Interventional Pharmacoepidemiology: Design and evaluation of interventions to improve prescribing.

Despite the value of modern therapeutics, many obstacles prevent their optimal use. Overuse, underuse and misuse are common, resulting in morbidity and mortality impacting billions of individuals across the world. Pharmacoepidemiology provides important insights into drug utilization, safety and effectiveness in large populations, and it is an important method to identify opportunities to improve the value of therapeutics in clinical practice. However, for these opportunities to be realized, interventions to improve prescribing must be developed, evaluated and implemented in the real world. We provide an overview of this process, focusing especially on how such interventions can be designed and deployed to maximize scalability, adoption and impact. Prescribing represents a complex behavior with barriers and enablers, and interventions to improve prescribing will be most successful when developed, piloted and refined to maximize provider and patient acceptability. Carefully developed evaluations of interventions are also critical, and varied methods are available to empirically evaluate the intended and potential unintended consequences of interventions. With illustrative examples from the peer-reviewed literature, we provide readers with an overview of approaches to the essential and growing field of interventional pharmacoepidemiology.

Deprescribing of antidepressants: development of indicators of high-risk and overprescribing using the RAND/UCLA Appropriateness Method.

BACKGROUND: Antidepressants are first-line medications for many psychiatric disorders. However, their widespread long-term use in some indications (e.g., mild depression and insomnia) is concerning. Particularly in older adults with comorbidities and polypharmacy, who are more susceptible to adverse drug reactions, the risks and benefits of treatment should be regularly reviewed. The aim of this consensus process was to identify explicit criteria of potentially inappropriate antidepressant use (indicators) in order to support primary care clinicians in identifying situations, where deprescribing of antidepressants should be considered. METHODS: We used the RAND/UCLA Appropriateness Method to identify the indicators of high-risk and overprescribing of antidepressants. We combined a structured literature review with a 3-round expert panel, with results discussed in moderated meetings in between rounds. Each of the 282 candidate indicators was scored on a 9-point Likert scale representing the necessity of a critical review of antidepressant continuation (1-3 = not necessary; 4-6 = uncertain; 7-9 = clearly necessary). Experts rated the indicators for the necessity of review, since decisions to deprescribe require considerations of patient risk/benefit balance and preferences. Indicators with a median necessity rating of ≥ 7 without disagreement after 3 rating rounds were accepted. RESULTS: The expert panel comprised 2 general practitioners, 2 clinical pharmacologists, 1 gerontopsychiatrist, 2 psychiatrists, and 3 internists/geriatricians (total N = 10). After 3 assessment rounds, there was consensus for 37 indicators of high-risk and 25 indicators of overprescribing, where critical reviews were felt to be necessary. High-risk prescribing indicators included settings posing risks of drug-drug, drug-disease, and drug-age interactions or the occurrence of adverse drug reactions. Indicators with the highest ratings included those suggesting the possibility of cardiovascular risks (QTc prolongation), delirium, gastrointestinal bleeding, and liver injury in specific patient subgroups with additional risk factors. Overprescribing indicators target patients with long treatment durations for depression, anxiety, and insomnia as well as high doses for pain and insomnia. CONCLUSIONS: Explicit indicators of antidepressant high-risk and overprescribing may be used directly by patients and health care providers, and integrated within clinical decision support tools, in order to improve the overall risk/benefit balance of this commonly prescribed class of prescription drugs.

[" Not Even in The Corridor!" - Subjective Perception Of Institutional Measures During The Covid-19 Pandemic Of Nursing Home Residents: A Qualitative Study]. / " nicht mal auf den Gang!" ­ Das subjektive Empfinden institutioneller Maßnahmen während der Covid-19 Pandemie von Pflegeheimbewohnern. Eine qualitative Studie.

BACKGROUND: In the context of the Covid-19 pandemic, institutional measures were decreed to protect nursing home residents from infection. Their appropriateness has been a subject of controversy. The aim of this work was to better understand the subjective perception of the protective measures during the Covid-19 pandemic by the nursing home residents in Bavaria and to shed light on the role of nursing staff and general practitioners in coping with the crisis. METHODS: Semi-structured interviews were conducted with residents of inpatient long-term care facilities. Data analysis was carried out by means of structured content analysis according to Kuckartz. RESULTS: A total of ten nursing home residents with various degrees of care were interviewed, five of whom had already been infected with Covid-19 at the time of the survey. The respondents reported, on the one hand, their need for protection and, on the other hand, the isolation they experienced during the pandemic. Trust in the care provided by the nursing staff was emphasized. A reliable personal contact to already known general practitioners was missing. CONCLUSION: The role of nurses and general practitioners deserves more attention and may be a key to better acceptance and management of such crisis situations.

Addressing the Challenge of Polypharmacy.

Polypharmacy describes the concomitant use of multiple medicines and represents a growing global challenge attributable to aging populations with an increasing prevalence of multimorbidity. Polypharmacy can be appropriate but is problematic when the increased risk of harm from interactions between drugs or between drugs and diseases or the burden of administering and monitoring medicines outweighs plausible benefits. Polypharmacy has a substantial economic impact in service demand and hospitalization as well as a detrimental impact on patients' quality of life. Apart from causing avoidable harm, polypharmacy can also lead to therapeutic failure, with up to 50% of patients who take four or more medications not taking them as prescribed. Guidance is needed to support patients and clinicians in defining and achieving realistic goals of drug treatment, and system change is necessary to aid implementation. This article outlines lessons from two programs that aim to address these challenges: the Scottish polypharmacy guidance on realistic prescribing and the European Union SIMPATHY project.

Single and combined use of fall-risk-increasing drugs and fracture risk: a population-based case-control study.

BACKGROUND: while many drug groups are associated with falls in older people, less is known about absolute increases in risk and how these risks vary across different groups of drugs or individuals. METHOD AND DESIGN: we conducted a population based nested case-control study among people aged ≥65 years in the Scottish regions of Tayside and Fife. Cases were individuals hospitalised with a fracture between 2010 and 2020, to whom we matched up to 10 controls. We examined relative and absolute risks of drug groups known as 'Fall-Risk-Increasing Drugs' (FRIDs), alone and in combination, and among younger and older (≥75 years) adults. Adjusting for previous hospitalisations, drug use and laboratory data, we used conditional logistic regression to quantify associations between drug exposures and outcomes. We conducted four sensitivity analyses to test the robustness of our findings. RESULTS: the cohort comprised 246,535 people aged ≥65 years, of whom 18,456 suffered an incident fracture. Fracture risks were significantly increased for most FRIDs examined. Absolute risks were much larger among older vs younger people and both relative and absolute risks increased with the number of FRIDs combined. Overall, the highest absolute increase in risk were found in people aged ≥75 years for selective serotonin reuptake inhibitors (number needed to harm 53), tricyclic antidepressants (NNH 81), antipsychotics (NNH 75) and use of three or more FRIDs (NNH ≤66). CONCLUSION: patients aged ≥75 years prescribed antidepressants or antipsychotics or taking three or more drugs that increase risk of falls may benefit most from deprescribing interventions.

Feasibility of the MELD score as a screening tool for pharmacists to identify patients with impaired hepatic function at hospital admission.

WHAT IS KNOWN AND OBJECTIVE: Hepatic impairment (HI) is a known risk factor for drug safety. The MELD score (Model-for-endstage-liver-disease), calculated from serum creatinine, bilirubin and International Normalized Ratio (INR), is a promising screening tool corresponding to Child-Pugh Score (CPS) for drug adjustment. We tested the feasibility of MELD as an automatic screening tool accounting for correct calculation, interfering factors (IF) and detection of patients corresponding to CPS-B/C potentially requiring drug adjustment. METHODS: We retrospectively calculated MELD for a 3-month cohort of surgical patients and assessed need for adjustment of MELD parameters to standard values. IF for INR (oral anticoagulants) and serum creatinine (renal insufficiency (RI; eGFR<60 ml/min/1.73m²); as well as drugs elevating creatinine levels (DECL)) and the number of patients with MELD scores corresponding to CPS-B/C were analysed. For MELD ≥7.5, liver and bile diagnoses were recorded. RESULTS AND DISCUSSION: Of 1183 patients, MELD was calculable for 761 (64%; median 7.5, range 6.4-36.8). Parameters had to be adjusted for 690 (91%) patients. IF of parameters were RI in 172 (23%), INR-elevating drugs in 105 (14%) and DECL in 33 (4%) patients. Of 335 (44%) patients with MELD ≥7.5, 122 (36%) had documented liver or bile diagnoses. MELD 10-<15 (corresponding to CPS-B) was found for 105 (14%), MELD ≥15 (corresponding to CPS-C) for 66 (9%) of the 761 patients with a calculated MELD. Referred to all patients, drug adjustments due to possible HI were recommendable for 14% of patients with suspected CPS-B/C. WHAT IS NEW AND CONCLUSION: MELD is a feasible screening tool for HI as a risk factor for drug safety at hospital admission when appropriately considering correct parameter adjustment and RI and INR-elevating drugs as IF. Further evaluation of sensitivity and specificity is needed.

Trajectories of depression in sepsis survivors: an observational cohort study.

BACKGROUND: Advances in critical care medicine have led to a growing number of critical illness survivors. A considerable part of them suffers from long-term sequelae, also known as post-intensive care syndrome. Among these, depressive symptoms are frequently observed. Depressive symptom trajectories and associated factors of critical illness survivors have rarely been investigated. Study objective was to explore and compare different trajectories of depressive symptoms in sepsis survivors over 1 year after discharge from ICU. METHODS: Data of a randomized controlled trial on long-term post-sepsis care were analyzed post hoc. Depressive symptoms were collected at 1, 6 and 12 months post-ICU discharge using the Major Depression Inventory (MDI), among others. Statistical analyses comprised descriptive analysis, univariate and multivariate, linear and logistic regression models and Growth Mixture Modeling. RESULTS: A total of 224 patients were included into this analysis. We identified three latent classes of depressive symptom trajectories: Over the course of 1 year, 152 patients recovered from mild symptoms, 27 patients showed severe persistent symptoms, and 45 patients recovered from severe symptoms. MDI sum scores significantly differed between the three classes of depressive symptom trajectories at 1 and 6 months after ICU discharge (p < 0.024 and p < 0.001, respectively). Compared with other classes, patients with the mild recovered trajectory showed lower levels of chronic pain (median sum score of 43.3 vs. 60.0/53.3 on the Graded Chronic Pain Scale, p < 0.010) and posttraumatic stress (4.6% with a sum score of ≥ 35 on the Posttraumatic Stress Scale 10 vs. 48.1%/33.3%, p < 0.003); and higher levels of health-related quality of life (HRQOL) using the Short Form-36 scale within 1 month after ICU discharge (p < 0.035). CONCLUSIONS: In the first year after discharge from ICU, sepsis survivors showed three different trajectories of depressive symptoms. Course and severity of depressive symptoms were associated with chronic pain, posttraumatic stress and reduced HRQOL at discharge from ICU. Regular screening of sepsis survivors on symptoms of depression, chronic pain and posttraumatic stress within 1 year after ICU may be considered. Trial registration ISRCTN, ISRCTN 61744782. Registered April 19, 2011-Retrospectively registered, http://www.isrctn.com/ISRCTN61744782 .

Impact of medicines regulatory risk communications in the UK on prescribing and clinical outcomes: Systematic review, time series analysis and meta-analysis.

AIMS: Regulatory risk communications are important to ensure medication safety, but their impact is poorly understood. The aim was to quantify the impact of UK risk communications on medication use and other outcomes. METHODS: We conducted a systematic review of studies reporting prescribing/health outcome data relevant to UK regulatory risk communication. Data were reanalysed using interrupted time series regression 12 months after each regulatory intervention. Mean changes were pooled using random-effects generic inverse variance examining the following subgroups: drug withdrawals; restrictions/changes in indications; be aware messages without specific recommendations for action; communication via direct healthcare practitioner communications; communication via drug bulletins. RESULTS: Of 11 466 articles screened, 40 studies examining 25 UK regulatory risk communications were included. Product withdrawals, restriction in indications and be aware communications were associated with relative mean changes of -78% (95% confidence interval [CI] -60 to -96%), -34% (95% confidence interval [CI] -12 to -55%) and -11% (95%CI -8 to -15%) in targeted drug prescribing respectively. Direct healthcare professional communications were associated with relative mean changes of -47% (95%CI -27 to -68%) compared to -13% (95%CI -6 to -20%) for drug bulletins. Of 7 studies examining unique health outcomes related to the safety concern, risk communications were associated with a mean -10% (95%CI -3 to -16%) decrease in intended and a 7% (95%CI 4 to 10%) increase in unintended health outcomes. DISCUSSION: UK regulatory risk communications were associated with significant changes in targeted prescribing and potential changes in clinical outcomes. Further research is needed to systematically study the impact of regulatory interventions.

Safer Prescribing--A Trial of Education, Informatics, and Financial Incentives.

BACKGROUND: High-risk prescribing and preventable drug-related complications are common in primary care. We evaluated whether the rates of high-risk prescribing by primary care clinicians and the related clinical outcomes would be reduced by a complex intervention. METHODS: In this cluster-randomized, stepped-wedge trial conducted in Tayside, Scotland, we randomly assigned participating primary care practices to various start dates for a 48-week intervention comprising professional education, informatics to facilitate review, and financial incentives for practices to review patients' charts to assess appropriateness. The primary outcome was patient-level exposure to any of nine measures of high-risk prescribing of nonsteroidal antiinflammatory drugs (NSAIDs) or selected antiplatelet agents (e.g., NSAID prescription in a patient with chronic kidney disease or coprescription of an NSAID and an oral anticoagulant without gastroprotection). Prespecified secondary outcomes included the incidence of related hospital admissions. Analyses were performed according to the intention-to-treat principle, with the use of mixed-effect models to account for clustering in the data. RESULTS: A total of 34 practices underwent randomization, 33 of which completed the study. Data were analyzed for 33,334 patients at risk at one or more points in the preintervention period and for 33,060 at risk at one or more points in the intervention period. Targeted high-risk prescribing was significantly reduced, from a rate of 3.7% (1102 of 29,537 patients at risk) immediately before the intervention to 2.2% (674 of 30,187) at the end of the intervention (adjusted odds ratio, 0.63; 95% confidence interval [CI], 0.57 to 0.68; P<0.001). The rate of hospital admissions for gastrointestinal ulcer or bleeding was significantly reduced from the preintervention period to the intervention period (from 55.7 to 37.0 admissions per 10,000 person-years; rate ratio, 0.66; 95% CI, 0.51 to 0.86; P=0.002), as was the rate of admissions for heart failure (from 707.7 to 513.5 admissions per 10,000 person-years; rate ratio, 0.73; 95% CI, 0.56 to 0.95; P=0.02), but admissions for acute kidney injury were not (101.9 and 86.0 admissions per 10,000 person-years, respectively; rate ratio, 0.84; 95% CI, 0.68 to 1.09; P=0.19). CONCLUSIONS: A complex intervention combining professional education, informatics, and financial incentives reduced the rate of high-risk prescribing of antiplatelet medications and NSAIDs and may have improved clinical outcomes. (Funded by the Scottish Government Chief Scientist Office; ClinicalTrials.gov number, NCT01425502.).

Risk of acute kidney injury following community prescription of antibiotics: self-controlled case series.

BACKGROUND: Development of acute kidney injury (AKI) following the use of antibiotics such as sulphonamides, trimethoprim and aminoglycosides is a frequently described phenomenon. More recently, an association between fluoroquinolone use and AKI has been suggested. The aim of this study was to evaluate the risk of AKI as an unintended consequence of commonly prescribed antibiotics in a large community cohort using a method that fully adjusts for underlying patient characteristics, including potential unmeasured confounders. METHODS: A self-controlled case study was conducted and included all individuals aged 18 years and over in the Tayside region of Scotland who had a serum creatinine measured between 1 January 2004 and 31 December 2012. AKI episodes were defined using the Kidney Disease: Improving Global Outcomes definition. Data on oral community-prescribed antibiotics (penicillins, cephalosporins, fluoroquinolones, sulphonamides and trimethoprim, macrolides and nitrofurantoin) were collected for all individuals. Incidence rate ratios (IRRs) for AKI associated with antibiotic exposure versus time periods without antibiotic exposure were calculated. RESULTS: Combined use of sulphonamides, trimethoprim and nitrofurantoin rose by 47% and incidence of community-acquired AKI rose by 16% between 2008 and 2012. During the study period 12 777 individuals developed 14 900 episodes of AKI in the community, of which 68% was AKI Stage 1, 16% Stage 2 and 16% Stage 3. The IRR of AKI during any antibiotic use was 1.16 [95% confidence interval (CI) 1.10-1.23], and this was highest during sulphonamides or trimethoprim use; IRR 3.07 (95% CI 2.81-3.35). Fluoroquinolone and nitrofurantoin use was not associated with a significantly increased rate of AKI; IRR 1.13 (95% CI 0.94-1.35) and 1.16 (95% CI 0.91-1.50), respectively. CONCLUSIONS: Incidence of AKI rose by 16% between 2008 and 2012. In the same period the use of sulphonamides, trimethoprim and nitrofurantoin increased by 47%. A significant increased risk of AKI was seen with the use of sulphonamides and trimethoprim, but not with fluoroquinolones or nitrofurantoin.

Respiratory effect of beta-blocker eye drops in asthma: population-based study and meta-analysis of clinical trials.

AIMS: To measure the prevalence of beta-blocker eye drop prescribing and respiratory effect of ocular beta-blocker administration in people with asthma. METHODS: We measured the prevalence of ocular beta-blocker prescribing in people with asthma and ocular hypertension, and performed a nested case-control study (NCCS) measuring risk of moderate exacerbations (rescue steroids in primary care) and severe exacerbations (asthma hospitalization) using linked data from the UK Clinical Practice Research Datalink. We then performed a systematic review and meta-analysis of clinical trials evaluating changes in lung function following ocular beta-blocker administration in people with asthma. RESULTS: From 2000 to 2012, the prevalence of non-selective and selective beta-blocker eye drop prescribing in people with asthma and ocular hypertension fell from 23.0% to 13.4% and from 10.5% to 0.9% respectively. In the NCCS, the relative incidence (IRR) of moderate exacerbations increased significantly with acute non-selective beta-blocker eye drop exposure (IRR 4.83, 95% CI 1.56-14.94) but not with chronic exposure. In the meta-analysis, acute non-selective beta-blocker eye drop exposure caused significant mean falls in FEV1 of -10.9% (95% CI -14.9 to -6.9), and falls in FEV1 of ≥20% affecting one in three. Corresponding values for selective beta-blockers in people sensitive to ocular non-selective beta-blockers was -6.3% (95% CI -11.7 to -0.8), and a non-significant increase in falls in FEV1 of ≥20%. CONCLUSION: Non-selective beta-blocker eye drops significantly affect lung function and increase asthma morbidity but are still frequently prescribed to people with asthma and ocular hypertension despite safer agents being available.

Combined use of nonsteroidal anti-inflammatory drugs with diuretics and/or renin-angiotensin system inhibitors in the community increases the risk of acute kidney injury.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of acute kidney injury (AKI) when used in triple combination with renin-angiotensin system inhibitors and diuretics, but previous research reported that NSAIDs in dual combinations with either renin-angiotensin system inhibitors or diuretics alone were not. However, earlier studies relied on hospital coding to define AKI, which may underestimate true risk. This nested case-control study characterized the risk of community-acquired AKI associated with NSAID use among 78,379 users of renin-angiotensin system inhibitors and/or diuretics, where AKI was defined as a 50% or greater increase in creatinine from baseline. The AKI incidence was 68/10,000 person-years. The relative increase in AKI risk was similar for NSAID use in both triple (adjusted rate ratio 1.64 (95% CI 1.25-2.14)) and dual combinations with either renin-angiotensin system inhibitors (1.60 (1.18-2.17)) or diuretics (1.64 (1.17-2.29)). However, the absolute increase in AKI risk was higher for NSAIDs used in triple versus dual combinations with renin-angiotensin system inhibitors or diuretics alone (numbers needed to harm for 1 year treatment with NSAID of 158 vs. over 300). AKI risk was highest among users of loop diuretic/aldosterone antagonist combinations, in those over 75 years of age, and in those with renal impairment. Thus, the nephrotoxic potential of both dual and triple combinations of NSAIDs with renin-angiotensin system inhibitors and/or diuretics yields a higher incidence of AKI than previously thought.

The rising tide of polypharmacy and drug-drug interactions: population database analysis 1995-2010.

BACKGROUND: The escalating use of prescribed drugs has increasingly raised concerns about polypharmacy. This study aims to examine changes in rates of polypharmacy and potentially serious drug-drug interactions in a stable geographical population between 1995 and 2010. METHODS: This is a repeated cross-sectional analysis of community-dispensed prescribing data for all 310,000 adults resident in the Tayside region of Scotland in 1995 and 2010. The number of drug classes dispensed and the number of potentially serious drug-drug interactions (DDIs) in the previous 84 days were calculated, and age-sex standardised rates in 1995 and 2010 compared. Patient characteristics associated with receipt of ≥ 10 drugs and with the presence of one or more DDIs were examined using multilevel logistic regression to account for clustering of patients within primary care practices. RESULTS: Between 1995 and 2010, the proportion of adults dispensed ≥ 5 drugs doubled to 20.8%, and the proportion dispensed ≥ 10 tripled to 5.8%. Receipt of ≥ 10 drugs was strongly associated with increasing age (20-29 years, 0.3%; ≥ 80 years, 24.0%; adjusted OR, 118.3; 95% CI, 99.5-140.7) but was also independently more common in people living in more deprived areas (adjusted OR most vs. least deprived quintile, 2.36; 95% CI, 2.22-2.51), and in people resident in a care home (adjusted OR, 2.88; 95% CI, 2.65-3.13). The proportion with potentially serious drug-drug interactions more than doubled to 13% of adults in 2010, and the number of drugs dispensed was the characteristic most strongly associated with this (10.9% if dispensed 2-4 drugs vs. 80.8% if dispensed ≥ 15 drugs; adjusted OR, 26.8; 95% CI 24.5-29.3). CONCLUSIONS: Drug regimens are increasingly complex and potentially harmful, and people with polypharmacy need regular review and prescribing optimisation. Research is needed to better understand the impact of multiple interacting drugs as used in real-world practice and to evaluate the effect of medicine optimisation interventions on quality of life and mortality.

Prescribing cascades in ambulatory care: A structured synthesis of evidence.

The strength of evidence for specific ambulatory care prescribing cascades, in which a marker drug is used to treat an adverse event caused by an index drug, has not been well characterized. To perform a structured, systematic, and transparent review of the evidence supporting ambulatory care prescribing cascades. Ninety-four potential prescribing cascades identified through a previously published systematic review. Systematic search of the literature to further characterize prescribing cascades. (1) Grading of evidence based on observational studies investigating associations between index and marker drugs, including: Level I-strong evidence [i.e. multiple high-quality studies]; Level II-moderate evidence [i.e. single high-quality study]; Level III-fair evidence [no high-quality studies but one or more moderate-quality studies]; and Level IV-poor evidence [other]. (2) Listing of the adverse event associated with the index drug in the product's United States Food and Drug Administration (FDA) label. (3) Synthesis of the evidence supporting mechanisms linking index drugs and associated adverse events. Of 99 potential cascades, 94 were supported by one or more confirmatory observational studies and were therefore included in this review. The 94 cascades related to 30 types of adverse drug reactions affecting 10 different anatomic/physiologic systems and were investigated by a total of 88 confirmatory studies, including prescription sequential symmetry analysis (n = 51), cohort (n = 30), and case-control (n = 7) studies. Overall, the evidence from observational studies was strong for 18 (19.1%) prescribing cascades, moderate for 61 (64.9%), fair for 13 (13.8%), and poor for 2 (2.1%). Although the evidence supporting mechanisms that link index drugs and associated adverse events was variable, FDA labels included information about the adverse event associated with the index drug for most (n = 86) but not all of the 94 prescribing cascades. Although we identified 18 of 94 prescribing cascades supported by strong clinical evidence and most adverse events associated with index drugs are included in FDA label, the evidentiary basis for prescribing cascades varies, with many requiring further evidence of clinical relevance.

Depression and vaccination behavior in patients with chronic physical illness - A cross-sectional survey.

OBJECTIVE: Chronically ill are vulnerable to vaccine preventable infections. Consequently, their vaccination behavior is highly relevant. Depressive comorbidities are frequent in these patients. Furthermore, these patients are mainly diagnosed, treated and vaccinated in primary care. Therefore, we aimed to investigate the associations between depression and vaccination behavior (COVID-19 and influenza) in adult chronically ill primary care patients. METHODS: In a cross-sectional survey, we examined depression (PHQ9), psychological antecedents of vaccinations (Confidence and Constraints), health care utilization, and vaccination status. Based on an effect model, descriptive statistics and mixed linear/logistic models were calculated. (German Clinical Trials Register, DRKS00030042). RESULTS: n = 795 patients were analyzed. Both psychological antecedents of vaccinations (Confidence and Constraints) mediated a negative association between depression and vaccination behavior, healthcare utilization mediated a positive association. The total effect of depression was negligible. CONCLUSIONS: As the effects of vaccination readiness and healthcare utilization are opposing, different total effects depending on the study population are possible. Further studies are needed to investigate additional predictors of vaccination behavior. PRACTICE IMPLICATIONS: We suggest tackling vaccine acceptance in chronically ill through increasing confidence using communication-based interventions, for which primary care is the suitable setting. Constraints might be reduced by reminder and recall systems.

Expectations of general practitioners on a practice based research network in Germany- a qualitative study within the Bavarian Research Practice Network (BayFoNet).

BACKGROUND: Despite general practitioners' (GPs') key role in Germany`s primary health care, clinical research in general practice is scarce. Clinical research is mainly conducted at inpatient facilities, although their results are rarely transferable. German GPs have no extra time or funding for research, as well as limited research training. To support clinical research in German primary health care, practice-based research networks (PBRNs) are developed. As they will be based on an active involvement of GPs, we need more information on GPs` participation-readiness. The aim of this study was to explore facilitators and barriers to participation in the Bavarian Research Practice Network (BayFoNet) from the GPs`perspective before clinical trials will be performed. METHODS: We have performed semi-structured qualitative interviews with a purposive sample of 20 Bavarian GPs in 2022 under the application of the consolidated framework for implementation research (CFIR). Transcriptions were analysed according to Kuckartz` qualitative content analysis. The five domains of the CFIR framework served as initial deductive codes. RESULTS: N = 14 interviewees already agreed to participate in BayFoNet, whereas n = 6 interviewees opted not to participate in BayFoNet at the time of data collection. Main facilitators to conduct clinical research within BayFoNet were the motivation to contribute to evidence strength and quality in general practice, professional development and training of practice staff, as well as networking. Barriers for an active participation were bad experiences with previous clinical studies and lack of resources. CONCLUSIONS: PBRNS in Germany have to be promoted and the entire practice team has to be involved at an early stage of development. Professional training of general practice staff and a living network might enhance engagement. Participatory approaches could help to develop acceptable and feasible study designs. Furthermore, PBRNs should support patient recruitment and data collection in general practices and disseminate the results of their research projects regularly to maintain GPs` engagement. TRIAL REGISTRATION: DRKS00028805, NCT05667207.

Associations of Mental Health Issues with Health Literacy and Vaccination Readiness against COVID-19 in Long-Term Care Facilities-A Cross-Sectional Analysis.

Vaccinations against COVID-19 are of the utmost importance in long-term care facilities. During the pandemic, mental health issues increased significantly. This cross-sectional analysis aimed to assess the associations of depression and anxiety with health literacy in people in need of care and the association of depression and burnout with vaccination readiness against COVID-19 in health care workers (HCWs). Within our cross-sectional study, people in need of care were assessed for symptoms of depression (PHQ-9), anxiety (GAD-7), and health literacy (HLS-EU-Q16). Among HCWs, we assessed symptoms of depression (PHQ-9) and burnout (MBI-HSS), as well as psychological antecedents of vaccination (5C) to measure vaccination readiness against COVID-19. A multivariate regression analysis was performed. Symptoms of a major depression were significantly associated with reduced health literacy (p = 0.010) in people in need of care. Among HCWs, symptoms of depression and burnout reduced vaccination readiness against COVID-19 significantly. In particular, collective responsibility was reduced in HCWs suffering from burnout symptoms (p = 0.001). People in need of care and their HCWs could benefit from intensified target group-specific vaccination counseling. Additionally, more attention should be paid to the protection of mental health in long-term care facilities.

Hepatic Impairment as a Risk Factor for Drug Safety: Suitability and Comparison of Four Liver Scores as Screening Tools.

Hepatic impairment (HI) influences the pharmacokinetics and pharmacodynamics of drugs and represents an important risk factor for drug safety. A reliable screening tool for HI identification at hospital admission by pharmacists would be desirable but is currently lacking. Therefore, we tested four liver scores as potential screening instruments. We retrospectively recorded liver/bile diagnoses, symptoms and abnormalities (summarized as hepatic findings) of 200 surgical patients followed by an assessment of the relevance of these findings for drug therapy (rating). The agreement between the Model of Endstage Liver Disease (MELD), Non-alcoholic fatty liver disease fibrosis score (NFS), Fibrosis 4 index (FIB-4), and aspartate-aminotransferase to platelet ratio index (APRI) and the rating was quantified by Cohen's Kappa. The performance of the scores in this setting was further evaluated by their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Of 200 patients, 18 (9%) had hepatic findings relevant for drug therapy. Fair agreement was found for FIB-4 and MELD and slight agreement for APRI and NFS compared to the rating. The highest values for sensitivity, specificity, PPV, and NPV were 41.2% (MELD), 99.3% (APRI), 66.7% (APRI), and 93.6% (MELD), respectively. Due to low performance, none of the scores can be recommended for clinical use as a single screening tool for HI at hospital admission.

CBT-Intervention for panic disorder in primary care: 5 years follow-up of a cRCT during the Covid-19 pandemic.

A practice team-based exercise programme with elements of cognitive behavioural therapy (CBT) and case management for patients with panic disorder with or without agoraphobia in primary care showed significant positive effects. Here, we analyse the long-term effects (>5 years) of this intervention in the stressful context of the Covid-19 pandemic. All participants of the original PARADIES cluster randomized controlled trial (cRCT; 2012-2016) were invited to participate in a follow-up during the Covid-19 pandemic. Clinical outcomes were anxiety symptoms, number and severity of panic attacks, agoraphobic avoidance behaviour, Covid-specific anxiety symptom severity, depression, and patient assessment of chronic illness care. Data were analysed cross-sectionally for group differences (intervention, control) and longitudinally (T0: baseline, T1: 6 months and TCorona: >60 months). Of the original 419 participants, 100 participated in the 60 months follow-up (October 2020-May 2021). In the cross-sectional analysis, the anxiety symptom severity in the intervention group was lower than in the control group (p = .011, Cohen's d = .517). In the longitudinal analysis, both groups showed an increase of anxiety and depression symptoms compared to pre-pandemic level. The intervention may have had a lasting impact regarding anxiety severity despite the challenging context of the Covid-19 pandemic. However, we cannot say to what extend the intervention still played a role in participants' lives; other factors may also have helped with coping. The increase of anxiety and depression symptoms in both groups over time could be attributed to external circumstances.

Psychological Determinants of Vaccination Readiness against COVID-19 and Seasonal Influenza of the Chronically Ill in Primary Care in Germany-A Cross-Sectional Survey.

Vaccines against COVID-19 and influenza are highly recommended for the chronically ill. They often suffer from co-morbid mental health issues. This cross-sectional observational study analyzes the associations between depression (PHQ-9) and anxiety (OASIS) with vaccination readiness (5C) against COVID-19 and influenza in chronically ill adults in primary care in Germany. Sociodemographic data, social activity (LSNS), patient activation measure (PAM), and the doctor/patient relationship (PRA) are examined as well. Descriptive statistics and linear mixed-effects regression models are calculated. We compare data from n = 795 study participants. The symptoms of depression are negatively associated with confidence in COVID-19 vaccines (p = 0.010) and positively associated with constraints to get vaccinated against COVID-19 (p = 0.041). There are no significant associations between symptoms of depression and vaccination readiness against influenza. Self-reported symptoms of a generalized anxiety disorder seem not to be associated with vaccination readiness. To address confidence in COVID-19 vaccines among the chronically ill, targeted educational interventions should be elaborated to consider mental health issues like depression. As general practitioners play a key role in the development of a good doctor/patient relationship, they should be trained in patient-centered communication. Furthermore, a standardized implementation of digital vaccination management systems might improve immunization rates in primary care.