Association between COVID-19 and subsequent vascular events in primary care patients in Germany.

OBJECTIVES: The aim of this study was to investigate the relationship between COVID-19 diagnosis and the risk of developing a first-ever vascular event (VE) compared with the same risk in those with respiratory tract infection (RTI). STUDY DESIGN: This was a retrospective cohort study. METHODS: This study using data from Disease Analyzer Database (IQVIA) included patients aged ≥18 years with at least one visit to a German practice during the index period. VEs were defined as cardiovascular or cerebrovascular events. Two cohorts were created: patients with a diagnosis of COVID-19 and those diagnosed with RTI. These were matched using propensity scores. Kaplan-Meier curves were created for the purposes of time to event analysis. A Poisson model was used to calculate incidence rates and derive incidence rate ratios (IRRs). RESULTS: A total of 58,904 patients were matched. There was no significant association between COVID-19 diagnosis and increased incidence of VE events among females (IRR [95% confidence interval (CI)]: 0.96 [0.82-1.11] and 1.30 [0.88-1.81]) or males (IRR, 95% CI: 0.91 [0.78-1.05] and 1.13 [0.80-1.62]). Overall, no significant association between COVID-19 diagnosis and incidence of VE was observed across age categories except for cardiovascular vascular events in the age category ≥70 years (IRR [95% CI]: 0.78 [0.67-0.94]). CONCLUSIONS: Overall, our study suggests that COVID-19 diagnosis was not associated with an increased risk of developing VE compared with RTI diagnosis. However, further research in a variety of healthcare settings and regions is needed to confirm these preliminary findings from our cohort, which is a good reflection of routine clinical practice in Germany.

No increased incidence of venous thrombosis or pulmonary embolism after SARS-CoV-2 vaccination in Germany.

OBJECTIVES: Vaccination is one of the most effective measures to combat the COVID-19 pandemic. The main reason for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination hesitancy is the potential side-effects. This study aimed to investigate the incidence of venous thrombosis and pulmonary embolism in patients who received SARS-CoV-2 vaccination. STUDY DESIGN: This was a retrospective cohort study. METHODS: Individuals aged ≥18 years who received an initial vaccination for COVID-19 in one of 1134 general practices in Germany between April and June 2021 were included in the study. Vaccinated patients were matched to unvaccinated individuals by age, sex, index month (April to June 2020 [unvaccinated cohort] or April to June 2021 [vaccinated cohort]) and diagnoses that may be associated with an increased incidence of thrombosis documented within 12 months before the index date. The incidences of thrombosis and non-fatal pulmonary embolism as a function of COVID-19 vaccination were analysed. RESULTS: The present study included 326,833 individuals who were vaccinated against COVID-19 and 326,833 matched unvaccinated individuals. During the follow-up period, 406 vaccinated patients and 342 individuals in the control group received a diagnosis of thrombosis or non-fatal pulmonary embolism. This resulted in an incidence rate of 11.9 vs 11.3 cases per 1000 patient-years for vaccinated vs unvaccinated individuals, respectively, and a non-significant overall incidence rate ratio (IRR: 1.06; 95% confidence interval [CI]: 0.93-1.22). The highest IRR was observed in the 41-60 years age group (IRR: 1.30; 95% CI: 0.98-1.73), and the lowest IRR was seen in the 18-40 years age group (IRR: 0.6; 95% CI: 0.0-1.05); however, none of the individual age group incidence rates was significant. CONCLUSIONS: The results indicate that the occurrence of thrombosis or pulmonary embolism after COVID-19 vaccination is a coincidental finding rather than a consequence of vaccination.

Investigation of the prevalence of non-COVID-19 infectious diseases during the COVID-19 pandemic.

OBJECTIVES: This study aimed to investigate non-COVID-19-related upper respiratory tract infections (URTIs), gastrointestinal infections (GIIs) and urinary tract infections (UTIs) during the COVID-19 pandemic in Germany. STUDY DESIGN: Cross-sectional study. METHODS: Patients with diagnoses of URTIs, GIIs and UTIs from 994 general practitioners (GP) and 192 paediatric practices that routinely send anonymous data to the Disease Analyzer database (IQVIA) were investigated. We studied the differences in recorded URTIs, GIIs and UTIs between April 2019-March 2020 (non-pandemic period) and April 2020-March 2021 (pandemic period) in terms of rates and baseline characteristics by comparing absolute frequencies. RESULTS: Compared with the non-pandemic period, the total number of patients with defined diagnoses was lower in the pandemic period (URTIs: 810,324 vs 520,800; GIIs: 253,029 vs 142,037; UTIs: 132,425 vs 117,932). The number of patients per practice with URTIs (683 vs 439, -36%, P < 0.001) and GIIs (213 vs 120, -44%, P < 0.001) decreased significantly during the pandemic period; the decrease in the number of recorded UTIs was smaller (112 vs 99, -11%, P < 0.05). The decrease in diagnoses was more pronounced among paediatricians than GPs (URTIs: -39% vs -35%; GIIs: -57% vs -39%; UTIs: -15% vs -9%). The decrease in URTIs varied between -35% and -40% depending on the age group. CONCLUSIONS: Measures introduced during the COVID-19 pandemic to reduce transmission of the virus also helped to reduce the spread of non-COVID-19-related URTIs and GIIs. UTIs were impacted to a lesser extent, with rates seeing a slight decrease. An increase in awareness of infectious diseases may have also contributed to the reduction in recorded diagnoses.

Factors associated with fracture after stroke and TIA: a long-term follow-up.

We assessed the long-term incidence of fractures after stroke and TIA and analyzed associated factors. The fracture incidence increases with age and is higher in stroke than in TIA. Dementia is associated with fractures after both. Our results indicate tailored measures are necessary for preventing fractures after stroke or TIA. INTRODUCTION: In the present study, we aimed to assess the long-term incidence of fractures and analyze associated factors after stroke or transient ischemic attack (TIA). METHODS: The current cohort study included patients who had received an initial ischemic stroke or TIA diagnosis documented anonymously in the Disease Analyzer database (IQVIA) between 2000 and 2016 by physicians in 1262 general practices in Germany. Univariate Cox and multivariate regression models were carried out. RESULTS: Three groups (stroke, TIA, no stroke/TIA), each with 12,265 individuals, were selected (mean age 67.3 years, 48.1% female). A fracture was diagnosed in 12.9% of stroke patients and in 11.4% of TIA patients. Among male stroke patients, 11.1% had a fracture (15.4% among female stroke patients). The hazard ratio (HR) for fractures after stroke was 1.26 (CI: 1.15-1.39) and for fractures after TIA, it was 1.14 (CI: 1.03-1.25). In female stroke patients, the HR for fractures was 1.32 (CI: 1.15-1.60), while in males, it was 1.20 (CI: 1.03-1.39). Among TIA patients, females had an elevated HR for fractures (HR: 1.21; CI: 1.06-1.37). In individuals aged ≥ 80 years, an increased risk for fractures was only detected among TIA patients (HR: 1.26; CI: 1.05-1.51). Dementia and non-opioid analgesic therapy were positively associated with fracture after both stroke and TIA. CONCLUSION: Stroke was positively associated with fracture in patients < 80 years, while TIA was positively associated with fracture in patients ≥ 80 years and females. Dementia and analgesic therapy were also associated with fracture after either stroke or TIA.

Long-term risk of stroke and its predictors in transient ischaemic attack patients in Germany.

BACKGROUND AND PURPOSE: Little is known about the long-term association between transient ischaemic attack (TIA) and stroke. Therefore, the goal of this study was to analyze the long-term risk of stroke and associated predictors in a large cohort of TIA patients followed in general practices in Germany. METHODS: This study included patients with an initial TIA diagnosis and subsequently followed up in one of 1262 general practices in Germany between January 2007 and December 2016 (N = 19 824 patients). The primary outcome of the study was the risk of ischaemic stroke within 10 years of the initial diagnosis of TIA. The secondary outcome was the identification of demographic, clinical and pharmaceutical variables significantly associated with stroke in TIA patients. RESULTS: Within 10 years of the initial TIA diagnosis, 18.3% of individuals were diagnosed with stroke. Age was positively associated with stroke, with hazard ratios ranging from 1.88 in patients aged 51-60 years to 4.00 in those aged >80 years (reference group: patients aged ≤50 years). Furthermore, male sex, hypertension, diabetes mellitus, atrial fibrillation and ischaemic heart diseases had an additional impact on the risk of stroke. Finally, new oral anticoagulants, heparins, diuretics, angiotensin II receptor blockers and platelet aggregation inhibitors were identified as protective factors. CONCLUSIONS: In a cohort of almost 20 000 TIA patients, 18.3% were diagnosed with stroke within 10 years after the TIA index event. Several demographic, clinical and pharmaceutical variables significantly predicted the long-term risk of stroke in TIA patients.

Frequency and predictors of acute ischaemic lesions on brain magnetic resonance imaging in young patients with a clinical diagnosis of transient ischaemic attack.

BACKGROUND AND PURPOSE: Acute lesions in patients with transient ischaemic attack (TIA) are important as they are associated with increased risk for recurrence. Characteristics associated with acute lesions in young TIA patients were therefore investigated. METHODS: The sifap1 study prospectively recruited a multinational European cohort (n = 5023) of patients aged 18-55 years with acute cerebrovascular event. The detection of acute ischaemic lesions was based on diffusion-weighted imaging (DWI). The frequency of DWI lesions was assessed in 829 TIA patients who met the criteria of symptom duration <24 h and their association with demographic, clinical and imaging variables was analysed. RESULTS: The median age was 46 years (interquartile range 40-51 years); 45% of the patients were female. In 121 patients (15%) ≥1 acute DWI lesion was detected. In 92 patients, DWI lesions were found in the anterior circulation, mostly located in cortical-subcortical areas (n = 63). Factors associated with DWI lesions in multiple regression analysis were left hemispheric presenting symptoms [odds ratio (OR) 1.92, 95% confidence interval (CI) 1.27-2.91], dysarthria (OR 2.17, 95% CI 1.38-3.43) and old brain infarctions on MRI (territories of the middle and posterior cerebral artery: OR 2.43, 95% CI 1.42-4.15; OR 2.41, 95% CI 1.02-5.69, respectively). CONCLUSIONS: In young patients with a clinical TIA 15% demonstrated acute DWI lesions on brain MRI, with an event pattern highly suggestive of an embolic origin. Except for the association with previous infarctions there was no clear clinical predictor for acute ischaemic lesions, which indicates the need to obtain MRI in young individuals with TIA.

Shunt volume dynamics in stroke patients with patent foramen ovale.

A variation in right atrial and pulmonary arterial pressure might result in a shunt dynamic across a patent foramen ovale (PFO). In the present study we tested if peak exercise facilitates a restoration of right to left shunt (RLS) in stroke patients who demonstrated a functional PFO closure (no evidence of RLS across an initially demonstrated PFO). In stroke patients with PFO demonstrating a functional closure, the RLS was reassessed on peak exercise using contrast-enhanced transcranial Doppler sonography. The exercise procedure consisted of a cardiopulmonary exercise test with supplementary stress echocardiography for assessment of pulmonary circulation. Four stroke patients with initially PFO curtain pattern and a subsequent functional PFO closure (no evidence for RLS) underwent the procedure. In all four patients a RLS could be resurrected during peak physical exercise after a Valsalva strain. While in two patients peak exercise led to an RLS in a countable range of microembolic signals, in two patients a curtain pattern was obtained. One patient showed evidence for reoccurrence of RLS on peak exercise without a Valsalva strain. The patients with curtain pattern had a better peak exercise performance. Although the systolic pulmonary arterial pressure increased during exercise in all patients, there was no direct correlation with the detected RLS. After a functional PFO closure peak exercise combined with a Valsalva strain facilitates the reoccurrence of RLS in stroke patients.

[Non-drug therapies for CRPS]. / Nicht medikamentöse Therapien beim CRPS.

State of the art CRPS therapy comprises medication, interventional therapies and non-pharmaceutical treatments like physiotherapy (PT), occupational therapy, PT with cognitive behavioural elements (mirror therapy, 'motor imagery', and 'graded exposure'), psychotherapeutic methods, local therapies and neurostimulation. These treatments are mostly as successful as medical or interventional treatment. These effects have been demonstrated in small but randomised controlled studies. Adjuvant therapies were shown to reduce pain and the severity of dysfunction in CRPS. Therefore, these non-drug therapies should be an essential part of any multimodal CRPS treatment.

Frequency of Fabry disease in patients with small-fibre neuropathy of unknown aetiology: a pilot study.

BACKGROUND: Early occurrence of small-fibre neuropathy (SFN) is a common feature of Fabry disease (FD) - an X-linked storage disorder caused by reduced activity of the α-galactosidase A (α-GAL). Although SFN may result from different disorders, the cause is often unclear. Therefore, we investigated the frequency of FD in patients with SFN of unknown aetiology. METHODS: Patients with idiopathic SFN, established by sensory quantitative testing and/or skin biopsy, were examined for mutations in the α-GAL gene. Where mutations in the α-GAL gene were identified, levels of globotriaosylceramide (Gb(3)) were measured in urine and blood and the α-GAL activity was evaluated. When new mutations were detected, a diagnostic work-up was performed as well as a Gb(3) accumulation in the skin, lyso-Gb(3) in blood and Gb(3)_24 in urine were proved. RESULTS: Twenty-four of 29 eligible patients were enrolled in the study. Mutations in the α-GAL gene were observed in five patients. A typical mutation for FD (c.424T>C, [C142R]) was detected in one patient. In four patients, a complex intronic haplotype within the α-GAL gene (IVS0-10C>T [rs2071225], IVS4-16A>G [rs2071397], IVS6-22C>T [rs2071228]) was identified. The relevance of this haplotype in the pathogenesis of FD remains unclear until now. However, these patients showed increased concentrations of Gb(3) and/or lyso-Gb(3), while no further manifestations for FD could be proved. CONCLUSIONS: Fabry disease should be considered in patients with SFN of unknown aetiology, and screening for FD should be included in the diagnostic guidelines for SFN. The significance of the intronic haplotype regarding SFN needs further evaluation.

Effect of daytime, weekday and year of admission on outcome in acute ischaemic stroke patients treated with thrombolytic therapy.

BACKGROUND: Since doubts were raised, if a challenging medical procedure such as acute stroke treatment including thrombolysis with recombinant tissue plasminogen activator (rTPA) is available with identical standard and outcome 24 h and 7 days a week our aim was to examine if acute stroke patients defined by onset-admission time (OAT) of

Diagnostic and prognostic value of contrast-enhanced ultrasound in acute stroke.

In the last decade transcranial color-coded sonography (TCCS) was established as a routine in neurovascular departments for the evaluation of brain-supplying vessels in cerebrovascular diseases. TCCS has demonstrated feasibility and validity for the evaluation of the basal cerebral arteries, especially for the middle cerebral artery (MCA). In some patients an insufficient bone window may limit the diagnostic power. The application of microbubble agents can overcome this limitation in most patients. Beside the demonstration of vessel pathology such as stenosis and occlusion, TCCS also provides prognostic information. In the case of proximal MCA occlusion shown by TCCS within 6 hours of stroke, nearly 90 % of the patients suffered an unfavorable outcome. Furthermore TCCS is suitable for monitoring thrombolysis in acute stroke to detect whether there is recanalization of the affected vessel. The possibility for bedside examination, the non-invasiveness and the cost-effectiveness are features which make TCCS an optimal tool for the evaluation of cerebral vessels in acute ischemic stroke.