Risk Assessment Models for Venous Thromboembolism in Medical Inpatients.

Importance: Thromboprophylaxis is recommended for medical inpatients at risk of venous thromboembolism (VTE). Risk assessment models (RAMs) have been developed to stratify VTE risk, but a prospective head-to-head comparison of validated RAMs is lacking. Objectives: To prospectively validate an easy-to-use RAM, the simplified Geneva score, and compare its prognostic performance with previously validated RAMs. Design, Setting, and Participants: This prospective cohort study was conducted from June 18, 2020, to January 4, 2022, with a 90-day follow-up. A total of 4205 consecutive adults admitted to the general internal medicine departments of 3 Swiss university hospitals for hospitalization for more than 24 hours due to acute illness were screened for eligibility; 1352 without therapeutic anticoagulation were included. Exposures: At admission, items of 4 RAMs (ie, the simplified and original Geneva score, the Padua score, and the IMPROVE [International Medical Prevention Registry on Venous Thromboembolism] score) were collected. Patients were stratified into high and low VTE risk groups according to each RAM. Main Outcomes and Measures: Symptomatic VTE within 90 days. Results: Of 1352 medical inpatients (median age, 67 years [IQR, 54-77 years]; 762 men [55.4%]), 28 (2.1%) experienced VTE. Based on the simplified Geneva score, 854 patients (63.2%) were classified as high risk, with a 90-day VTE risk of 2.6% (n = 22; 95% CI, 1.7%-3.9%), and 498 patients (36.8%) were classified as low risk, with a 90-day VTE risk of 1.2% (n = 6; 95% CI, 0.6%-2.6%). Sensitivity of the simplified Geneva score was 78.6% (95% CI, 60.5%-89.8%) and specificity was 37.2% (95% CI, 34.6%-39.8%); the positive likelihood ratio of the simplified Geneva score was 1.25 (95% CI, 1.03-1.52) and the negative likelihood ratio was 0.58 (95% CI, 0.28-1.18). In head-to-head comparisons, sensitivity was highest for the original Geneva score (82.1%; 95% CI, 64.4%-92.1%), while specificity was highest for the IMPROVE score (70.4%; 95% CI, 67.9%-72.8%). After adjusting the VTE risk for thromboprophylaxis use and site, there was no significant difference between the high-risk and low-risk groups based on the simplified Geneva score (subhazard ratio, 2.04 [95% CI, 0.83-5.05]; P = .12) and other RAMs. Discriminative performance was poor for all RAMs, with an area under the receiver operating characteristic curve ranging from 53.8% (95% CI, 51.1%-56.5%) for the original Geneva score to 58.1% (95% CI, 55.4%-60.7%) for the simplified Geneva score. Conclusions and Relevance: This head-to-head comparison of validated RAMs found suboptimal accuracy and prognostic performance of the simplified Geneva score and other RAMs to predict hospital-acquired VTE in medical inpatients. Clinical usefulness of existing RAMs is questionable, highlighting the need for more accurate VTE prediction strategies.

Association of pharmacologic thromboprophylaxis with clinically relevant bleeding and hospital-acquired anemia in medical inpatients: the risk stratification for hospital-acquired venous thromboembolism in medical patients study.

BACKGROUND: Pharmacologic thromboprophylaxis (pTPX) might exacerbate the risk of clinically relevant bleeding (CRB) and hospital-acquired anemia (HAA) in older multimorbid inpatients. OBJECTIVES: We aimed to evaluate the association of pTPX use with CRB and HAA. METHODS: We used data from a prospective cohort study conducted in 3 Swiss university hospitals. Adult patients admitted to internal medicine wards with no therapeutic anticoagulation were included. pTPX use was ascertained during hospitalization. Outcomes were in-hospital CRB and HAA. We calculated incidence rates by status of pTPX. We assessed the association of pTPX with CRB using survival analysis and with HAA using logistic regression, adjusted for infection, length of stay, and the International Medical Prevention Registry on Venous Thromboembolism bleeding risk score. RESULTS: Among 1305 patients (mean age, 63.7 years; 44% women, 90% at low risk of bleeding), 809 (62%) received pTPX. The incidence of CRB was 2.4 per 1000 patient-days and was not significantly higher in patients with pTPX than in those without. We found no significant association between pTPX and CRB. HAA was frequent (20.2%) and higher in patients with pTPX than in those without (23.2% vs 15.3%). The incidence of HAA was 21.2 per 1000 patient-days and did not significantly differ between patients with pTPX and those without. We found an association between pTPX and HAA (adjusted odds ratio, 1.4; 95% CI, 1.0-2.1). CONCLUSION: Our study confirmed the safety of pTPX in medical inpatients at low risk of bleeding but identified an association between pTPX and HAA. Adherence to guidelines that recommend administering pTPX to medical inpatients at increased venous thromboembolism risk and low bleeding risk is necessary.

Impact of an INtervention to increase MOBility in older hospitalized medical patients (INTOMOB): Study protocol for a cluster randomized controlled trial.

BACKGROUND: Low mobility during an acute hospitalization is frequent and associated with adverse effects, including persistent functional decline, institutionalization and death. However, we lack effective interventions to improve mobility that are scalable in everyday practice. The INTOMOB trial - INtervention to increase MOBility in older hospitalized medical patients - will test the effect of a multilevel intervention to improve mobility of older hospitalized patients on functional mobility. METHODS: The INTOMOB multicenter superiority parallel cluster randomized controlled trial will enroll in total 274 patients in Swiss hospitals. Community-dwelling adults aged ≥ 60 years, admitted to a general internal medicine ward with an anticipated length of hospital stay of ≥ 3 days, will be eligible for participation. Unit of randomization will be the wards. A multilevel mobility intervention will be compared to standard of care and target the patients (information and exercise booklets, mobility diary, iPad with exercise videos), healthcare professionals (e-learning, oral presentation, mobility checklist), and environment (posters and pictures on the wards). The primary outcome will be life-space level, measured by the University of Alabama at Birmingham Study of Aging Life-Space Assessment (LSA), at 30 days after enrollment. The LSA is a measure of functional mobility, i.e., how far participants move from bedroom to outside town. Secondary outcomes include, among others, LSA at 180 days, mobility and falls during hospitalization, muscle strength at discharge, and falls, emergency room visits, readmissions, and death within 180 days. DISCUSSION: This study has the potential to improve outcomes of older hospitalized patients through an intervention that should be scalable in clinical practice because it fosters patient empowerment and does not require additional resources. The tools provided to the patients can help them implement better mobility practices after discharge, which can contribute to better functional outcomes. The choice of a functional patient-reported outcome measure as primary outcome (rather than a "simple" objective mobility measure) reinforces the patient-centeredness of the study. TRIAL REGISTRATION: clinicaltrials.gov (NCT05639231, released on December 19 2022); Swiss National Clinical Trial Portal (SNCTP000005259, released on November 28 2022).

Feasibility and Acceptability of an INtervention TO Increase MOBility in Older Hospitalized Medical Patients (INTOMOB): A Mixed-Methods Pilot Study.

Background: To reduce adverse outcomes of low hospital mobility, we need interventions that are scalable in everyday practice. This study assessed the feasibility and acceptability of the INTOMOB multilevel intervention addressing barriers to hospital mobility without requiring unavailable resources. Methods: The INTOMOB intervention, targeting older patients, healthcare professionals (HCPs) and the hospital environment, was implemented on acute general internal medicine wards of three hospitals (12/2022-03/2023). Feasibility and acceptability of the intervention were assessed and two types of accelerometers compared in a mixed methods study (patient and HCP surveys and interviews). Quantitative data were analyzed descriptively and qualitative data using a deductive approach. Results were integrated through meta-inferences. Results: Of 20 patients (mean age 74.1 years), 90% found the intervention helpful and 82% said the environment intervention (posters) stimulated mobility. The majority of 44 HCPs described the intervention as clear and helpful. There was no major implementation or technical issue. About 60% of patients and HCPs preferred a wrist-worn over an ankle-worn accelerometer. Conclusions: The INTOMOB intervention is feasible and well accepted. Patients' and HCPs' feedback allowed to further improve the intervention that will be tested in a cluster randomized trial and provides useful information for future mobility-fostering interventions.

Subsegmental Pulmonary Embolism.

Subsegmental pulmonary embolism (SSPE) is increasingly diagnosed with the growing use and technological advancements of multidetector computed tomography pulmonary angiography. Its diagnosis is challenging, and some presumed SSPE may actually represent imaging artifacts. Indirect evidence and results from small observational studies suggest that SSPE may be more benign than more proximal pulmonary embolism, and may thus not always require treatment. Therefore, guidelines suggest to consider a management strategy without anticoagulation in selected patients with SSPE at low risk of recurrent venous thromboembolism (VTE), in whom proximal deep vein thrombosis is excluded. Recently, a large prospective study among low-risk patients with SSPE who were left untreated showed a higher VTE recurrence risk than initially deemed acceptable by the investigators, and thus was prematurely interrupted after recruitment of 97% of the target population. However, the risk-benefit ratio of anticoagulation for low-risk patients with SSPE remains unclear, and results from randomized trials are needed to answer the question about their optimal management.

Nociception in Chicken Embryos, Part I: Analysis of Cardiovascular Responses to a Mechanical Noxious Stimulus.

Although it is assumed that chicken embryos acquire the capacity for nociception while developing in the egg, an exact time point has not yet been specified. The present research was an exploratory study aiming to determine when the capacity of nociception emerges during embryonic development in chickens. Changes in blood pressure and heart rate (HR) in response to a noxious mechanical stimulus at the base of the beak versus a light touch on the beak were examined in chicken embryos between embryonic days (EDs) 7 and 18. Mean arterial pressure (MAP) was the most sensitive parameter for assessing cardiovascular responses. Significant changes in MAP in response to a noxious stimulus were detected in embryos at ED16 to ED18, whereas significant changes in HR were observed at ED17 and ED18. Infiltration anesthesia with the local anesthetic lidocaine significantly reduced the response of MAP on ED18, so the measured cardiovascular changes may be interpreted as nociceptive responses.

Electroanatomical Conduction Characteristics of Pig Myocardial Tissue Derived from High-Density Mapping.

BACKGROUND: Ultra-high-density mapping systems allow more precise measurement of the heart chambers at corresponding conduction velocities (CVs) and voltage amplitudes (VAs). Our aim for this study was to define and compare a basic value set for unipolar CV and VA in all four heart chambers and their separate walls in healthy, juvenile porcine hearts using ultra-high-density mapping. METHODS: We used the Rhythmia Mapping System to create electroanatomical maps of four pig hearts in sinus rhythm. CVs and VAs were calculated for chambers and wall segments with overlapping circular areas (radius of 5 mm). RESULTS: We analysed 21 maps with a resolution of 1.4 points/mm2. CVs were highest in the left atrium (LA), followed by the left ventricle (LV), right ventricle (RV), and right atrium (RA). As for VA, LV was highest, followed by RV, LA, and RA. The left chambers had a higher overall CV and VA than the right. Within the chambers, CV varied more in the right than in the left chambers, and VA varied in the ventricles but not in the atria. There was a slightly positive correlation between CVs and VAs at velocity values of <1.5 m/s. CONCLUSIONS: In healthy porcine hearts, the left chambers showed higher VAs and CVs than the right. CV differs mainly within the right chambers and VA differs only within the ventricles. A slightly positive linear correlation was found between slow CVs and low VAs.

Nociception in Chicken Embryos, Part II: Embryonal Development of Electroencephalic Neuronal Activity In Ovo as a Prerequisite for Nociception.

Chicken culling has been forbidden in Germany since 2022; male/female selection and male elimination must be brought to an embryonic status prior to the onset of nociception. The present study evaluated the ontogenetic point at which noxious stimuli could potentially be perceived/processed in the brain in ovo. EEG recordings from randomized hyperpallial brain sites were recorded in ovo and noxious stimuli were applied. Temporal and spectral analyses of the EEG were performed. The onset of physiological neuronal signals could be determined at developmental day 13. ERP/ERSP/ITC analysis did not reveal phase-locked nociceptive responses. Although no central nociceptive responses were documented, adequate EEG responses to noxious stimuli from other brain areas cannot be excluded. The extreme stress impact on the embryo during the recording may overwrite the perception of noniceptive stimuli. The results suggest developmental day 13 as the earliest embryonal stage being able to receive and process nociceptive stimuli.

Nociception in Chicken Embryos, Part III: Analysis of Movements before and after Application of a Noxious Stimulus.

Many potentially noxious interventions are performed on chicken embryos in research and in the poultry industry. It is therefore essential and in the interest of animal welfare to be able to precisely define the point at which a chicken embryo is capable of nociception in ovo. The present part III of a comprehensive study examined the movements of developing chicken embryos with the aim of identifying behavioral responses to a noxious stimulus. For this purpose, a noxious mechanical stimulus and a control stimulus were applied in a randomized order. The recorded movements of the embryos were evaluated using the markerless pose estimation software DeepLabCut and manual observations. After the application of the mechanical stimulus, a significant increase in beak movement was identified in 15- to 18-day-old embryos. In younger embryos, no behavioral changes related to the noxious stimulus were observed. The presented results indicate that noxious mechanical stimuli at the beak base evoke a nocifensive reaction in chicken embryos starting at embryonic day 15.

Overuse and underuse of thromboprophylaxis in medical inpatients.

Background: Thromboprophylaxis (TPX) prescription is recommended in medical inpatients categorized as high risk of venous thromboembolism (VTE) by validated risk assessment models (RAMs), but how various RAMs differ in categorizing patients in risk groups, and whether the choice of RAM influences estimates of appropriate TPX use is unknown. Objectives: To determine the proportion of medical inpatients categorized as high or low risk according to validated RAMs, and to investigate the appropriateness of TPX prescription. Methods: This is a prospective cohort study of acutely ill medical inpatients from 3 Swiss university hospitals. Participants were categorized as high or low risk of VTE by validated RAMs (ie, the Padua, the International Medical Prevention Registry on Venous Thromboembolism, simplified, and original Geneva scores). We assessed prescription of any TPX at baseline. We considered TPX prescription in high-risk and no TPX prescription in low-risk patients as appropriate. Results: Among 1352 medical inpatients, the proportion categorized as high risk ranged from 29.8% with the International Medical Prevention Registry on Venous Thromboembolism score to 66.1% with the original Geneva score. Overall, 24.6% were consistently categorized as high risk, and 26.3% as low risk by all 4 RAMs. Depending on the RAM used, TPX prescription was appropriate in 58.7% to 63.3% of high-risk (ie, 36.7%-41.3% underuse) and 52.4% to 62.8% of low-risk patients (ie, 37.2%-47.6% overuse). Conclusion: The proportion of medical inpatients considered as high or low VTE risk varied widely according to different RAMs. Only half of patients were consistently categorized in the same risk group by all RAMs. While TPX remains underused in high-risk patients, overuse in low-risk patients is even more pronounced.

Association of part-time clinical work with well-being and mental health in General Internal Medicine: A survey among Swiss hospitalists.

INTRODUCTION: Burnout and low job satisfaction are increasing among the General Internal Medicine (GIM) workforce. Whether part-time compared to full-time clinical employment is associated with better wellbeing, job satisfaction and health among hospitalists remains unclear. MATERIALS AND METHODS: We conducted an anonymized cross-sectional survey among board-certified general internists (i.e. hospitalists) from GIM departments in 14 Swiss hospitals. Part-time clinical work was defined as employment of <100% as a clinician. The primary outcome was well-being, as measured by the extended Physician Well-Being Index (ePWBI), an ePWBI ≥3 indicating poor wellbeing. Secondary outcomes included depressive symptoms, mental and physical health, and job satisfaction. We compared outcomes in part-time and full time workers using propensity score-adjusted multivariate regression models. RESULTS: Of 199 hospitalists invited, 137 (69%) responded to the survey, and 124 were eligible for analysis (57 full-time and 67 part-time clinicians). Full-time clinicians were more likely to have poor wellbeing compared to part-time clinicians (ePWBI ≥3 54% vs. 31%, p = 0.012). Part-time compared to full-time clinical work was associated with a lower risk of poor well-being in adjusted analyses (odds ratio 0.20, 95% confidence interval 0.07-0.59, p = 0.004). Compared to full-time clinicians, there were fewer depressive symptoms (3% vs. 18%, p = 0.006), and mental health was better (mean SF-8 Mental Component Summary score 47.2 vs. 43.2, p = 0.028) in part-time clinicians, without significant differences in physical health and job satisfaction. CONCLUSIONS: Full-time clinical hospitalists in GIM have a high risk of poor well-being. Part-time compared to full-time clinical work is associated with better well-being and mental health, and fewer depressive symptoms.

Quality of life in elderly patients with venous thromboembolism assessed using patient-reported outcome measures.

BACKGROUND: We aimed to evaluate the quality of life (QoL), using patient-reported outcome measures (PROMs), in elderly patients with venous thromboembolism (VTE) and to explore whether VTE complications (recurrence, bleeding, or postthrombotic syndrome) had an impact on later QoL. METHODS: We used data from the SWIss venous Thromboembolism COhort of older patients(SWITCO65+), a prospective multicenter cohort of patients aged ≥65 years with acute, symptomatic VTE. Primary outcome was changes in QoL up to 24 months, assessed using generic (36-Item Short-Form Health Survey), with physical (PCS) and mental component score (MCS), and disease-specific (Venous Insufficiency Epidemiological and Economic Study [VEINES]-QoL, [VEINES-Sym], and Pulmonary Embolism QoL) PROMs. PROM scores ranged from 0 to 100 points, higher scores indicating a better QoL. Longitudinal latent class analysis was used to group patients with similar PCS trajectories. Repeated-measures linear regression analyses were used to assess effects of VTE complications on changes in QoL scores. RESULTS: In 923 patients (median age, 75; male, 54%), 140 (15%) patients died, 97 (11%) experienced recurrent VTE, and 106 (12%) major bleeding during follow-up. Compared with patients with higher PCS trajectories, patients with lower PCS trajectories were more likely to be older, female, sicker, and less physically active. On average, generic and disease-specific QoL scores improved over time (+11% in PCS, +3% in MCS, +6% in VEINES QoL, and +16% in Pulmonary Embolism QoL at 3 months). VTE complications were always associated with significantly lower QoL scores (for VTE recurrence: PCS adjusted difference -2.57, 95% CI, -4.47 to -0.67). CONCLUSION: Although QoL following VTE tended to improve over time, patients with VTE-related complications had lower QoL than patients without complications.

Prediction of in-hospital bleeding in acutely ill medical patients: External validation of the IMPROVE bleeding risk score.

INTRODUCTION: Pharmacological thromboprophylaxis slightly increases bleeding risk. The only risk assessment model to predict bleeding in medical inpatients, the IMPROVE bleeding risk score, has never been validated using prospectively collected outcome data. METHODS: We validated the IMPROVE bleeding risk score in a prospective multicenter cohort of medical inpatients. Primary outcome was in-hospital clinically relevant bleeding (CRB) within 14 days of admission, a secondary outcome was major bleeding (MB). We classified patients according to the score in high or low bleeding risk. We assessed the score's predictive performance by calculating subhazard ratios (sHRs) adjusted for thromboprophylaxis use, positive and negative predictive values (PPV, NPV), and the area under the receiver operating characteristic curves (AUC). RESULTS: Of 1155 patients, 8 % were classified as high bleeding risk. CRB and MB within 14 days occurred in 0.94 % and 0.47 % of low-risk and in 5.6 % and 3.4 % of high-risk patients, respectively. Adjusted for thromboprophylaxis, classification in the high-risk group was associated with an increased risk of 14-day CRB (sHR 4.7, 95 % confidence interval [CI] 1.5-14.5) and MB (sHR 4.9, 95%CI 1.0-23.4). PPV was 5.6 % and 3.4 %, while NPV was 99.1 % and 99.5 % for CRB and MB, respectively. The AUC was 0.68 (95%CI 0.66-0.71) for CRB and 0.73 (95%CI 0.71-0.76) for MB. CONCLUSION: The IMPROVE bleeding risk score showed moderate to good discriminatory power to predict bleeding in medical inpatients. The score may help identify patients at high risk of in-hospital bleeding, in whom careful assessment of the risk-benefit ratio of pharmacological thromboprophylaxis is warranted.

Application of a topical anesthetic reduces pain-associated parameters during spermatic cord transection in piglet castration using a minimal anesthesia model.

OBJECTIVE: This study assessed the use of a topical anesthetic as a feasible approach to reduce pain during piglet castration using a minimal anesthesia protocol. ANIMALS: 18 male piglets, aged 3-6 days, were included in this study. METHODS: A minimal anesthetic state was induced with isoflurane administered by facemask, with anesthetic depth individually adjusted based on responses to interdigital pinch. To desensitize the scrotal skin, a vapocoolant was applied 3 times. Scrotal incisions were made subsequently and Tri-Solfen (TS) or Placebo (P) was administered in both incisional gaps. After 30 seconds, the spermatic cords were severed followed by a further application of TS/P to both incision edges. Nociception-related variables, such as mean arterial blood pressure (MAP), heart rate (HR), and nocifensive movements, were assessed. RESULTS: Significant differences in MAP changes were assessed between the TS (14 ± 4 mmHg) and the P group (36 ± 8 mmHg) for cutting the spermatic cords. Furthermore, significantly fewer nocifensive movement score points appeared in the TS than in the P group (0; IQR = 0 vs 5; IQR = 6). CLINICAL RELEVANCE: In this anesthesia model, the application of TS after skin incision significantly reduced MAP responses and nocifensive movements with spermatic cord transection compared with the application of P. However, the waiting period between TS-application and spermatic cord transection might limit the benefit of the method in conscious piglets, as pain during castration is reduced but additional stress is caused by the prolonged handling. Furthermore, using a vapocoolant did not provide anesthesia for skin incisions.

Behavior of Piglets in an Observation Arena before and after Surgical Castration with Local Anesthesia.

Surgical castration of piglets is generally recognized as a painful procedure, but there is currently no gold standard for the assessment of pain behavior in piglets. However, pain assessment is essential for evaluating the effectiveness of local anesthetics. In this study, we investigated the efficacy of four local anesthetics in terms of pain relief during and after surgical castration in three sequential study parts. To do so, we filmed 178 piglets before the applied procedures, after injection of the local anesthetic, and up to 24 h after castration (five observation times in total) in an observation arena and compared their behavior before and after castration and between treatments and control groups. The results showed significant differences in the behavior of the piglets before and after castration and between the sham-castrated control group and the control group castrated without anesthesia. The different local anesthesia treatment groups showed diverging differences to the control groups. The most frequently shown pain-associated behaviors of the piglets were changes in tail position and hunched back posture. We observed a reduction but no complete elimination of the expressed pain-associated behaviors after local anesthesia. Several behavioral changes-such as changes in tail position, hunched back posture or tail wagging-persisted until the day after castration. Owing to the limited duration of the effects of the local anesthetics, local anesthesia did not influence long-term pain.

Haemoglobin thresholds for transfusion: how are we doing in the era of Choosing Wisely? A retrospective cohort study.

INTRODUCTION:  Clinical practice guidelines and the Choosing Wisely initiative launched in 2012 recommend a haemoglobin (Hb) threshold of 70-80 g/lfor red blood cell (RBC) transfusions in stable hospitalised patients. Data on transfusion practices and their trends in medical inpatients are limited. To address this gap, we investigated transfusion practices and their trends in general internal medicine and other clinics. METHODS: This retrospective cohort study analysed data from all hospitalisations with RBC transfusions at a Swiss university hospital between 2012 and 2019. We included all first transfusion episodes if pretransfusion Hb was available. The primary endpoint was mean pretransfusion Hb; secondary endpoints included potentially inadequate transfusions (i.e., transfusions at Hb ≥80 g/l) and receipt of a single RBC unit. Trends in mean pretransfusion Hb over time were estimated using generalised estimating equations, and risk factors for potentially inadequate transfusions were identified using multivariable adjusted generalised estimating equations models. RESULTS:  Of 14,598 hospitalisations with RBC transfusions, 1980 (13.6%) were discharged from general internal medicine. From 2012 to 2019, mean pretransfusion Hb decreased from 74.0 g/l to 68.8 g/l in general internal medicine (mean annual decrease -0.76 g/l, 95% confidence interval [CI] -0.51 to -1.02) and from 78.2 g/l to 72.7 g/l in other clinics (mean annual decrease -0.69, 95% CI -0.62 to -0.77; p for interaction 0.53). The overall proportion of potentially inadequate transfusions was 17.8% in general internal medicine and 24.1% in other clinics (p <0.001) and decreased over the study period from 26.9% to 5.5% in general internal medicine and from 37.0% to 15.2% in other clinics. In contrast, the proportion of cases receiving a single RBC unit increased (39.5% to 81.4% in general internal medicine, 42.7% to 66.1% in other clinics). Older age (adjusted odds ratio [aOR] 1.45, 95% CI 1.32-1.58 for ≥65 vs <65 years), having surgery (aOR 1.24, 95% CI 1.14-1.36), acute haemorrhage (aOR 1.16, 95% CI 1.02-1.33), chronic heart failure (aOR 1.17, 95% CI 1.04-1.32), ischaemic heart diseases (aOR 1.27, 95% CI 1.15-1.41), chronic pulmonary diseases (aOR 1.24, 95% CI 1.08-1.42), malignancy (aOR 1.11, 95% CI 1.01-1.21), and rheumatic disease (aOR 1.27, 95% CI 1.01-1.59) were risk factors for potentially inadequate transfusions. CONCLUSIONS:  More restrictive transfusion practices were adopted in general internal medicine and other clinics over time, suggesting that guideline recommendations and the Choosing Wisely initiative may have been increasingly followed. Interventions to reduce potentially inadequate transfusions should target providers who care for older patients and those with surgery or chronic cardiac and pulmonary diseases.

Prevalence and risk of inappropriate dosing of direct oral anticoagulants in two Swiss atrial fibrillation registries.

BACKGROUND: Direct oral anticoagulants (DOACs) have a favourable risk-benefit profile compared to vitamin K-antagonists (VKAs) in atrial fibrillation (AF). Dosing is based on age, weight and renal function, without need of routine monitoring. METHODS AND RESULTS: In two prospective, multicentre AF cohorts (Swiss-AF, BEAT-AF) patients were stratified as receiving VKAs or adequately-, under- or overdosed DOACs, according to label. Primary outcome was a composite of major adverse clinical events (MACE), defined as cardiovascular death, myocardial infarction (MI), ischaemic stroke and systemic embolism. Secondary outcomes included major bleeding. Adjustment for confounding was performed. Median follow-up was 4 years. Of 3236 patients, 1875 (58%) were on VKAs and 1361 (42%) were on DOACs, of which 1137 (83%) were adequately-, 134 (10%) over- and 90 (7%) under-dosed. Compared to adequately dosed individuals, overdosed patients were more likely to be older and female. Underdosing correlated with concomitant aspirin therapy and coronary artery disease. Both groups had higher CHA2DS2-VASc scores. Patients on overdosed DOACs had higher incidence of MACE (HR 1.75; CI 1.10-2.79; adjusted-HR: 1.22) and major bleeding (HR 1.99; CI 1.14-3.48; adjusted-HR: 1.51). Underdosing was not associated with a higher incidence of MACE (HR 0.94; CI 0.46-1.92; adjusted-HR 0.61) or major bleeding (HR 1.07; CI 0.46-2.46; adjusted-HR 0.82). After adjustment, all CIs crossed 1.0. CONCLUSION: Inappropriate DOAC-dosing was more prevalent in multimorbid patients, but did not correlate with higher risks of adverse events after adjusting for confounders. DOAC prescription should follow label.

Nociception-Induced Changes in Electroencephalographic Activity and FOS Protein Expression in Piglets Undergoing Castration under Isoflurane Anaesthesia.

The objective of this study was to investigate the electroencephalographic reaction pattern and FOS protein expression in male piglets undergoing surgical castration under light isoflurane anaesthesia with or without local anaesthesia. The experiment was conducted under isoflurane anaesthesia to exclude the effect of the affective components of pain on the measurements. Changes in the oscillatory activity of the cerebral cortex over a 90 s period after noxious stimulation or simulated interventions were analysed. FOS expression was determined postmortem by performing immunohistochemistry in the dorsal horn of the spinal cord. The analysis of the response to an interdigital pinch revealed a biphasic reaction pattern in the electroencephalogram (EEG) that similarly was observed for the surgical stimuli during the castration procedure in the group without analgesia. This EEG response was attenuated or altered by the application of local anaesthetics. Immunohistochemical staining for FOS indicated a lower expression in the handling and in three local anaesthetic groups than in the animals castrated without pain relief. The findings indicate that EEG and FOS expression may serve as indicators for nociception in piglets under light isoflurane anaesthesia. A lower activation of nociceptive pathways occurs during castration after the application of local anaesthetics. However, EEG and FOS analyses should be combined with additional parameters to assess nociception, e.g., haemodynamic monitoring.