Molecular Basis for poly(A) RNP Architecture and Recognition by the Pan2-Pan3 Deadenylase.

The stability of eukaryotic mRNAs is dependent on a ribonucleoprotein (RNP) complex of poly(A)-binding proteins (PABPC1/Pab1) organized on the poly(A) tail. This poly(A) RNP not only protects mRNAs from premature degradation but also stimulates the Pan2-Pan3 deadenylase complex to catalyze the first step of poly(A) tail shortening. We reconstituted this process in vitro using recombinant proteins and show that Pan2-Pan3 associates with and degrades poly(A) RNPs containing two or more Pab1 molecules. The cryo-EM structure of Pan2-Pan3 in complex with a poly(A) RNP composed of 90 adenosines and three Pab1 protomers shows how the oligomerization interfaces of Pab1 are recognized by conserved features of the deadenylase and thread the poly(A) RNA substrate into the nuclease active site. The structure reveals the basis for the periodic repeating architecture at the 3' end of cytoplasmic mRNAs. This illustrates mechanistically how RNA-bound Pab1 oligomers act as rulers for poly(A) tail length over the mRNAs' lifetime.

Concerted structural rearrangements enable RNA channeling into the cytoplasmic Ski238-Ski7-exosome assembly.

The Ski2-Ski3-Ski8 (Ski238) helicase complex directs cytoplasmic mRNAs toward the nucleolytic exosome complex for degradation. In yeast, the interaction between Ski238 and exosome requires the adaptor protein Ski7. We determined different cryo-EM structures of the Ski238 complex depicting the transition from a rigid autoinhibited closed conformation to a flexible active open conformation in which the Ski2 helicase module has detached from the rest of Ski238. The open conformation favors the interaction of the Ski3 subunit with exosome-bound Ski7, leading to the recruitment of the exosome. In the Ski238-Ski7-exosome holocomplex, the Ski2 helicase module binds the exosome cap, enabling the RNA to traverse from the helicase through the internal exosome channel to the Rrp44 exoribonuclease. Our study pinpoints how conformational changes within the Ski238 complex regulate exosome recruitment for RNA degradation. We also reveal the remarkable conservation of helicase-exosome RNA channeling mechanisms throughout eukaryotic nuclear and cytoplasmic exosome complexes.

Nuclear mRNPs are compact particles packaged with a network of proteins promoting RNA-RNA interactions.

Messenger RNAs (mRNAs) are at the center of the central dogma of molecular biology. In eukaryotic cells, these long ribonucleic acid polymers do not exist as naked transcripts; rather, they associate with mRNA-binding proteins to form messenger ribonucleoprotein (mRNP) complexes. Recently, global proteomic and transcriptomic studies have provided comprehensive inventories of mRNP components. However, knowledge of the molecular features of distinct mRNP populations has remained elusive. We purified endogenous nuclear mRNPs from Saccharomyces cerevisiae by harnessing the mRNP biogenesis factors THO and Sub2 in biochemical procedures optimized to preserve the integrity of these transient ribonucleoprotein assemblies. We found that these mRNPs are compact particles that contain multiple copies of Yra1, an essential protein with RNA-annealing properties. To investigate their molecular and architectural organization, we used a combination of proteomics, RNA sequencing, cryo-electron microscopy, cross-linking mass spectrometry, structural models, and biochemical assays. Our findings indicate that yeast nuclear mRNPs are packaged around an intricate network of interconnected proteins capable of promoting RNA-RNA interactions via their positively charged intrinsically disordered regions. The evolutionary conservation of the major mRNA-packaging factor (yeast Yra1 and Aly/REF in metazoans) points toward a general paradigm governing nuclear mRNP packaging.

The human SKI complex regulates channeling of ribosome-bound RNA to the exosome via an intrinsic gatekeeping mechanism.

The superkiller (SKI) complex is the cytoplasmic co-factor and regulator of the RNA-degrading exosome. In human cells, the SKI complex functions mainly in co-translational surveillance-decay pathways, and its malfunction is linked to a severe congenital disorder, the trichohepatoenteric syndrome. To obtain insights into the molecular mechanisms regulating the human SKI (hSKI) complex, we structurally characterized several of its functional states in the context of 80S ribosomes and substrate RNA. In a prehydrolytic ATP form, the hSKI complex exhibits a closed conformation with an inherent gating system that effectively traps the 80S-bound RNA into the hSKI2 helicase subunit. When active, hSKI switches to an open conformation in which the gating is released and the RNA 3' end exits the helicase. The emerging picture is that the gatekeeping mechanism and architectural remodeling of hSKI underpin a regulated RNA channeling system that is mechanistically conserved among the cytoplasmic and nuclear helicase-exosome complexes.

Nse5/6 inhibits the Smc5/6 ATPase and modulates DNA substrate binding.

Eukaryotic cells employ three SMC (structural maintenance of chromosomes) complexes to control DNA folding and topology. The Smc5/6 complex plays roles in DNA repair and in preventing the accumulation of deleterious DNA junctions. To elucidate how specific features of Smc5/6 govern these functions, we reconstituted the yeast holo-complex. We found that the Nse5/6 sub-complex strongly inhibited the Smc5/6 ATPase by preventing productive ATP binding. This inhibition was relieved by plasmid DNA binding but not by short linear DNA, while opposing effects were observed without Nse5/6. We uncovered two binding sites for Nse5/6 on Smc5/6, based on an Nse5/6 crystal structure and cross-linking mass spectrometry data. One binding site is located at the Smc5/6 arms and one at the heads, the latter likely exerting inhibitory effects on ATP hydrolysis. Cysteine cross-linking demonstrated that the interaction with Nse5/6 anchored the ATPase domains in a non-productive state, which was destabilized by ATP and DNA. Under similar conditions, the Nse4/3/1 module detached from the ATPase. Altogether, we show how DNA substrate selection is modulated by direct inhibition of the Smc5/6 ATPase by Nse5/6.

Symmetric and asymmetric receptor conformation continuum induced by a new insulin.

Cone snail venoms contain a wide variety of bioactive peptides, including insulin-like molecules with distinct structural features, binding modes and biochemical properties. Here, we report an active humanized cone snail venom insulin with an elongated A chain and a truncated B chain, and use cryo-electron microscopy (cryo-EM) and protein engineering to elucidate its interactions with the human insulin receptor (IR) ectodomain. We reveal how an extended A chain can compensate for deletion of B-chain residues, which are essential for activity of human insulin but also compromise therapeutic utility by delaying dissolution from the site of subcutaneous injection. This finding suggests approaches to developing improved therapeutic insulins. Curiously, the receptor displays a continuum of conformations from the symmetric state to a highly asymmetric low-abundance structure that displays coordination of a single humanized venom insulin using elements from both of the previously characterized site 1 and site 2 interactions.

Validation of patient- and GP-reported core sets of quality indicators for older adults with multimorbidity in primary care: results of the cross-sectional observational MULTIqual validation study.

BACKGROUND: Older adults with multimorbidity represent a growing segment of the population. Metrics to assess quality, safety and effectiveness of care can support policy makers and healthcare providers in addressing patient needs. However, there is a lack of valid measures of quality of care for this population. In the MULTIqual project, 24 general practitioner (GP)-reported and 14 patient-reported quality indicators for the healthcare of older adults with multimorbidity were developed in Germany in a systematic approach. This study aimed to select, validate and pilot core sets of these indicators. METHODS: In a cross-sectional observational study, we collected data in general practices (n = 35) and patients aged 65 years and older with three or more chronic conditions (n = 346). One-dimensional core sets for both perspectives were selected by stepwise backward selection based on corrected item-total correlations. We established structural validity, discriminative capacity, feasibility and patient-professional agreement for the selected indicators. Multilevel multivariable linear regression models adjusted for random effects at practice level were calculated to examine construct validity. RESULTS: Twelve GP-reported and seven patient-reported indicators were selected, with item-total correlations ranging from 0.332 to 0.576. Fulfilment rates ranged from 24.6 to 89.0%. Between 0 and 12.7% of the values were missing. Seventeen indicators had agreement rates between patients and professionals of 24.1% to 75.9% and one had 90.7% positive and 5.1% negative agreement. Patients who were born abroad (- 1.04, 95% CI = - 2.00/ - 0.08, p = 0.033) and had higher health-related quality of life (- 1.37, 95% CI = - 2.39/ - 0.36, p = 0.008), fewer contacts with their GP (0.14, 95% CI = 0.04/0.23, p = 0.007) and lower willingness to use their GPs as coordinators of their care (0.13, 95% CI = 0.06/0.20, p < 0.001) were more likely to have lower GP-reported healthcare quality scores. Patients who had fewer GP contacts (0.12, 95% CI = 0.04/0.20, p = 0.002) and were less willing to use their GP to coordinate their care (0.16, 95% CI = 0.10/0.21, p < 0.001) were more likely to have lower patient-reported healthcare quality scores. CONCLUSIONS: The quality indicator core sets are the first brief measurement tools specifically designed to assess quality of care for patients with multimorbidity. The indicators can facilitate implementation of treatment standards and offer viable alternatives to the current practice of combining disease-related metrics with poor applicability to patients with multimorbidity.

The moderating effects of social support and depressive symptoms on pain among elderly multimorbid patients-data from the multicentre, prospective, observational cohort study MultiCare.

OBJECTIVES: Depressive symptoms and chronic pain are common among patients with multimorbidity creating a complex medical condition for both the patient and the general practitioner. Perceived social support may function as a protective measure.To examine the impact of perceived social support as a potential moderator between depressive symptoms and pain intensity and pain disability in daily activities in multimorbid patients aged 75+. METHOD: Data from 3,189 patients of the German longitudinal cohort study MultiCare were obtained at baseline and follow-ups during 5 years. Multilevel linear mixed-effects analyses were conducted for pain intensity (model 1) and pain disability in daily activities (model 2). The interaction term social support by depression score was included to test for moderation. RESULTS: The interaction between social support and depressive symptoms was significantly associated with the pain intensity score 0.41 (SE=.17; 95-CI[.08;.74]) but not with the pain disability score 0.35 (SE=.19; 95-CI[-.01;.72]). Additionally, men and individuals with medium or higher educational level showed reduced pain intensity and disability scores. Pain disability scores increased with age and depressive symptoms. Increased pain scores were also found for body mass index and burden of multimorbidity. CONCLUSION: Perceived social support amplified the association of depressive symptoms on pain intensity and did not show a protective function. The high scores of perceived social support among the participants may point to the practice of secondary gain due to the patients immense health burden.

Predictors of change in depressive symptoms in older and multimorbid patients: a longitudinal analysis of the multicare cohort.

BACKGROUND: Depression in older adults is becoming an increasing concern. As depressive symptoms change over time, it is important to understand the determinants of change in depressive symptoms. The aim of our study is to use a longitudinal study design to explore the predictors of change, remission and incident depression in older patients with multimorbidity. METHODS: Data from the MultiCare cohort study were used. The cohort studied 3,189 multimorbid general practice patients aged 65-85. Data were collected during personal interviews. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS-15). Predictors of change in depressive symptoms were determined using multivariate linear regression, while multivariate logistic regression was used to analyze predictors of remission and incident depression. Models included depressive symptoms at baseline and follow-up, socio-demographics and data on health status and social support. RESULTS: Overall, 2,746 participants with complete follow-up data were analyzed. Mean age was 74.2 years, 59.2% were female, and 11.3% were classified as depressed at baseline. Burden of multimorbidity and social support were statistically significant predictors in all regression analyses. Further predictors of change in depressive symptoms were: income, pain, nursing grade, self-rated health and self-efficacy. LIMITATIONS: The sample size for prediction of remission limited statistical certainty. Assessment of depressive symptoms using GDS-15 differs from routine clinical diagnoses of depression. CONCLUSIONS: Predictors of change in depressive symptoms in older multimorbid patients are similar to those predicting remission and incident depression, and do not seem to differ significantly from other older patient populations with depressive symptoms.

CENP-C unwraps the human CENP-A nucleosome through the H2A C-terminal tail.

Centromeres are defined epigenetically by nucleosomes containing the histone H3 variant CENP-A, upon which the constitutive centromere-associated network of proteins (CCAN) is built. CENP-C is considered to be a central organizer of the CCAN. We provide new molecular insights into the structure of human CENP-A nucleosomes, in isolation and in complex with the CENP-C central region (CENP-CCR ), the main CENP-A binding module of human CENP-C. We establish that the short αN helix of CENP-A promotes DNA flexibility at the nucleosome ends, independently of the sequence it wraps. Furthermore, we show that, in vitro, two regions of human CENP-C (CENP-CCR and CENP-Cmotif ) both bind exclusively to the CENP-A nucleosome. We find CENP-CCR to bind with high affinity due to an extended hydrophobic area made up of CENP-AV532 and CENP-AV533 . Importantly, we identify two key conformational changes within the CENP-A nucleosome upon CENP-C binding. First, the loose DNA wrapping of CENP-A nucleosomes is further exacerbated, through destabilization of the H2A C-terminal tail. Second, CENP-CCR rigidifies the N-terminal tail of H4 in the conformation favoring H4K20 monomethylation, essential for a functional centromere.

Low health literacy is associated with higher risk of type 2 diabetes: a cross-sectional study in Germany.

BACKGROUND: Low health literacy is believed to be associated with behaviours that increase the risk of type 2 diabetes. But there is limited knowledge on the relation between health literacy (HL) and diabetes risk, and whether improving HL could be a potential prevention strategy. Therefore, the main purpose of this study was to examine the link between HL and diabetes risk among non-diabetic adults. METHODS: We used data from the Hamburg Diabetes Prevention Survey, a population-based cross-sectional study in Germany. One thousand, two hundred and fifty-five non-diabetic subjects aged 18-60 years were eligible. The German Diabetes Risk Score (GDRS, ranging 0 to 123 points) was used to determine the individual risk of type 2 diabetes. The short version of the European Health Literacy Questionnaire (HLS-EU-Q16, ranging 0 to 16 points) was applied to assess the individual self-reported HL. Subjects were asked to self-estimate their diabetes risk, which was then compared with the calculated GDRS. Descriptive statistics were calculated to investigate group differences in the GDRS and self-estimated diabetes risk. Linear as well as logistic regression models were performed to analyse potential influencing variables of the GDRS as well as incorrect self-estimated diabetes risk. In three nested statistical models for each outcome, these analyses were adjusted for age, gender, educational level and the presence of chronic conditions. RESULTS: According to the criteria of the GDRS, 996 (79.4%) subjects showed "low risk", 176 (14.0%) "still low risk", 53 (4.2%) "elevated risk", and 30 (2.4%) "high to very high risk" to develop type 2 diabetes within the next 5 years. In the statistical models including all control variables, subjects with "inadequate HL" scored 2.38 points higher on the GDRS (95% CI 0.378 to 4.336; P = 0.020) and had a 2.04 greater chance to estimate their diabetes risk incorrectly (OR 2.04; 95% CI 1.33 to 3.14; P = 0.001) compared to those with "sufficient HL". CONCLUSION: The risk of type 2 diabetes is increased in people with inadequate self-reported HL. People with high diabetes risk and inadequate HL might be provided with educational programs to improve diabetes knowledge and reduce behavioural risk factors.

The effect of COVID-19 pandemic and lockdown on consultation numbers, consultation reasons and performed services in primary care: results of a longitudinal observational study.

OBJECTIVES: The aims of our study were to describe the effect of the COVID-19 pandemic and lockdown on primary care in Germany regarding the number of consultations, the prevalence of specific reasons for consultation presented by the patients, and the frequency of specific services performed by the GP. METHODS: We conducted a longitudinal observational study based on standardised GP interviews in a quota sampling design comparing the time before the COVID-19 pandemic (12 June 2015 to 27 April 2017) with the time during lockdown (21 April to 14 July 2020). The sample included GPs in urban and rural areas 120 km around Hamburg, Germany, and was stratified by region type and administrative districts. Differences in the consultation numbers were analysed by multivariate linear regressions in mixed models adjusted for random effects on the levels of the administrative districts and GP practices. RESULTS: One hundred ten GPs participated in the follow-up, corresponding to 52.1% of the baseline. Primary care practices in 32 of the 37 selected administrative districts (86.5%) could be represented in both assessments. At baseline, GPs reported 199.6 ± 96.9 consultations per week, which was significantly reduced during COVID-19 lockdown by 49.0% to 101.8 ± 67.6 consultations per week (p < 0.001). During lockdown, the frequency of five reasons for consultation (-43.0% to -31.5%) and eleven services (-56.6% to -33.5%) had significantly decreased. The multilevel, multivariable analyses showed an average reduction of 94.6 consultations per week (p < 0.001). CONCLUSIONS: We observed a dramatic reduction of the number of consultations in primary care. This effect was independent of age, sex and specialty of the GP and independent of the practice location in urban or rural areas. Consultations for complaints like low back pain, gastrointestinal complaints, vertigo or fatigue and services like house calls/calls at nursing homes, wound treatments, pain therapy or screening examinations for the early detection of chronic diseases were particularly affected.

Regional and patient-related factors influencing the willingness to use general practitioners as coordinators of the treatment in northern Germany - results of a cross-sectional observational study.

BACKGROUND: In most countries, the general practitioner (GP) is the first point of contact in the healthcare system and coordinator of healthcare. However, in Germany it is possible to consult an outpatient specialist even without referral. Coordination by a GP might thus reduce health expenditures and inequalities in the healthcare system. The study describes the patients' willingness/commitment to use the GP as coordinator of healthcare and identifies regional and patient-related factors associated with the aforementioned commitment to the GP. METHODS: Cross-sectional observational study using a standardised telephone patient survey in northern Germany. All counties and independent cities within a radius of 120 km around Hamburg were divided into three regional categories (urban areas, environs, rural areas) and stratified proportionally to the population size. Patients who had consulted the GP within the previous three months, and had been patients of the practice for at least three years were randomly selected from medical records of primary care practices in these districts and recruited for the study. Multivariate linear regression models adjusted for random effects at the level of federal states, administrative districts and practices were used as statistical analysis methods. RESULTS: Eight hundred eleven patients (25.1%) from 186 practices and 34 administrative districts were interviewed. The patient commitment to a GP attained an average of 20 out of 24 possible points. Significant differences were found by sex (male vs. female: + 1.14 points, p < 0.001), morbidity (+ 0.10 per disease, p = 0.043), education (high vs. low: - 1.74, p < 0.001), logarithmised household net adjusted disposable income (- 0.93 per step on the logarithmic scale, p = 0.004), regional category (urban areas: - 0.85, p = 0.022; environs: - 0.80, p = 0.045) and healthcare utilisation (each GP contact: + 0.30, p < 0.001; each contact to a medical specialist: - 0.75, p = 0.018). Professional situation and age were not significantly associated with the GP commitment. CONCLUSION: On average, the patients' commitment to their GP was relatively strong, but there were large differences between patient groups. An increase in the patient commitment to the GP could be achieved through better patient information and targeted interventions, e.g. to women or patients from regions of higher urban density. TRIAL REGISTRATION: The study was registered in ClinicalTrials.gov (NCT02558322).

Regional differences in reasons for consultation and general practitioners' spectrum of services in northern Germany - results of a cross-sectional observational study.

BACKGROUND: Among other factors, the patients' consultation reasons and GPs' spectrum of services determine the process and outcome of the medical treatment. So far, however, there has been little information on differences in reasons for consultation and GPs' services between urban and rural areas. Our study's goal was thus to investigate these factors in relation to the regional location of GPs' practices. METHODS: We conducted a cross-sectional observational study based on standardised GP interviews in a quota sampling design. All counties and independent cities within a radius of 120 km around Hamburg were divided into three regional categories (urban area, environs, rural area) and stratified proportionally to the population size. Differences in the number of reasons for consultation and services were analysed by multivariate linear regressions in mixed models adjusted for random effects on the levels of the German federal states and administrative districts. Differences in individual consultation reasons and services were identified by logistic regression via stepwise forward and backward selection. RESULTS: Primary care practices in 34 of the 37 selected administrative districts (91.9%) were represented in the dataset. In total, 211 GPs were personally interviewed. On average, GPs saw 344 patients per month with a slightly higher number of patients in rural areas. They reported 59.1 ± 15.4 different reasons for consultation and 30.3 ± 3.9 different services. There was no statistically significant regional variation in the number of different consultation reasons, but there was a broader service spectrum by rural GPs (ß = - 1.42; 95% confidence interval - 2.75/- 0.08; p = 0.038) which was statistically explained by a higher level of medical training. Additionally, there were differences in the frequency of individual consultation reasons and services between rural and urban areas. CONCLUSION: GPs in rural areas performed more frequently services usually provided by medical specialists in urban areas. This might be caused by a low availability of specialists in rural areas. The association between medical training and service spectrum might imply that GPs compensate the specific needs of their patients by completing advanced medical training before or after setting up a medical practice. TRIAL REGISTRATION: The study was registered in ClinicalTrials.gov (NCT02558322).

Episodes of care in a primary care walk-in clinic at a refugee camp in Germany - a retrospective data analysis.

BACKGROUND: From 2015 to 2016 Germany faced an influx of 1.16 million asylum seekers. In the state of Hamburg Primary Care walk-in clinics (PCWC) were commissioned at refugee camps because the high number of residents (57,000 individuals) could not be provided with access to regular healthcare services. Our study aims were (1) to describe the utilization of a PCWC by camp residents, (2) to compare episodes of continuous care with shorter care episodes and (3) to analyse which diagnoses predict episodes of continuous care in this setting. METHODS: A retrospective longitudinal observational study was conducted by reviewing all anonymized electronic medical records of a PCWC that operated from 4th November 2015 to 22nd July 2016 at a refugee camp in Hamburg. Episodes of care (EOC) were extracted based on the international classification of primary care-2nd edition (ICPC-2). Outcome parameters were episode duration, principal diagnoses, and medical procedures. RESULTS: We analysed 5547 consultations of 1467 patients and extracted 4006 EOC. Mean patient age was 22.7 ± 14.8 years, 37.3% were female. Most common diagnoses were infections (44.7%), non-communicable diseases (22.2%), non-definitive diagnoses describing symptoms (22.0%), and injuries (5.7%). Most patients (52.4%) had only single encounters, whereas 19.8% had at least one EOC with a duration of ≥ 28 days (defined as continuous care). Several procedures were more prevalent in EOC with continuous care: Blood tests (5.2 times higher), administrative procedures (4.3), imaging (3.1) and referrals to secondary care providers (3.0). Twenty prevalent ICPC-2-diagnosis groups were associated with continuous care. The strongest associations were endocrine/metabolic system and nutritional disorders (hazard ratio 5.538, p < 0.001), dermatitis/atopic eczema (4.279, p < 0.001) and psychological disorders (4.056, p < 0.001). CONCLUSION: A wide spectrum of acute and chronic health conditions could be treated at a GP-led PCWC with few referrals or use of medical resources. But we also observed episodes of continuous care with more use of medical resources and referrals. Therefore, we conclude that principles of primary care like continuity of care, coordination of care and management of symptomatic complaints could complement future healthcare concepts for refugee camps.

[Patients with chronic diseases in emergency rooms in Germany : Cross-sectional analysis of consultations, reasons for use, and discharge diagnosis]. / Chronisch Kranke in deutschen Notaufnahmen : Querschnittsanalysen zu Konsultationsanlässen, Gründen für die Inanspruchnahme und Entlassungsdiagnosen.

BACKGROUND: The number of patients in emergency rooms without a medical emergency is increasing. Outpatient services for mutual support and relief between the in-patient and out-patient sector are not yet fully established. AIM OF THE WORK: The aim was to determine the extent to which patients in emergency rooms have real medical emergencies by comparing patients with at least two and those with a maximum of one chronic illness. An additional aim was to identify factors influencing the previous use of outpatient structures. MATERIAL AND METHODS: The study participants included emergency room patients from the cross-sectional study "PiNo-Nord." All persons in five emergency rooms in northern Germany between October 2015 and July 2016 who were not treated as "immediate" or "very urgent" were interviewed. An exploratory data analysis and multivariate logistic regression were performed. RESULTS: The 293 patients with ≥2 chronic diseases were just as often a medical emergency compared to the 847 patients with a maximum of 1 chronic disease. The most frequent occasions for consultation were musculoskeletal trauma (33%, n = 293 vs. 42%, n = 847) or trauma of the skin (11%, n = 293 vs. 13%, n = 847). In both groups, the general practitioner or specialist caregiver, as well as diagnostic or treatment options, rarely played a role in visiting the emergency department. The strongest predictors of previous outpatient treatment were the duration of the appeal in the last six months, a high subjective treatment urgency, the presence of at least two chronic conditions, and a consultation event concerning the musculoskeletal injuries. CONCLUSIONS: In both patient groups, no evidence of unnecessary visits to the emergency room was found. For the most part, outpatient structures are used in advance and the emergency department is only visited in the event of an actual medical emergency.

Cross-cultural validation of the German version of the Four-Dimensional Symptom Questionnaire (4DSQ) in multimorbid elderly people.

PURPOSE: Psychosomatic symptoms and mental health problems are highly prevalent in multimorbid elderly people challenging general practitioners to differentiate between normal stress and psychopathological conditions. The 4DSQ is a Dutch questionnaire developed to detect anxiety, depression, somatization, and distress in primary care. This study aims to analyze measurement equivalence between a German version and the original Dutch instrument. METHODS: A Dutch and a German sample of multimorbid elderly people, matched by gender and age, were analyzed. Equivalence of scale structures was assessed by confirmatory factor analysis (CFA). To evaluate measurement equivalence across languages, differential item functioning (DIF) was analyzed using Mantel-Haenszel method and hybrid ordinal logistic regression analysis. Differential test functioning (DTF) was assessed using Rasch analysis. RESULTS: A total of 185 German and 185 Dutch participants completed the questionnaire. The CFA confirmed one-factor models for all scales of both 4DSQ versions. Nine items in three scales were flagged with DIF. The anxiety scale showed to be free of DIF. DTF analysis revealed negligible scale impact of DIF. CONCLUSIONS: The German 4DSQ demonstrated measurement equivalence to the original Dutch instrument. Hence, it can be considered a valid questionnaire for the screening for mental health problems in primary care.

General practitioners' perception of being a doctor in urban vs. rural regions in Germany - A focus group study.

Background: Inadequate recruitment numbers for GPs in rural regions give cause for concern. Working in rural regions is less attractive among medical students because of strong associations concerning a higher workload, restriction of privacy and demands exceeding their competences. We aimed to explore perceptions of GPs working in urban versus rural regions to contrast these prejudices. Methods: We conducted nine focus groups with GPs [female = 21, male = 44] from urban and rural regions, using a semi-structured guideline. Transcripts were content analyzed using deductive and inductive categories. Results: Urban GPs perceived themselves as a provider of medical services and rural GPs as being a medical companion. Compared to urban GPs, GPs from non-urban regions portray themselves more strongly as a family physician that accompanies patients 'from the cradle to the grave' and is responsible for the treatment of any medical issue. They emphasized their close relationship with their patients. Rural GPs establish a close relationship with their patients and considered this as beneficial for the treatment relationship. This aspect seems to play a subordinate role for urban GPs. Conclusions: GPs enjoy their work and the role they play in their patients' lives. Being a rural GP was described very positively. Greater emphasis should be made on positive aspects of being a GP in rural regions, e.g. by university lectures given by rural GPs, campaigns emphasizing the positive aspects of working as a GP [in rural regions], promotion of work placements or incentives for working in rural general practices.

Satisfaction with general practice care in German patients with multimorbidity: a cross-sectional study.

Background: Little is known about the quality of general practice care received by patients suffering from multimorbidity. Objectives: To assess how patients with multimorbidity evaluate their General Practitioners (GPs') performance and to identify factors associated with high patient satisfaction levels. Methods: Cross-sectional study in Germany using the EUROPEP questionnaire consisting of 23 items with a five-point Likert scale and covering two dimensions: clinical performance of the GP and organisation of care. Mixed logistic regression was used in the analysis, with the EUROPEP score as a dependent variable. Results: The study included 651 patients (54.8% female), with a mean age of 73.7 ± 4.9 years. Of 22 of 23 questionnaire items, >80% of patients rated their satisfaction as 'good' or 'excellent'. The highest level of satisfaction (excellent) varied among items between 28.0 and 73.1%. Lower age and female sex of GPs were associated with better patient evaluations in 15 and 12 of the 23 items, respectively. Patient characteristics were not associated with their satisfaction with their GP. Conclusions: This study found high levels of satisfaction with primary care in patients with multimorbidity. However, since high levels of patient satisfaction are not necessarily equivalent to high quality of care, a broader view is necessary to integrate the subjective views of patients and objective quality indicators into a comprehensive concept of good quality of care.

Overutilization of ambulatory medical care in the elderly German population?--An empirical study based on national insurance claims data and a review of foreign studies.

BACKGROUND: By definition, high utilizers receive a large proportion of medical services and produce relatively high costs. The authors report the results of a study on the utilization of ambulatory medical care by the elderly population in Germany in comparison to other OECD countries. Evidence points to an excessive utilization in Germany. It is important to document these utilization figures and compare them to those in other countries since the healthcare system in Germany stopped recording ambulatory healthcare utilization figures in 2008. METHODS: The study is based on the claims data of all insurants aged ≥ 65 of a statutory health insurance company in Germany (n = 123,224). Utilization was analyzed by the number of contacts with physicians in ambulatory medical care and by the number of different practices contacted over one year. Criteria for frequent attendance were ≥ 50 contacts with practices or contacts with ≥ 10 different practices or ≥ 3 practices of the same discipline per year. Descriptive statistical analysis and logistic regression were applied. Morbidity was analyzed by prevalence and relative risk for frequent attendance for 46 chronic diseases. RESULTS: Nineteen percent of the elderly were identified as high utilizers, corresponding to approximately 3.5 million elderly people in Germany. Two main types were identified. One type has many contacts with practices, belongs to the oldest age group, suffers from severe somatic diseases and multimorbidity, and/or is dependent on long-term care. The other type contacts large numbers of practices, consists of younger elderly who often suffer from psychiatric and/or psychosomatic complaints, and is less frequently multimorbid and/or nursing care dependent. CONCLUSION: We found a very high rate of frequent attendance among the German elderly, which is unique among the OECD countries. Further research should clarify its reasons and if this degree of utilization is beneficial for elderly people.