Smoking and γ-Glutamyltransferase: Opposite Interactions with Alcohol Consumption and Body Mass Index

BACKGROUND: Smoking has recently been suggested to synergistically interact with alcohol intake as a determinant of serum gamma-glutamyltransferase (γ-GT), an emergent powerful predictor of disease and mortality. This study investigated whether this also applies to higher smoking and alcohol exposure ranges and to body mass index (BMI), which likewise is strongly associated with γ-GT. METHODOLOGY/PRINCIPAL FINDINGS: Analyses were based on occupational health examinations of more than 15,000 German male workers aged 16-64 years, predominantly from the construction industry. Sociodemographics and other health-related information were collected during the exam. Joint associations of smoking and alcohol consumption or BMI with elevated or log-transformed γ-GT were examined by tabulation and multiple adjusted regression models. Cigarette smoking exerted no effect on γ-GT in teetotalers, but there was a statistically significant effect of smoking among participants with higher alcohol consumption intensity, odds of elevated γ-GT being increased by 24% and 27% per additional 10 cigarettes smoked per day in subjects drinking 61-90 and >90 gram alcohol per day, respectively (P for interaction = 0.039). The interaction was opposite for BMI, where no association was seen in obese subjects, whereas odds of elevated γ-GT were increased by 24% per 10 cigarettes below 25 kg/m(2) (P for interaction = 0.040). This novel interaction was replicable in an independent cohort. CONCLUSION: The evidence for opposite interactions of smoking with alcohol and BMI as determinants of serum γ-GT suggests that different physiological pathways are responsible for the associations between these factors

Associations of Human Milk Oligosaccharides With Otitis Media and Lower and Upper Respiratory Tract Infections up to 2 Years: The Ulm SPATZ Health Study

Background: Humanmilk oligosaccharides (HMOs) support and concurrently shape the neonatal immune system through various mechanisms. Thereby, they may contribute to lower incidence of infections in infants. However, there is limited evidence on the role of individual HMOs in the risk of otitis media (OM), as well as lower and upper respiratory tract infections (LRTI and URTI, respectively) in children up to 2 years. Objective: To investigate whether individual HMO concentrations measured at 6 weeks of lactation were associated with risk of OM, LRTI or URTI up to 2 years in breastfed infants. Associations with OM, LRTI and URTI were determined for the most prominent human milk oligosaccharides including 13 neutral, partly isomeric structures (trioses up to hexaoses), two acidic trioses, and lactose. Design: HMO measurements and physician reported data on infections were available from human milk samples collected at 6 weeks postpartum (n = 667). Associations of HMOs with infections were assessed in crude and adjusted models using modified Poisson regression. Results: Absolute concentrations (median [min, max], in g/L) of 2′-fucosyllactose (2′-FL) tended (p = 0.04) to be lower, while lacto-N-tetraose (LNT) was higher in the milk for infants with OM in the 1st year of life (p = 0.0046). In the milk of secretor mothers, LNT was significantly higher in the milk for infants with OM (RR [95% CI]: 0.98 [0.15, 2.60]) compared to infants without OM (RR [95% CI]: 0.76 [0.14, 2.90]) at 1 year (p = 0.0019). No statistically significant milk group differences and associations were observed for OM, LRTI, and URTI (p > 0.0031). Conclusion: Our findings suggest that neither prominent neutral individual HMOs (ranging from 2′-FL to LNDFHs) nor acidic human milk sialyllactoses or lactose are significantly associated with a reduced or increased risk of infections in infants up to 2 years of age. Further research is needed to determine whether specific HMOs could potentially reduce the incidence or alleviate the course of distinct infections in early life

Is Sedentary Behavior or Physical Activity Associated With Loneliness in Older Adults? Results of the European-Wide SITLESS Study

Research has found that social relationships are central to the health and well-being of an aging population. Evidence exploring the association between physical activity (PA) and sedentary behavior (SB) with social isolation and loneliness is limited. This study uses objectively measured PA and SB (ActiGraph®) and self-reported measures of loneliness (the De Jong Gierveld Loneliness Scale) and social engagement (the Lubben Social Network Scale) from the SITLESS study, a European-wide study of community-dwelling older adults. Social isolation was associated with SB where higher levels of SB were associated with an increase in the level of social isolation, controlling for age, sex, living arrangements, employment status, body mass index, educational background, marital status, and self-reported general health. In contrast, PA was not associated with social isolation, and neither SB nor PA was a statistically significant predictor of loneliness. SB may be linked to social isolation in older adults, but PA and SB are not necessarily linked to loneliness in older community-dwelling adults

Prognostic value of interleukin-1 receptor antagonist gene polymorphism and cytomegalovirus seroprevalence in patients with coronary artery disease

BACKGROUND: Chronic inflammatory stimuli such as cytomegalovirus (CMV) infection and various genetic polymorphisms determining the inflammatory response are assumed to be important risk factors in atherosclerosis. We investigated whether patients with stable coronary artery disease (CAD) and homozygous for allele 2 of the interleukin 1 receptor antagonist (IL-1RA) gene and seropositive for CMV represent a group particular susceptible for recurrent cardiovascular events. METHODS: In a series of 300 consecutive patients with angiographically defined CAD a prospective follow-up was conducted (mean age 57.9 years, median follow-up time 38.2 months). RESULTS: No statistically significant relationship was found between CMV serostatus and IL-1RN*2 (alone or in combination) and risk for future cardiovascular events (CVE). The hazard ratio (HR) for a CVE given positive CMV-serology and IL-1RN*2 was 1.07 (95% confidence interval (CI) 0.32–3.72) in the fully adjusted model compared to seronegative CMV patients not carrying the IL-1RN*2 allele. In this prospective cohort study involving 300 patients with angiographically defined CAD at baseline, homozygousity for allele 2 of the IL-1 RA and seropositivity to CMV alone and in combination were not associated with an increased risk for cardiovascular events during follow-up; in addition, combination of the CMV-seropositivity and IL-1RN*2 allele were not associated with a proinflammatory response CONCLUSION: Our study suggests that seropositivity to CMV and IL-1RA*2 genotype alone or in combination might not be a strong risk factor for recurrent cardiovascular events in patients with manifest CAD, and is not associated with levels of established inflammatory markers

Human milk oligosaccharide profiles and child atopic dermatitis up to 2 years of age: The Ulm SPATZ Health Study

Background: Human milk oligosaccharides (HMOs) have several biological functions. Yet, very few studies have investigated the effect of HMOs on the development of allergies and even fewer on their specific associations with atopic dermatitis (AD) during early childhood. Objective: This study investigated whether individual HMO concentrations, measured at two time points of lactation, were associated with reported diagnosis of AD in children up to two years of age. Method: Outcome data were available for HMOs measured in human milk samples collected at 6 weeks (n = 534) and 6 months (n = 356) of lactation. Associations of HMOs with AD, ascertained from parents and pediatricians at ages one and two years, were assessed in crude and adjusted logistic regression models. Results: Few associations were statistically significant at the conventional level (p .0031, which is the threshold for statistical significance after correction for multiple testing). Conclusion: Our findings suggest that the intake of different levels (or even absence) of the individual HMOs measured at 6 weeks and 6 months of lactation, in the current study, is not significantly associated with the development of AD in early childhood. Given the exploratory nature of our study and the limited sample size, these results should be interpreted with caution. The specific HMOs for which we show plausible associations at conventional level may warrant further research and investigation

Potential sex differences in human milk fatty acids and their association with atopic dermatitis: Results of the Ulm SPATZ health study

Background: Polyunsaturated fatty acids (PUFAs) in human milk are essential in immune system maturation and might play a role in the development of allergic conditions, such as atopic dermatitis (AD) in infants. Immune system responses are modulated by sex, but data on the sex-specific associations with PUFAs are limited. We therefore explored sex-specific differences in human milk PUFAs and their association with AD up to 2 years. Methods: PUFAs were measured in human milk samples from the Ulm SPATZ Health Study at 6 weeks (n = 512) and 6 months (n = 367). Associations with AD up to 2 years were evaluated using crude and multivariable logistic regression. Interactions between infant sex and PUFAs were explored by including the product term. Results: No significant associations were observed with 6-week data. At 6 months, the median relative proportion of docosahexaenoic acid (DHA) was significantly higher in milk for female than male infants (p =.001). Female infants whose milk was lower in quintile proportions of alpha-linolenic acid (ALA) at 6 months had lower odds of AD compared to males [first vs. fifth quintile OR (95% confidence interval): 0.13 (0.02, 0.66), p =.02]. This interaction was not significant when correcting for multiple testing (α threshold: p =.004). No other statistically significant associations were observed. Conclusion: Individual quintile PUFA proportions in human milk were not associated with AD, overall and in a sex-specific manner. More comprehensive and statistically powered longitudinal studies are needed to determine whether potential sex differences in human milk, if any, could be of clinical relevance for infants including the investigation of mediating factors

Prognostic value of physicians' assessment of compliance regarding all-cause mortality in patients with type 2 diabetes: primary care follow-up study

BACKGROUND: Whether the primary care physician's assessment of patient compliance is a valuable prognostic marker to identify patients who are at increased risk of death, or merely reflects measurement of various treatment parameters such as HbA(1C )or other laboratory markers is unclear. The objective of this prospective cohort study was to investigate the prognostic value of the physicians' assessment of patient compliance and other factors with respect to all-cause mortality during a one year follow-up period. METHODS: A prospective cohort study was conducted among 1014 patients with type 2 diabetes aged 40 and over (mean age 69 years, SD 10.4, 45% male) who were under medical treatment in 11 participating practices of family physicians and internists working in primary care in a defined region in South Germany between April and June 2000. Baseline data were gathered from patients and physicians by standardized questionnaire. The physician's assessment of patient compliance was assessed by means of a 4-point Likert scale (very good, rather good, rather bad, very bad). In addition, we carried out a survey among physicians by means of a questionnaire to find out which aspects for the assessment of patient compliance were of importance to make this assessment. Active follow-up of patients was conducted after one year to determine mortality. RESULTS: During the one year follow-up 48 (4.7%) of the 1014 patients died. Among other factors such as patient type (patients presenting at office, nursing home or visited patients), gender, age and a history of macrovascular disease, the physician's assessment of patient compliance was an important predictor of all-cause mortality. Patients whose compliance was assessed by the physician as "very bad" (6%) were significantly more likely to die during follow-up (OR = 2.67, 95% CI 1.02–6.97) after multivariable adjustment compared to patients whose compliance was assessed as "rather good" (45%) or "very good" (18%). The HbA(1C)-value and the cholesterol level at baseline showed no statistically significant association with all-cause mortality. According to our survey for most of the physicians self-acceptance of disease, treatment adherence, patient's interest in physician's explanations, attendance at appointments, a good self-management, and a good physician-patient relationship were key elements in the assessment of patient compliance. CONCLUSION: The primary care physician's assessment of patient compliance is a valuable prognostic marker for mortality among patients with type 2 diabetes. Identification of patients in need of improved compliance may help to target preventive measures

Cost-effectiveness of a programme to address sedentary behaviour in older adults: results from the SITLESS RCT

Background: This study details the within-trial economic evaluation and long-term economic model of SITLESS, a multi-country, three-armed randomized controlled trial comparing a combined intervention of exercise referral schemes (ERS) enhanced by self-management strategies (SMS) against ERS alone and usual care (UC). Methods: A cost-utility analysis, conducted from the base-case perspective of the National Health Service and personal and social services, estimated the incremental cost per incremental quality-adjusted life year (QALY) and years in full capability (YFC). A secondary analysis combined the costs with a broad set of outcomes within a cost-consequence framework, from a societal perspective. A Markov-type decision-analytic model was developed to project short-term changes in physical activity to long-term outcomes and costs, over a 5- and 15-year time horizon. Results: The results of the within-trial analysis show that SMS+ERS is highly likely to be cost-effective compared to ERS alone (ICER €4270/QALY), but not compared to UC. Participants allocated to the SMS+ERS group also showed an improvement in YFC compared to ERS alone and UC. The long-term analysis revealed that SMS+ERS is likely to be a cost-effective option compared to ERS and UC over a 5-year, but not with a 15-year horizon, being then dominated by ERS alone. Conclusion: This research provides new evidence that SMS is a cost-effective add-on to ERS strategies. This economic evaluation informs the case for further, cost-effective, refinement of lifestyle change programmes targeted to older adults, with the aim of ultimately reducing the impact of non-communicable diseases in this population