A mixed methods analysis of the medication review intervention centered around the use of the 'Systematic Tool to Reduce Inappropriate Prescribing' Assistant (STRIPA) in Swiss primary care practices.

BACKGROUND: Electronic clinical decision support systems (eCDSS), such as the 'Systematic Tool to Reduce Inappropriate Prescribing' Assistant (STRIPA), have become promising tools for assisting general practitioners (GPs) with conducting medication reviews in older adults. Little is known about how GPs perceive eCDSS-assisted recommendations for pharmacotherapy optimization. The aim of this study was to explore the implementation of a medication review intervention centered around STRIPA in the 'Optimising PharmacoTherapy In the multimorbid elderly in primary CAre' (OPTICA) trial. METHODS: We used an explanatory mixed methods design combining quantitative and qualitative data. First, quantitative data about the acceptance and implementation of eCDSS-generated recommendations from GPs (n = 21) and their patients (n = 160) in the OPTICA intervention group were collected. Then, semi-structured qualitative interviews were conducted with GPs from the OPTICA intervention group (n = 8), and interview data were analyzed through thematic analysis. RESULTS: In quantitative findings, GPs reported averages of 13 min spent per patient preparing the eCDSS, 10 min performing medication reviews, and 5 min discussing prescribing recommendations with patients. On average, out of the mean generated 3.7 recommendations (SD=1.8). One recommendation to stop or start a medication was reported to be implemented per patient in the intervention group (SD=1.2). Overall, GPs found the STRIPA useful and acceptable. They particularly appreciated its ability to generate recommendations based on large amounts of patient information. During qualitative interviews, GPs reported the main reasons for limited implementation of STRIPA were related to problems with data sourcing (e.g., incomplete data imports), preparation of the eCDSS (e.g., time expenditure for updating and adapting information), its functionality (e.g., technical problems downloading PDF recommendation reports), and appropriateness of recommendations. CONCLUSIONS: Qualitative findings help explain the relatively low implementation of recommendations demonstrated by quantitative findings, but also show GPs' overall acceptance of STRIPA. Our results provide crucial insights for adapting STRIPA to make it more suitable for regular use in future primary care settings (e.g., necessity to improve data imports). TRIAL REGISTRATION: Clinicaltrials.gov NCT03724539, date of first registration: 29/10/2018.

Awareness of the impact of sex and gender in the disease risk and outcomes in hematology and medical oncology-a survey of Swiss clinicians.

BACKGROUND: Although male and female cancer patients are distinct in many ways, there is a limited understanding in the differences between male and female biology and differing pharmacokinetic responses to cancer drugs. In fact, sex and gender are currently not considered in most treatment decisions in the fields of oncology and hematology. The lack of knowledge about potential sex differences in both disciplines may lead to differences in treatment efficacy, toxicity, and the overall survival (OS) of patients. AIM: To evaluate their awareness about sex and gender in clinical practice we surveyed Swiss hematologists and oncologists from September to November 2022. METHODS: We collected data about the clinical knowledge, experimental research, palliative care, quality of life, as well as the participant perception of the importance of sex and gender. We identified 767 eligible clinicians, of whom 150 completed the survey (20% response rate). RESULTS: While most participants agreed that sex and gender were relevant when treating patients, it became clear that fewer participants knew about sex and gender differences in treatment toxicity and survival, which in turn would affect the treatment of their patients. Most participants agreed that this topic should be integrated into continuing education and research. CONCLUSION: Our findings indicate the need for more awareness and training on sex and gender in cancer research and clinical care among oncologists and hematologists. Ideally, by better educating medical students and health professionals, a demand is created for improving research policies, publications and therefore patient care.

Comparative Safety of the BNT162b2 Messenger RNA COVID-19 Vaccine vs Other Approved Vaccines in Children Younger Than 5 Years.

Importance: SARS-CoV-2 vaccines are authorized for use in most age groups. The safety of SARS-CoV-2 vaccines is unknown in children younger than 5 years. Objective: To retrospectively evaluate the safety of the BNT162b2 vaccine used off-label in children younger than 5 years compared with the safety of non-SARS-CoV-2 vaccines in the same sample. Design, Setting, and Participants: This investigator-initiated retrospective cohort study included parents or caregivers who registered children for SARS-CoV-2 vaccination in outpatient care facilities in Germany. The study was performed as an authenticated online survey. A total of 19 000 email addresses were contacted from vaccination registration databases between April 14 and May 9, 2022. Inclusion criteria were child age younger than 5 years at the first BNT162b2 vaccination and use of a correct authentication code to prove invitation. Exposures: Off-label BNT162b2 vaccination and on-label non-SARS-CoV-2 vaccinations. Main Outcomes and Measures: Reported short-term safety data of 1 to 3 doses of 3 to 10 µg BNT162b2 in children from birth to younger than 60 months are presented. Coprimary outcomes were the frequencies of 11 categories of symptoms after vaccination with bivariate analyses and regression models adjusting for age, sex, weight, and height. Results: The study included 7806 children (median age, 3 years [IQR, 2-4 years]; 3824 [49.0%] female) who were followed up of for a mean (SD) of 91.4 (38.8) days since first BNT162b2 vaccination (survey response rate, 41.1%). A 10-µg dosage was more frequently associated with local injection-site symptoms compared with lower dosages. In the active-comparator analysis, the probability of any symptoms (odds ratio [OR], 1.62; 95% CI, 1.43-1.84), local symptoms (OR, 1.68; 95% CI, 1.38-2.05), musculoskeletal symptoms (OR, 2.55; 95% CI, 1.32-4.94), dermatologic symptoms (OR, 2.18; 95% CI, 10.7-4.45), or otolaryngologic symptoms (OR, 6.37; 95% CI, 1.50-27.09) were modestly elevated after BNT162b2 compared with non-SARS-CoV-2 vaccines, whereas the probabilities of general symptoms (OR, 0.77; 95% CI, 0.63-0.95) and fever (OR, 0.42; 95% CI, 0.32-0.55) were lower after BNT162b2. Symptoms requiring hospitalization (n = 10) were reported only at BNT162b2 dosages above 3 µg. Conclusions and Relevance: In this cohort study, the symptoms reported after BNT162b2 administration were comparable overall to those for on-label non-SARS-CoV-2 vaccines in this cohort of children younger than 5 years. The present data may be used together with prospective licensure studies of BNT162b2 efficacy and safety and could help guide expert recommendations about BNT162b2 vaccinations in this age group.

Validation of the 2019 European Society of Cardiology Risk Stratification Algorithm for Pulmonary Embolism in Normotensive Elderly Patients.

BACKGROUND: The 2019 European Society of Cardiology (ESC) guidelines recommend evaluation for right ventricular dysfunction in all normotensive patients with acute pulmonary embolism (PE). We compared the predictive performance of the 2019 and 2014 ESC risk stratification algorithms and the Pulmonary Embolism Severity Index (PESI). METHODS: We performed a posthoc analysis of normotensive patients aged ≥ 65 years with acute PE from a prospective cohort. The primary outcome was overall mortality; secondary outcomes were PE-related mortality and adverse outcomes (PE-related death, cardiopulmonary resuscitation, intubation, catecholamine use, recurrent venous thromboembolism) at 30 days. We assessed outcomes in intermediate-high, intermediate-low, and low-risk groups according to the 2019 and 2014 ESC algorithms and the PESI. Discriminative power was compared using the area under the receiver operating characteristic curve (AUC). RESULTS: Among 419 patients, 14 (3.3%) died (7 from PE) and 16 (3.8%) had adverse outcomes within 30 days. The 2019 ESC algorithm classified more patients as intermediate-high risk (45%) than the 2014 ESC algorithm (24%) or the PESI (37%), and only 19% as low risk (32% with 2014 ESC or the PESI). Discriminatory power for overall mortality was lower with the 2019 ESC algorithm (AUC: 63.6%), compared with the 2014 ESC algorithm (AUC: 71.5%) or the PESI (AUC: 75.2%), although the difference did not reach statistical significance (p = 0.063). Discrimination for PE-related mortality and adverse outcomes was similar. CONCLUSION: While categorizing more patients in higher risk groups, the 2019 ESC algorithm for PE did not improve prediction of short-term outcomes compared with the 2014 ESC algorithm or the PESI.

Nonverbal communication remains untouched: No beneficial effect of symptomatic improvement on poor gesture performance in schizophrenia.

BACKGROUND: Gestures are an important part of communication. Patients with schizophrenia present gesture deficits that tend to deteriorate in the course of the disease and hamper functional outcome. This gesture deficit has been associated with motor abnormalities, cognitive impairment, and psychotic symptoms. Unaffected, first-degree relatives of schizophrenia patients share some subclinical motor and cognitive abnormalities. We aimed to investigate, whether gesture performance changes with symptomatic improvement in patients, and to test the longitudinal performance in unaffected, first-degree relatives. METHODS: In this study, we measured gesture performance using a validated test in 33 patients, 29 first-degree relatives and 38 healthy controls. Measurements were completed shortly after admission and before discharge in patients. Performance was rated blindly by experts using video recordings of the gesture task. Additionally, we evaluated cognitive function and psychotic symptoms at both visits. RESULTS: Gesture performance was poorer in relatives compared to controls and poorer in patients compared to both relatives and controls. Patients showed an improvement in psychopathology but a significant decrease in gesture performance at follow-up, while performance in the other groups remained stable. Proportional change of gesture performance correlated with change of cognitive function in patients, whereas there were no correlations with change of cognitive function in the other groups. CONCLUSION: While symptom severity was reduced, the gesture deficit further deteriorated in schizophrenia. The finding argues for distinct processes contributing to poor nonverbal communication skills in patients, requiring novel alternative treatment efforts.

Clinical Surveillance vs. Anticoagulation For low-risk patiEnts with isolated SubSegmental Pulmonary Embolism: protocol for a multicentre randomised placebo-controlled non-inferiority trial (SAFE-SSPE).

INTRODUCTION: The clinical significance of subsegmental pulmonary embolism (SSPE) is currently unclear. Although growing evidence from observational studies suggests that withholding anticoagulant treatment may be a safe option in selected patients with isolated SSPE, most patients with this condition receive anticoagulant treatment, which is associated with a 90-day risk of recurrent venous thromboembolism (VTE) of 0.8% and major bleeding of up to 5%. Given the ongoing controversy concerning the risk-benefit ratio of anticoagulation for isolated SSPE and the lack of evidence from randomised-controlled studies, the aim of this clinical trial is to evaluate the efficacy and safety of clinical surveillance without anticoagulation in low-risk patients with isolated SSPE. METHODS AND ANALYSIS: SAFE-SSPE (Surveillance vs. Anticoagulation For low-risk patiEnts with isolated SubSegmental Pulmonary Embolism, a multicentre randomised placebo-controlled non-inferiority trial) is an international, multicentre, placebo-controlled, double-blind, parallel-group non-inferiority trial conducted in Switzerland, the Netherlands and Canada. Low-risk patients with isolated SSPE are randomised to receive clinical surveillance with either placebo (no anticoagulation) or anticoagulant treatment with rivaroxaban. All patients undergo bilateral whole-leg compression ultrasonography to exclude concomitant deep vein thrombosis before enrolment. Patients are followed for 90 days. The primary outcome is symptomatic recurrent VTE (efficacy). The secondary outcomes include clinically significant bleeding and all-cause mortality (safety). The ancillary outcomes are health-related quality of life, functional status and medical resource utilisation. ETHICS AND DISSEMINATION: The local ethics committees in Switzerland have approved this protocol. Submission to the Ethical Committees in the Netherlands and Canada is underway. The results of this trial will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04263038.

Gesture Performance in First- and Multiple-Episode Patients with Schizophrenia Spectrum Disorders.

BACKGROUND/AIM: Gesturing plays an important role in social behavior and social learning. Deficits are frequent in schizophrenia and may contribute to impaired social functioning. Information about deficits during the course of the disease and presence of severity and patterns of impairment in first-episode patients is missing. Hence, we aimed to investigate gesturing in first- compared to multiple-episode schizophrenia patients and healthy controls. METHODS: In 14 first-episode patients, 14 multiple-episode patients and 16 healthy controls matched for age, gender and education, gesturing was assessed by the comprehensive Test of Upper Limb Apraxia. Performance in two domains of gesturing - imitation and pantomime - was recorded on video. Raters of gesture performance were blinded. RESULTS: Patients with multiple episodes had severe gestural deficits. For almost all gesture categories, performance was worse in multiple- than in first-episode patients. First-episode patients demonstrated subtle deficits with a comparable pattern. CONCLUSIONS: Subjects with multiple psychotic episodes have severe deficits in gesturing, while only mild impairments were found in first-episode patients independent of age, gender, education and negative symptoms. The results indicate that gesturing is impaired at the onset of disease and likely to further deteriorate during its course.

Structural brain correlates of defective gesture performance in schizophrenia.

INTRODUCTION: The neural correlates of impaired performance of gestures are currently unclear. Lesion studies showed variable involvement of the ventro-dorsal stream particularly left inferior frontal gyrus (IFG) in gesture performance on command. However, findings cannot be easily generalized as lesions may be biased by the architecture of vascular supply and involve brain areas beyond the critical region. The neuropsychiatric syndrome of schizophrenia shares apraxic-like errors and altered brain structure without macroanatomic lesions. Schizophrenia may therefore qualify as a model disorder to test neural correlates of gesture impairments. METHODS: We included 45 schizophrenia patients and 44 healthy controls in the study to investigate the structural brain correlates of defective gesturing in schizophrenia using voxel based morphometry. Gestures were tested in two domains: meaningful gestures (transitive and intransitive) on verbal command and imitation of meaningless gestures. Cut-off scores were used to separate patients with deficits, patients without deficits and controls. Group differences in gray matter (GM) volume were explored in an ANCOVA. RESULTS: Patients performed poorer than controls in each gesture category (p < .001). Patients with deficits in producing meaningful gestures on command had reduced GM predominantly in left IFG, with additional involvement of right insula and anterior cingulate cortex. Patients with deficits differed from patients without deficits in right insula, inferior parietal lobe (IPL) and superior temporal gyrus. CONCLUSIONS: Impaired performance of meaningful gestures on command was linked to volume loss predominantly in the praxis network in schizophrenia. Thus, the behavioral similarities between apraxia and schizophrenia are paralleled by structural alterations. However, few associations between behavioral impairment and structural brain alterations appear specific to schizophrenia.