Epigenetic upregulation of FKBP5 by aging and stress contributes to NF-κB-driven inflammation and cardiovascular risk.

Aging and psychosocial stress are associated with increased inflammation and disease risk, but the underlying molecular mechanisms are unclear. Because both aging and stress are also associated with lasting epigenetic changes, a plausible hypothesis is that stress along the lifespan could confer disease risk through epigenetic effects on molecules involved in inflammatory processes. Here, by combining large-scale analyses in human cohorts with experiments in cells, we report that FKBP5, a protein implicated in stress physiology, contributes to these relations. Across independent human cohorts (total n > 3,000), aging synergized with stress-related phenotypes, measured with childhood trauma and major depression questionnaires, to epigenetically up-regulate FKBP5 expression. These age/stress-related epigenetic effects were recapitulated in a cellular model of replicative senescence, whereby we exposed replicating human fibroblasts to stress (glucocorticoid) hormones. Unbiased genome-wide analyses in human blood linked higher FKBP5 mRNA with a proinflammatory profile and altered NF-κB-related gene networks. Accordingly, experiments in immune cells showed that higher FKBP5 promotes inflammation by strengthening the interactions of NF-κB regulatory kinases, whereas opposing FKBP5 either by genetic deletion (CRISPR/Cas9-mediated) or selective pharmacological inhibition prevented the effects on NF-κB. Further, the age/stress-related epigenetic signature enhanced FKBP5 response to NF-κB through a positive feedback loop and was present in individuals with a history of acute myocardial infarction, a disease state linked to peripheral inflammation. These findings suggest that aging/stress-driven FKBP5-NF-κB signaling mediates inflammation, potentially contributing to cardiovascular risk, and may thus point to novel biomarker and treatment possibilities.

Health disparities: Intracellular consequences of social determinants of health.

Health disparities exist dependent on socioeconomic status, living conditions, race/ethnicity, diet, and exposures to environmental pollutants. Herein, the various exposures contributing to a person's exposome are collectively considered social determinants of health (SDOH), and the SDOH-exposome impacts health more than health care. This review discusses the extent of evidence of the physiologic consequences of these exposures at the intracellular level. We consider how the SDOH-exposome, which captures how individuals live, work and age, induces cell processes that modulate a conceptual "redox rheostat." Like an electrical resistor, the SDOH-exposome, along with genetic predisposition and age, regulate reductive and oxidative (redox) stress circuits and thereby stimulate inflammation. Regardless of the source of the SDOH-exposome that induces chronic inflammation and immunosenescence, the outcome influences cardiometabolic diseases, cancers, infections, sepsis, neurodegeneration and autoimmune diseases. The endogenous redox rheostat is connected with regulatory molecules such as NAD+/NADH and SIRT1 that drive redox pathways. In addition to these intracellular and mitochondrial processes, we discuss how the SDOH-exposome can influence the balance between metabolism and regulation of immune responsiveness involving the two main molecular drivers of inflammation, the NLRP3 inflammasome and NF-κB induction. Mitochondrial and inflammasome activities play key roles in mediating defenses against pathogens and controlling inflammation before diverse cell death pathways are induced. Specifically, pyroptosis, cell death by inflammation, is intimately associated with common disease outcomes that are influenced by the SDOH-exposome. Redox influences on immunometabolism including protein cysteines and ion fluxes are discussed regarding health outcomes. In summary, this review presents a translational research perspective, with evidence from in vitro and in vivo models as well as clinical and epidemiological studies, to outline the intracellular consequences of the SDOH-exposome that drive health disparities in patients and populations. The relevance of this conceptual and theoretical model considering the SARS-CoV-2 pandemic are highlighted. Finally, the case of asthma is presented as a chronic condition that is modified by adverse SDOH exposures and is manifested through the dysregulation of immune cell redox regulatory processes we highlight in this review.

Development of a Nursing Assignment Tool Using Workload Acuity Scores.

OBJECTIVE: To determine a just and consistent practice for creating nursing assignments. BACKGROUND: Traditional methods of assigning patients to nurses may lead to unbalanced nursing workload. This article describes the ongoing, hospital-wide effort to evaluate and implement a nursing assignment tool based on electronic health record (EHR) functionality and auto-calculated nursing workload scores. METHODS: EHR records of individual patient workload scores from all hospital units were collected from August 2017 to June 2018. A nurse-specific total workload score was summed for each staff. Then, each hospital unit's mean nurse workload score and standard deviation, along with the unit's nurse-to-patient ratio, were used to calculate levels of high, medium, and low nursing workload measurement (NWM). RESULTS: Mean patient-specific workload scores varied greatly across hospital units. Unit-specific nurse-to-patient ratios were factored into NWM scores to create ranges for assignments that were relatively consistent across the institution. CONCLUSION: The use of objective, electronically generated nursing workload scores, combined with traditional nurse-to-patient ratios, provides accurate real-time nurse staffing needs that can inform best practice in staffing. The confirmation of individual patient workload scores and an appreciation for the complexity of EHR vendor rules are necessary for successful implementation. Automation ensures patient safety, staff satisfaction, and optimal resource allocation.

Prenatal exposure to mercury in relation to infant infections and respiratory symptoms in the New Hampshire Birth Cohort Study.

BACKGROUND: Mechanistic studies support the potential for mercury (Hg) to alter immunity, including via in utero exposure. As yet, there are few prospective studies of in utero Hg exposure and subsequent immune-related outcomes, especially in infancy. OBJECTIVES: We investigated the association of biomarkers of prenatal Hg exposure and maternal silver-mercury dental amalgams with the occurrence of infant allergy, respiratory infection, and respiratory symptoms in the first year of life. METHODS: The New Hampshire Birth Cohort Study (NHBCS) ascertained information on infant allergies, infections and symptoms through telephone interviews at 4, 8 and 12 months postpartum and measured total Hg in maternal toenails collected at ~28-30 weeks gestation. Information on maternal fish consumption and presence of dental amalgams was obtained from a questionnaire administered at study enrollment at 24-28 weeks. A total of 1321 NHBCS mother-infant pairs had at least one Hg exposure measure (toenail Hg or information on dental amalgams) and information on dietary fish intake. Generalized linear models and generalized estimating equation models with Poisson regression adjusted for potential confounders (maternal age, level of education, parity, smoking, alternative Healthy Eating Index-2010, infant sex, gestational age, feeding mode, and day care attendance) were used to assess the association between infant outcomes and prenatal toenail Hg levels. We subsetted this analysis on mothers who consumed fish (n = 706) as a measure of in utero methylmercury (MeHg) exposure. Associations between infant outcomes and dental amalgams as a measure of in utero inorganic Hg exposure were assessed among mothers who did not consume fish (n = 218). RESULTS: Among women who ate fish during pregnancy, higher maternal toenail Hg concentrations were associated with an increased risk of lower respiratory infections and respiratory symptoms requiring a doctor visit among infants age 9-12 months (relative risk (RR) 1.4 (95% CI: 1.1, 1.9) and 1.2 (95% CI: 1.0, 1.4) respectively), whereas a reduced risk of lower respiratory infections was observed among infants 0-4 months of age (RR = 0.7 (95% CI: 0.5, 1.0). We found little to no evidence of associations of toenail Hg with upper respiratory infections, allergy or eczema at any age to one year. Among infants of mothers who did not consume fish, we found an elevated risk of upper respiratory infections requiring a doctor visit in relation to having dental amalgams during pregnancy (RR = 1.5 (95% CI: 1.1, 2.1)). Overall, weaker associations were observed with lower respiratory infections, respiratory symptoms, and medically confirmed allergies, and there was no association with eczema. CONCLUSIONS: Our analyses of a US birth cohort, along with prior mechanistic work, raise the possibility that gestational Hg exposure through fish/seafood consumption and dental amalgams may alter respiratory infections and respiratory symptoms in infants.

Lack of supportive leadership behavior predicts suboptimal self-rated health independent of job strain after 10 years of follow-up: findings from the population-based MONICA/KORA study.

OBJECTIVES: Emerging cross-sectional research has identified lack of supportive leadership behavior (SLB) as a risk factor for workforce health. However, prospective evidence is hitherto lacking. SLB denotes support in difficult situations, recognition and feedback on work tasks. This study aims to determine the effect of SLB on suboptimal self-rated health (SRH) after 10 years considering potential moderators such as ages, sex, occupation and job strain. METHODS: The sample included 884 employed participants drawn from the population-based prospective MONICA/KORA Study. SLB, SRH, as well as job strain were assessed by questionnaire. Logistic regressions estimated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the effect of SLB at baseline on suboptimal SRH at follow-up. Analyses were adjusted for age, gender, lifestyle (alcohol, smoking, physical activity), socioeconomic status as well as for SRH and job strain at baseline. RESULTS: Lack of SLB was associated with suboptimal SRH at baseline [OR 2.00, (95% CI 1.19-3.46)] and at follow-up [OR 2.33, (95% CI 1.40-3.89)]. Additional adjustment for job strain did not substantially alter this association [OR 2.06, (95% CI 1.20-3.52)]. However, interactions between SLB and job strain as well as gender became evident, indicating moderating influences on the association between SLB and SRH. CONCLUSION: Lack of supportive leadership was associated with suboptimal SRH at 10 years' follow-up in men, even if SRH at baseline and other risk factors were taken into account. This effect is likely to be moderated by job strain.

Outcome of gastric cancer in the elderly: a population-based evaluation of the Munich Cancer Registry.

BACKGROUND: Gastric cancer accounts for 5 % of cancer deaths. Proportions of older stomach cancer patients are increasing. Despite the still poor prognosis, standardised treatment has achieved improvements; nonetheless it is questionable whether all age groups have benefitted. Age and outcome need to be examined in a population-based setting. METHODS: Analyses included Munich Cancer Registry (MCR) data from 8601 invasive gastric cancer patients, diagnosed between 1998 and 2012. Tumour and therapy characteristics and outcome were analysed by two age groups (<70 vs. ≥70 years). Survival was analysed using the Kaplan-Meier method and relative survival was computed as an estimation for cancer-specific survival. Additional landmark analyses were conducted by calculating conditional survival of patients who survived more than 6 months. RESULTS: Fifty-nine per cent of the cohort were ≥70 years old. These patients had tumours with a slightly better prognosis and were treated with less radical surgery and adjuvant therapy than younger patients. The 5-year relative survival was 40 % for the youngest (<50 years) and 23 % for the oldest patients (≥80 years). Survival differences were diminished or eliminated after landmark analyses: The 5-year relative survival in age groups 50-59, 60-69 and 70-79 years was comparable (between 48 and 49.6 %) and slightly worse in the youngest and oldest (45 %), which may be explained by more aggressive tumours and effects of cellular senescence, respectively. CONCLUSION: The treatment and care of elderly gastric cancer patients in the MCR catchment area seems appropriate: if a patient's general condition allows oncologic resection and chemotherapy, it is conducted and the result is comparable between age groups.

A physical/psychological and biological stress combine to enhance endoplasmic reticulum stress.

The generation of an immune response against infectious and other foreign agents is substantially modified by allostatic load, which is increased with chemical, physical and/or psychological stressors. The physical/psychological stress from cold-restraint (CR) inhibits host defense against Listeria monocytogenes (LM), due to early effects of the catecholamine norepinephrine (NE) from sympathetic nerves on ß1-adrenoceptors (ß1AR) of immune cells. Although CR activates innate immunity within 2h, host defenses against bacterial growth are suppressed 2-3 days after infection (Cao and Lawrence 2002). CR enhances inducible nitric oxide synthase (iNOS) expression and NO production. The early innate activation leads to cellular reduction-oxidation (redox) changes of immune cells. Lymphocytes from CR-treated mice express fewer surface thiols. Splenic and hepatic immune cells also have fewer proteins with free thiols after CR and/or LM, and macrophages have less glutathione after the in vivo CR exposure or exposure to NE in vitro. The early induction of CR-induced oxidative stress elevates endoplasmic reticulum (ER) stress, which could interfere with keeping phagocytized LM within the phagosome or re-encapsuling LM by autophagy once they escape from the phagosome. ER stress-related proteins, such as glucose-regulated protein 78 (GRP78), have elevated expression with CR and LM. The results indicate that CR enhances the unfolded protein response (UPR), which interferes with host defenses against LM. Thus, it is postulated that increased stress, as exists with living conditions at low socioeconomic conditions, can lower host defenses against pathogens because of oxidative and ER stress processes.

Job strain as a risk factor for the onset of type 2 diabetes mellitus: findings from the MONICA/KORA Augsburg cohort study.

OBJECTIVE: To examine whether job strain is associated with an increased risk of subsequent Type 2 diabetes mellitus (T2DM) development in a population-based study of men and women. METHODS: Data were derived from the prospective MONICA/KORA Augsburg study. We investigated 5337 working participants aged 29 to 66 years without diabetes at one of the three baseline surveys. Job strain was measured by the Karasek job content questionnaire. High job strain was defined by the quadrant approach, where high job demands combined with low job control were classified as high job strain. Continuous job strain (quotient of job demands divided by job control) was additionally analyzed as sensitivity analysis. Hazard ratios (HRs) were estimated using multivariable Cox proportional hazards models with adjustment for age, sex, survey, socioeconomic and life-style variables, parental history of diabetes, and body mass index. RESULTS: During a median follow-up of 12.7 years, 291 incident cases of T2DM were observed. The participants with high job strain at baseline had a 45% higher fully adjusted risk to develop T2DM than did those with low job strain (HR = 1.45 [95% confidence interval = 1.00-2.10], p = .048). On the continuous scale, more severe job strain in the magnitude of 1 standard deviation corresponded to a 12% increased fully adjusted T2DM risk (HR = 1.12 [95% confidence interval = 1.00-1.25], p = .045). CONCLUSIONS: Men and women who experience high job strain are at higher risk for developing T2DM independently of traditional risk factors. Preventive strategies to combat the globally increasing T2DM epidemic should take into consideration the adverse effects of high strain in the work environment.

A pattern of unspecific somatic symptoms as long-term premonitory signs of type 2 diabetes: findings from the population-based MONICA/KORA cohort study, 1984-2009.

BACKGROUND: Unspecific symptoms often proceed a serious chronic disease condition long before the onset of the disease. The role of an unspecific premonitory symptom (UPMS) pattern as premonitory signs of subsequent type 2 diabetes mellitus (T2DM) diagnosis independent of established cardio-metabolic risk factors is unclear and therefore was examined in the present study. METHODS: The study population consisted of 10,566 participants aged 25-74 years at baseline drawn from the population-based MONICA/KORA Cohort Study conducted in 1984-2009 in the Augsburg region (Germany). Unspecific premonitory symptoms were assessed following the Somatic Symptom Scale-8 (SSS-8). The impact of the score on T2DM risk within a mean follow-up time of 16 years was estimated by Cox regression. RESULTS: Within follow-up, 974 newly diagnosed T2DM cases were observed. The risk for T2DM increased by a hazard ratio (HR) of 1.03 (95% CI 1.01-1.04, p value < 0.001) for a one unit increase of the UPMS score in a Cox model adjusted for age, sex and survey. Additional adjustment for cardio-metabolic risk factors attenuated this effect (HR = 1.02) but significance remained (p value = 0.01). CONCLUSIONS: Suffering from an elevated burden of unspecific somatic symptoms is associated with T2DM long before the onset and independent of established cardio-metabolic risk factors. Further research is needed to obtain insight in potential underlying pathophysiological mechanisms.

Quality of life in women with localised breast cancer or malignant melanoma 2 years after initial treatment: a comparison.

BACKGROUND: Two thirds of female breast cancer patients and more than 80 % of malignant melanoma patients are diagnosed with localised disease and good prognosis with a 5-year relative survival of more than 90 % in Germany. PURPOSE: This study was conducted to present quality of life (QoL) data from a German population-based cohort of female breast cancer and melanoma patients without recurrence for approximately 2 years after initial diagnosis. METHODS: In 2003-2004, patients with localised breast cancer and melanoma were recruited from the Munich Cancer Registry (Upper Bavaria, Germany) to answer QoL questionnaires. Differences between breast cancer and melanoma patients were investigated with regard to age and aspects of communication with their medical caregivers. RESULTS: One thousand three hundred and four breast cancer and 348 melanoma patients were included. Breast cancer patients were about 7 years older and had significantly lower QoL and higher symptom scores than melanoma patients. Communication needs were generally similar in both groups; however, breast cancer patients experienced more empathy from their medical caregivers. In breast cancer patients, communication was an independent factor for all QoL functioning scores. CONCLUSIONS: Even when faced with a similarly good prognosis, breast cancer patients have a worse QoL than melanoma patients 2 years after diagnosis. An explanation may be more distinctive surgery and systemic therapy, older patients with comorbidities and misunderstood risk communication in breast cancer patients that may stoke anxiety and fears. Further reasons could be unceasing public discussion about breast cancer and its instrumentalisation for political purposes.

[Obesity and symptoms of depression and anxiety in pre- and postmenopausal women: a comparison of different obesity indicators]. / Adipositas und Depressions- und Angstsymptome -bei prä- und post-menopausalen Frauen: Ein Vergleich verschiedener Adipositasmaße.

This study examines differences in the rates of depression and anxiety symptoms in overweight vs. normal weight women before and after the menopause. In a population sample of 1 416 participants of the KORA-Survey F3 2004-2005 (age 35-74 years), body mass index (BMI), waist circumference (WC), waist-to-hip-ratio (WHR) und waist-to-height-ratio (WHtR) were measured via physical examination. Depression and anxiety were assessed with the Hospital Anxiety and Depression Scale. Compared with normal weight, obesity was associated with depression in premenopausal women. This held for elevated BMI-, WC- and WHtR-scores (OR=3.7, 4.2, and 2.8), underlining the relevance of both general and abdominal obesity. Menopausal status may be a moderator for the association of obesity and depression, which - given the interaction between these 2 risk factors - may be of preventive importance in regard to the development of cardiovascular outcomes such as coronary heart disease.

Causes of Childhood Cancer: A Review of the Recent Literature: Part I-Childhood Factors.

PURPOSE: To review the childhood risk factors for pediatric cancer (diagnosis before age 20). METHODS: We conducted literature searches using Ovid Medline and Scopus to find primary research studies, review articles, and meta-analyses published from 2014 to 3 March 2021. RESULTS: Strong evidence indicates that an array of genetic and epigenetic phenomena, structural birth defects, and chromosomal anomalies are associated with an increased risk of various childhood cancers. Increased risk is also associated with prior cancer, likely due to previous treatment agents and therapeutic ionizing radiation. Convincing evidence supports associations between several pediatric cancers and ionizing radiation, immunosuppression, and carcinogenic virus infection both in healthy children and in association with immune suppression following organ transplantation. Breastfeeding and a childhood diet rich in fruits and vegetables appears to reduce the risk of pediatric leukemia but the evidence is less strong. Childhood vaccination against carcinogenic viruses is associated with a lower risk of several cancers; there is less strong evidence that other childhood vaccinations more broadly may also lower risk. Ultraviolet (UV) radiation is associated with increased melanoma risk, although most melanomas following childhood UV exposure occur later, in adulthood. Evidence is weak or conflicting for the role of body mass index, other childhood infections, allergies, and certain treatments, including immunomodulator medications and human growth therapy.

Positive lymph nodes do not metastasize.

Our understanding of the role of lymph nodes (LN) in the metastasization process (MET) is marginal. Positive LNs (pLN) are the most important prognostic factor and lymph node dissection (LND) is still standard practice in primary treatment. However, up to now, there is almost no evidence that elective LND has a survival benefit. Based on many clinical and experimental findings, we propose that tumor foci in regional LN are incapable of metastasization and can therefore not infiltrate further LN and organs. Available data demonstrate a very early infiltration of MET capable tumor cells from the primary tumor into regional LN, and thereafter an increased probability of subsequent LN infiltrations. Disparate growth rates of the first versus subsequent infiltrating tumors as well as the asymptotic growth and prognosis of large tumor foci in LN explain many clinical observations for solid tumors. The consequence of the hypothesis "pLN do not metastasize" would impact clinical treatment and research and contribute to understanding the mounting evidence against LND.

Job strain-associated inflammatory burden and long-term risk of coronary events: findings from the MONICA/KORA Augsburg case-cohort study.

BACKGROUND: We examined the association between job strain and coronary heart disease (CHD) and investigated the role of markers of inflammation and endothelial dysfunction as possible mediators of job strain-associated CHD risk. METHODS: The sample (n = 1027) included employed participants (35-64 years old, 68% male) from the population-based MONICA/KORA (Monitoring of Trends and Determinants in Cardiovascular Disease/Kooperative Gesundheitsforschung in der Region Augsburg) studies. At baseline Karasek's Job Strain Index was assessed during standardized personal interviews, and nine biological markers were measured (1984-1995). Participants were followed (average, 12 years) to assess incident events (sudden cardiac death or fatal and nonfatal myocardial infarction). In this case-cohort design, the final sample contained 114 cases and 913 noncases. RESULTS: Baseline distributions of cardiometabolic risk factors were significantly different between cases and noncases, with no detectable job strain-specific differences. However, cases with high job strain had higher monocyte chemoattractant protein-1, interleukin (IL)-8, and IL-18 compared with noncases with high job strain. High-sensitivity C-reactive protein, IL-6, and soluble intercellular adhesion molecule-1 were increased in cases versus noncases, regardless of work stress. Job strain was associated with incident coronary events in Cox proportional hazards models adjusted for age, sex, and survey (hazard ratio = 2.57, 95% confidence interval = 1.09-6.07) and after adjustment for CHD risk factors (2.35, 1.003-5.49). Adjustment for monocyte chemoattractant protein-1 or IL-8 increased this risk estimate by 14.5% or 9.4%, respectively, whereas adjustment for C-reactive protein and soluble intercellular adhesion molecule-1 led to decreased hazard ratios (-9.9% and -5.5%, respectively). CONCLUSIONS: Job strain increased CHD risk in healthy workers; the associated inflammatory burden may contribute to stress-related coronary pathogenesis.

No evidence for an association of posttraumatic stress disorder with circulating levels of CRP and IL-18 in a population-based study.

Several studies have shown associations of posttraumatic stress disorder (PTSD) with the development of cardiometabolic diseases. The underlying psychopathological mechanisms, including potential links to inflammatory processes, have been discussed but remain elusive. Therefore, the aim of the present study was to evaluate the association of PTSD symptoms with the inflammatory biomarkers C-reactive protein (CRP) and interleukin-18 (IL-18). The study population consisted of 3012 participants aged 32-81years drawn from the population-based KORA F4 study conducted in 2006-08 in the Augsburg region (Southern Germany). PTSD symptoms were measured by the Impact of Event Scale, the Posttraumatic Diagnostic Scale and interview data and classified as no, partial or full PTSD. The associations of PTSD with CRP and IL-18 concentrations were estimated by multiple regression analyses with adjustments for age, sex and cardiometabolic risk factors. Linear regression analyses showed no significant association between PTSD and CRP or IL-18 concentration: adjusted for age and sex, the geometric mean concentrations in participants with full PTSD was for CRP 9% lower and for IL-18 1% higher than in participants with no PTSD (p values 0.53 and 0.89). However, further analyses indicated that individuals with partial PTSD had an increased chance of belonging to the highest quartile of the IL-18 concentration. No significant association was observed for any of the three subscales intrusion, avoidance or hyperarousal with CRP or IL-18 concentration. This large, population-based study could not find an association of full PTSD with CRP and IL-18 concentrations. Further research is needed to analyse these relationships.

Distribution and determinants of functioning and disability in aged adults--results from the German KORA-Age study.

BACKGROUND: Today industrialized countries face a burgeoning aged population. Thus, there is increasing attention on the functioning and disabilities of aged adults as potential determinants of autonomy and independent living. However, there are few representative findings on the prevalence and determinants of disability in aged persons in the German population.The objective of our study is to examine the frequency, distribution and determinants of functioning and disability in aged persons and to assess the contribution of diseases to the prevalence of disability. METHODS: Data originate from the MONICA/KORA study, a population-based epidemiological cohort. Survivors of the original cohorts who were 65 and older were examined by telephone interview in 2009. Disability was assessed with the Health Assessment Questionnaire Disability Index (HAQ-DI). Minimal disability was defined as HAQ-DI > 0. Logistic regression was used to adjust for potential confounders and additive regression to estimate the contribution of diseases to disability prevalence. RESULTS: We analyzed a total of 4117 persons (51.2% female) with a mean age of 73.6 years (SD = 6.1). Minimal disability was present in 44.7% of all participants. Adjusted for age and diseases, disability was positively associated with female sex, BMI, low income, marital status, physical inactivity and poor nutritional status, but not with smoking and education. Problems with joint functions and eye diseases contributed most to disability prevalence in all age groups. CONCLUSIONS: In conclusion, this study could show that there are vulnerable subgroups of aged adults who should receive increased attention, specifically women, those with low income, those over 80, and persons with joint or eye diseases. Physical activity, obesity and malnutrition were identified as modifiable factors for future targeted interventions.

Lifetime traumatic experiences and their impact on PTSD: a general population study.

OBJECTIVE: Exploring the relationship of exposure to a traumatic event and the subsequent onset of posttraumatic stress disorder (PTSD) in the population. METHODS: Posttraumatic stress disorder was assessed using the Impact of Event Scale (IES), Posttraumatic Diagnostic Scale (PDS) and interview data. Logistic regression analyses with sex, age, marital status, educational level and traumatic event characteristics were performed. Prevalences were standardised to the sex and age distribution of the German population. RESULTS: A total of 41 % of the subjects reported exposure to a trauma, leading to full PTSD in 1.7 % and to partial PTSD in 8.8 % of the participants. Logistic regression revealed accidents (OR 2.5, 95 % CI 1.3-4.7), nonsexual assault by known assailants (4.5, 2.1-9.8), combat/war experiences (5.9, 2.0-17.4), life-threatening illness (4.9, 2.7-8.9) and interpersonal conflicts (15.5, 2.5-96.0) as risk factors for full PTSD; risk factors for partial PTSD were accidents (3.2, 2.4-4.3), sexual (4.6, 2.2-9.6) or nonsexual (2.3, 1.4-3.8) assault by known assailants, life-threatening illness (6.2, 4.6-8.3), death of relatives (5.0, 3.2-7.8) and interpersonal conflicts (22.0, 8.3-58.1). CONCLUSIONS: Of subjects exposed to traumatic events, only a minority developed PTSD indicating a relationship between characteristics of the exposure and the individual and the onset of PTSD.

The New Hampshire Hospital Screening and Referral Algorithm (NHHSRA) for Substance Use in People With Serious Mental Illness.

Objective: Substance use is a common co-occurrence among psychiatrically hospitalized adults, yet it is especially difficult to identify in those with serious mental illness. Existing screening instruments are not feasible for individuals with serious mental illness, as they rely heavily on subjective self-report. This study aimed to develop and validate an objective substance use screening instrument for use in seriously mentally ill patient populations.Methods: Objective elements were extracted from existing substance use screening instruments and used to develop a new, data-driven referral tool, the New Hampshire Hospital screening and referral algorithm (NHHSRA). Descriptive statistics were employed to compare NHHSRA summed score and individual patient data elements in a convenience sample of patients who were referred to the Addiction Services by expert addiction psychiatrist evaluation to those who were not referred. Pearson correlation coefficients and logistic regression models assessed the association between patient referral and the overall NHHSRA score and individual items. The NHHSRA was then piloted in a smaller convenience sample of patients against the standard clinical-based identification for substance use treatment needs.Results: The instrument consists of 5 objective items. These were tested in a sample of 302 sequentially admitted adults with serious mental illness. Three of the items were significantly associated with likelihood of benefitting from referral for substance use interventions (maximum likelihood estimate and standard deviation [SD] for positive non-tetrahydrocannabinol [non-THC] toxicology screen or > 0% blood alcohol level = 3.61 [0.6]; diagnosis of a substance use disorder = 4.89 [0.73]; and medication-assisted treatment or relapse prevention = 2.78 [0.67]), and these were prioritized in building a decision tree algorithm. The area under the receiver operating characteristic (ROC) curve for the NHHSRA was 0.96, indicating that the NHHSRA has high overall sensitivity and the algorithm was capable of distinguishing between patients needing substance use intervention versus those who do not with 96% accuracy. In the pilot implementation study of another 20 patient admissions, the NHHSRA accurately identified 100% (n = 6) of patients deemed to benefit from substance use interventions by expert addiction psychiatric evaluation. The standard clinical-based referral process identified only 33% (n = 2) and erroneously identified another 4 for referral to substance use intervention that would not have been warranted.Conclusions: The NHHSRA holds promise in its ability to improve objective and timely identification of substance use in a seriously mentally ill inpatient population, helping to facilitate treatment.