Digital Medication Management in Polypharmacy­Findings of a Cluster-Randomized, Controlled Trial With a Stepped-Wedge Design in Primary Care Practices (AdAM).

BACKGROUND: Inappropriate drug prescriptions for patients with polypharmacy can have avoidable adverse consequences. We studied the effects of a clinical decision-support system (CDSS) for medication management on hospitalizations and mortality. METHODS: This stepped-wedge, cluster-randomized, controlled trial involved an open cohort of adult patients with polypharmacy in primary care practices (=clusters) in Westphalia-Lippe, Germany. During the period of the intervention, their medication lists were checked annually using the CDSS. The CDSS warns against inappropriate prescriptions on the basis of patient-related health insurance data. The combined primary endpoint consisted of overall mortality and hospitalization for any reason. The secondary endpoints were mortality, hospitalizations, and high-risk prescription. We analyzed the quarterly health insurance data of the intention-to-treat population with a mixed logistic model taking account of clustering and repeated measurements. Sensitivity analyses addressed effects of the COVID-19 pandemic and other effects. RESULTS: 688 primary care practices were randomized, and data were obtained on 42 700 patients over 391 994 quarter years. No significant reduction was found in either the primary endpoint (odds ratio [OR] 1.00; 95% confidence interval [0.95; 1.04]; p = 0.8716) or the secondary endpoints (hospitalizations: OR 1.00 [0.95; 1.05]; mortality: OR 1.04 [0.92; 1.17]; high-risk prescription: OR 0.98 [0.92; 1.04]). CONCLUSION: The planned analyses did not reveal any significant effect of the intervention. Pandemic-adjusted analyses yielded evidence that the mortality of adult patients with polypharmacy might potentially be lowered by the CDSS. Controlled trials with appropriate follow-up are needed to prove that a CDSS has significant effects on mortality in patients with polypharmacy.

[Loss of information in cross-sectoral treatment: causes and solutions]. / Informationsverluste bei sektorübergreifender Behandlung: Ursachen und Lösungen.

Missing information on patients and their medication is a leading cause of medication errors and preventable harm. The TOP Projects uses pharmacy claim data and electronic decision support to improve quality and safety of care on hospital admission. In a survey 100 % of responding hospitals in Germany consider this approach helpful and important to improve availability of necessary information and medication safety and to reduce workload.

Spontaneously reported persistent symptoms related to coronavirus disease 2019 one year after hospital discharge : A retrospective cohort single-center study.

BACKGROUND: There are no outcome studies for coronavirus disease 2019 (COVID-19) survivors one year after hospital discharge in Germany. METHODS: This retrospective cohort study included all patients with polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hospitalized in the departments of internal medicine of the Klinikum Saarbrücken, a tertiary care hospital, between March 15 and December 31, 2020. A telephone interview with survivors was conducted at least 12 months after discharge. The interview was initiated with an open-ended question whether the patient had fully recovered from the disease. In the event of a subjective incomplete recovery, the patient was prompted to report any continuous or frequent symptoms that had not occurred prior to COVID-19. Finally, independent of the open-ended question response, all patients were asked closed questions which addressed new symptom onset of persistent fatigue, cognitive dysfunction, headache, muscle and joint pain following COVID-19. RESULTS: In all, 235 survivors were contacted and 162 could be included in the analysis. In 55 of 162 interviews (34.0%) at least one persistent COVID-19 symptom (PCS) was spontaneously reported. Four of 55 survivors with PCS reported five additional symptoms on the closed questions. One survivor, who responded positively to the open-ended question, reported new onset PCS in response to the closed questions. Physical fatigue (24.7%), cognitive dysfunction (14.8%), shortness of breath (8.6%), muscle and joint pain (6.8%) and headache (6.2%) were the most frequently reported PCS. CONCLUSIONS: Despite an interview technique aimed to reduce attribution bias by patients, one third of COVID-19 inpatient survivors report PCS one year after hospitalization. The complete article is written in English.

Comparison of the Covered Self-Expandable Viatorr CX Stent with the Covered Balloon-Expandable BeGraft Peripheral Stent for Transjugular Intrahepatic Portosystemic Shunt (TIPS) Creation: a Single-Centre Retrospective Study in Patients with Variceal Bleeding.

PURPOSE: This study compares the safety and efficacy of the ePTFE-covered self-expansible nitinol stent (VIATORR® Controlled Expansion, Gore, Flagstaff, USA) with the ePTFE-covered, balloon-expandable, metallic stent (BeGraft peripheral, Bentley, Hechingen, Germany) for the creation of the transjugular intrahepatic portosystemic shunt (TIPS). MATERIAL AND METHODS: From September 2016 to December 2020, 72 consecutive patients receiving TIPS for acute variceal bleeding (rescue and early TIPS, n = 15) or for prophylaxis of variceal rebleeding (n = 57) were enrolled. The main contraindications were patients with vascular liver disease (portal vein thrombosis and Budd-Chiari syndrome). Forty patients (55.6%) received a Viatorr CX stent and 32 patients (44.4%) a BeGraft peripheral stent. Safety endpoints were technical and clinical adverse events and early deaths within 30 days after TIPS implantation. Efficacy endpoints were rebleeding rates, recurrence of large varices requiring endoscopic band ligation, or TIPS revision. RESULTS: Groups receiving the Viatorr CX or BeGraft peripheral stent were comparable in all respects except the TIPS indication for acute variceal bleeding (5% vs. 25%, p = 0.015). All patients had a successful intervention, and the physical variables of stent implantation (intervention and fluoroscopy time, reduction of the portosystemic pressure gradient) as well as adjunctive embolization of varices were similar in both groups. Severe clinical complications (Viatorr CX: 5% vs. BeGraft peripheral: 3.1%, p = 0.692), post-TIPS hepatic encephalopathy (12.5% vs. 18.8%, p = 0.743) and death (5% vs. 0%, p = 0.793) were not different between Viatorr CX and BeGraft peripheral groups. With respect to efficacy, freedom from rebleeding and from variceal band ligation during follow-up (100% vs. 100%, p = 1.0), as well as the need for shunt revision (10.5% vs. 18.8%, p = 0.327), was comparable. CONCLUSION: Compared to the present gold standard, the Viatorr CX stent, the balloon-expandable BeGraft peripheral stent, showed similar results with respect to safety and efficacy.

Effectiveness of the application of an electronic medication management support system in patients with polypharmacy in general practice: a study protocol of cluster-randomised controlled trial (AdAM).

INTRODUCTION: Clinically complex patients often require multiple medications. Polypharmacy is associated with inappropriate prescriptions, which may lead to negative outcomes. Few effective tools are available to help physicians optimise patient medication. This study assesses whether an electronic medication management support system (eMMa) reduces hospitalisation and mortality and improves prescription quality/safety in patients with polypharmacy. METHODS AND ANALYSIS: Planned design: pragmatic, parallel cluster-randomised controlled trial; general practices as randomisation unit; patients as analysis unit. As practice recruitment was poor, we included additional data to our primary endpoint analysis for practices and quarters from October 2017 to March 2021. Since randomisation was performed in waves, final study design corresponds to a stepped-wedge design with open cohort and step-length of one quarter. SCOPE: general practices, Westphalia-Lippe (Germany), caring for BARMER health fund-covered patients. POPULATION: patients (≥18 years) with polypharmacy (≥5 prescriptions). SAMPLE SIZE: initially, 32 patients from each of 539 practices were required for each study arm (17 200 patients/arm), but only 688 practices were randomised after 2 years of recruitment. Design change ensures that 80% power is nonetheless achieved. INTERVENTION: complex intervention eMMa. FOLLOW-UP: at least five quarters/cluster (practice). recruitment: practices recruited/randomised at different times; after follow-up, control group practices may access eMMa. OUTCOMES: primary endpoint is all-cause mortality and hospitalisation; secondary endpoints are number of potentially inappropriate medications, cause-specific hospitalisation preceded by high-risk prescribing and medication underuse. STATISTICAL ANALYSIS: primary and secondary outcomes are measured quarterly at patient level. A generalised linear mixed-effect model and repeated patient measurements are used to consider patient clusters within practices. Time and intervention group are considered fixed factors; variation between practices and patients is fitted as random effects. Intention-to-treat principle is used to analyse primary and key secondary endpoints. ETHICS AND DISSEMINATION: Trial approved by Ethics Commission of North-Rhine Medical Association. Results will be disseminated through workshops, peer-reviewed publications, local and international conferences. TRIAL REGISTRATION: NCT03430336. ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT03430336).

Distinct Patterns of Blood Cytokines Beyond a Cytokine Storm Predict Mortality in COVID-19.

BACKGROUND: COVID-19 comprises several severity stages ranging from oligosymptomatic disease to multi-organ failure and fatal outcomes. The mechanisms why COVID-19 is a mild disease in some patients and progresses to a severe multi-organ and often fatal disease with respiratory failure are not known. Biomarkers that predict the course of disease are urgently needed. The aim of this study was to evaluate a large spectrum of established laboratory measurements. PATIENTS AND METHODS: Patients from the prospective PULMPOHOM and CORSAAR studies were recruited and comprised 35 patients with COVID-19, 23 with conventional pneumonia, and 28 control patients undergoing elective non-pulmonary surgery. Venous blood was used to measure the serum concentrations of 79 proteins by Luminex multiplex immunoassay technology. Distribution of biomarkers between groups and association with disease severity and outcomes were analyzed. RESULTS: The biomarker profiles between the three groups differed significantly with elevation of specific proteins specific for the respective conditions. Several biomarkers correlated significantly with disease severity and death. Uniform manifold approximation and projection (UMAP) analysis revealed a significant separation of the three disease groups and separated between survivors and deceased patients. Different models were developed to predict mortality based on the baseline measurements of several protein markers. A score combining IL-1ra, IL-8, IL-10, MCP-1, SCF and CA-9 was associated with significantly higher mortality (AUC 0.929). DISCUSSION: Several newly identified blood markers were significantly increased in patients with severe COVID-19 (AAT, EN-RAGE, myoglobin, SAP, TIMP-1, vWF, decorin) or in patients that died (IL-1ra, IL-8, IL-10, MCP-1, SCF, CA-9). The use of established assay technologies allows for rapid translation into clinical practice.

[Recommendations for Drug Treatment in Patients with Multimorbidity]. / Entwicklung von Empfehlungen zum Management von Arzneimitteltherapie bei Multimorbidität.

Applying guidelines in patients with multimorbidity can result in dangerous or contraindicated drug-drug and drug-disease-interactions. A representative working group of medical scientific associations identifies such therapeutic conflicts and develops management strategies that will be published as a formally consensus based (S2K) guideline. Rational, aims and methods used are described, as well as evaluation and updating of recommendations.

A prospective, multicentre study in acute non-cirrhotic, non-malignant portal vein thrombosis: comparison of medical and interventional treatment.

BACKGROUND: To evaluate medical versus interventional treatment (transjugular thrombus fragmentation, local thrombolysis with or without stent implantation) in patients with acute non-cirrhotic, non-malignant portal vein thrombosis (PVT). METHODS: This prospective, observational study enrolled 65 patients with acute (<28 days since begin of symptoms, no cavernoma) PVT in nine centres. Thirty patients received medical treatment and 35 patients received interventional treatment. PVT was graded into grade 1: short thrombosis and incomplete occlusion of the vessel lumen and grade 2: extended thrombosis or complete occlusion. Treatment response was classified as partial or complete, if thrombosis was reduced by one grade or to <25% of the vessel diameter respectively. RESULTS: Partial and complete response rates were 7% and 30% in the medical compared to 17% and 54% (P < 0.001) in the interventional treatment group. In the multivariate analysis, interventional treatment showed a strong positive (OR 4.32, P < 0.016) and a myeloproliferative aetiology a negative (OR 0.09, P = 0.006) prediction of complete response. Complications were rare in the medical group and consisted of septicaemia and upper gastrointestinal bleeding of unknown origin in one patient each. Interventional treatment was accompanied by mild and self-limiting bleeding complications in nine patients, moderate intra-abdominal bleeding requiring transfusions (2 units) in one patient and peritoneal bleeding requiring surgical rescue in one patient. Four patients in each group developed intestinal gangrene requiring surgery. One patient died 52 days after unsuccessful interventional treatment. CONCLUSIONS: Compared to medical treatment alone, interventional treatment doubled response rates at the cost of increased bleeding complications.

The federal standard medication plan in practice: An observational cross-sectional study on prevalence and quality.

BACKGROUND: Medication plans are instruments used to document drug therapies, guide patients, and ensure medication safety. In Germany, patients who take at least 3 long-term medications are eligible to receive a medication plan. It has been statutory to use the federal standard layout (German: "Bundeseinheitlicher Medikationsplan") since April 2017. OBJECTIVES: This study explores the prevalence, availability, medication discrepancies, and conformance with statutory regulations of medication plans since the introduction of the format of the federal standard medication plan in Germany. METHODS: Medication reconciliation was performed for hospitalized patients according to the Best Possible Medication History principle. The collected medication lists were analyzed for medication discrepancies and conformance with the statutory regulations. The medication discrepancies were (1) omitted drugs, (2) additional drugs, and (3) dosing errors. RESULTS: After hospitalization, 524 patients taking drugs were included. The majority (n = 424 patients) were eligible for a medication plan. While 241 medication lists were present, only 24.1% (n = 58) matched the federal standard format. The mean number of drugs was 6.3 ± 3.6, with 3315 medications (3046 long-term and 269 as needed) reconciled totally. The 84 medication lists with omitted or additional drugs included 166 medication discrepancies upon 774 drugs listed. Of the 253 patients with dosing errors, 146 had a medication list. Inappropriate dosages were due to single dose (n = 195), daily dose (n = 225) or frequency of application (n = 255). CONCLUSION: Medication plans are valuable tools for patients and health care providers. This study shows that the introduced paper-based federal standard medication plan in Germany falls short of its expectations regarding availability and correctness. Switching to an electronic patient record system may overcome some of the current pitfalls.

Influence of hospitalization on prescribing safety across the continuum of care: an exploratory study.

BACKGROUND: Transitions between different levels of healthcare, such as hospital admission and discharge, pose a considerable threat to the quality and continuity of drug therapy. This study aims to further explore the current role of hospitalization in prescribing error exposure and medication-related communication as patients are transferred from and back to ambulatory care. METHODS: Assisted by electronic decision support, pre-admission and discharge medication regimens of 187 adult patients in a German university hospital were comparatively screened for clinically relevant categories of potentially inadequate prescribing. Binary logistic regression analyses were conducted to identify risk factors predisposing individuals to prescribing errors as a result of hospitalization. Additionally, it was established to what extent medication changes and potentially inappropriate prescribing decisions originating from inpatient treatment were communicated in discharge letters. RESULTS: 94.7% of the patients are subjected to differences between pre-admission and discharge prescriptions occurring at a rate of 461 per 100 hospitalizations. However, these modifications in drug therapy do not have a significant effect on the total number of potential prescribing errors per patient (p = 0.135) even though a large potential for improvement exists throughout the care continuum. For instance, almost a quarter of study participants with impaired kidney function lacks appropriate dose adjustment for one or more drugs before onset and at the end of inpatient treatment alike (22.5% [95% CI: 13.5%-34.0%] vs. 22.8% [95% CI: 14.1%-33.6%]). Overall, the probability of error exposure following hospitalization rises with an increasing number of prescribed drugs per patient, while individuals treated on surgical wards are four times more likely to be discharged with a prescribing-related safety hazard than their counterparts from medical departments (OR: 4.069 [95% CI: 1.126-14.703]; p = 0.032). In the study population's discharge summaries only 14.8% of medication changes and none of the potentially inappropriate prescribing decisions made during inpatient care are addressed, despite the latter occurring at a rate of 91 per 100 hospitalizations. CONCLUSIONS: There is urgent need for standardized and evidence-based measures contributing to patient safety across sectorial interfaces of drug therapy. Our findings provide useful orientation for the targeted and rational design of such improvement strategies.

The use of health information technology in seven nations.

OBJECTIVE: To assess the state of health information technology (HIT) adoption and use in seven industrialized nations. DESIGN: We used a combination of literature review, as well as interviews with experts in individual nations, to determine use of key information technologies. MAIN OUTCOME MEASURES: We examined rates of electronic health record (EHR) use in ambulatory care and hospital settings, along with current activities in health information exchange (HIE) in seven countries: the United States (U.S.), Canada, United Kingdom (UK), Germany, Netherlands, Australia, and New Zealand (NZ). RESULTS: Four nations (the UK, Netherlands, Australia, and NZ) had nearly universal use of EHRs among general practitioners (each >90%) and Germany was far along (40-80%). The U.S. and Canada had a minority of ambulatory care physicians who used EHRs consistently (10-30%). While there are no high quality data for the hospital setting from any of the nations we examined, evidence suggests that only a small fraction of hospitals (<10%) in any single country had the key components of an EHR. HIE efforts were a high priority in all seven nations but the early efforts have had varying degrees of active clinical data exchange. CONCLUSION: We examined HIT adoption in seven industrialized nations and found that many have achieved high levels of ambulatory EHR adoption but lagged with respect to inpatient EHR and HIE. These data suggest that increased efforts will be needed if interoperable EHRs are soon to become ubiquitous in these seven nations.

[Comorbidity of internal inpatients in the german diagnosis related groups-system]. / Abbildung komorbider psychischer Störungen bei internistischen Patienten im G-DRG-System.

The representation of comorbid mental disorders within the German Diagnosis Related Groups-System was investigated. First the complication and complexity level CCL of diagnoses of mental disorders (ICD-10 category F) within the G-DRG-calculation handbooks 2004 and 2005 were checked. Second the revenue based on a fictitious base rate of 3000 with the G-DRG versions 2004/2005 respectively was calculated with and without inclusion of diagnosed comorbid mental disorders of 6610 cases of both medical departments of a hospital of tertiary care level (year 2004). Only F0-diagnoses could lead to a CCL of 3. In 28.2 % of the patients at least one comorbid diagnosis of the category F of the International Classification of Diseases (mental and substance induced disorders) had been coded. Renunciation of the diagnosed mental disorders would have been resulted in a fictitious reduction in revenues based on the G-DRG version 2004 of 93 600 and on the G-DRG version 2005 of 69 000 . The Patient Clinical Complexity Level PCCL was increased 0.15 by the comorbid mental disorders in each year. To achieve an adequate representation of comorbid mental disorders in the G-DRG-system and to ensure a financial survival of psychosomatic/psychiatric CL-services coordinated efforts of psychosomatic scientific societies and hospitals taking part in the G-DRG-calculation sample are necessary.

Biopsychosocial predictors of health-related quality of life in patients with chronic hepatitis C.

OBJECTIVES: To assess biopsychosocial predictors of health-related quality of life (HRQOL) in patients with chronic hepatitis C. METHODS: In 94 consecutive patients with chronic hepatitis C attending a liver center, HRQOL was assessed by the Medical Outcome Study Short Form Health Survey 36 (SF-36) and by the German version of the Chronic Liver Disease Questionnaire. The predictive effect on HRQOL of disease-related worries measured by the worry subscale of the Chronic Liver Disease Questionnaire, psychiatric comorbidity (defined by at least one Hospital Anxiety and Depression Scale German Version Score > or =11), the Child-Pugh score in case of cirrhosis, interferon therapy, and active medical comorbidities was assessed by a multiple regression analysis. RESULTS: From 88 patients (age, 48.6 +/- 14.6 years; 50% female), 62 (70%) had no cirrhosis, 15 (17%) Child A, 5 (6%) Child B, and 6 patients (7%) Child C cirrhosis. The mental summary score of SF-36 was predicted by the amount of disease-related worries (corrected R2 = 0.33; beta = 3.2; p < .001) and psychiatric comorbidity (corrected R2 = 0.42; beta = -9.0; p < .001), by the physical summary score of SF-36 by the amount of disease related worries (corrected R2 = 0.33; beta = 4.0; p < .001), and by the number of active medical comorbidities (corrected R2 = 0.39; beta = -2.0; p = .006). CONCLUSIONS: The HRQOL in chronic hepatitis C is not determined by the severity of the liver disease but by psychiatric and medical comorbidities and disease-related worries.

TIPS: an update.

During the last 15 years the transjugular intrahepatic portosystemic shunt (TIPS) procedure has become a safe and effective treatment of portal hypertension. Its major obstacle, the high rate of shunt insufficiency, is going to be solved by the availability of covered stents showing a patency rate of up to 90%. The treatment of acute oesophageal and gastric variceal bleeding is an unsolved problem because variceal bleeding remains the major cause of death in patients with cirrhosis. TIPS has become the rescue treatment of choice because it combines high efficacy with low invasiveness. In this context, the timing of the rescue TIPS is of major importance for achieving definitive haemostasis before multi-organ failure develops. In the prevention of re-bleeding, TIPS is accepted as a second-line treatment, required in about 10-20% of patients. TIPS may be indicated when more than two significant re-bleedings occurred within a time frame of 12 months in spite of adequate first-line measures i.e. drugs or ligation. Refractory ascites is the third main indication for TIPS. Five randomized studies comparing TIPS with paracentesis show good response and comparable survival. Interpretations of authors and comments of reviewers are, however, controversial and do not permit a definitive recommendation.

Validation of the German version of the Chronic Liver Disease Questionnaire.

OBJECTIVE: The Chronic Liver Disease Questionnaire is an instrument for the assessment of health-related quality of life in patients with chronic liver diseases. So far it has not been validated for German speaking countries. METHODS: Two hundred and three consecutive patients with chronic liver diseases (age, 52.7 +/- 13.9 years; 47% female; 45% no cirrhosis, 21% Child's class A, 15% Child's class B and 17% Child's class C cirrhosis; 52% with chronic viral hepatitis, 32% with alcoholic and 16% with other liver diseases) of a liver centre completed the German version of the Chronic Liver Disease Questionnaire (CLDQ-D), the Short Form Health Survey SF-36, the Hospital Anxiety and Depression Scale (HADS) and the Giessener Symptom List GBB-24. Fifty stable patients filled in the CLDQ-D a second time within 3 - 8 days. RESULTS: With 97.7% completed items the acceptance by the patients was high. The internal consistency (Cronbach alpha) for the subscales ranged from 0.69 to 0.95, the test-retest reliability ranged from 0.79 to 0.88. The correlation coefficients with similar subscales of the instruments used for validation ranged between 0.5 and 0.9 (convergent validity). Patients with liver cirrhosis Child-Pugh stage C scored significantly lower in the subscales 'Abdominal Symptoms', 'Activity' and 'Worry', indicating a reduced health-related quality of life than in patients without cirrhosis (P < 0.05) (discriminant validity). CONCLUSION: The CLDQ-D is well accepted by patients with chronic liver diseases and has good reliability and satisfactory discriminant validity.

The Budd-Chiari syndrome: outcome after treatment with the transjugular intrahepatic portosystemic shunt.

BACKGROUND: The role of portosystemic shunting in the treatment of the Budd-Chiari syndrome is still under debate. Medical therapy and liver transplantation are alternative treatments. The aim of this study was to determine the outcome of a transjugular intrahepatic portosystemic shunt implantation. METHODS: Thirty-five patients with severe Budd-Chiari syndrome and a Child-Pugh score of 9.2+/-1.9, who were not responsive to medical therapy, were elected for the transjugular shunt treatment, which was successfully accomplished in 33. Eleven patients had a fulminant/acute (history <2 months); 13, a subacute (<6 months); and 11, a chronic course of the disease. The shunt was established by using conventional self-expandable stents in 25 patients and polytetrafluoroethylene-covered stents in 8 patients. The mean follow-up was 37+/-29 months. RESULTS: The shunt reduced the portosystemic pressure gradient from 29+/-7 to 10+/-4 mm Hg and improved the portal flow velocity from 9.2+/-11 to 51+/-17 cm/s. Clinical symptoms as well as the biochemical test results improved significantly during 4 weeks after shunt treatment. Three patients died and 2 received liver transplants. The cumulative 1- and 5-year survival rate without transplantation in all patients was 93% and 74%, respectively, and in patients with fulminant/acute disease 91% and 91% respectively (no deaths in this time period). On the average, 1.4+/-2.2 revisions per patient were needed during the mean follow-up of 3 years with a 1-year probability of 47%. CONCLUSIONS: The transjugular shunt provides an excellent outcome in patients with severe fulminant/acute, subacute, and chronic Budd-Chiari syndrome. It may be regarded as a treatment for the acute and long-term management of these patients.