Duplicate prescriptions in the emergency department: a retrospective cohort study.

PURPOSE: To determine the nature and frequency of duplicate prescriptions (DPs) in the emergency department (ED) by utilization of a novel categorization of DPs which differentiates between appropriate DPs (ADPs) and potentially inappropriate DPs (PIDPs). METHODS: In this retrospective cohort study, adult patients who presented to the ED for internal medicine of a large university hospital in northern Germany in 2018 and 2019 were screened for the presence of DPs. Descriptive statistical methods were used to characterize the nature and frequency of PIDPs compared to the frequency of ADPs. RESULTS: A total of 4208 patients were enrolled into the study. The median age of the study population was 63 years (interquartile range (IQR) 48-77), 53.9% were female. The patients took a median of 5 drugs (IQR 3-9). 10.9% of the study population were affected by at least one PIDP (at least one grade-1 PIDP: 6.1%; at least one grade-2 PIDP: 4.5%; at least one grade-3 PIDP: 1.1%). Non-opioid analgesics accounted for the majority of grade-1 PIDPs, while inhalatives were most frequently responsible for grade-2 and grade-3 PIDPs. Nearly half of the study population (48.6%) displayed at least one ADP. CONCLUSION: PIDPs pose a frequent pharmacological challenge in the ED. The medication review should comprise a systematic screening for PIDPs with a particular focus on non-opioid analgesics and inhalatives. ADPs were detected more frequently than PIDPs, questioning the predominant notion in the medical literature that DPs are exclusively deleterious.

Students' guide to documentation in clinical trials.

PURPOSE: In the wake of the coronavirus disease 2019 (COVID-19) pandemic, support in clinical trials by students of human medicine and related disciplines has become of even greater importance than in pre-pandemic times. Documentation in clinical trials adheres to the principles of Good Clinical Practice (GCP), and healthcare professionals involved in the conduct of clinical trials-including students-are obliged to perform documentation in accordance with GCP principles. Unprecedented challenges have arisen with regard to the appropriate training of students as training courses in presence had largely to be suspended due to social-distancing regulations during the heyday of the COVID-19 pandemic. Therefore, novel training formats and self-study training materials for students working in clinical trials are urgently warranted. METHODS: To overcome this shortcoming and to define a common quality standard, an interdisciplinary, multiprofessional (physicians, study nurses, medical students), and binational (Germany, The Netherlands) expert panel convened and devised the Students' guide to documentation in clinical trials. RESULTS: Following a brief description of the different roles in clinical trials (e.g., sponsor, (principal) investigator, monitor) and an introduction into the principles of GCP, the documentation of adverse events, concomitant medication, medical history, and quality control are comprehensively discussed. The Guide concludes with a trilingual medical dictionary (English, German, Dutch) and with recommendations of pertinent literature for further reading. CONCLUSION: Serving both as textbook for self-training and as (quick-) reference work for the daily routine, the Guide has specifically been designed to complement, but not to replace practical training courses for students. While primarily addressed at students of human medicine and related disciplines, the Guide can also be of high relevance and utility to other healthcare professionals involved in the conduct of clinical trials.

Preoperative Recipient Parameters Allow Early Estimation of Postoperative Outcome and Intraoperative Transfusion Requirements in Liver Transplantation.

CONTEXT: Liver transplantation is a complex intervention, and early anticipation of personnel and logistic requirements is of great importance. Early identification of high-risk patients could prove useful. We therefore evaluated prognostic values of recipient parameters commonly available in the early preoperative stage regarding postoperative 30- and 90-day outcomes and intraoperative transfusion requirements in liver transplantation. DESIGN, SETTING, AND PARTICIPANTS: All adult patients undergoing first liver transplantation at Hannover Medical School between January 2005 and December 2010 were included in this retrospective study. Demographic, clinical, and laboratory data as well as clinical courses were recorded. Prognostic values regarding 30- and 90-day outcomes were evaluated by uni- and multivariate statistical tests. Identified risk parameters were used to calculate risk scores. RESULTS: There were 426 patients (40.4% female) included with a mean age of 48.6 (11.9) years. Absolute 30-day mortality rate was 9.9%, and absolute 90-day mortality rate was 13.4%. Preoperative leukocyte count >5200/µL, platelet count <91 000/µL, and creatinine values ≥77 µmol/L were relevant risk factors for both observation periods ( P < .05, respectively). A score based on these factors significantly differentiated between groups of varying postoperative outcomes and intraoperative transfusion requirements ( P < .05, respectively). CONCLUSION: A score based on preoperative creatinine, leukocyte, and platelet values allowed early estimation of postoperative 30- and 90-day outcomes and intraoperative transfusion requirements in liver transplantation. Results might help to improve timely logistic and personal strategies.

Drowning Injuries: Analysis of a Decennial Air Medical Rescue Center Experience.

OBJECTIVE: Drowning is one of the leading injury death causes in younger children. Common intensive care measures seem not to improve neurologic outcome, and early prognostic options appear partially unreliable. Therefore, we evaluated a cohort of drowning patients cotreated by a helicopter emergency medical service regarding typical incident constellations, early and subsequent prognostic options, and relevant interventions. METHODS: All patients prehospitally cotreated by helicopter emergency medical service "Christoph 4" in primary missions because of drowning incidents during a 10-year period were evaluated. Patient, prehospital, and clinical data were recorded retrospectively; correlations and prognostic values were evaluated with appropriate statistical tests. RESULTS: Fifty-one patients were included. Various examination results (several vital, neurologic, and laboratory parameters) and sufficient prehospital first aid measures were significantly correlated with the final outcome (P < .05, respectively). Aspartate aminotransferase and alanine aminotransferase values precisely discriminated between the final outcome groups (P = .001 and area under the receiver operating characteristic curve = 1.0 in both cases). CONCLUSION: Aspartate aminotransferase and alanine aminotransferase values were the most useful predictors of outcome in our study. Sufficient prehospital first aid measures were correlated with improved outcome. Regular first aider training is recommended.

Concordance of emergency department physicians' decisions on HIV post-exposure prophylaxis with national guidelines: results from a retrospective cohort study.

BACKGROUND: Post-exposure prophylaxis (PEP) is an effective tool to prevent infection with HIV. Patients seeking PEP after potential HIV exposure usually present to the emergency department (ED). Our study sought to determine the concordance of ED physicians' decisions on HIV-PEP with national guidelines (primary objective) and to assess the clinical relevance of drug-drug interactions (DDIs) between the HIV-PEP regimen and patients' concomitant medication (secondary objective). METHODS: We conducted a retrospective cohort study at the ED of Hannover Medical School, Germany. Between 1 January 2018 and 31 December 2019, 113 of 11 246 screened patients presented to the ED after potential HIV exposure and were enrolled in the study. RESULTS: The median age of the patients (82.3% male) was 30 y (IQR 25-35.5), 85.8% of potential HIV exposures were characterised as sexual and 85.0% presented within 72 h. ED physicians' decisions on HIV-PEP were concordant with national guidelines in 93.8%. No clinically relevant DDIs were detected. CONCLUSIONS: ED physicians' decisions on HIV-PEP were highly concordant with national guidelines. Approximately 1% of patient presentations to the ED were related to HIV exposure; therefore, training ED physicians on HIV transmission risk assessment and indications/contraindications for HIV-PEP is paramount.

A novel orf virus vector-based COVID-19 booster vaccine shows cross-neutralizing activity in the absence of anti-vector neutralizing immunity.

Next-generation COVID-19 vaccines are being developed to expand the breadth of coverage against existing and future variants and to extend the duration of protection. Prime-2-CoV_Beta is an orf virus (ORFV) based multi-antigen COVID-19 vaccine that co-expresses Spike (S) and Nucleocapsid (N) antigens. The safety and immunogenicity of Prime-2-CoV_Beta is investigated in a phase 1 first-in-human (FIH) dose-finding trial (ORFEUS study, ClinicalTrials.gov: NCT05367843). Participants of two age groups (18-55 and 65-85 years) who previously completed at least two doses of mRNA vaccines were enrolled and sequentially assigned to different dose groups to receive one intramuscular dose of 3 × 105, 3 × 106, 1.5 × 107, or 3 × 107 plaque-forming units (PFU) of Prime-2-CoV_Beta on day 1 and a second dose on day 29. Here, we report safety and immunogenicity data collected up to 6 months after the first study vaccination. Prime-2-CoV_Beta is safe and well tolerated and elicits immune responses at higher dose levels in participants aged 18-55. A single dose of 3 × 107 PFU boosted binding and cross-neutralizing antibody responses that are maintained through 6 months after the first booster vaccination. Polyfunctional S-specific CD4+ and CD8+ T cell responses are observed after vaccination. No pre-existing or vaccine-induced neutralizing anti-vector antibodies are detected. Our findings highlight the potential of the ORFV vector as a safe platform for future vaccine design, which provides the ability to deliver multiple antigens and allows for repeat immunization.

Clinical-pharmacological drug information center of Hannover Medical School: experiences and analysis from a tertiary care university hospital.

Drug information centers (DICs) are institutions dedicated to provide objective, independent, and up-to-date information on drugs and their rational use. To overcome the lack of recent DIC reports from central Europe, we analyzed all queries (n = 594) submitted to the DIC run by the Institute for Clinical Pharmacology of Hannover Medical School between October 2018 and April 2022. Approximately one in three queries (31.1%; 185/594) was submitted by internists. 82.8% (492/594) of the queries were patient-specific, while the remaining 17.2% (102/594) were general queries. Adverse drug reactions (ADRs), indications/contraindications, and pharmacodynamic interactions (PDIs) represented the three most frequently addressed query categories, being involved in 44.8% (266/594), 43.3% (257/594), and 34.3% (204/594) of all queries, respectively (assignment of more than one category per query was possible). As compared to general queries, patient-specific queries were statistically significantly more often related to ADRs, PDIs, and pharmacokinetic interactions (PKIs) (ADRs: 35.3% vs. 46.7%, P = 0.034; PDIs: 14.7% vs. 38.4%, P < 0.001; PKIs: 20.6% vs. 31.5%, P = 0.028). To demonstrate the complexity of queries submitted to the clinical-pharmacological DIC, we present and comment on an illustrative selection of queries.

Influence of alcohol consumption on blood coagulation in rotational thromboelastometry (ROTEM): an in-vivo study.

BACKGROUND: Twenty-five to 85% of trauma patients are under the influence of alcohol in addition to experiencing injury-related coagulation impairment. Viscoelastic point-of-care tests (thrombelastography [TEG], rotational thromboelastometry [ROTEM]) are popular tools for rapid hemostasis assessment and therapeutic decision-making in this and other settings. While alcohol affects these tests in-vitro, their specific effects in-vivo are unclear. Therefore, we evaluated the effects of alcohol ingestion on ROTEM parameters. METHODS: Twenty volunteers provided informed consent to drinking red wine, whisk(e)y, or vodka to a target blood alcohol concentration of 1 ‰ within one hour, calculated with the Widmark formula. Blood samples were collected before drinking, at a breath alcohol concentration of 0.5 ‰, and at 1.0 ‰, but no later than one hour. After each blood collection, ExTEM and FibTEM tests were performed directly "at the bedside." RESULTS: All participants had a blood alcohol concentration (BAC) of 0.00 ‰ at the beginning. The mean BACs at the second and third collection were 0.48 and 0.76 ‰, respectively. There were no significant differences in the ExTEM parameters. FibTEM measurements showed a significant difference at the A10 value (13.0 vs. 14.0 mm, P = 0.014) and a trend at the maximum amplitude (maximum clot firmness [MCF] 13.7 vs. 16.2 mm, P = 0.075). We saw no significant differences in fibrinolysis parameters and no hyperfibrinolysis in our ROTEM measurements. CONCLUSIONS: Ethanol ingestion can impair early fibrin polymerization. These results might be of special relevance in trauma and support routine application of ROTEM/TEG in such cases.

Coagulation monitoring and transfusion in major non-emergency orthopaedic surgery - An observational study.

OBJECTIVE: Perioperative coagulation monitoring and transfusions were evaluated. METHODS: 70 cases were included. Time points: before (PRE), after surgery (POST), day 1, day 3, day 7. Standard and patient near tests were assessed. Groups were: Transfused (TG); Control (CG). RESULTS: 23 patients were transfused (TG), 47 were not (CG). PRE haemoglobin was reduced, coagulation time (CT) was prolonged in TG. FIBTEM decrease was higher in TG. Leukocytes were elevated in TG. ASPI decreased, TRAP and ADP aggregability increased in both groups. CONCLUSION: CT, haemoglobin and fibrinogen were associated with transfusion. TRAP and ADP aggregability increased and could account for thromboembolism.

The CANNA-TICS Study Protocol: A Randomized Multi-Center Double-Blind Placebo Controlled Trial to Demonstrate the Efficacy and Safety of Nabiximols in the Treatment of Adults With Chronic Tic Disorders.

Background: Gilles de la Tourette syndrome (TS) is a chronic neuropsychiatric disorder characterized by motor and vocal tics. First-line treatments for tics are antipsychotics and tic-specific behavioral therapies. However, due to a lack of trained therapists and adverse events of antipsychotic medication many patients seek alternative treatment options including cannabis. Based on the favorable results obtained from case studies on different cannabis-based medicines as well as two small randomized controlled trials using delta-9-tetrahydrocannabinol (THC), we hypothesize that the cannabis extract nabiximols can be regarded as a promising new and safe treatment strategy in TS. Objective: To test in a double blind randomized clinical trial, whether treatment with the cannabis extract nabiximols is superior to placebo in patients with chronic tic disorders. Patients and Methods: This is a multicenter, randomized, double-blind, placebo controlled, parallel-group, phase IIIb trial, which aims to enroll 96 adult patients with chronic tic disorders (TS or chronic motor tic disorder) across 6 centers throughout Germany. Patients will be randomized with a 2:1 ratio into a nabiximols and a placebo arm. The primary efficacy endpoint is defined as tic reduction of at least 30% (compared to baseline) according to the Total Tic Score of the Yale Global Tic Severity Scale (YGTSS-TTS) after 13 weeks of treatment. In addition, several secondary endpoints will be assessed including changes in different psychiatric comorbidities, quality of life, driving ability, and safety assessments. Discussion: This will be the first large, controlled study investigating efficacy and safety of a cannabis-based medicine in patients with TS. Based on available data using different cannabis-based medicines, we expect not only a reduction of tics, but also an improvement of psychiatric comorbidities. If the cannabis extract nabiximols is proven to be safe and effective, it will be a valuable alternative treatment option. The results of this study will be of high health-economic relevance, because a substantial number of patients uses cannabis (illegally) as self-medication. Conclusion: The CANNA-TICS trial will clarify whether nabiximols is efficacious and safe in the treatment of patients with chronic tic disorders. Clinical Trial Registration: This trial is registered at clinicaltrialsregister.eu (Eudra-CT 2016-000564-42) and clinicaltrials.gov (NCT03087201).

Use of Rotational Thromboelastometry in Liver Transplantation Is Associated With Reduced Transfusion Requirements.

OBJECTIVES: Increased transfusion requirements in liver transplantation have been reported to be associated with worsened outcomes, more frequent reinterventions, and higher expenses. Anesthesiologists might counteract this through improved coagulation management. We evaluated the effects of rotational thromboelastometry on transfusion and coagulation product requirements and on outcome measurements. MATERIALS AND METHODS: Patients who were 14 years or older and who were undergoing liver transplant at Hannover Medical School between January 2005 and December 2009 were included in this retrospective analysis. Demographic, clinical, and laboratory data, use of rotational thromboelastometry, intraoperative need for blood or coagulation products and antifibrinolytic substances, and clinical course were recorded. Correlations were examined using appropriate statistical tests. RESULTS: Our study included 413 patients. Use of rotational thromboelastometry was associated with less frequent intraoperative administration of red blood cell concentrates, fresh frozen plasma, platelet concentrates, prothrombin complex concentrates, and antithrombin concentrates (all P < .05). In addition, univariate and multivariate tests showed that rotational thromboelastometry was correlated with decreased need for red blood cell concentrates and fresh frozen plasma (all P < .05). Intraoperative administration rates of antifibrinolytic substances and fibrinogen concentrate were significantly increased in patients who received rotational thromboelastometry monitoring (both P < .05). However, use of rotational thromboelastometry was not associated with massive transfusion rates (> 10 units vs less), clinical outcome, or length of stay in the intensive care unit (all P > .05). CONCLUSIONS: Use of rotational thromboelastometry during liver transplant may reduce the need for intraoperative transfusion and coagulation products. Relevant effects of rotational thromboelastometry on patient outcomes or lengths of stay in the intensive care unit could not be ascertained. However, readjustment of therapeutic thresholds may improve the clinical impact.

Porcine model for the study of liver regeneration enhanced by non-invasive 13C-methacetin breath test (LiMAx test) and permanent portal venous access.

INTRODUCTION: Despite advances in perioperative management and surgical technique, postoperative liver failure remains a feared complication after hepatic resection. Various supportive treatment options are under current discussion, but lack of structured evaluation. We therefore established a porcine model of major liver resection to study regeneration after partial hepatectomy in a reliable and well-defined pre-clinical setting. METHODS: Major hepatectomy was performed on seven minipigs with the intention to set up a non-lethal but relevant transient impairment of liver function. For steady postoperative vascular access (e.g. for blood withdrawal, measurement of venous pressure), permanent catheters were implanted into the internal jugular and portal veins, respectively. Animals were followed up for 30 days; clinical and laboratory results were recorded in detail. Monitoring was enhanced by non-invasive determination of the maximum liver function capacity (LiMAx test). RESULTS AND CONCLUSIONS: The established porcine model appeared suitable for evaluation of postoperative liver regeneration. Clinical characteristics and progression of liver function impairment as well as subsequent recovery were comparable to courses known from surgery in humans. Laboratory parameters (e.g. liver enzymes, bilirubin, INR, coagulation factor II) showed relevant derangements during postoperative days (POD) 0 to 3 followed by normalization until POD 7. Application of the LiMAx test was feasible in minipigs, again showing values comparable to humans and kinetics in line with obtained laboratory parameters. The exteriorized portal vein catheters enabled intra- and postoperative monitoring of portal venous pressures as well as easy access for blood withdrawal without relevant risk of postoperative complications.

Application of the Liver Maximum Function Capacity Test in Acute Liver Failure: A Helpful Tool for Decision-Making in Liver Transplantation?

Background. Despite aggressive intensive medical management acute liver failure (ALF) may require high-urgency liver transplantation (LTx). Available prognostic scores do not apply for all patients; reliable tools to identify individuals in need of LTx are highly required. The liver maximum function capacity test (LiMAx) might represent an appropriate option. Referring to a case of ALF after Amanita phalloides-intoxication the potential of the LiMAx-test in this setting is discussed. Presentation of Case. LiMAx was performed in a 27-year-old patient prior to and after high-urgency LTx. In accordance with clinical appearance of hepatic encephalopathy, coagulopathy, and acute kidney failure, the LiMAx-test constituted a fulminant course of ALF with hardly any detectable metabolic activity. Following LTx with a marginal donor organ (95% hepatosteatosis), uptake of liver function was demonstrated by postoperative increase of the LiMAx-value. The patient was discharged from hospital on postoperative day 26. Discussion. ALF often is associated with a critical state of the patient that requires almost immediate decision-making regarding further therapy. Application of a noninvasive liver function test might help to determine the prognosis of ALF and support decision-making for or against LTx as well as acceptance of a critical donor organ in case of a critically ill patient.