors. In contrast, sedentary time showed no independent associations with cardio-metabolic risk after correction for fitness and MVPA.

Introduction: Sedentary time has been associated with detrimental health effects, so in some countries, guidelines to reduce sedentary time have been developed. As reducing sedentary time inevitably results in more nonsedentary time, effects of this reduction may depend on the activity with which it is replaced. Purpose: This study aimed to examine associations of theoretical reallocations of sedentary time to standing or stepping with cardiometabolic outcomes and type 2 diabetes. Methods: We included 2213 participants (51% men, mean +/- SD age = 60.0 +/- 8.1 yr) of the Maastricht Study who were asked to wear an accelerometer 24 h.d(-1) for a week. We calculated daily sedentary, standing, and stepping time. An isotemporal substitution modeling approach was applied to examine effects on waist circumference; body mass index; cholesterol, triacylglycerol, glucose, and insulin levels; metabolic syndrome; and type 2 diabetes. Results: Replacement of sedentary time (30 min.d(-1)) with stepping was associated with lower odds for metabolic syndrome (odds ratio [OR] = 0.72, 95% confidence interval [CI] = 0.66-0.78) and type 2 diabetes (OR = 0.79, 95% CI = 0.72-0.87), more favorable waist circumference (B = -1.42, 95% CI = -1.78 to -1.06), and body mass index (B = -0.48, 95% CI = -0.62 to -0.35) and improved cholesterol, triacylglycerol, glucose, and insulin levels. Replacing sedentary time with standing was associated with lower odds for metabolic syndrome and type 2 diabetes and favorable outcomes in waist circumference, cholesterol, triacylglycerol, and insulin levels. Conclusion: Theoretical replacements of sedentary time with nonsedentary time (both standing and stepping) were associated with lower odds for metabolic syndrome, type 2 diabetes, and beneficial metabolic outcomes. These results could be important for the general population, including those who cannot meet physical activity guidelines. Consideration should be given to developing recommendations for daily reallocating sedentary time. This study was supported by the European Regional Development Fund via OP-Zuid, the Province of Limburg, the Dutch Ministry of Economic Affairs (grant no. 31O.041), Stichting De Weijerhorst (Maastricht, the Netherlands), the Pearl String Initiative Diabetes (Amsterdam, the Netherlands), the Cardiovascular Center (CVC, Maastricht, the Netherlands), CARIM School for Cardiovascular Diseases (Maastricht, the Netherlands), CAPHRI School for Public Health and Primary Care (Maastricht, the Netherlands), NUTRIM School for Nutrition and Translational Research in Metabolism (Maastricht, the Netherlands), Stichting Annadal (Maastricht, the Netherlands), and Health Foundation Limburg (Maastricht, the Netherlands) and by unrestricted grants from Janssen-Cilag B.V. (Tilburg, the Netherlands), Novo Nordisk Farma B.V. (Alphen aan den Rijn, the Netherlands), and Sanofi-Aventis Netherlands B.V. (Gouda, the Netherlands). A Koster has received funding from the European Union Seventh Framework Programme (FP7-PEOPLE-2011-CIG) under grant agreement PCIG09-GA-2011-293621.

Purpose: This cross-sectional study examined the mutual independent associations of sedentary behavior, lower intensity physical activity (LPA) and higher intensity physical activity (HPA) (an approximation of moderate to vigorous physical activity with cardiorespiratory fitness (CRF). Methods: Two thousand twenty-four participants were included from The Maastricht Study (mean +/- SD age, 59.7 +/- 8.1 yr; 49.6% men). With the activPAL3 activity monitor, we assessed sedentary time (ST), sedentary pattern variables (number of sedentary breaks, average sedentary bout duration, and number of prolonged sedentary bouts [>= 30 min]), LPA, and HPA. CRF was calculated as maximum power output per kilogram body mass (W-max.kg(-1)) estimated from a submaximal cycle ergometer test. Linear regression analyses and isotemporal substitution analyses were used to examine associations of ST, sedentary pattern variables, and HPA with CRF. Analyses were stratified by sex. Results: One hour of ST per day was associated with a lower W-max.kg(-1) : B-men = -0.03 (95% confidence interval [CI], -0.05 to -0.01) and B-women = -0.02 (95% CI, -0.04 to 0.00), independent of HPA. No statistically significant associations between sedentary patterns variables and CRF were observed. LPA was associated with a higher W-max.kg(-1): B-men = 0.12 (95% CI, 0.07-0.17) and B-women = -0.12 (95% CI, 0.07-0.18). HPA was associated with a higher W-max.kg(-1) : B-men = 0.48 (95% CI, 0.38-0.58) and B-women = 0.27 (95% CI, 0.18-0.36). Replacing ST with LPA (B-men, 0.08; 95% CI, 0.03-0.14; B-women, 0.10; 95% CI, 0.05-0.16) or with HPA (B-men, 0.49; 95% CI, 0.39-0.59; B-women = 0.28; 95% CI, 0.19-0.36), but not with standing was associated with higher CRF. Conclusions: Modest associations between sedentary behavior and CRF were observed. Replacing ST with LPA was associated with higher CRF, which could be of particular importance for individuals who cannot engage in HPA. Nonetheless, replacing ST with HPA was associated with greatest estimated change in CRF.

INTRODUCTION The aim of this study was to evaluate how the textile composition of torso undergarment fabrics may impact upon thermal strain, moisture transfer, and the thermal and clothing comfort of fully clothed, armored individuals working in a hot-dry environment (41.2 degrees C and 29.8% relative humidity). METHODS Five undergarment configurations were assessed using eight men who walked for 120 min (4 km x h(-1)), then alternated running (2 min at 10 km x h(-1)) and walking (2 min at 4 km x h(-1)) for 20 min. Trials differed only in the torso undergarments worn: no t-shirt (Ensemble A); 100% cotton t-shirt (Ensemble B); 100% woolen t-shirt (Ensemble C); synthetic t-shirt (Ensemble D: nylon, polyethylene, elastane); hybrid shirt (Ensemble E). RESULTS Thermal and cardiovascular strain progressively increased throughout each trial, with the average terminal core temperature being 38.5 degrees C and heart rate peaking at 170 bpm across all trials. However, no significant between-trial separations were evident for core or mean skin temperatures, or for heart rate, sweat production, evaporation, the within-ensemble water vapor pressures, or for thermal or clothing discomfort. CONCLUSION Thus, under these conditions, neither the t-shirt textile compositions, nor the presence or absence of an undergarment, offered any significant thermal, central cardiac, or comfort advantages. Furthermore, there was no evidence that any of these fabrics created a significantly drier microclimate next to the skin.

Objective The most widely used neck-specific measure in intervention trials is the 10-item Neck Disability Index (NDI), which is assumed to be a unidimensional interval scale, as shown by how NDI data are scored, analyzed, and interpreted. Our objective was to use modern measurement methods to test this assumption (and thereby to also test the validity of calculating summed scores and parametric statistics on NDI data) through Rasch analysis. Methods NDI data from 521 trial subjects with neck pain were fit to the Rasch model. We examined threshold ordering of NDI items, fit of data to model expectations, presence of differential item functioning, and whether or not the set of NDI items collectively measure a single construct, which is a requirement for calculating summative scores. Results There was a lack of fit of data to the Rasch model (χ2 = 140.35, 70 df; P < 0.001). Five items (personal care, lifting, headaches, work, and recreation) had disordered response thresholds. Differential item functioning was detected for age and sex. The NDI items did not contribute to a single construct. Unidimensionality and interval scaling were achieved by removing 2 of the 10 items (resulting in the NDI-8), and converting NDI-8 ordinal (paper) summative scores to NDI-8 interval (Rasch-weighted) scores. Conclusion As originally proposed and conventionally used, the NDI is not a unidimensional scale, and has only ordinal scaling. This raises fundamental doubts about the practice of calculating change scores and other parametric statistics on NDI data. A revised 8-item version provides unidimensional interval-level measurement of neck pain disability.

Women at high risk of ovarian cancer due to a genetic predisposition may opt for either surveillance or prophylactic bilateral salpingo-oophorectomy (pBSO). Main objective of our study was to determine the effectiveness of ovarian cancer screening in women with a BRCA1/2 mutation. We evaluated 241 consecutive women with a BRCA1 or BRCA2 mutation who were enrolled in the surveillance program for hereditary ovarian cancer from September 1995 until May 2006 at the University Medical Center Groningen (UMCG), The Netherlands. The ovarian cancer screening included annual pelvic examination, transvaginal ultrasound (TVU) and serum CA125 measurement. To evaluate the effectiveness of screening in diagnosing (early stage) ovarian cancer sensitivity, specificity, positive and negative predictive values (PPV and NPV) of pelvic examination, TVU and CA125 were calculated. Three ovarian cancers were detected during the surveillance period; 1 prevalent cancer, 1 interval cancer and 1 screen-detected cancer, all in an advanced stage (FIGO stage IIIc). A PPV of 20% was achieved for pelvic examination, 33% for TVU and 6% for CA125 estimation alone. The NPV were 99.4% for pelvic examination, 99.5% for TVU and 99.4% for CA125. All detected ovarian cancers were in an advanced stage, and sensitivities and positive predictive values of the screening modalities are low. Restricting the analyses to incident contacts that contained all 3 screening modalities did not substantially change the outcomes. Annual gynecological screening of women with a BRCA1/2 mutation to prevent advanced stage ovarian cancer is not effective.

BACKGROUND: The significance of commensal oropharyngeal flora (COF) as a potential cause of ventilator-associated pneumonia (VAP) is scarcely investigated and consequently unknown. Therefore, the aim of this study was to explore whether COF may cause VAP. METHODS: Retrospective clinical, microbiological and radiographic analysis of all prospectively collected suspected VAP cases in which bronchoalveolar lavage fluid exclusively yielded >/= 10(4) cfu/ml COF during a 9.5-year period. Characteristics of 899 recent intensive care unit (ICU) admissions were used as a reference population. RESULTS: Out of the prospectively collected database containing 159 VAP cases, 23 patients were included. In these patients, VAP developed after a median of 8 days of mechanical ventilation. The patients faced a prolonged total ICU length of stay (35 days [P < .001]), hospital length of stay (45 days [P = .001]), and a trend to higher mortality (39 % vs. 26 %, [P = .158]; standardized mortality ratio 1.26 vs. 0.77, [P = .137]) compared to the reference population. After clinical, microbiological and radiographic analysis, COF was the most likely cause of respiratory deterioration in 15 patients (9.4 % of all VAP cases) and a possible cause in 2 patients. CONCLUSION: Commensal oropharyngeal flora appears to be a potential cause of VAP in limited numbers of ICU patients as is probably associated with an increased length of stay in both ICU and hospital. As COF-VAP develops late in the course of ICU admission, it is possibly associated with the immunocompromised status of ICU patients.

Recent studies demonstrate widespread expression of ghrelin among tissues and have uncovered its pleiotropic nature. We have examined gene expression of ghrelin and its two receptor splice variants, growth hormone secretagogue receptors (GHS-R) 1a and 1b, in human bone biopsies and in the human pre-osteoblastic SV-HFO cell line during differentiation. Additionally, we examined proliferative effects of ghrelin and unacylated ghrelin (UAG) in differentiating and non-differentiating cells. We detected GHS-R1b mRNA in human bone and osteoblasts but not ghrelin’s cognate receptor GHS-R1a, using two different real-time PCR assays and both total RNA and mRNA. In osteoblasts GHS-R1b mRNA expression remained low during the first 14 days of culture, but increased 300% in differentiating cells by day 21. Both human bone biopsies and osteoblasts expressed ghrelin mRNA, and osteoblasts were found to secrete ghrelin. Overall, ghrelin gene expression was greater in differentiating than non-differentiating osteoblasts, but was not increased during culture in either group. Ghrelin and UAG induced thymidine uptake dose-dependently, peaking at 1 and 10 nM respectively, at day 6 of culture in both non-differentiating and differentiating osteoblasts. The proliferative response to ghrelin and UAG declined with culture time and state of differentiation. The proliferative effects of ghrelin and UAG were suppressed by inhibitors of extracellular-signal-regulated kinase (ERK) and phosphoinositide-3 kinase, and both peptides rapidly induced ERK phosphorylation. Overall, our data suggest new roles for ghrelin and UAG in modulating human osteoblast proliferation via a novel signal transduction pathway.

BackgroundShoulder pain is a common musculoskeletal condition in the general population. Passive physical modalities are commonly used to treat shoulder pain. However, previous systematic reviews reported conflicting results.PurposeThe aim of this study was to evaluate the effectiveness of passive physical modalities for the management of soft tissue injuries of the shoulder.Data SourcesMEDLINE, EMBASE, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials were searched from January 1, 1990, to April 18, 2013.Study SelectionRandomized controlled trials (RCTs) and cohort and case-control studies were eligible. Random pairs of independent reviewers screened 1,470 of 1,760 retrieved articles after removing 290 duplicates. Twenty-two articles were eligible for critical appraisal. Eligible studies were critically appraised using the Scottish Intercollegiate Guidelines Network criteria. Of those, 11 studies had a low risk of bias.Data ExtractionThe lead author extracted data from low risk of bias studies and built evidence tables. A second reviewer independently checked the extracted data.Data SynthesisThe findings of studies with a low risk of bias were synthesized according to principles of best evidence synthesis. Pretensioned tape, ultrasound, and interferential current were found to be noneffective for managing shoulder pain. However, diathermy and corticosteroid injections led to similar outcomes. Low-level laser therapy provided short-term pain reduction for subacromial impingement syndrome. Extracorporeal shock-wave therapy was not effective for subacromial impingement syndrome but provided benefits for persistent shoulder calcific tendinitis.LimitationsNon-English studies were excluded.ConclusionsMost passive physical modalities do not benefit patients with subacromial impingement syndrome. However, low-level laser therapy is more effective than placebo or ultrasound for subacromial impingement syndrome. Similarly, shock-wave therapy is more effective than sham therapy for persistent shoulder calcific tendinitis.

van der Velde G, Mierau D. Effect of exercise on percentile rank aerobic capacity, pain, and self-rated disability in patients with chronic low-back pain: a retrospective chart review. Arch Phys Med Rehabil 2000;81:1457-63. Objective: To determine the effect of 6 weeks of exercise on aerobic capacity and on measures of pain and disability in patients with chronic low-back pain (LBP). Design: Retrospective chart survey. Setting: A fitness facility in Saskatoon, Saskatchewan. Patients: Patients with chronic LBP with an average duration of pain of 10 months. Interventions: Six-week exercise program to improve aerobic capacity, muscular endurance, and flexibility. Main Outcome Measures: Data were collected from 258 charts of patients with chronic LBP treated from 1991 to 1994, including age, sex, and aerobic capacity. Patients completed the numeric ratings scale-101 (pain scale) and Oswestry LBP disability questionnaire. Pre- and postexercise data were compared for patients with LBP who completed the exercise prescription. Comparative data from the same time period were also collected from the records of individuals not treated for chronic pain (controls) and who had volunteered for a test of general fitness at the same facility. Results: Both the control groups and the patients with LBP groups had statistically significant lower levels of aerobic capacity than a large group of Canadians tested in the early 1980s, the benchmark on which the age- and sex-matched standardized scores are based. The percentile rank of aerobic capacity for the patients with LBP was statistically significant and lower than those measures for the controls. Patients with LBP who completed the exercise therapy showed statistically significant improvement in percentile rank aerobic capacity, as well as statistically significant decreases in pain and disability scores. Aerobic capacity improved to a level above the norm. Conclusions: This study supports the hypothesis that exercise may be helpful in the management of chronic LBP. © 2000 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

To determine the prevalence of gestational diabetes mellitus in high-risk pregnancies during the second or third trimester diagnosed by screening with the 75-gram oral glucose tolerance test (75 g-OGTT) and, to determine the prevalence of the need for insulin therapy after an initial dietary intervention.Prospective cohort study.Pregnant women at high-risk for gestational diabetes mellitus were challenged with the 75 g-OGTT in the second or third trimester, ideally between the 24th and the 28th week of pregnancy. The diagnosis of gestational diabetes mellitus was established when the fasting plasma glucose was ≥ 7.0 mmol/l or when the plasma glucose was ≥ 7.8 mmol/l two hours after the oral ingestion of 75 g glucose. The women with gestational diabetes were initially treated with a dietary regime. Insulin treatment was added if the hyperglycaemia persisted.A total of 471 pregnant women were included. Of these women, 75.8% underwent the 75 g-OGTT between the 24th and 28th week of pregnancy; 24.2% underwent the test between the 28th and 35th week. The diagnosis of gestational diabetes mellitus was established in 24.2% of the pregnant women. Dietary intervention was successful in normalising the blood glucose levels in 77.2% of the cases. The remaining 22.8% needed the additional insulin treatment.We ascertained that the prevalence of gestational diabetes mellitus in high-risk pregnancies was high. In most cases, the gestational diabetes mellitus could be managed by diet. A multidisciplinary approach involving obstetricians, gynaecologists, dieticians and internists is needed to ensure a timely diagnosis and adequate treatment during pregnancy.

Sir, With great interest, we read the publication ‘Surveillance of women at high risk for hereditary ovarian cancer is inefficient' published by Oei et al (2006) in your journal. The authors evaluated the efficacy of 10-year gynaecological surveillance in 512 women at risk for hereditary ovarian cancer in a tertiary referral centre. This gynaecological surveillance included annual pelvic examination, transvaginal ultrasound (TVU) and serum CA125 measurements. In case of abnormal findings in at least one of the surveillance tests, revision of the abnormal test after 3–6 months was advised. A total of 1621 surveillance tests were performed. In 317 contacts (21%), TVU showed abnormal findings. Of these, 295 (93%) were not present during repeat TVU after 3–6 months. Because only two cases of ovarian cancer were diagnosed during this annual surveillance, it can be calculated that the highest estimate for a positive predictive value of an abnormal TVU is 0.6%. This figure of 21% abnormal findings on TVU needs further discussion than the authors give in this paper. The criteria in the method section of this study, according to which TVU was considered as abnormal were: multiple cysts, cysts with thick septa, papillary projection, irregular patterns or a variety in sonolucency. In the discussion section, the authors explain their high percentage of false-positive findings on TVU with the observation that the majority of their patients were premenopausal and that a variety of benign conditions (e.g. follicle cysts) have contributed to the high incidence of normalising abnormalities. It is remarkable that the list of criteria used in this study according to which TVU was considered abnormal, does not include the presence and/or size of monolocular cysts. According to the Sassone criteria, only cysts of more than 6 cm need further investigation in premenopausal women (Sassone et al, 1991). A second point of attention is that it is not mentioned whether the authors found any adverse effects in this group of patients who had to wait for 3–6 months before they could be reassured by a repeat TVU. It is known from literature that ovarian cancer screening in high-risk women can have a great impact on the anxiety score, especially of premenopausal women (Hensley et al, 2003). We agree with the authors that surveillance is highly ineffective to detect early ovarian (tubal) cancer in high-risk women. It can be questioned whether their suggestion to conduct a study with a larger group of BRCA mutation carriers with a longer follow-up is in line with this conclusion. However, if they need more definitive conclusions, as they suggested, they should define their TVU criteria more precisely in order to avoid this high percentage of false-positive TVU findings and the high loss of quality of life in women with a false-positive TVU finding.

Lactoferrin is a metal binding protein, which is present in high concentrations in human tears. Little is known concerning the exact molecular shape of lactoferrin in tears. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting experiments showed that this protein is present in multiple forms in tear fluid. SDS-PAGE analysis of human tears under non reducing conditions and pretreatment of tears in sample buffer at room temperature revealed lactoferrin in a major form of 60 kD, a minor form of 64 kD and a third form of 52 kD. Pretreatment of tears at elevated temperatures prior to sample application resulted in the loss of this third form. Disruption of intrachain disulfide bridges prior to SDS-PAGE analysis resulted in a shift in the apparent molecular weight of lactoferrin to 78 kD and 83 kD for the major and minor form, respectively. Chromatography of human tears on ConA-Sepharose as well as enzymatic deglycosylation showed that the difference in molecular weight of the major and minor lactoferrin form was not due to a variation in the carbohydrate side chains. The presence of the minor form could also not be ascribed to iron saturation. Instead we found that addition of iron ions to human tears resulted in a shift of tear lactoferrin to a lower molecular weight species of about 52 kD, coinciding with the third lactoferrin form mentioned above and a small protein band of approximately 57 kD, representing the iron saturated minor lactoferrin form. Similar findings were observed using purified milk lactoferrin. Increasing the temperature prior to sample application or disruption of disulfide bridges dissociated the iron-lactoferrin complex.(ABSTRACT TRUNCATED AT 250 WORDS)

CO levels in exhaled breath were measured in 29 residents of flats, equipped with a flueless geiser (an instantaneous gas-fired water heater). The flats were selected because they had a geiser with a CO concentration of more than 250 parts per million in its flue gases. Small, but in some cases statistically significant increases in CO levels in exhaled breath were found in both smokers and non smokers, and after periods of cooking and dishwashing when the geisers had been used. Calculated COHb levels remained well below 2.5% for non smokers, but were generally higher for smokers.