Risk stratification and long-term outcome of patients receiving in-hospital medical emergency team critical care: experience from Austria's largest medical center.

BACKGROUND: We aimed to investigate predictors for long-term survival of in-hospital patients with medical emergency team (MET) consultation with or without in-hospital cardiac arrest (IHCA) in Austria's largest medical center. METHODS: Data of patients, who needed an intervention of a MET between 01/2014 and 03/2020 were reviewed for this retrospective analysis. RESULTS: In total, 708 MET calls were analyzed. The minimum follow-up was 7 months, the maximum 6.2 years. The main MET indications were circulatory failure (63%) followed by respiratory failure (27.1%), and bleeding events (3.5%). IHCA with subsequent cardiopulmonary resuscitation (CPR) was experienced by 425 (60%) patients. Of those, 274 (64%) reached return of spontaneous circulation (ROSC), and 221 (52%) survived the first 24-hours (median survival: 146 days) and 22.1% the first year. After adjustment for potential confounders, age (P<0.001), time to ROSC (P<0.001), a non-shockable rhythm (P=0.041), chronic kidney disease (CKD, P=0.041), peak lactate levels (P<0.001), and C-reactive protein (P=0.001) were associated with long-term all-cause mortality in IHCA patients in Cox regression analysis. The 283 MET calls (40%) which were due to other reasons than IHCA were associated with a much better 24-hours (93%) and 1-year survival (61.8%). Beside age (P<0.001), the main risk factors associated with mortality in MET patients without IHCA were comorbidities such as chronic obstructive pulmonary disease (COPD, P=0.008), CKD (P=0.001), pulmonary hypertension/chronic thromboembolic pulmonary hypertension (PH/CTEPH, P=0.024), and cancer (P=0.040). CONCLUSIONS: Patients triggering MET calls have an increased mortality, especially those with IHCA. Predictors of mortality comprise age, comorbidities, and cardiac arrest-related parameters. A better characterization of MET call populations and their outcome might help to improve clinical decision making.

Antibiotic prescription after tooth extraction in adults: a retrospective cohort study in Austria.

BACKGROUND: Broad spectrum antibiotics are often used for the prophylaxis of infectious endocarditis and treatment of odontogenic infections, but there are limited data related to antibiotic use and adherence to prescription guidelines.  METHODS: Data from patients with tooth extraction between 2014 and 2018 were selected from a database of a regional health insurance fund. We created three data sets, one based on all tooth extractions, one on multiple teeth extractions, and one including only single tooth extraction. After data collection, descriptive analysis was carried out. The differences in prescription pattern of antibiotic medicine were tested by χ2 test, Student´s t-test or ANOVA. RESULTS: From 43,863 patients with tooth extraction, 53% were female, and 3,983 patients (9.1%) filled a prescription for antibiotic medicine. From 43,863 patients, 157 patients (0.4%) had endocarditis risk, but only 8 patients of these (5.1%) filled an antibiotic prescription. In total, 9,234 patients had multiple and 34,437 patients had only one tooth extraction. Patients with more than one tooth extraction received more often antibiotic treatment (10.7%) compared to those with single tooth extractions (χ2 = 36; p < 0,001). Patients with more than one tooth extraction were older, however, younger patients received antibiotics more frequently (t = 28,774, p = 0.001). There was no relationship with endocarditis risk status. Clindamycin and amoxicillin/clavulanic acid were the most frequently prescribed antibiotic medicines. CONCLUSIONS: In this retrospective cohort study, dentists did not discriminate prophylactic antibiotic prescription with regard to endocarditis risk status. A factor influencing prescribing behaviour of antibiotic medicines was the number of extracted teeth.

The ABC-Stroke Score Refines Stroke Risk Stratification in Patients With Atrial Fibrillation at the Emergency Department.

Aims: To evaluate the performance of the ABC (Age, Biomarkers, Clinical history) and CHA2DS2-VASc stroke scores under real-world conditions in an emergency setting. Methods and Results: The performance of the biomarker-based ABC-stroke score and the clinical variable-based CHA2DS2-VASc score for stroke risk assessment were prospectively evaluated in a consecutive series of 2,108 patients with acute symptomatic atrial fibrillation at a tertiary care emergency department. Performance was assessed according to methods for the development and validation of clinical prediction models by Steyerberg et al. and the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis. During a cumulative observation period of 3,686 person-years, the stroke incidence rate was 1.66 per 100 person-years. Overall, the ABC-stroke and CHA2DS2-VASc scores revealed respective c-indices of 0.64 and 0.55 for stroke prediction. Risk-class hazard ratios comparing moderate to low and high to low were 3.51 and 2.56 for the ABC-stroke score and 1.10 and 1.62 for the CHA2DS2-VASc score. The ABC-stroke score also provided improved risk stratification in patients with moderate stroke risk according to the CHA2DS2-VASc score, who lack clear recommendations regarding anticoagulation therapy (HR: 4.35, P = 0.001). Decision curve analysis indicated a superior net clinical benefit of using the ABC-stroke score. Conclusion: In a large, real-world cohort of patients with acute atrial fibrillation in the emergency department, the ABC-stroke score was superior to the guideline-recommended CHA2DS2-VASc score at predicting stroke risk and refined risk stratification of patients labeled moderate risk by the CHA2DS2-VASc score, potentially easing treatment decision-making.

Oral anticoagulant therapy and outcome in patients with stroke. A retrospective nation-wide cohort study in Austria 2012-2017.

PURPOSE: Patients with stroke are at high risk of recurrence of vascular events. Non-vitamin K oral anticoagulant (NOAC) and vitamin K antagonists (VKA) are used as secondary prophylaxis. The aim of this study was to evaluate the utilization of NOAC and VKA, and their impact on re-stroke or death in Austria. METHODS: We analyzed retrospective data between 2012 and 2017 from medical services covered by the health insurance funds, which provides health care for all residents in Austria. Patients without anticoagulant medication 3 months preceding the index event were eligible. RESULTS: 76 354 patients were discharged with a hospital diagnosis of stroke. From these, 16 436 patients with a median age of 78 years received VKA or NOAC. After adjustment, the recurrence of stroke was less frequent in patients with NOAC compared to those with VKA (HR 0.87; 95%CI 0.77-0.97). However, there was no difference in mortality rate after adjustment for age, sex, and co-morbidities for patients with NOAC (HR 1.0; 95%CI 0.92-1.08). Diabetes (HR 1.25, 95%CI 1.08-1.45; HR 1.25, 95% CI 1.13-1.38) and cardiovascular disease (HR 1.43, 95%CI 1.24-1.65; HR 1.27, 95%CI 1.16-1.39) were significantly associated with re-stroke or death. Younger age (p = 0.0028; HR 0.99, 95%CI 0.99-0.99) was significantly associated with re-stroke, and advanced age (p < 0.0001; HR 1.09, 95%CI 1.08-1.09) with death. CONCLUSION: NOAC prescription is related with a reduced risk of re-stroke but increased mortality compared to patients with VKA. The event risk is associated with diabetes, cardiovascular disease and age.

Utilization of potentially inappropriate medication and risk of adverse drug events among older adults with chronic renal insufficiency: a population-wide cohort study.

BACKGROUND: The use of potentially inappropriate medication (PIM) in population of older adults may result in adverse drug events (ADE) already after short term exposure, especially when it is prescribed to patients with chronic kidney disease (CKD). In order to limit ADE in the treatment of older adults PIM lists have been constructed as a source of information for healthcare professionals. The aim of this study was to estimate the utilization of PIM and incidence of ADE in older adults (≥70 years) with CKD. METHODS: We conducted a retrospective population-wide cohort study including patients from Lower Austria who were 70 years or older and diagnosed with CKD in the period from 2008 to 2011. Utilization of PIM was estimated from prescriptions filled by target population. We estimated risks of hospitalization due to ADE within 30 days after incident PIM prescription and compared them to a PIM-free control group by using marginal structural models (MSM). RESULTS: We identified 11,547 patients (women: 50.6%, median age in 2008: 78 years) who fulfilled the inclusion criteria. In total 24.7 and 8.1% of all prescriptions from that period contained a medication with a substance listed in the EU (7)-PIM and AT-PIM list, respectively. Proton pump inhibitors and Ginkgo biloba were the most often prescribed PIMs in this population. 94.6 and 79.3% patients filled at least one EU(7)-PIM and AT-PIM prescription, respectively. Despite the relatively high utilization of PIM there was only a low incidence of clinically relevant ADE. No event type exceeded the threshold level of 1% in the analysis of risks of ADE after filling a prescription for PIM. Nevertheless, MSM analysis showed an increased risk for 11 drugs and reduced risk for 4 drugs. CONCLUSIONS: PIM prescription was common among older adults with CKD, however, only a small number of these drugs eventually led to hospitalization due to ADE within 30 days after incident PIM was filled. In the absence of a clinically important PIM-related increase in risk, an assessment of potential ADE severity to a PIM list by using a warning score system seems prudent.

Use of Clopidogrel, Prasugrel, or Ticagrelor and Patient Outcome after Acute Coronary Syndrome in Austria from 2015 to 2017.

BACKGROUND: Dual antiplatelet therapy improves patient outcome after acute coronary syndrome (ACS), but prescription differences of P2Y12 inhibitor treatments exist. The aim of the present investigation was to study the long-term utilization and patient outcomes of clopidogrel, prasugrel, and ticagrelor in patients with ACS from 2015 to 2017 in Austria. METHODS: Data from 13 Austrian health insurance funds of patients with a hospital discharge diagnosis of ACS for the years 2015 to 2017 were analyzed. The primary end point was to investigate the recurrence of ACS or death. RESULTS: Of 49,124 P2Y12 inhibitor-naive patients with a hospital discharge diagnosis of ACS, 25,147 subjects filled a P2Y12 inhibitor prescription within 30 days after the index event. Of these patients, 10,626 (42.9%) subjects had a prescription for clopidogrel, 4788 (19.3%) for prasugrel, and 9383 (37.8%) for ticagrelor. Ticagrelor was the most frequently prescribed P2Y12 inhibitor among patients below 70 years old, and clopidogrel in those aged ≥70 years. Occurrence of an endpoint was highest in elderly patients. After adjustment for age, sex, and pre-existing medication as proxy for comorbidity, the hazard ratio for ACS or death for prasugrel vs. clopidogrel of 0.70 (95% CI: 0.61; 0.79) was similar to that of ticagrelor vs. clopidogrel (0.70; 95% CI: 0.64; 0.77). CONCLUSION: Prescription of ticagrelor or prasugrel after ACS were associated with a lower risk of ACS recurrence or death compared to clopidogrel.

Topical application of highly concentrated water-in-oil emulsions: Physiological skin parameters and skin penetration in vivo - A pilot study.

Important aspects in the development of new dermal drug delivery systems are the formulations' physicochemical properties and stability. Moreover, their influence on skin physiology and their penetration performance in vivo are of crucial interest. We have recently developed novel concentrated water-in-oil emulsions based on a non-ionic silicone surfactant; the present study deals with the effect of these formulations on physiological skin parameters of healthy volunteers after repeated application. Variations in skin condition and barrier integrity were investigated using classical biophysical and spectroscopic techniques. After four weeks of continuous treatment, no signs of skin irritation could be observed. Both tested emulsions had a positive effect on skin properties despite their relatively high water content and low lipid content. In vivo tape stripping studies revealed penetrated amounts of the incorporated model drug fluorescein sodium of almost 50% of the applied dose, with a superior performance of emulsions with isopropyl myristate when compared to liquid paraffin. In summary, our study confirmed the suitability of the developed W/O emulsions for pharmaceutic and cosmetic applications.

SSRI co-medication with NOAC or VKA does not increase hospitalisation for bleeding: A retrospective nationwide cohort study in Austria 2010-2015.

OBJECTIVES: Non-vitamin K oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) are used for the prophylaxis and treatment of thromboembolic events. A potential drug-drug interaction and increased bleeding events have been reported with co-medication of selective serotonin receptor inhibitors (SSRIs) and VKA. The aim of this study was to investigate the bleeding risk of a coprescription of NOAC or VKA with SSRI. METHODS: Patients with prescription of NOAC or VKA and an antidepressant drug therapy (ADTx) were selected from the drug reimbursement database of 13 Austrian health insurance funds. For this cohort, hospital discharge diagnoses for gastrointestinal bleeding, cerebral haemorrhage, and bleeding anaemia between 2010 and 2015 were analysed. RESULTS: Data were available from 50 196 female and 31 308 male patients. Among these, 892 patients had 987 hospitalisations with bleeding events. The most frequent bleeding cases were gastrointestinal bleedings with 588 events (59.6%), followed by cerebral haemorrhage with 344 (34.8%), and bleeding anaemia with 55 events (5.6%), respectively. The risk of bleeding events was similar between SSRI and other ADTx, when combined with oral anticoagulants (p = 0.51). Concomitant treatment of patients with SSRI or other ADTx and NOAC was associated with an increased bleeding risk compared with cotreatment with VKA (1.21, 95% CI: 1.05-1.40; p = 0.0097). CONCLUSION: Co-medication of SSRI with VKA or NOAC has little if any impact on hospital discharge diagnoses for bleeding events compared with cotreatment of those anticoagulants with other antidepressant medications.

ADMA and NT pro-BNP are associated with overall mortality in elderly.

BACKGROUND: Increased asymmetrical dimethylarginine (ADMA) and NT pro-BNP concentrations have been associated with mortality in patients with cardiovascular (CV) disease and the general population. The use of these prognostic markers in an older population is not established yet. The aim of the present study was to investigate the prognostic value of age, sex, BMI, co-medication and CV laboratory risk markers in geriatric care patients. MATERIALS AND METHODS: In this prospective observational single-centre cohort study data of long-term geriatric care patients were collected. Blood samples were collected between 14.09.2009 and 16.12.2009, and mortality was recorded up to 90 months. ADMA, its symmetric isomer SDMA, L-arginine, NT pro-BNP and CRP were determined at study entry. Simple associations of risk factors for survival period were explored by Spearman correlation coefficient. Significant univariate predictors for survival period were used in the Cox proportional hazard model. RESULTS: A total of 481 patients were screened, and data from 449 patients were analysed. A total of 381 patients died during the observation period. Full data sets from 344 patients were used for Cox regression analysis. Male sex, older age, lower BMI, use of neuroleptic medicine, peripheral artery disease, and elevated plasma concentrations of ADMA, NT pro-BNP, and CRP were significant predictors of mortality. CONCLUSION: The concentration of ADMA and NT pro-BNP may be used as an early risk marker for overall mortality in geriatric care. Neuroleptic medicine is associated with increased mortality in this population.

Clopidogrel, prasugrel, or ticagrelor use and clinical outcome in patients with acute coronary syndrome: A nationwide long-term registry analysis from 2009 to 2014.

BACKGROUND: The beneficial use of dual antiplatelet therapy (DAPT) with acetylsalicylic acid (ASA) and P2Y12 õinhibitors has been established for patients after acute coronary syndrome (ACS). However, the optimal duration of DAPT is under debate. The aim of the present study was to investigate the long-term utilization and clinical outcome of clopidogrel, prasugrel, and ticagrelor in patients with ACS from 2009 to 2014 in Austria. METHODS: We analysed data from 13 Austrian health insurance funds for the years 2009 to 2014, on 72,676 patients with a hospital discharge diagnosis of ACS. The primary end point was recurrence of ACS or death >30days after the index event. RESULTS: 32,830 subjects received a prescription of a P2Y12 inhibitor within 30days after the index ACS. 18,640 (56.8%) subjects were discharged with clopidogrel, 6683 (20.4%) with prasugrel, and 7507 (22.9%) with ticagrelor, respectively. Data from 32,174 patients with 4975 events during a median follow-up period of 24.9months were available for survival analysis. The cumulative incidence for recurrence of ACS or death at two years was 18.7% in patients receiving clopidogrel, and 8.7% and 12.0% in those receiving prasugrel or ticagrelor, respectively. CONCLUSION: Utilization of P2Y12 inhibitors in patients with ACS was consistent with guideline recommendations. Prasugrel and ticagrelor are increasingly used in ACS patients and associated with a lower number of recurrence of ACS or death compared to clopidogrel. However, clopidogrel was predominantly used in older patients with more co-morbidities.

Men's sexual response to female partner's intranasal oxytocin administration for hypoactive sexual desire disorder: an open prospective cohort study.

OBJECTIVE: To study sexual function, quality of life, and depression in men, whose female partners are undergoing double-blind placebo-controlled randomized treatment for hypoactive sexual desire disorder (HSDD). DESIGN: Open prospective cohort study of 22 weeks. SETTING: Academic medical center. PATIENT(S): Male partners of 30 premenopausal and postmenopausal women with HSDD. INTERVENTION(S): Baseline, 3-month, and 5-month assessment (for 8 weeks each) of male response to female partner's use of oxytocin nasal spray (32 IE) and placebo within 50 minutes before sexual intercourse. MAIN OUTCOME MEASURE(S): Primary outcome parameters were Sexual Life Quality Questionnaire-Male, Sexual Activity Record, Partner Performance Questionnaire, and Hamilton Depression Scale. RESULT(S): Male Sexual Life Quality questionnaire improved significantly from -7.4 ± 9.9 at baseline to 8.2 ± 12 with female partners' treatment with oxytocin nasal spray and to 10.8 ± 13.8 with placebo. Frequency of intercourse improved slightly but not significantly from 6.3 ± 3.9 at baseline to 7.3 ± 4 with female oxytocin therapy, but not with placebo. Male desire and arousal remained stable throughout the study period. Evaluation of female partners' performance by men improved significantly from 8.9 ± 2.8 at baseline to 10.6 ± 2.2 with oxytocin and to 11.2 ± 2.6 with placebo. CONCLUSION(S): Female treatment with either oxytocin or placebo for HSDD significantly improves male sexual quality of life and evaluation of female partner's sexual performance with no difference between oxytocin and placebo on any outcome parameters. A nonsignificant improvement was seen in the frequency of intercourse, male arousal, desire, satisfaction, and Hamilton depression scale. CLINICAL TRIAL REGISTRATION NUMBER: NCT02229721.

Effect of long-term intranasal oxytocin on sexual dysfunction in premenopausal and postmenopausal women: a randomized trial.

OBJECTIVE: To assess the effect of on-demand intranasal oxytocin administration on female sexual function and activity. DESIGN: Randomized, prospective, double-blind, placebo-controlled, crossover trial with duration of 22 weeks. SETTING: Academic medical center. PATIENT(S): Thirty pre-and postmenopausal women with sexual dysfunction. INTERVENTION(S): Over 8 weeks, intranasal oxytocin (32 IU) or placebo self-administered by women within 50 minutes before sexual intercourse; after a washout period of 2 weeks, crossover with patients switched to the alternate group for another 8 weeks. MAIN OUTCOME MEASURE(S): Primary outcome parameter: Female Sexual Function Index (FSFI); secondary outcome parameters: Female Sexual Distress Scale (FSDS), Sexual Quality of Life-Female (SQOL-F), Sexual Interest and Desire Inventory-Female (SIDI-F), and Hamilton depression scale (HDS). RESULT(S): After oxytocin and placebo, the FSFI score increased by 26% and 31%, SQOL-F score by 144% and 125%, and SIDI-F score by 29% and 23%, respectively (repeated measures analysis of variance between groups). After oxytocin and placebo, the FSDS score decreased by 36% and 45%, respectively (repeated measures analysis of variance between groups). There was no statistically significant treatment, sequence (placebo first/second), or interaction effect. CONCLUSION(S): Long-term intranasal oxytocin and placebo administration both improved sexual function and symptoms of depression in women over time with no treatment, sequence (placebo first/second), or interaction effect. CLINICAL TRIAL REGISTRATION NUMBER: NCT02229721.