Do patients referred to emergency departments after being assessed in primary care differ from other ED patients? Retrospective analysis of a random sample from two German metropolitan EDs.

BACKGROUND: To assess differences between patients referred to emergency departments by a primary care physician (PCP) and those presenting directly and the impact of referral on the likelihood of admission. DESIGN OF STUDY: Retrospective cohort study. SETTING: EDs of two nonacademic general hospitals in a German metropolitan region. PARTICIPANTS: Random sample of 1500 patients out of 80,845 presentations during the year 2019. RESULTS: Age was 55.8 ± 22.9 years, and 51.4% was female. A total of 34.7% presented by emergency medical services (EMS), and 47.7% were walk-ins. One-hundred seventy-four (11.9%) patients were referred by PCPs. Referrals were older (62.4 ± 20.1 vs 55.0 ± 23.1 years, p < .001) and had a higher Charlson Comorbidity Index (CCI) (3 (1-5) vs 2 (0-4); p < .001). Referrals received more ultrasound examinations independently from their admission status (27.6% vs 15.7%; p < .001) and more CT and laboratory investigations. There were no differences in sex, Manchester Triage System (MTS) category, or pain-scale values. Referrals presented by EMS less often (9.2% vs 38.5%; p < .001). Admission rates were 62.6% in referrals and 37.1% in non-referrals (p < .001). Referral (OR 3.976 95% CI: 2.595-6.091), parenteral medication in ED (OR 2.674 (1.976-3.619)), higher MTS category (1.725 (1.421-2.093)), transport by EMS (1.623 (1.212-2.172)), abnormal vital parameters (1.367 (0.953-1.960)), higher CCI (1.268 (1.196-1.344)), and trauma (1.268 (1.196-1.344)) were positively associated with admission in multivariable analysis, whereas ultrasound in ED (0.450 (0.308-0.658)) and being a nursing home resident (0.444 (0.270-0.728)) were negatively associated. CONCLUSION: Referred patients were more often admitted. They received more laboratory investigations, ultrasound examinations, and computed tomographies. Difficult decisions regarding the necessity of admission requiring typical resources of EDs may be a reason for PCP referrals.

The quality of acute stroke care- an analysis of evidence-based indicators in 260 000 patients.

BACKGROUND: Stroke patients should be cared for in accordance with evidence-based guidelines. The extent of implementation of guidelines for the acute care of stroke patients in Germany has been unclear to date. METHODS: The regional quality assurance projects that cooperate in the framework of the German Stroke Registers Study Group (Arbeitsgemeinschaft Deutscher Schlaganfall-Register, ADSR) collected data on the care of stroke patients in 627 hospitals in 2012. The quality of the acute hospital care of patients with stroke or transient ischemic attack (TIA) was assessed on the basis of 15 standardized, evidence-based quality indicators and compared across the nine participating regional quality assurance projects. RESULTS: Data were obtained on more than 260 000 patients nationwide. Intravenous thrombolysis was performed in 59.7% of eligible ischemic stroke patients patients (range among participating projects, 49.7-63.6%). Dysphagia screening was documented in 86.2% (range, 74.8-93.1%). For the following indicators, the defined targets were not reached for all of Germany: anti-aggregation within 48 hours, 93.4% (range, 86.6-96.4%); anticoagulation for atrial fibrillation, 77.6% (range, 72.4-80.1%); standardized dysphagia screening, 86.2% (range, 74.8-93.1%); oral and written information of the patients or their relatives, 86.1% (range, 75.4-91.5%). The rate of patients examined or treated by a speech therapist was in the target range. CONCLUSION: The defined targets were reached for most of the quality indicators. Some indicators, however, varied widely across regional quality assurance projects. This implies that the standardization of care for stroke patients in Germany has not yet been fully achieved.

Influence of acute complications on outcome 3 months after ischemic stroke.

BACKGROUND: Early medical complications are potentially modifiable factors influencing in-hospital outcome. We investigated the influence of acute complications on mortality and poor outcome 3 months after ischemic stroke. METHODS: Data were obtained from patients admitted to one of 13 stroke units of the Berlin Stroke Registry (BSR) who participated in a 3-months-follow up between June 2010 and September 2012. We examined the influence of the cumulative number of early in-hospital complications on mortality and poor outcome (death, disability or institutionalization) 3 months after stroke using multivariable logistic regression analyses and calculated attributable fractions to determine the impact of early complications on mortality and poor outcome. RESULTS: A total of 2349 ischemic stroke patients alive at discharge from acute care were included in the analysis. Older age, stroke severity, pre-stroke dependency and early complications were independent predictors of mortality 3 months after stroke. Poor outcome was independently associated with older age, stroke severity, pre-stroke dependency, previous stroke and early complications. More than 60% of deaths and poor outcomes were attributed to age, pre-stroke dependency and stroke severity and in-hospital complications contributed to 12.3% of deaths and 9.1% of poor outcomes 3 months after stroke. CONCLUSION: The majority of deaths and poor outcomes after stroke were attributed to non-modifiable factors. However, early in-hospital complications significantly affect outcome in patients who survived the acute phase after stroke, underlining the need to improve prevention and treatment of complications in hospital.

Association between socioeconomic status and functional impairment 3 months after ischemic stroke: the Berlin Stroke Register.

BACKGROUND AND PURPOSE: We aimed to analyze the association between patient socioeconomic status and functional impairment 3 months after ischemic stroke and to identify factors that influence this association. METHODS: Data were obtained from the Berlin Stroke Register, a network of 14 stroke units in Berlin. Ischemic stroke patients consecutively admitted to 1 of the hospitals in the Berlin Stroke Register between June 2010 and September 2011, were followed-up 3 months after the index event by postal or telephone interview. We used multivariable logistic regression to examine the association between highest education as marker of socioeconomic status and functional impairment after stroke defined by Barthel Index categories. We adjusted for age, sex, prestroke dependency, stroke severity, functional deficit after stroke onset, and comorbidities as possible confounding factors. RESULTS: A total of 1688 ischemic stroke patients who were alive at 3 months and completed the questionnaire were included in the analysis; 40% of the patients were female and 50% of the patients were 70 years or older. Age, prestroke dependency, stroke severity, and the absence of comorbidities were significantly associated with good functional outcome at 3 months. In multivariable analysis, a higher probability of good outcome was observed in patients with college or university degree (odds ratio, 2.18; 95% confidence interval, 1.39-3.42) compared with patients with no completed education. CONCLUSIONS: Patients with lower education have considerably lower rates of good functional outcome after stroke that cannot be fully explained by variations in the patients' clinical and demographic characteristics.

Development of a clinical score (A2DS2) to predict pneumonia in acute ischemic stroke.

BACKGROUND AND PURPOSE: Poststroke pneumonia is a potentially preventable complication after stroke associated with poor outcome. We developed and externally validated a prognostic score for predicting risk of pneumonia after ischemic stroke. METHODS: The prognostic score was developed based on clinical data routinely collected after admission from the Berlin Stroke Register, Germany. The association of demographics, comorbidities, and clinical characteristics with poststroke pneumonia was investigated using multivariable logistic regression analyses. Independent predictors of poststroke pneumonia were translated into a point scoring system based on the corresponding regression coefficients. The predictive properties of the developed prognostic score were externally validated using an independent data set from the Stroke Register Northwest-Germany. RESULTS: Between 2007 and 2009, 15 335 patients with ischemic stroke were registered within the Berlin Stroke Register. The observed rate of pneumonia in hospital was 7.2%. A 10-point score was derived for prediction of poststroke pneumonia (Age ≥ 75 years=1, Atrial fibrillation=1, Dysphagia=2, male Sex=1, stroke Severity, National Institutes of Health Stroke Scale 0-4=0, 5-15=3, ≥ 16=5; A(2)DS(2)). The proportion of pneumonia varied between 0.3% in patients with a score of 0 point to 39.4% in patients with a score of 10 points. The score demonstrated excellent discrimination (C-statistic 0.84; 95% CI, 0.83-0.85) and calibration (McFadden R(2)=0.21). Prediction, discrimination, and calibration properties were reproduced in the validation cohort consisting of 45 085 patients with ischemic stroke. CONCLUSIONS: The A(2)DS(2) score is a valid tool for predicting poststroke pneumonia based on routinely available data. A(2)DS(2) might be useful for guiding monitoring of high-risk patients or prophylactic pneumonia management in clinical routine.

Stilbene-based inhibitors of estrone sulfatase with a dual mode of action in human breast cancer cells.

Estrone sulfate (E1S) is an endogenous prodrug that delivers estrone and, subsequently, estradiol to target cells, after hydrolysis by the enzyme estrone sulfatase, which is active in various tissues including hormone-dependent breast cancer. Blockade of this enzyme should reduce the estrogen level in breast cancer cells and prevent hormonal growth stimulation. In this study, a number of sulfamoyloxy-substituted stilbenes with side chains that guarantee antiestrogenic activity were synthesized and evaluated as inhibitors of estrone sulfatase. They inhibited this enzyme in human MDA-MB 231 breast cancer cells, with IC(50) values in the submicromolar range. The effects of both the free hydroxy derivatives and the sulfamates on gene activation were determined in transfected MCF-7/2a breast cancer cells stimulated either with estradiol or with estrone sulfate. The analysis of data revealed a dual mode of action of the majority of compounds. They blocked gene expression by inhibition of estrone sulfatase and by antiestrogenic action. This pharmacological profile was also observed in assays on antiproliferative activity. The most potent derivative 8 g inhibited the growth of wild-type human MCF-7 cells with an IC(50) value of 13 nM.

Synthesis and biological evaluation of stilbene-based pure estrogen antagonists.

Replacement of one of the ethyl substituents in diethylstilbestrol by side chains with functional groups converted this potent estrogen into pure antiestrogens with the potential for the treatment of breast cancer. These agents completely suppressed estrogen receptor-mediated gene activation and inhibited the growth of estrogen-sensitive MCF-7 breast cancer cells in submicromolar concentrations. The most potent derivative displayed similar activity as fulvestrant (ICI 182,780) in vitro and in the mouse uterine weight test. Obviously, the stilbene structure can act as a substitute for estradiol in the development of pure estrogen antagonists.

2-phenylindole sulfamates: inhibitors of steroid sulfatase with antiproliferative activity in MCF-7 breast cancer cells.

A number of 2-phenylindole sulfamates with lipophilic side chains in 1- or 5-position of the indole were synthesized and evaluated as steroid sulfatase (estrone sulfatase) inhibitors. Most of the new sulfamates inhibited the enzymatic hydrolysis of estrone sulfate in MDA-MB 231 breast cancer cells with IC(50) values between 2 nM and 1 microM. A favorable position for a long side chain is the nitrogen of a carbamoyl group at C-5 of the indole when the phenyl ring carries the sulfamate function. These derivatives inhibit gene activation in estrogen receptor (ER)-positive MCF-7 breast cancer cells in submicromolar concentrations and reduce cell proliferation with IC(50) values of ca. 1 microM. All of the potent inhibitors were devoid of estrogenic activity and have the potential for in vivo application as steroid sulfatase inhibitors.