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Purpose: Post-COVID-19-Syndrome (PCS) frequently occurs after an infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the understanding of causative mechanisms is still limited. Aim of this study was to determine the PCS rate among SARS-CoV-2 seropositive blood donors as representatives of supposedly healthy adults, who had experienced an asymptomatic or mild COVID-19 disease course, and to examine whether Epstein-Barr virus (EBV) is reactivated in individuals reporting PCS., Methods: The PCS rate was determined using questionnaires that included questions about infection and persistent symptoms. Pre-pandemic blood samples and samples collected at regular, pre-defined times after a SARS-CoV-2 infection were analysed for neopterin, a marker for antiviral immune responses, by an enzyme-linked immunosorbent assay (ELISA). Additionally, we determined the rate of SARS-CoV-2 anti-N total antibodies using an electrochemiluminescence immunoassay (ECLIA). Furthermore, quantitative real-time polymerase chain reaction (qPCR) to detect EBV DNA and ECLIA screening for EBV viral capsid-antigen (VCA) IgM, IgG and EBV nuclear antigen 1 (EBNA) IgG were performed., Results: Our data reveal that 18% of all infections result in PCS, with symptoms lasting for up to one year. In individuals reporting PCS, no elevated levels of neopterin were detected, indicating no persisting pro-inflammatory, antiviral immune response. SARS-CoV-2 antibody levels were declining in all participants in comparable manner over time, pointing to a successful virus clearance. In individuals with PCS, no EBV DNA could be detected. Furthermore, no differences in EBV specific antibody levels could be shown in PCS groups compared to non-PCS groups., Conclusion: Our data suggest that PCS in per se healthy, immunocompetent adults cannot be ascribed to a reactivation of EBV., (© 2023. The Author(s).)

Background: Previous studies have been inconclusive about racial disparities in sepsis. This study evaluated the impact of ethnic background on management and outcome in sepsis and septic shock., Methods: This analysis included 17,146 patients suffering from sepsis and septic shock from the multicenter eICU Collaborative Research Database. Generalized estimated equation (GEE) population-averaged models were used to fit three sequential regression models for the binary primary outcome of hospital mortality., Results: Non-Hispanic whites were the predominant group (n = 14,124), followed by African Americans (n = 1,852), Hispanics (n = 717), Asian Americans (n = 280), Native Americans (n = 146) and others (n = 830). Overall, the intensive care treatment and hospital mortality were similar between all ethnic groups. This finding was concordant in patients with septic shock and persisted after adjusting for patient-level variables (age, sex, mechanical ventilation, vasopressor use and comorbidities) and hospital variables (teaching hospital status, number of beds in the hospital)., Conclusion: We could not detect ethnic disparities in the management and outcomes of critically ill septic patients and patients suffering from septic shock. Disparate outcomes among critically ill septic patients of different ethnicities are a public health, rather than a critical care challenge., (© 2023. The Author(s).)

Background: In order to ensure the provision of appropriate and safe medication therapy in long-term care, close interprofessional cooperation and high levels of expertise are required. Online digital documentation and communication technology facilitate this process. The aim of the present study (sub-study 2 of the SiMbA-Study) was to evaluate a three-part health information technology (HIT) driven intervention on medication therapy safety in Austrian nursing homes (NHs) regarding its usefulness, practicability and implementation in routine care., Methods: A concurrent embedded mixed-methods design was conducted to evaluate the intervention. Data was collected via expert interviews, focus group discussions and quantitative survey of general practitioners, nurses, and pharmacists in 3 NHs. Usefulness and effectiveness of the intervention were investigated through summative evaluation. Formative evaluation was utilized to gain insights regarding features and factors of the implementation process necessary to a successful integration in routine care., Results: The sample comprised general practitioners, pharmacists, and nurses. 23 participants were interviewed, of which 17 participated in the focus group discussions and completed the quantitative Survey. All components of the intervention were deemed to be useful and effective. Effort and benefit of using health information technology were well balanced. Implementation success was mainly attributed to socio-normative factors., Conclusions: The implementation of HIT-based measures can be effective but is prone to various pitfalls that are highlighted in the study. A critical challenge for successful implementation is the combination of both, ensuring its prerequisites, while anticipating new problems that arise from HIT-integration on the one hand and changes in interprofessional cooperation on the other., Trial Registration: DRKS Data Management, ID: DRKS00012246 . Registered 16.05.2017 - Retrospectively registered., (© 2022. The Author(s).)

Background: This study aimed to explore which measures and risk factors for a COVID - 19 infection are considered most important in the general population, health experts and policymakers and to assess the level of agreement across the groups from Austria and Germany., Methods: A two-phased survey was conducted, participants were matched according to age and gender. Three different groups were asked which measures they considered most relevant in reducing a COVID-19 transmission, to determine which factors contribute most to the risk of disease, and to evaluate the level of agreement in the assessment of risk factor relevance for (a) the transmission of the disease and (b) the risk of a severe course of COVID-19., Results: Risk factors for an infection that were selected from all three groups were immunosuppression/deficiency, cancer, chronic lung disease, smoking, age and working as a health care professional. Interrater agreement per population was only poor to slight and results were highly heterogeneous., Conclusions: Our survey shows a broad spectrum of opinions and the associated general uncertainty about the risk factors for infection and a severe course of disease across the groups. Profound knowledge of politicians and experts is of high relevance to provide the public with valid information to ensure cooperation fighting the pandemic., Trial Registration: https://apps.who.int/trialsearch/ (ID: DRKS00022166). Registered 15 June 2020., (© 2021. The Author(s).)

Background: In nursing home residents (NHRs), polypharmacy is widespread, accompanied by elevated risks of medication related complications. Managing medication in NHRs is a priority, but prone to several challenges, including interprofessional cooperation. Against this background, we implemented and tested an interprofessional intervention aimed to improve medication appropriateness for NHRs., Methods: A non-randomized controlled study (SiMbA; "Sicherheit der Medikamentherapie bei AltenheimbewohnerInnen", Safety of medication therapy in NHRs) was conducted in six nursing homes in Austria (2016-2018). Educational training, introduction of tailored health information technology (HIT) and a therapy check process were combined in an intervention aimed at healthcare professionals. Medication appropriateness was assessed using the Medication Appropriateness Index (MAI). Data was collected before (t0), during (t1, month 12) and after (t2, month 18) intervention via self-administered assessments and electronic health records., Results: We included 6 NHs, 17 GPs (52.94% female) and 240 NHRs (68.75% female; mean age 85.0). Data of 159 NHRs could be included in the analysis. Mean MAI-change was - 3.35 (IG) vs. - 1.45 (CG). In the subgroup of NHRs with mean MAI ≥23, MAI-change was - 10.31 (IG) vs. -3.52 (CG). The intervention was a significant predictor of improvement in MAI when controlled for in a multivariable regression model., Conclusions: Improvement of medication appropriateness was clearest in residents with inappropriate baseline MAI-scores. This improvement was independent of variances in certain covariates between the intervention and the control group. We conclude that our intervention is a feasible approach to improve NHRs' medication appropriateness., Trial Registration: DRKS Data Management, ID: DRKS00012246 . Registered 16.05.2017 - Retrospectively registered.

Background: Uncoordinated interprofessional communication in nursing homes increases the risk of polypharmacy and inappropriate medication use. This may lead to augmented frequency of adverse drug events, hospitalizations and mortality. The aims of this study were (1) to improve interprofessional communication and medication safety using a combined intervention and thus, (2) to improve medication appropriateness and health-related outcomes of the included residents., Methods: The single-arm interventional study (2014-2017) was conducted in Muenster, Germany and involved healthcare professionals and residents of nursing homes. The intervention consisted of systematic education of participating healthcare professionals and of a structured interprofessional medication review which was performed via an online communication platform. The primary endpoint was assessed using the Medication Appropriateness Index MAI. Secondary endpoints were: cognitive performance, delirium, agitation, mobility, number of drugs, number of severe drug-drug interactions and appropriateness of analgesics. Outcomes were measured before, during and after the intervention. Data were analyzed using descriptive and inference-statistical methods., Results: Fourteen general practitioners, 11 pharmacists, 9 nursing homes and 120 residents (n = 83 at all testing times) participated. Overall MAI sum-score decreased significantly over time (mean reduction: -7.1, CI 95% -11.4 - - 2.8; median = - 3.0; d Cohen  = 0.39), especially in cases with baseline sum-score ≥ 24 points (mean reduction: -17.4, CI 95% -27.6 - - 7.2; median = - 15.0; d Cohen  = 0.86). MAI sum-score of analgesics also decreased (d Cohen  = 0.45). Mean number of severe drug-drug interactions rose slightly over time (d Cohen  = 0.17). The proportion of residents showing agitated behavior diminished from 83.9 to 67.8%. Remaining secondary outcomes were without substantial change., Conclusion: Medication appropriateness increased particularly in residents with high baseline MAI sum-scores. Cognitive decline of participating residents was seemingly decelerated when compared with epidemiologic studies. A controlled trial is required to confirm these effects. Interprofessional interaction was structured and performance of medication reviews was facilitated as the online communication platform provided unlimited and consistent access to all relevant and updated information., Trial Registration: DRKS Data Management, ID: DRKS00007900 , date of registration: 2015-09-02 (retrospectively registered i.e. 6 weeks after commencement of the first data collection).

Background: Type 2 diabetes is a chronic disease associated with poorer health outcomes and decreased health related quality of life (HRQoL). The aim of this analysis was to explore the impact of a disease management programme (DMP) in type 2 diabetes on HRQoL. A multilevel model was used to explain the variation in EQ-VAS., Methods: A cluster-randomized controlled trial-analysis of the secondary endpoint HRQoL. Our study population were general practitioners and patients in the province of Salzburg. The DMP "Therapie-Aktiv" was implemented in the intervention group, and controls received usual care. Outcome measure was a change in EQ-VAS after 12 months. For comparison of rates, we used Fisher's Exact test; for continuous variables the independent T test or Welch test were used. In the multilevel modeling, we examined various models, continuously adding variables to explain the variation in the dependent variable, starting with an empty model, including only the random intercept. We analysed random effects parameters in order to disentangle variation of the final EQ-VAS., Results: The EQ-VAS significantly increased within the intervention group (mean difference 2.19, p = 0.005). There was no significant difference in EQ-VAS between groups (mean difference 1.00, p = 0.339). In the intervention group the improvement was more distinct in women (2.46, p = 0.036) compared to men (1.92, p = 0.063). In multilevel modeling, sex, age, family and work circumstances, any macrovascular diabetic complication, duration of diabetes, baseline body mass index and baseline EQ-VAS significantly influence final EQ-VAS, while DMP does not. The final model explains 28.9% (EQ-VAS) of the total variance. Most of the unexplained variance was found on patient-level (95%) and less on GP-level (5%)., Conclusion: DMP "Therapie-Aktiv" has no significant impact on final EQ-VAS. The impact of DMPs in type 2 diabetes on HRQoL is still unclear and future programmes should focus on patient specific needs and predictors in order to improve HRQoL. Trial registration Current Controlled trials Ltd., ISRCTN27414162.

Background: Pharmacotherapy in residents of nursing homes is critical due to the special vulnerability of this population. Medical care and interprofessional communication in nursing homes are often uncoordinated. As a consequence, polypharmacy and inappropriate medication use are common and may lead to hospitalizations and health hazards. The aim of this study is to optimize communication between the involved professional groups by specific training and by establishing a structured medication review process, and to improve medication appropriateness and patient-relevant health outcomes for residents of nursing homes., Methods/design: The trial is designed as single-arm study. It involves 300 nursing home residents aged ≥ 65 years and the members of the different professional groups practising in nursing home care (15-20 general practitioners, nurses, pharmacists). The intervention consists of interprofessional education on safe medication use in geriatric patients, and a systematic interprofessional therapy check (recording, reviewing and adapting the medication of the participating residents by means of a specific online platform). The intervention period is divided into two phases; total project period is 3 years. Primary outcome measure is the change in medication appropriateness according to the Medication Appropriateness Index. Secondary outcomes are cognitive performance, occurrence of delirium, agitation, tendency of falls, total number of drugs, number of potentially dangerous drug-drug interactions and appropriateness of recorded analgesic therapy regimens according to the Medication Appropriateness Index. Data are collected at t 0 (before the start of the intervention), t 1 (after the first intervention period) and t 2 (after the second intervention period). Cooperation and communication between the professional groups are investigated twice by qualitative interviews., Discussion: The project aims to establish a structured system for monitoring of drug therapy in nursing home residents. The newly developed online platform is designed to systematize and to improve the communication between the professional groups and, thus, to enhance quality and safety of drug therapy. Limitations of the study are the lack of a control group and the non-randomly recruited study sample., Trial Registration: DRKS Data Management, DRKS-ID: DRKS00007900.

Background: Multimorbidity is increasing in aging populations with a corresponding increase in polypharmacy as well as inappropriate prescribing. Depending on definitions, 25-50 % of patients aged 75 years or older are exposed to at least five drugs. Evidence is increasing that polypharmacy, even when guidelines advise the prescribing of each drug individually, can potentially cause more harm than benefit to older patients, due to factors such as drug-drug and drug-disease interactions. Several approaches reducing polypharmacy and inappropriate prescribing have been proposed, but evidence showing a benefit of these measures regarding clinically relevant endpoints is scarce. There is an urgent need to implement more effective strategies. We therefore set out to develop an evidence-based electronic decision support (eDS) tool to aid physicians in reducing inappropriate prescribing and test its effectiveness in a large-scale cluster-randomized controlled trial., Methods: The "Polypharmacy in chronic diseases-Reduction of Inappropriate Medication and Adverse drug events in older populations" (PRIMA)-eDS tool is a tool comprising an indication check and recommendations for the reduction of polypharmacy and inappropriate prescribing based on systematic reviews and guidelines, the European list of inappropriate medications for older people, the SFINX-database of interactions, the PHARAO-database on adverse effects, and the RENBASE-database on renal dosing. The tool will be evaluated in a cluster-randomized controlled trial involving 325 general practitioners (GPs) and around 3500 patients across five study centres in the United Kingdom, Germany, Austria and Italy. GP practices will be asked to recruit 11 patients aged 75 years or older who are taking at least eight medications and will be cluster-randomized after completion of patient recruitment. Intervention GPs will have access to the PRIMA-eDS tool, while control GPs will treat their patients according to current guidelines (usual care) without access to the PRIMA-eDS tool. After an observation time of 2 years, intervention and control groups will be compared regarding the primary composite endpoint of first non-elective hospitalization or death., Discussion: The principal hypothesis is that reduction of polypharmacy and inappropriate prescribing can improve the clinical composite outcome of hospitalization or death. A positive result of the trial will contribute substantially to the improvement of care in multimorbidity. The trial is necessary to investigate not only whether the reduction of polypharmacy improves outcome, but also whether GPs and patients are willing to follow the recommendations of the PRIMA-eDS tool., Trial Registration: This trial has been registered with Current Controlled Trials Ltd. on 31 July 2014 (ISRCTN10137559).

Background: Patients do not always receive guideline-adherent therapy, yet little is known about the underlying causes on the patients' side. We quantified non-guideline-adherent treatment of chronic diseases (diabetes mellitus, hypertension, cardiovascular disease, heart failure, atrial fibrillation) in primary care and analysed the causes from the physician's as well as the patient's view., Methods: With the intention to analyze the frequency and causes of non-guideline-adherent treatment of patients with chronic diseases, we drew a random sample of 124 general practitioners (GP) in Salzburg, Austria, of which 58 (46.8%) participated. In the participating GP surgeries, we consecutively recruited 501 patients with at least one of the target-diseases and checked the guideline conformity of treatment using 9 quality indicators. We then interviewed the patients as well as the general practitioners regarding factors affecting deviation from guideline recommendations., Results: Of the 501 patients, a total of 1224 quality indicators could be analysed. Non-adherence to guideline recommendations were present in 16.8% (n = 205, 95% CI 14.7 to 18.8%) of all quality indicators. In 61.5% of these cases (n = 126, 95% CI 53.0 to 70.0%) the treatment was wrongly judged as not recommended by the physicians. In 10.2% (n = 21, 95% CI 0 to 23.2%) physicians attributed non-adherence to patient's non-compliance, and in 10.7% (n = 22, 95% CI 0 to 23.7%) to an adverse drug event, whereas only 5.4% (n = 11, 95% CI 0 to 18.7%) of non-adherence was related to an adverse drug event reported by the patients. Patients were unaware regarding the reason for non-adherent therapy in 64.4% (n = 132, 95% CI 56.2 to 72.6%) of the quality indicators. In 20.0% (n = 41, 95% CI 7.8 to 32.2%) patients regarded a drug as not needed., Conclusions: Guideline adherence in chronic care was relatively good in our study sample, but still leaving room for improvement. Physicians' lack of knowledge and patients' lack of awareness account for about 70% of non-adherence, indicating the necessity to improve physician education, and patient involvement. In about 30% of the quality indicators not fulfilled, non-adherence is due to other reasons like adverse drug events or patients not willing to take a recommended drug.

Background: Self-management support is a key component of effective chronic care management, yet in practice appears to be the least implemented and most challenging. This study explores whether and how self-management support is integrated into chronic care approaches in 13 European countries. In addition, it investigates the level of and barriers to implementation of support strategies in health care practice., Methods: We conducted a review among the 13 participating countries, based on a common data template informed by the Chronic Care Model. Key informants presented a sample of representative chronic care approaches and related self-management support strategies. The cross-country review was complemented by a Dutch case study of health professionals' views on the implementation of self-management support in practice., Results: Self-management support for chronically ill patients remains relatively underdeveloped in Europe. Similarities between countries exist mostly in involved providers (nurses) and settings (primary care). Differences prevail in mode and format of support, and materials used. Support activities focus primarily on patients' medical and behavioral management, and less on emotional management. According to Dutch providers, self-management support is not (yet) an integral part of daily practice; implementation is hampered by barriers related to, among others, funding, IT and medical culture., Conclusions: Although collaborative care for chronic conditions is becoming more important in European health systems, adequate self-management support for patients with chronic disease is far from accomplished in most countries. There is a need for better understanding of how we can encourage both patients and health care providers to engage in productive interactions in daily chronic care practice, which can improve health and social outcomes.

Background: Disease management programmes (DMPs) are costly and impose additional work load on general practitioners (GPs). Data on their effectiveness are inconclusive. We therefore conducted a cluster-randomised controlled trial to evaluate the effectiveness of the Austrian DMP for diabetes mellitus type 2 on HbA1c and quality of care for adult patients in primary care., Methods: All GPs of Salzburg-province were invited to participate. After cluster-randomisation by district, all patients with diabetes type 2 were recruited consecutively from 7-11/2007. The DMP, consisting mainly of physician and patient education, standardised documentation and agreement on therapeutic goals, was implemented in the intervention group while the control group received usual care. We aimed to show superiority of the intervention regarding metabolic control and process quality. The primary outcome measure was a change in HbA1c after one year. Secondary outcomes were days in the hospital, blood pressure, lipids, body mass index (BMI), enrolment in patient education and regular guideline-adherent examination. Blinding was not possible., Results: 92 physicians recruited 1489 patients (649 intervention, 840 control). After 401 ± 47 days, 590 intervention-patients and 754 controls had complete data. In the intention to treat analysis (ITT) of all 1489 patients, HbA1c decreased 0.41% in the intervention group and 0.28% in controls. The difference of -0.13% (95% CI -0.24; -0.02) was significant at p = 0.026. Significance was lost in mixed models adjusted for baseline value and cluster-effects (adjusted mean difference -0.03 (95% CI -0.15; 0.09, p = 0.607). Of the secondary outcome measures, BMI and cholesterol were significantly reduced in the intervention group compared to controls in ITT after adjustments (-0.53 kg/m²; 95% CI -1.03;-0.02; p = 0.014 and -0.10 mmol/l; 95% CI -0.21; -0.003; p = 0.043). Additionally, more patients received patient education (49.5% vs. 20.1%, p < 0.0001), eye- (71.0% vs. 51.2%, p < 0.0001), foot examinations (73.8% vs. 45.1%, p < 0.0001), and regular HbA1c checks (44.1% vs. 36.0%, p < 0.01) in the intervention group., Conclusion: The Austrian DMP implemented by statutory health insurance improves process quality and enhances weight reduction, but does not significantly improve metabolic control for patients with type 2 diabetes mellitus. Whether the small benefit seen in secondary outcome measures leads to better patient outcomes, remains unclear., Trial Registration: Current Controlled trials Ltd., ISRCTN27414162.