Lifestyle and infections : an epidemiological approach on the role of obesity, physical activity, sleep and stress

The immune system plays a fundamental role in defending the human body from external pathogens. Some individuals, however, have a weaker immune system leading to more frequent infections. Infections are associated with high burden to society, both in terms of economic costs and morbidity. In this thesis we limited our attention to observational studies to investigate the association between lifestyle and infections. Our findings could be used in support of public health interventions to reduce the susceptibility to infections. Study I examined the association between physical activity and the occurrence of upper respiratory tract infections (URTI) in a cohort of about 2,000 employed adults. Sleep duration and sleep quality were also investigated in relation to URTI. Participants filled in five questionnaires on demographics and lifestyle and were followed for 9-months for the occurrence of URTI, which was prospectively self-reported through symptoms questionnaires. Due to the excess of individuals with zero infections, hurdle regression models were used to estimate the associations under investigation. During follow-up, 1,597 URTI occurred, but our findings do not support an association of URTI with either physical activity or sleep habits. Study II investigated the relationship between Body Mass Index (BMI) and infections requiring health care support. Participants in the study are 39,163 Swedish individuals who filled in a questionnaire in autumn 1997 and were followed through record-linkages until December 2016. Infections were identified from the Swedish national inpatient and outpatient registers. Cox proportional hazard models with age as time-scale were fitted to estimate Hazard Ratios and 95% confidence intervals. Extensions of the traditional Cox model, taking into account several infections for each individual, were used in a secondary analysis. Obesity emerged to be a risk factor for infections in both genders. In particular, obese women were at higher risk of skin infections, gastrointestinal tract infections, urinary tract infections and sepsis. Men with obesity showed an increased risk of skin infections. Findings from the extended Cox model were comparable to those from the traditional Cox model. Study III describes the association between work-related stress and infections. Around 25,000 employed Swedish adults were followed prospectively from September 1997—when they completed a lifestyle questionnaire—until their retirement, emigration, death or December 2016, whichever occurred first. A Swedish version of the Demand-Control Questionnaire was used to assess job stress, whereas infections were identified as in Study II from the National Patient Register. In the main analysis we fitted Cox models accounting for repeated events. We found that higher job demands are associated with increased incidence of infections, in particular upper respiratory tract infections and urinary tract infections. On the other hand, our findings do not support the hypothesis that high job control is associated with a lower occurrence of infections. When combining demand and control dimensions into job strain, we found that workers with active jobs had an increased risk of infections compared to workers with low strain jobs. No difference was observed in workers with high strain jobs compared to those with low strain jobs. Study IV aimed to explore the relationship between sleep characteristics and inflammatory markers, namely C-Reactive Protein (CRP), Interleukin-6 (IL-6) and Tumor Necrosis Factor (TNF ) in a random sample of 319 non-pregnant women from Uppsala, Sweden. Participants underwent overnight in-home polysomnography (PSG), answered a sleep questionnaire and had blood samples collected the morning after PSG. We first used principal component analysis to reduce the dimensionality of the data and then estimated linear regression (after log-transformation of the outcomes) and quantile regression models to infer on the associations of interest. We found increased CRP levels in women presenting insomnia symptoms (difficulties maintaining sleep or early morning awakenings), whereas sleep duration did not appear to be related with inflammation. From PSG measurements, a reduced REM sleep was associated with higher CRP levels. No association was found with the other markers of inflammation. Taken together, results from these studies suggest that sleep, stress and obesity might influence the susceptibility to infections, whereas the role of total physical activity is less clear. With these studies we contributed to fill some of the knowledge gaps about the association between lifestyle and infections, but further studies are warranted to overcome the limitations encountered in our research. Furthermore, our studies serve as examples of the wide possibilities offered by statistical tools in the analysis of epidemiological data

Obesity and risk of infections: results from men and women in the Swedish National March Cohort.

Abstract Background Previous studies have shown an association between body mass index (BMI) and infections, but the literature on type-specific community acquired infections is still limited. Methods We included 39 163 Swedish adults who completed a questionnaire in September 1997 and were followed through record-linkages until December 2016. Information on BMI was self-reported and infections were identified from the Swedish National Patient Register using International Classification of Diseases (ICD), Tenth Revision (ICD-10) codes. We fitted multivariable Cox proportional hazards models for time-to-first-event analysis, and we used extensions of the standard Cox model when repeated events were included. Results During a 19-year follow-up 32% of the subjects had at least one infection requiring health care contact, leading to a total of 27 675 events. We found an increased incidence of any infection in obese women [hazard ratio (HR) = 1.22; 95% confidence interval (CI) = 1.12; 1.33] and obese men (HR = 1.25; 95% CI = 1.09; 1.43) compared with normal weight subjects. For specific infections, higher incidences were observed for skin infections in both genders (HR = 1.76; 95% CI = 1.47; 2.12 for obese females and HR = 1.74; 95% CI = 1.33; 2.28 for obese males) and gastrointestinal tract infections (HR = 1.44; 95% CI = 1.19; 1.75), urinary tract infections (HR = 1.30; 95% CI = 1.08; 1.55) and sepsis (HR = 2.09; 95% CI = 1.46; 2.99) in obese females. When accounting for repeated events, estimates similar to the aforementioned ones were found. Conclusions Obesity was associated with an increased risk of infections in both genders. Results from multiple-failure survival analysis were consistent with those from classic Cox models

Adjusted Comparison of Outcomes between Patients from CARTITUDE-1 versus Multiple Myeloma Patients with Prior Exposure to PI, Imid and Anti-CD-38 from a German Registry

Ciltacabtagene autoleucel (cilta-cel) is a Chimeric antigen receptor T-cell therapy with the potential for long-term disease control in heavily pre-treated patients with relapsed/refractory multiple myeloma (RRMM). As cilta-cel was assessed in the single-arm CARTITUDE-1 clinical trial, we used an external cohort of patients from the Therapie Monitor registry fulfilling the CARTITUDE-1 inclusion criteria to evaluate the effectiveness of cilta-cel for overall survival (OS) and time to next treatment (TTNT) vs. real-world clinical practice. Individual patient data allowed us to adjust the comparisons between both cohorts, using the inverse probability of treatment weighting (IPW; average treatment effect in the treated population (ATT) and overlap population (ATO) weights) and multivariable Cox proportional hazards regression. Outcomes were compared in intention-to-treat (HR, IPW-ATT: TTNT: 0.13 (95% CI: 0.07, 0.24); OS: 0.14 (95% CI: 0.07, 0.25); IPW-ATO: TTNT: 0.24 (95% CI: 0.12, 0.49); OS: 0.26 (95% CI: 0.13, 0.54)) and modified intention-to-treat (HR, IPW-ATT: TTNT: 0.24 (95% CI: 0.09, 0.67); OS: 0.26 (95% CI: 0.08, 0.84); IPW-ATO: TTNT: 0.26 (95% CI: 0.11, 0.59); OS: 0.31 (95% CI: 0.12, 0.79)) populations. All the comparisons were statistically significant in favor of cilta-cel. These results highlight cilta-cel’s potential as a novel, effective treatment to address unmet needs in patients with RRMM

Adjusted comparison of outcomes between patients from CARTITUDE-1 <i>versus</i> multiple myeloma patients with prior exposure to proteasome inhibitors, immunomodulatory drugs and anti-CD38 antibody from the prospective, multinational LocoMMotion study of real-world clinical practice

Ciltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor T-cell therapy studied in patients with multiple myeloma exposed to three classes of treatment in the single-arm CARTITUDE-1 study. To assess the effectiveness of cilta-cel compared to real-world clinical practice (RWCP), we performed adjusted comparisons using individual patients’ data from CARTITUDE-1 and LocoMMotion, a prospective, multinational study of patients with multiple myeloma triple-class exposed of treatment. Comparisons were performed using inverse probability weighting. In CARTITUDE-1, 113 patients were enrolled, and 97 patients were infused with cilta-cel. In LocoMMotion, 248 patients were enrolled, and 170 patients were included in the comparisons versus infused patients. Ninety-two unique regimens were used in LocoMMotion, most frequently carfilzomib-dexamethasone (13.7%), pomalidomide-cyclophosphamide-dexamethasone (13.3%) and pomalidomidedexamethasone (11.3%). Adjusted comparisons showed that patients treated with cilta-cel were 3.12-fold more likely to respond to treatment than those managed by RWCP (response rate, 3.12, 95% confidence interval [95% CI]: 2.24-4.00), had their risk of progression or death reduced to by 85% (progression-free survival hazard ratio=0.15, 95% CI: 0.08-0.29), and a risk of death lowered by 80% (overall survival hazard ratio HR=0.20, 95% CI: 0.09-0.41). The incremental improvement in healthrelated quality of life from baseline for cilta-cel versus RWCP at week 52, as measured by EORTC QLQ-C30 Global Health Status, was 13.4 (95% CI: 3.5-23.6) and increased to 30.8 (95% CI: 21.8-39.8) when including death as additional information regarding patients’ health status. Patients treated with cilta-cel experienced more adverse events than those managed with RWCP (any grade: 100% vs. 83.5%). The results from this study demonstrate improved efficacy outcomes of cilta-cel versus RWCP and highlight its potential as a novel and effective treatment option for patients with multiple myeloma triple-class exposed of antimyeloma treatment. CARTITUDE-1 is registered with clinicaltrials gov. Identifier: NCT03548207. LocoMMotion is registered with clinicaltrials gov. Identifier: NCT04035226

Cohort profile: Studies of Work Environment and Disease Epidemiology-Infections (SWEDE-I), a prospective cohort on employed adults in Sweden.

The aim of this article is to provide a detailed description of the SWEDE-I cohort, a prospective study designed to investigate work-related risk factors for transmission of viral infections. A total of 2,237 subjects aged 25-64, working and residing in Eskilstuna (central Sweden), enrolled in the study in August 2011. They filled in five detailed questionnaires including information on demography, personal characteristics, work tasks, work place, contact patterns, family structure, health status, physical activity and diet. During a 9-month follow-up period, the participants self-reported-via internet or telephone-any onset of fever, upper respiratory tract infection, or gastroenteritis immediately as they occurred. For each disease episode, the participants were asked to submit a self-sampled nasal swab for viral diagnosis. In total, 1,733 disease reports were recorded and 1,843 nasal swabs were received, of which 48% tested positive for one or more of 14 analyzed viruses. The cohort has been used to date to study diet, sleep and physical activity as determinants for upper respiratory tract infections. Analyses of contact patterns and occupational circumstances as risk factors for the transmission of infections are ongoing. The SWEDE-I study should be seen as a first pioneering effort to provide new insight in the epidemiology and prevention of viral infections. Potential joint collaborations can be discussed with the principal investigators

Biologics, colchicine, corticosteroids, immunosuppressants and interferon-alpha for Neuro-Behcet's Syndrome

Backgroun

Relationship between sleep characteristics and markers of inflammation in Swedish women from the general population

Systemic inflammation is thought to mediate the link between sleep and cardiovascular outcomes, but previous studies on sleep habits and inflammation markers have found inconsistent results. This study investigated the relationship between sleep characteristics and C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor α (TNFα). A representative sample of 319 Swedish women was randomly selected from the general population for in-home polysomnography, sleep questionnaire and blood samples. As variables were highly correlated, principal component analysis was used to reduce the number of original variables. Linear regression with log-transformation of the outcomes (lnCRP, lnIL-6 and lnTNFα) and quantile regression were fitted to estimate cross-sectional relationships. Multivariable linear regression models suggested a significant association of insomnia symptoms (self-reported) with higher lnCRP levels (β = 0.11; 95% confidence interval [CI] = 0.02; 0.21), but not with lnIL-6 and lnTNFα. From quantile regression analysis we found that a high non-restorative index (subjective) and insomnia symptoms (self-reported) were associated with higher values of CRP, especially in the highest quantiles of the CRP distribution (90th percentile: β = 0.71; 95% CI = 0.17; 1.24. β = 1.23; 95% CI = 0.44; 2.02, respectively). Additionally, higher amounts of rapid eye movement (REM) sleep were associated with lower CRP values (90th percentile: β = -0.80; 95% CI = -0.14; -1.46). In conclusion, sleep disturbances (self-reported), specifically difficulties maintaining sleep and early morning awakenings, but not sleep duration (neither subjective nor objective), were associated with higher CRP levels. No association was found with IL-6 or TNFα. Elevated REM sleep was associated with lower CRP levels. The results suggest that inflammation might be an intermediate mechanism linking sleep and health in women

Crude and adjusted URTI incidence rate ratio (IRR) estimates by level of sleep duration, sleep quality and studied covariates, fitted in a hurdle regression model.

<p>Crude and adjusted URTI incidence rate ratio (IRR) estimates by level of sleep duration, sleep quality and studied covariates, fitted in a hurdle regression model.</p