[Changes in Prescription Patterns of Oral Anticoagulants in Family Practices after Marketing Approval of Direct Oral Anticoagulants]. / Änderungen bei der Verordnung oraler Antikoagulation in Hausarztpraxen nach Einführung der direkten oralen Antikoagulanzien.

AIM OF THE STUDY: Since 2011, non-vitamin-K-dependent oral anticoagulants (NOAC) have extended the spectrum of anticoagulation therapy. Initially, the approval of NOAC was limited to the prophylaxis of postoperative thrombosis, but in the course of time the spectrum was extended to the therapy of thrombosis and embolism as well as anticoagulation in non-valvular atrial fibrillation. The study was designed to examine how the approval of NOAC had affected the prescribing behaviour of general practitioners in the first years of their approval. METHODS: In a retrospective longitudinal study, the prescriptions of anticoagulants between 2012 and 2017 were analysed in 3 general practitioners' practices in the Bonn area. The study included all patients for whom at least one prescription from a NOAC or a vitamin K antagonist (VKA) was documented in the administrative system of the practices during this period. RESULTS: A total of n=579 patient files were evaluated (47% female; median age 75 years). Of these, 47% received a VKA, and 40% a NOAC (59% rivaroxaban, 29% apixaban, 9% dabigatran and 3% edoxaban). During the period under examination, the share of VKA prescriptions decreased from 45% to 14% and the share of NOAC increased from 28% to 87%. Anti-coagulation was changed in 12%. The most frequent change was from a VKA to a NOAC (70%). CONCLUSION: After marketing approval, the use of NOAC in the initial prescriptions increased steadily. This trend can also be seen in other European studies. VKA are mainly prescribed to patients with stable oral anticoagulation. As recommended in the guidelines, anticoagulation is changed mainly when problems occur during therapy. If the trend in the prescription of anticoagulants continues, in the medium term, VKA will only be prescribed for patients who have been stable for many years and for patients with artificial heart valves.

Why are women deciding against birth in alongside midwifery units? A prospective single-center study from Germany.

OBJECTIVES: For healthy women entering labor after an uneventful pregnancy, advantages of birth in midwife-led models of care have been demonstrated. We aimed to study the level of awareness regarding care in alongside midwifery units (AMU), factors involved in the decision for birth in obstetrician-led units (OLU), and wishes for care and concerns about birth in women registering for birth in OLU who would have been eligible for care in AMU. METHODS: Healthy women with a term singleton cephalic fetus after an uneventful pregnancy course booking for birth in OLU were prospectively recruited. Data were collected by questionnaire. RESULTS: In total, 324 questionnaires were analyzed. One quarter (23.1%) of participants never had heard of care in AMU. Two thirds (64.2%) of women had made their choice regarding model of care before entering late pregnancy; only 16.4% indicated that health professionals had the biggest impact on their decision. One-to-one care and the availability of a pediatrician were most commonly quoted wishes (30.8 and 34.0%, respectively), and the occurrence of an adverse maternal or perinatal event the greatest concern (69.5%). CONCLUSIONS: Although the majority of respondents had some knowledge about care in AMU, expressed wishes for birth matching core features of AMU and concerns matching those of OLU, a decision for birth in OLU was taken. This finding may be a result of lack of knowledge about details of care in AMU; additionally, wishes and concerns may be put aside in favor of other criteria.

[Specialized Outpatient Palliative Care: Results of a Cross-Sectional Study]. / Spezialisierte ambulante Palliativversorgung (SAPV) ­ Querschnittsanalyse von Symptomlast, Diagnosen und Sterbeort über 7 Jahre an einem Standort in NRW.

OBJECTIVE: Specialized outpatient palliative care (SAPV) is an important component in the care of people in their final days of life in Germany. The analysis of a representative cohort allows important conclusions to be drawn for improving the situation of people in palliative care in Germany. METHODS: We analyzed the routine data of 2691 palliative patients collected during the care of an SAPV team. Statistical analyses were performed using SPSS version 24. RESULTS: In SAPV, approximately three-fourths of patients died in their homes. Of the total of 2691 patients, 1972 suffered from a malignancy and 719 patients had a non-malignant, chronic disease. The age at first contact with SAPV was significantly higher in patients without malignancy. Patients with or without malignancy did not differ from each other in terms of quality of life (Karnofsky's score) or symptom frequency. Only disorientation was documented significantly more frequently in non-tumor patients and was also more pronounced. CONCLUSION: SAPV enables the fulfilment of the wish of most patients to die in their homes.

Maternal and neonatal outcome of births planned in alongside midwifery units: a cohort study from a tertiary center in Germany.

BACKGROUND: For healthy women entering birth after uneventful pregnancy, midwife-led models of care have the potential to reduce interventions and increase the vaginal birth rate. In Germany, 98.4% of women are giving birth in consultant-led obstetric units. Alongside midwifery units (AMU) have been established in 2003. We compared the outcome of women registered for planned birth in the AMU at our hospital with a matched group of low-risk women who gave birth in standard obstetric care during the same period of time. METHODS: We used a retrospective cohort study design. The study group consisted of all women admitted to labor ward who had registered for birth in AMU from 2010 to 2017. For the control group, low-risk women were selected; additionally, matching was performed for parity. Mode of birth was chosen as primary outcome parameter for the mother. For the neonate, a composite primary outcome (5-min Apgar < 7 or umbilical cord arterial pH < 7.10 or transfer to specialist neonatal care) was defined. Secondary outcomes included epidural anesthesia, duration of the second stage of labor, episiotomy, obstetric injury, and postpartum hemorrhage. Non-inferiority was assessed, and multiple logistic regression analysis was performed. RESULTS: Six hundred twelve women were admitted for labor in AMU, the control group consisted of 612 women giving birth in standard obstetric care. Women in the study group were on average older and had a higher body mass index (BMI); birthweight was on average 95 g higher. Non-inferiority could be established for the primary outcome parameters. Epidural anesthesia and episiotomy rates were lower, and the mean duration of the second stage of labor was shorter in the study group; second-degree perineal tears were less common, higher-order obstetric lacerations occurred more frequently. Overall, 50.3% of women were transferred to standard obstetric care. Regression analysis revealed effects of parity, age and birthweight on the chance of transfer. CONCLUSION: Compared to births in our consultant-led obstetric unit, the outcome of births planned in the AMU was not inferior, and intervention rates were lower. Our results support the integration of AMU as a complementary model of care for low-risk women.

Risk factors for a positive SARS-CoV-2 PCR in patients with common cold symptoms in a primary care setting - a retrospective analysis based on a joint documentation standard.

BACKGROUND: Combating the COVID-19 pandemic is a major challenge for health systems, citizens and policy makers worldwide. Early detection of affected patients within the large and heterogeneous group of patients with common cold symptoms is an important element of this effort, but often hindered by limited testing resources, false-negative test results and the lack of pathognomonic symptoms in COVID-19. Therefore, we aimed to identify anamnestic items with an increased/decreased odds ratio for a positive SARS-CoV-2 PCR (CovPCR) result in a primary care setting. METHODS: We performed a multi-center cross-sectional cohort study on predictive clinical characteristics for a positive CovPCR over a period of 4 weeks in primary care patients in Germany. RESULTS: In total, 374 patients in 14 primary care centers received CovPCR and were included in this analysis. The median age was 44.0 (IQR: 31.0-59.0) and a fraction of 10.7% (n = 40) tested positive for COVID-19. Patients who reported anosmia had a higher odds ratio (OR: 4.54; 95%-CI: 1.51-13.67) for a positive test result while patients with a sore throat had a lower OR (OR: 0.33; 95%-CI: 0.11-0.97). Furthermore, patients who had a first grade contact with an infected persons and showed symptoms themselves also had an increased OR for positive testing (OR: 5.16; 95% CI: 1.72-15.51). This correlation was also present when they themselves were still asymptomatic (OR: 12.55; 95% CI: 3.97-39.67). CONCLUSIONS: Several anamnestic criteria may be helpful to assess pre-test probability of COVID-19 in patients with common cold symptoms.

[Health Expertise of Seasonal Influenza Vaccination among Midwife Trainees in North Rhine-Westphalia: Results of a Cross-Sectional Study]. / Wissen und Einstellungen über die saisonale Influenza-Impfung von Hebammenschülerinnen in Nordrhein-Westfalen: Ergebnisse einer Querschnittsstudie.

OBJECTIVE: For the first time, the level of knowledge and attitude towards vaccinations in general as well as seasonal influenza vaccination of midwife trainees in Germany was assessed. METHODS: The cross-sectional study was conducted between May and July 2017. The written standardized questionnaire was completed by all midwife-trainees in North Rhine-Westphalia. The statistical analysis included frequency tables and multiple logistic regression models. RESULTS: All of the 10 Schools for Midwifery in North Rhine-Westphalia participated in the survey and 315 questionnaires (response rate: 95.7%) were analyzed. The efficacy of seasonal influenza vaccinations was misjudged by 77.8% and possible adverse events were correctly estimated by only 35.2%. Regarding the safety of the seasonal influenza vaccination during pregnancy, 56.2% of midwife trainees were not convinced of it. Factors associated with a higher risk for insufficient knowledge regarding the influenza vaccination were age (22-25 years vs. 18-21 years, adjusted odds ratio (aOR) 1.99 95% confidence interval (CI) 1.12-3.52)), an inaccurate evaluation of the risk of infection (aOR 3.68 95%-CI 1.85-7.29) and insufficient knowledge of the influenza disease (aOR 1.78 95%-CI 1.04-3.06). By contrast, 76.8% of midwife trainees reported a positive attitude towards vaccinations in general, although 73.3% complained of getting too little information on complications due to vaccines. CONCLUSION: The lack of knowledge regarding seasonal influenza vaccination in midwife trainees impedes the expansion of vaccine protection of midwives, pregnant women and newborns. Information campaigns among midwife trainees as well as an evaluation and optimization of teaching units including scientifically validated information seem necessary. Moreover, these findings should encourage physicians to increasingly draw attention to the importance and efficacy of seasonal influenza vaccination among all medical professionals.

Tree-based modeling of time-varying coefficients in discrete time-to-event models.

Hazard models are popular tools for the modeling of discrete time-to-event data. In particular two approaches for modeling time dependent effects are in common use. The more traditional one assumes a linear predictor with effects of explanatory variables being constant over time. The more flexible approach uses the class of semiparametric models that allow the effects of the explanatory variables to vary smoothly over time. The approach considered here is in between these modeling strategies. It assumes that the effects of the explanatory variables are piecewise constant. It allows, in particular, to evaluate at which time points the effect strength changes and is able to approximate quite complex variations of the change of effects in a simple way. A tree-based method is proposed for modeling the piecewise constant time-varying coefficients, which is embedded into the framework of varying-coefficient models. One important feature of the approach is that it automatically selects the relevant explanatory variables and no separate variable selection procedure is needed. The properties of the method are investigated in several simulation studies and its usefulness is demonstrated by considering two real-world applications.

Underestimation of Pearson's product moment correlation statistic.

Pearson's product moment correlation coefficient (more commonly Pearson's r) tends to underestimate correlations that exist in the underlying population. This phenomenon is generally unappreciated in studies of ecology, although a range of corrections are suggested in the statistical literature. The use of Pearson's r as the classical measure for correlation is widespread in ecology, where manipulative experiments are impractical across the large spatial scales concerned; it is therefore vital that ecologists are able to use this correlation measure as effectively as possible. Here, our literature review suggests that corrections for the issue of underestimation in Pearson's r should not be adopted if either the data deviate from bivariate normality or sample size is greater than around 30. Through our simulations, we then aim to offer advice to researchers in ecology on situations where both distributions can be described as normal, but sample sizes are lower than around 30. We found that none of the methods currently offered in the literature to correct the underestimation bias offer consistently reliable performance, and so we do not recommend that they be implemented when making inferences about the behaviour of a population from a sample. We also suggest that, when considering the importance of the bias towards underestimation in Pearson's product moment correlation coefficient for biological conclusions, the likely extent of the bias should be discussed. Unless sample size is very small, the issue of sample bias is unlikely to call for substantial modification of study conclusions.

Over-indebtedness and its association with sleep and sleep medication use.

BACKGROUND: Over-indebtedness is currently rising in high-income countries. Millions of citizens are confronted with the persistent situation when household income and assets are insufficient to cover payment obligations and living expenses. Previous research shows that over-indebtedness increases the risk of various adverse health effects. However, its association with sleep problems has not yet been examined. The objective of this study was to investigate the association between over-indebtedness and sleep problems and sleep medication use. METHODS: A cross-sectional study on over-indebtedness (OID survey) was conducted in 70 debt advisory centres in Germany in 2017 that included 699 over-indebted respondents. The survey data were combined with the nationally representative German Health Interview and Examination Survey for Adults (DEGS1; n = 7987). We limited analyses to participants with complete data on all sleep variables (OID: n = 538, DEGS1: n = 7447). Descriptive analyses and logistic regression analyses were used to examine the association between over-indebtedness and difficulty initiating and maintaining sleep, and sleep medication use. RESULTS: A higher prevalence of sleep problems and sleep medication use was observed among over-indebted individuals compared to the general population. After adjustment for socio-economic and health factors (age, sex, education, marital status, employment status, subjective health status and mental illness), over-indebtedness significantly increased the risk of difficulties with sleep onset (adjusted odds ratio (aOR) 1.79, 95%-confidence interval (CI) 1.45-2.21), sleep maintenance (aOR 1.45, 95%-CI 1.17-1.80) and sleep medication use (aOR 3.94, 95%-CI 2.96-5.24). CONCLUSIONS: Evidence suggests a strong association between over-indebtedness and poor sleep and sleep medication use independent of conventional socioeconomic measures. Considering over-indebtedness in both research and health care practice will help to advance the understanding of sleep disparities, and facilitate interventions for those at risk. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00013100 (OID survey, ArSemü); Date of registration: 23.10.2017; Date of enrolment of the first participant: 18.07.2017, retrospectively registered.

Cost-related medication nonadherence among over-indebted individuals enrolled in statutory health insurance in Germany: a cross-sectional population study.

BACKGROUND: Millions of citizens in high-income countries face over-indebtedness that implies being unable to cover payment obligations with available income and assets on an ongoing basis. Studies have shown an association between over-indebtedness and health outcomes, independent of standard socioeconomic status measures. Patterns of cost-related medication nonadherence (CRN) among over-indebted individuals are yet unclear. The aim of this study was to examine the frequency of nonadherence to prescribed medications due to cost, and to identify risk factors for CRN among over-indebted individuals in Germany. METHODS: In 2017, we conducted a cross-sectional survey among over-indebted individuals recruited in 70 debt advice agencies in North Rhine-Westphalia, Germany. Data on CRN in the last 12 months (i.e. not filling prescriptions, skipping or decreasing doses of prescribed medication due to financial problems) were collected by a survey using a self-administered written questionnaire that was returned by 699 individuals with a response rate of 50.2%. Prevalence of CRN was assessed using descriptive statistics. Multiple logistic regression analysis was performed to examine risk factors of CRN, including participants enrolled in statutory health insurance with complete data (n = 521). RESULTS: The prevalence of CRN was 33.6%. The chronically ill had significantly greater odds of cost-related medication nonadherence (aOR 1.96; 95% CI 1.27-3.03) than individuals without a chronic illness. CRN was more likely to occur in individuals who had discussed financial problems with their general practitioner (aOR 1.58; 95% CI 1.01-2.47). There was no association between CRN and other sociodemographic factors or socioeconomic status. CONCLUSIONS: Medication nonadherence due to financial pressures is common among over-indebted citizens enrolled in statutory health insurance in Germany. Stakeholders in social policy, research and health care need to address over-indebtedness to develop strategies to safeguard access to relevant medications, especially among those with high morbidity. TRIAL REGISTRATION: Arzneimittelkonsum, insbesondere Selbstmedikation bei überschuldeten Bürgerinnen und Bürgern in Nordrhein-Westfalen (ArSemü), (engl. 'Medication use, particularly self-medication among over-indebted citizens in North Rhine-Westphalia'), German Clinical Trials Register: DRKS00013100. Date of registration: 23.10.2017. Date of enrolment of the first participant: 18.07.2017, retrospectively registered.

Prevalence and predictors of having no general practitioner - analysis of the German health interview and examination survey for adults (DEGS1).

BACKGROUND: Although patients in Germany are generally free to choose their primary healthcare provider, this role should mainly be assumed by general practitioners (GPs). While some predictors of the frequency of use of GP services have been reported in international studies, there is still a lack in knowledge what could deter people from contacting a GP in Germany. To improve healthcare, it is important to identify characteristics of people without a GP. METHODS: This cross-sectional analysis was based on the first wave of the "German Health Interview and Examination Survey for Adults" (DEGS1) conducted by the Robert Koch Institute in 2008-2011. Descriptive analyses and multiple logistic regression by gender were performed to analyze the association between having no GP and age, gender, residential area, socioeconomic status (SES), marital status, working hours per week, general state of health, chronic diseases and health insurance. RESULTS: Overall, 9.5% (95% confidence interval (CI): 8.4-10.7) of the 7755 participants stated to have no GP, more often men (11.4%) than women (7.6%). Life in urban areas (big cities vs. rural: adjusted odds ratio (aOR): 2.9, 95% CI: 2.1-3.9), younger age (18-29 years vs. 65-79 years: aOR: 4.4, 95% CI: 2.5-7.7) and the presence of chronic diseases (yes vs. no: aOR: 0.4, 95% CI: 0.3-0.6) showed significant associations of not having a GP. For men, the type of health insurance (private vs. statutory: aOR: 2.1, 95% CI: 1.5-3.0; other vs. statutory: aOR: 2.1, 95% CI: 1.4-3.1) and for women, SES (low vs. medium: aOR: 1.8, 95% CI: 1.2-2.7; high vs. medium: aOR: 2.1, 95% CI: 1.4-3.0) increased the risk of having no GP. CONCLUSIONS: Our analysis offers new insights into the use of GPs in Germany and revealed differences between men and women. Public health strategies regarding access to a GP have to focus on men and on women with a low SES. Further analyses are needed to determine whether men with private health insurance prefer to consult a specialist rather than a GP. For young adults, improving the transition process from a pediatrician to a GP could fill a gap in health care.

[Advance Directives in Family Practices: Results of a Survey of GP Patients on their Care Situation]. / Patientenverfügungen in Hausarztpraxen ­ Ergebnisse einer Befragung von Hausarztpatienten zur ihrer Versorgungssituation.

BACKGROUND: Advance directives (AD) are an important tool for documentation of patients' wishes and are therefore recommended to the elderly as well as patients with chronic diseases. However, there is no standardized procedure in Germany and no guideline for counseling patients who wish to write an AD with or without health care proxy. The aim of this study was to evaluate the care situation concerning the ADs and the role of the primary care physician in drafting the document METHOD: We conducted semi-structured interviews with patients in primary care in North Rhine-Westphalia using a cross-sectional study design. RESULT: Most of the 154 patients who were interviewed (average age: 58 years; 52% female) suffered from chronic diseases (79%), and about one-third (32%) already had an AD. Fear of "loss of autonomy" was the main reason for preparing an AD. Patients without AD were generally not opposed to the concept and named procrastination (43%) as the main reason for not having prepared one. The chance for preparing an AD increased by the factor 1.08 per life-year (Odds ratio (OR): 1.08; CI: 1.04-1.11). Patients with AD mostly got advice via the internet (22%), their primary care physicians (12%) and relatives (12%). Most patients were satisfied with their AD. CONCLUSION: The majority of primary care patients do not make use of ADs. The primary care physicians play an important role in counseling and should motivate patients to complete ADs. Here, the establishment of quality standards would be desirable in the future.

Barriers in general practitioners' dementia diagnostics among people with a migration background in Germany (BaDeMi) - study protocol for a cross-sectional survey.

BACKGROUND: Considering the targeted general practitioner-centred healthcare in Germany, general practitioners (GPs) are in the best possible position to increase awareness of all sorts of dementia, an age-related syndrome with rising relevance in the future. In Germany, a doubling of the number of cases from 1.55 million up to 3 million in 2050 is predicted. Diagnostics can be challenging, especially among patients with a migration background. Complicating factors include: Language-based diagnostic tools, cultural differences in handling the syndrome and its underlying diseases as well as a differing use of the healthcare system. Because of missing research in this field in Germany, the type, frequency and intensity of barriers as well as the way GPs cope with them is unknown. That is why it's crucial to focus research on diagnostics in total and especially among this population group. METHODS: A cross-sectional study among a random sample of 1000 general practitioners in Germany is conducted in October 2017. A self-administered standardized questionnaire was developed, evaluated and send to the GP practices. A response rate of 30% is expected with one reminder letter. Descriptive statistics as well as, depending on the results, multivariable analyses will be executed. Based on these results and the stated needs, a cluster-randomized intervention study will be constructed to improve healthcare. DISCUSSION: This study is the first in Germany focusing on how dementia diagnostics in general practice is performed, what problems occur, especially because of a migration background of patients, and how GPs cope with them. Depending on the results, it should emphasize the necessity of dementia diagnostics to be adjusted to the needs of the rising amount of people with a migration background (22.5% in Germany, 2016) like concluded from international studies. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00012503 , date of registration: 05.09.2017. Clinical register of the study coordination office of the University hospital of Bonn: ID530 , date of registration: 05.09.2017.

Determinants of having no general practitioner in Germany and the influence of a migration background: results of the German health interview and examination survey for adults (DEGS1).

BACKGROUND: It is aspired in the German healthcare system that general practitioners (GPs) act as initial contact for patients and guide through at all steps of medical treatment. This study aims at identifying factors associated with the odds of having no GP within the general population and especially among people with migration background. METHODS: This cross-sectional analysis was based on the "German Health Interview and Examination Survey for Adults" (DEGS1) conducted by the Robert Koch Institute. Descriptive analyses as well as multiple logistic regression models were performed to analyse the impact of a migration background, age, gender, residential area, socioeconomic status (SES) and other factors on having no GP among 7755 participants. RESULTS: 9.5% of the total study population and 14.8% of people with a migration background had no GP, especially men, adults living in big cities and without chronic diseases. The odds of not having a GP were higher for people with a two-sided migration background (aOR: 1.90, 95% CI: 1.42-2.55). Among the population with a migration background, particularly young adults, men, people living in big cities and having a private health insurance showed higher odds to have no GP. CONCLUSIONS: It is necessary to investigate the causes of the differing utilization of healthcare of people with a migration background and, if necessary, to take measures for an equal access to healthcare for all population groups. Further research needs to be done to evaluate how to get young people into contact with a GP.

Prevalence and comorbidity of osteoporosis- a cross-sectional analysis on 10,660 adults aged 50 years and older in Germany.

BACKGROUND: Knowledge on prevalence of osteoporosis stratifying for socioeconomic background is insufficient in Germany. Little is known in Europe about other diseases that go along with it although these aspects are important for implementing effective public health strategies. METHODS: This cross-sectional analysis was based on the national telephone survey "German Health Update" (GEDA 2012) performed in 2012/2013. GEDA 2012 provides information on self-reported diseases and sociodemographic characteristics for nearly 20,000 adults. Descriptive statistical analysis and multiple logistic regression were used to examine the association between osteoporosis and age, sex, other diseases and education defined by ISCED. Analyses were limited to participants aged 50 years and older. RESULTS: Overall, 8.7% of the 10,660 participants aged 50+ years had osteoporosis (men 4.7%, women 12.2%). More than 95% of the adults with osteoporosis had at least one coexisting disease. The odds for arthrosis (OR 3.3, 95% CI 2.6-4.1), arthritis (OR 3.0, 95% CI 2.2-4.2), chronic low back pain (OR 2.8, 95% CI 2.3-3.5), depression (OR 2.3, 95% CI 1.7-3.1) and chronic heart failure (OR 2.3, 95% CI 1.6-3.1), respectively, were greater for adults with osteoporosis. Education showed no significant association with osteoporosis. CONCLUSIONS: There was no clear evidence of socioeconomic differences regarding osteoporosis for adults in Germany. However, clinicians need to be aware that multimorbidity is very common in adults with osteoporosis. Health care interventions for osteoporosis could be improved by offering preventive care for other diseases that go along with it. Over- or under-diagnosis in different socioeconomic levels has to be further explored.

Prevalence of multimorbidity in Germany: impact of age and educational level in a cross-sectional study on 19,294 adults.

BACKGROUND: Multimorbidity is one of the most important and challenging aspects in public health. Multimorbid people are associated with more hospital admissions, a large number of drug prescriptions and higher risks of mortality. As there is evidence that multimorbidity varies with age and socioeconomic disparity, the main objective aimed at determining age-specific prevalence rates as well as exploring educational differences relating to multimorbidity in Germany. METHODS: This cross-sectional analysis is based on the national telephone health interview survey "German Health Update" (GEDA2012) conducted between March 2012 and March 2013 with nearly 20,000 adults. GEDA2012 provides information on 17 self-reported health conditions along with sociodemographic characteristics. Multimorbidity was defined as the occurrence of two or more chronic conditions in one individual at the same time. Descriptive statistical analysis was used to examine multimorbidity according to age and education, which was defined by the International Standard Classification of Education (ISCED 1997). RESULTS: Overall, 39.6% (95% confidence interval (CI) 38.7%-40.6%) of the 19,294 participants were multimorbid and the proportion of adults with multimorbidity increased substantially with age: nearly half (49.2%, 95% CI 46.9%-51.5%) of the adults aged 50-59 years had already two or more chronic health conditions. Prevalence rates of multimorbidity differed considerably between the levels of education. Low-level educated adults aged 40-49 years were more likely to be multimorbid with a prevalence rate of 47.4% (95% CI 44.2%-50.5%) matching those of highly educated men and women aged about ten years older. CONCLUSIONS: Our findings demonstrate that both, age and education are associated with a higher risk of being multimorbid in Germany. Hence, special emphasis in the development of new approaches in national public health and prevention programs on multimorbidity should be given to low-level educated people aged <65 years.

On the variety of methods for calculating confidence intervals by bootstrapping.

Researchers often want to place a confidence interval around estimated parameter values calculated from a sample. This is commonly implemented by bootstrapping. There are several different frequently used bootstrapping methods for this purpose. Here we demonstrate that authors of recent papers frequently do not specify the method they have used and that different methods can produce markedly different confidence intervals for the same sample and parameter estimate. We encourage authors to be more explicit about the method they use (and number of bootstrap resamples used). We recommend the bias corrected and accelerated method as giving generally good performance; although researchers should be warned that coverage of bootstrap confidence intervals is characteristically less than the specified nominal level, and confidence interval evaluation by any method can be unreliable for small samples in some situations.

High maternal BMI and low maternal blood BDNF may determine the limit of detection of amniotic fluid BDNF throughout gestation: Analysis of mother-fetus trios and literature review.

OBJECTIVE: An increasing number of studies show the importance of brain-derived neurotrophic factor (BDNF) acting at the feto-placental interface, however, only a few studies describe BDNF levels in amniotic fluid (AF). METHODS: In this cross-sectional, prospective study, 109 maternal blood-amniotic fluid pairs (including 66 maternal blood-fetal-blood-amniotic fluid trios) were analyzed. BDNF concentrations were measured with a commercially available immunoassay. RESULTS: In 71 AF from 109 samples, AF-BDNF concentrations were below the lowest limit of Quantitation (LLoQ) of 1.19 pg/ml (group A), leaving 38 samples with measurable BDNF concentrations (group B). Patients in group A showed significantly higher maternal BMI before pregnancy (mean±SD 26.3± 6.7 (kg/m2) vs. 23.8 ±4.5 (kg/m2) p = 0.04) and lower maternal blood BDNF concentrations than the other group (mean±SD 510.6 ± 554.7 pg/ml vs. mean±SD 910.1± 690.1 pg/ml; p<0.0001). Spearman correlation showed a negative correlation between maternal BMI before pregnancy and maternal BDNF concentrations (r = -0.25, p = 0.01). CONCLUSION: Our study is the first to correlate AF-BDNF samples with the corresponding maternal and fetal blood-BDNF samples. The significant negative correlation between maternal BMI before pregnancy and maternal BDNF and AF-BDNF concentrations below the limit of detection has to be evaluated in further studies.

Correction: Rate of opioid use disorder in adults who received prescription opioid pain therapy-A secondary data analysis.

[This corrects the article DOI: 10.1371/journal.pone.0236268.].

Short-Term Annoyance Due to Night-Time Road, Railway, and Air Traffic Noise: Role of the Noise Source, the Acoustical Metric, and Non-Acoustical Factors.

Field studies on traffic noise-induced annoyance have predominantly used estimated outside noise levels. We intended to complement existing knowledge with exposure-response relationships that are based on precise indoor noise measurements. Acoustic recordings inside the bedrooms of nightly road traffic and annoyance ratings in the following morning were obtained from 40 suburban residents (mean age 29.1 years ± 11.7; 26 females). We derived exposure-response functions for the probability to be "annoyed at least a little" (%LA). Further analyses compared data from the current study with those from two earlier studies on railway and aircraft noise. Annoyance increased with the number of traffic events and the equivalent sound pressure level. The inclusion of non-acoustical factors (such as assessment of road transport) improved the prediction considerably. When comparing the different traffic noise sources, %LA was higher for road than for air traffic at a given LAeq,night, but higher for road and railway than for air traffic at a given number of noise events. Acoustical as well as non-acoustical factors impact short-term annoyance induced by road, railway, and air traffic. Annoyance varies across noise sources, which may be due to differences in acoustical characteristics or in the temporal noise distribution throughout the night.