Prediction of non-resectability using the updated Predictive Index Value model assessed by imaging and surgery in tubo-ovarian cancer: a prospective multicenter ISAAC study.

BACKGROUND: A laparoscopy-based scoring system was developed by Fagotti et al (Fagotti or Predictive Index Value (PIV)score) based on the intraoperative presence or absence of carcinomatosis on predefined sites. Later, the authors updated the PIV score calculated only in the absence of one or both absolute criteria of non-resectability (mesenteric retraction and miliary carcinomatosis of the small bowel) (updated PIV model). OBJECTIVE: The aim was to demonstrate the non-inferiority of ultrasound to other imaging methods (contrast enhanced computed tomography (CT) and whole-body diffusion-weighted (WB DWI)/MRI) in predicting non-resectable tumor (defined as residual disease>1 cm) using the updated PIV model in patients with tubo-ovarian cancer. The agreement between imaging and intraoperative findings as a reference was also calculated. STUDY DESIGN: This was a European prospective multicenter observational study. We included patients with suspected tubo-ovarian carcinoma who underwent preoperative staging and prediction of non-resectability at ultrasound, CT, WB-DWI/MRI and surgical exploration. The predictors of non-resectability were suspicious mesenteric retraction and/or miliary carcinomatosis of the small bowel or if absent, a PIV>8 (updated PIV model). The PIV score ranges from 0 to 12 according to the presence of disease in six predefined intra-abdominal sites (great omentum, liver surface, lesser omentum/stomach/spleen, parietal peritoneum, diaphragms, bowel serosa/mesentery). The reference standard was surgical outcome, in terms of residual disease>1 cm, assessed by laparoscopy and/or laparotomy. The area under the receiver operating characteristic curve (AUC) to assess the performance of the methods in predicting non-resectability was reported. Concordance between index tests at detection of disease at six predefined sites and intraoperative exploration as reference standard was also calculated using Cohen's kappa. RESULTS: The study was between 2018 and 2022 in five European gynecological oncology centers. Data from 242 patients having both mandatory index tests (ultrasound and CT) were analyzed. 145/242 (59.9%) patients had no macroscopic residual tumor after surgery (R0) (5/145 laparoscopy and 140/145 laparotomy) and 17/242 (7.0%) had residual tumor ≤1cm (R1) (laparotomy). In 80/242 patients (33.1%), the residual tumor was >1 cm (R2), 30 of them underwent laparotomy and maximum surgery was carried out and 50/80 underwent laparoscopy and cytoreduction was not feasible in all of them. After excluding 18/242 (7.4%) patients operated on but not eligible for extensive surgery, the predictive performance of three imaging methods was analyzed in 167 women. The AUCs of all methods in discriminating between resectable and non-resectable tumor was 0.80 for ultrasound, 0.76 for CT, 0.71 for WB-DWI/MRI and 0.90 for surgical exploration. Ultrasound had the highest agreement (Cohen's kappa ranging from 0.59 to 0.79) compared to CT and WB-DWI/MRI to assess all parameters included in the updated PIV model. CONCLUSIONS: Ultrasound showed non-inferiority to CT and to WB-DWI/MRI in discriminating between resectable and non-resectable tumor using the updated PIV model. Ultrasound had the best agreement between imaging and intraoperative findings in the assessment of parameters included in the updated PIV model. Ultrasound is an acceptable method to assess abdominal disease and predict non-resectability in patients with tubo-ovarian cancer in the hands of specially trained ultrasound examiners.

Diagnostic performance of ultrasonography in pre-operative assessment of lymph nodes in patients with cervical cancer.

OBJECTIVES: To assess the diagnostic performance of ultrasonography in pre-operative assessment of lymph nodes in patients with cervical cancer, to compare the outcomes for pelvic and para-aortic regions, and to detect macrometastases and micrometastases separately. METHODS: Patients were retrospectively included if they met the following inclusion criteria: pathologically verified cervical cancer; ultrasonography performed by one of four experienced sonographers; surgical lymph node staging, at least in the pelvic region-sentinel lymph node biopsy or systematic pelvic lymphadenectomy or debulking. The final pathological examination was the reference standard. RESULTS: 390 patients met the inclusion criteria between 2009 and 2019. Pelvic node macrometastases (≥2 mm) were confirmed in 54 patients (13.8%), and micrometastases (≥0.2 mm and <2 mm) in another 21 patients (5.4%). Ultrasonography had sensitivity 72.2%, specificity 94.0%, and area under the curve (AUC) 0.831 to detect pelvic macrometastases, while sensitivity 53.3%, specificity 94.0%, and AUC 0.737 to detect both pelvic macrometastases and micrometastases (pN1). Ultrasonography failed to detect pelvic micrometastases, with sensitivity 19.2%, specificity 85.2%, and AUC 0.522. There was no significant impact of body mass index on diagnostic accuracy. Metastases in para-aortic nodes (macrometastases only) were confirmed in 16 of 71 patients who underwent para-aortic lymphadenectomy. Ultrasonography yielded sensitivity 56.3%, specificity 98.2%, and AUC 0.772 to identify para-aortic node macrometastases. CONCLUSION: Ultrasonography performed by an experienced sonographer can be considered a sufficient diagnostic tool for pre-operative assessment of lymph nodes in patients with cervical cancer, showing similar diagnostic accuracy in detection of pelvic macrometastases as reported for other imaging methods (18F-fluorodeoxyglucose positron emission tomography/CT or diffusion-weighted imaging/MRI). It had low sensitivity for detection of small-volume macrometastases (largest diameter <5 mm) and micrometastases. The accuracy of para-aortic assessment was comparable to that for pelvic lymph nodes, and assessment of the para-aortic region should be an inseparable part of the examination protocol.

Long-term trajectory of renal dysfunction and related risk factors in patients with apparently treatment-resistant and non-resistant arterial hypertension.

Objectives: Evidence suggests that renal function increasingly deteriorates in patients with apparently treatment-resistant hypertension (ATRH) in comparison with those who have non-resistant arterial hypertension (NAH). We aimed to assess the long-term decline in renal function between these patient groups and identify specific risk factors contributing to the progression of renal dysfunction. Methods: Data for 265 patients with ATRH and NAH in a hypertension excellence centre were retrospectively evaluated. Demographic characteristics, co-morbidities, laboratory findings, secondary causes of hypertension, medication and exposure to contrast agents were assessed. To address differences between groups, adjustment with linear mixed-effect models was used. Results: Data from the first 4 years of follow-up were evaluated. After adjustment for age and diabetes, which were identified as independent risk factors for renal dysfunction progression in the study cohort, the mean decrease in estimated glomerular filtration rate per year was steeper with ATRH than with NAH (-1.49 vs. -0.65 mL/min/1.73 m2 per year; difference in slope, 0.83 mL/min/1.73 m2 per year; 95% confidence interval [CI]: 0.25-1.41, p = 0.005). In subgroup analyses, without Holm-Bonferroni correction, the prescription of MRA indicated a faster decline in renal function in ATRH. Following correction, no specific therapeutic risk factor was associated with faster progression of renal dysfunction. Conclusions: Renal function declines twice as fast with ATRH compared with NAH, independently of age and diabetes. Larger studies are needed to reveal risk factors for renal dysfunction in patients with hypertension.

High blood pressure (arterial hypertension) is a significant risk factor for kidney function decline. Resistant hypertension represents a subtype of hypertension that is difficult to treat and requires multiple antihypertensive agents to achieve effective blood pressure control. Recent research suggests that individuals with resistant hypertension are at greater risk of kidney dysfunction.This study analyses data from adult patients with arterial hypertension and resistant hypertension followed-up for a mean duration of 6.4 years.A faster decline in kidney function was observed in patients with resistant hypertension. This suggests that renal function in these patients should be closely monitored.After statistical evaluation, no medication was found to be associated with an increased risk of kidney failure progression. However, two specific medications, spironolactone and eplerenone, raised suspicion and require further exploration in larger prospective studies.

Sentinel lymph node pathological ultrastaging: Final outcome of the Sentix prospective international study in patients with early-stage cervical cancer.

OBJECTIVE: To report the outcome of SLN staging in the SENTIX international prospective trial of SLN biopsy in patients with cervical cancer with an intensive ultrastaging protocol and central quality control and to evaluate how the intensity of pathological assessment correlates with metastatic detection rate in SLNs. METHODS: Eligible were patients with stages T1a1/LVSI+ to T1b2 (<4 cm, ≤2 cm for fertility sparing), common tumor types, no suspicious lymph nodes on imaging, and bilateral SLN detection. SLNs were examined intraoperatively and processed by an intensive protocol for ultrastaging (paraffin blocks sectioned completely in 150-µm intervals/levels). SLNs from each site were submitted for central quality control. RESULTS: In the SENTIX SLN study, 647 out of 733 enrolled patients underwent SLN ultrastaging, identifying 12.5% (81/647) with node positive, N1 cases. Intraoperative detection revealed metastases in 56.8% (46/81) of these cases, categorized into macrometastases (83.7%), micrometastases (26.3%), and isolated tumor cells (9.1%). Ultrastaging identified additional metastatic involvement in 43.2% (35/81) of patients, with detailed sectioning revealing metastases (MAC/MIC) at first level in 20 cases (24.7%), at levels 2-4 in 9 cases (11.1%), and at level ≥5 in 6 cases (7.4%). CONCLUSION: SLN ultrastaging detects additional 43% of N1 (MAC/MIC) in patients with negative LNs by imaging and intraoperative pathological assessment. The detection rate of positive SLN correlates with the intensity (number of levels) of ultrastaging. Examination of four levels from paraffin blocks, which detects >90% of patients with N1, is a reasonable compromise for an international standard for ultrastaging. STUDY REGISTRATION: NCT02494063 (ClinicalTrials.gov).

Evaluation of viscoelastic parameters and photo-based assessment of newly developed dermal substitutes modified with thermostabilized fibroblast growth factor 2.

BACKGROUND: The purpose of dermal substitutes is to mimic the basic properties of the extracellular matrix of human skin. The application of dermal substitutes to the defect reduces the formation of hypertrophic scars and improves the scar quality. This study aims to develop an original dermal substitute enriched with stable fibroblast growth factor 2 (FGF2-STAB®) and test it in an animal model. METHODS: Dermal substitutes based on collagen/chitosan scaffolds or collagen/chitosan scaffolds with nanofibrous layer were prepared and enriched with FGF2-STAB® at concentrations of 0, 0.1, 1.0, and 10.0 µg ‧ cm-2. The performance of these dermal substitutes was tested in vivo on artificially formed skin defects in female swine. The outcomes were evaluated using cutometry at 3 and 6 months. In addition, visual appearance was assessed based on photos of the scars at 1-month, 3-month and 6-month follow-ups using Yeong scale and Visual Analog Scale. RESULTS: The dermal substitute was fully integrated into all defects and all wounds healed successfully. FGF2-STAB®-enriched matrices yielded better results in cutometry compared to scaffolds without FGF2. Visual evaluation at 1, 3, and 6 months follow-ups detected no significant differences among groups. The FGF2-STAB® effectiveness in improving the elasticity of scar tissues was confirmed in the swine model. This effect was independently observed in the scaffolds with nanofibres as well as in the scaffolds without nanofibres. CONCLUSION: The formation of scars with the best elasticity was exhibited by addition 1.0 µg ‧ cm-2of FGF2-STAB® into the scaffolds, although it had no significant effect on visual appearance at longer follow-ups. This study creates the basis for further translational studies of the developed product and its progression into the clinical phase of the research.

Cartilage tympanoplasty for retraction pocket of the tympanic membrane in children.

Background: Retraction pocket (RP) of the tympanic membrane (TM) is a common pathology in children that can cause ossicular chain erosion, cholesteatoma formation, and potentially life-threatening complications of cholesteatoma. This study assessed the functional and anatomical results of cartilage grafting in children with severe RP of the TM. Methods: This was a retrospective review of 212 children from a tertiary referral center. Results: We identified significant differences in hearing results, indication criteria, and location of TM fixation between stages II and III of RP (according to Charachon). We observed a significantly higher incidence of RP in boys than in girls. Conclusions: Cartilage tympanoplasty for retraction pocket of the tympanic membrane in children is a safe procedure with good anatomical and hearing results.

Outcomes of patients with myocardial infarction and cardiogenic shock treated with culprit vessel-only versus multivessel primary PCI.

INTRODUCTION AND OBJECTIVES: Multivessel primary percutaneous coronary intervention (pPCI) is still often used in patients with ST-elevation myocardial infarction (STEMI) and cardiogenic shock (CS). The study aimed to compare the characteristics and prognosis of patients with CS-STEMI and multivessel coronary disease (MVD) treated with culprit vessel-only pPCI or multivessel-pPCI during the initial procedure. MATERIAL AND METHODS: From 2016 to 2020, 23,703 primary PCI patients with STEMI were included in a national all-comers registry of cardiovascular interventions. Of them, 1,213 (5.1%) patients had CS and MVD at admission to the hospital. Initially, 921 (75.9%) patients were treated with culprit vessel (CV)-pPCI and 292 (24.1%) with multivessel (MV)-pPCI. RESULTS: Patients with 3-vessel disease and left main disease had a higher probability of being treated with MV-pPCI than patients with 2-vessel disease and patients without left main disease (28.5% vs. 18.6%; p < 0.001 and 37.7% vs. 20.6%; p < 0.001). Intra-aortic balloon pump, extracorporeal membrane oxygenation (ECMO), and other mechanical circulatory support systems were more often used in patients with MV-pPCI. Thirty (30)-day and 1-year all-cause mortality rates were similar in the CV-pPCI and MV-pPCI groups (odds ratio, 1.01; 95% confidence interval [CI] 0.77 to 1.32; p = 0.937 and 1.1; 95% CI 0.84 to 1.44; p = 0.477). The presence of 3-vessel disease and the use of ECMO were the strongest adjusted predictors of 30-day and 1-year mortality. CONCLUSIONS: Our data from an extensive all-comers registry suggests that selective use of MV-pPCI does not increase the all-cause mortality rate in patients with CS-STEMI and MVD compared to CV-pPCI.

Clinical characteristics and mortality in all Czech patients after pacemaker implantation in the last decade.

Background and aims: Analysis of mortality from the national health registries and data from a specific central registry dealing with the implantation of pacemakers (REPACE) in Czech patients. Methods and results: Retrospective observational analysis of pacemakers' implantation in all Czech patients [n = 82,791; 47,070 (56.9%) men, 75.9 ± 10.4 years old] between 2010 and 2021. Almost 114,000 pacemakers were implanted between 2010 and 2021, of which 27.9% were single-chamber, 67.4% were dual-chamber and 4.6% were biventricular. The annual number of implantations has been steadily increasing with a 6% annual decline in 2020 with increased mortality and reductions in care provided, likely related to COVID-19. The observed 5-year relative survival was 88.6% (overall survival 60.6%) and the 10-year relative survival was 75.9% (overall survival 32.7%). Causes of death 5ary according to the age of the patient. The highest difference 1n the reported numbers in the REPACE Registry did not exceed 2% in comparison with the National Register of Reimbursed Health Services. Conclusion: This study followed all Czech patients with pacemaker's implantation in between 2010 and 2021. The annual number of 1mplantations has been steadily 1ncreasing. Patients with implanted pacemakers had a significantly higher mortality than the average population. Number of patients in the registry corresponded almost perfectly with the National Register of Reimbursed Health Services.

Serum concentrations of proinflammatory biomarker interleukin-6 (IL-6) as a predictor of postoperative complications after elective colorectal surgery.

BACKGROUND: The aim of this prospective study was to evaluate the role of serum IL-6 as a potential predictive biomarker of postoperative complications (POC) in elective colorectal surgery. METHOD: A total of 115 patients underwent colorectal surgery for malignancy. IL-6 was measured on the first and third postoperative days (POD1, POD3), and C-reactive protein (CRP) was measured on the POD3. POC was analysed in subgroups according to Clavien‒Dindo (CD), antibiotic (ATB) treatment, intensive care unit (ICU) and hospital length of stay. The predictive power of variables for evaluated endpoints was analysed using receiver-operating characteristic (ROC) analysis and described by area under the curve (AUC). ROC analysis was adopted for the identification of optimal cut-offs. Histological analysis was performed to verify IL-6 production by the tumour. RESULTS: Out of 115 patients who were analysed, 42% had POC. Patients with POC had significantly higher serum levels of IL-6 on POD1 (p < 0.001) and POD3 (p < 0.001). IL-6 early on POD1 as a predictor of antibiotic treatment, ICU stay and hospital stay (AUC 0.818; 0.811; 0.771) did not significantly differ from the AUC of CRP late on POD3 (0.879; 0.838, 0.752). A cut-off IL-6 value of 113 pg/ml on POD1 and 180.5 pg/ml on POD3 in severe complications (CD > 3a) resulted in 75% and 72% sensitivity, 78.6% and 99% specificity, negative predictive value 96.4% and 97% and positive predictive value 29% and 88.9%. CONCLUSION: The serum level of interleukin-6 can predict severe (CD > 3a) POC early on POD1. On POD3, IL-6 is superior to CRP in terms of high positive predictive power of severe POC. Interestingly, the advantage of IL-6 on POD1 is early prediction of the need for antibiotic treatment, ICU stay and hospital stay, which is comparable to the CRP serum level late on the third POD.

Efficacy of the intranasal application of azaperone for sedation in weaned piglets.

The aim of the study was to compare the efficacy of the intranasal and parenteral administration of azaperone in order to achieve pig sedation. A total of 32 weaned piglets divided into 4 groups (8 piglets in each group) were used. Group A was injected intramuscularly (i.m.) with azaperone (Stresnil®, 40 mg/ml inj.; Elanco Animal Health) at a dose of 2 mg/kg of body weight (b.w.). Group B received a dose of 2 mg/kg b.w. of azaperone intranasally. Group C was given azaperone intranasally at a dose of 4 mg/kg b.w. Group D was given 1 ml of saline intranasally and served as the control group. The response to the defined stimulus (a blunt blow of a metal rod into a metal edge of a pen), the degree of salivation, movement level, body temperature and serum azaperone concentration were included in the trial. We found that in order to induce an adequate level of sedation comparable to the standard method of application, i.e., 2 mg/kg b.w. i.m., the intranasal administration of azaperone at a dose of 4 mg/kg body weight is required.

RETRO-POPE: A Retrospective, Multicenter, Real-World Study of All-Cause Mortality in COPD.

Purpose: The Phenotypes of COPD in Central and Eastern Europe (POPE) study assessed the prevalence and clinical characteristics of four clinical COPD phenotypes, but not mortality. This retrospective analysis of the POPE study (RETRO-POPE) investigated the relationship between all-cause mortality and patient characteristics using two grouping methods: clinical phenotyping (as in POPE) and Burgel clustering, to better identify high-risk patients. Patients and Methods: The two largest POPE study patient cohorts (Czech Republic and Serbia) were categorized into one of four clinical phenotypes (acute exacerbators [with/without chronic bronchitis], non-exacerbators, asthma-COPD overlap), and one of five Burgel clusters based on comorbidities, lung function, age, body mass index (BMI) and dyspnea (very severe comorbid, very severe respiratory, moderate-to-severe respiratory, moderate-to-severe comorbid/obese, and mild respiratory). Patients were followed-up for approximately 7 years for survival status. Results: Overall, 801 of 1,003 screened patients had sufficient data for analysis. Of these, 440 patients (54.9%) were alive and 361 (45.1%) had died at the end of follow-up. Analysis of survival by clinical phenotype showed no significant differences between the phenotypes (P=0.211). However, Burgel clustering demonstrated significant differences in survival between clusters (P<0.001), with patients in the "very severe comorbid" and "very severe respiratory" clusters most likely to die. Overall survival was not significantly different between Serbia and the Czech Republic after adjustment for age, BMI, comorbidities and forced expiratory volume in 1 second (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.65-0.99; P=0.036 [unadjusted]; HR 0.88, 95% CI 0.7-1.1; P=0.257 [adjusted]). The most common causes of death were respiratory-related (36.8%), followed by cardiovascular (25.2%) then neoplasm (15.2%). Conclusion: Patient clusters based on comorbidities, lung function, age, BMI and dyspnea were more likely to show differences in COPD mortality risk than phenotypes defined by exacerbation history and presence/absence of chronic bronchitis and/or asthmatic features.

Challenges in prospective observational studies evaluating pressure ulcer costs: how to price the items correctly.

OBJECTIVE: Pressure ulcers (PUs) are a significant healthcare problem with a negative impact on patients' quality of life and incurring substantial healthcare expenses. Our study aimed to analyse the costs of treating PUs in hospitalised patients in the Czech Republic, in the context of current treatment procedures and price levels, and to pilot-test the detailed methodology developed. METHOD: A prospective, observational, non-interventional study was conducted at the Clinic of Anesthesiology, Resuscitation and Intensive Medicine, the Internal Medicine Department and the Surgical Department of the University Hospital Ostrava. The study included all hospitalised patients with a PU from March-May 2021. Data were collected using the hospital information system. A bottom-up, person-based approach to cost analysis was used, based on a comprehensive cost structure using accurate patient-specific consumption records. RESULTS: The length of hospitalisations ranged from 1-31 (mean: 12.7) days. The average cost of PU treatment per hospitalisation was calculated at €1579. The average daily cost of PU treatment was €179, including antibiotic therapy (ATB) and €112 without ATB. Most of the costs were associated with ATB (38.6%) and caregivers' time (35.9%). Based on the results, a predictive model was developed to estimate the cost of treating a hospitalised patient with a PU, which could be used in future research to assess the costs of treating these patients. CONCLUSION: We have faced many challenges in the methodology of preparation of cost analysis (e.g., how to count amorphous topical agents and sprays, how to properly identify PUs, how to price the positioning aids and mattresses, and how to relate the ATB treatment to the PU). This analysis provides important input for developing a comprehensive and more accurate methodology for monitoring PU costs in hospitalised patients, applicable in clinical practice for inpatient healthcare providers.

Can variants, reinfection, symptoms and test types affect COVID-19 diagnostic performance? A large-scale retrospective study of AG-RDTs during circulation of Delta and Omicron variants, Czechia, December 2021 to February 2022.

BackgroundThe sensitivity and specificity of selected antigen detection rapid diagnostic tests (AG-RDTs) for SARS-CoV-2 were determined in the unvaccinated population when the Delta variant was circulating. Viral loads, dynamics, symptoms and tissue tropism differ between Omicron and Delta.AimWe aimed to compare AG-RDT sensitivity and specificity in selected subgroups during Omicron vs Delta circulation.MethodsWe retrospectively paired AG-RDT results with PCRs registered in Czechia's Information System for Infectious Diseases from 1 to 25 December 2021 (Delta, n = 20,121) and 20 January to 24 February 2022 (Omicron, n = 47,104).ResultsWhen confirmatory PCR was conducted on the same day as AG-RDT as a proxy for antigen testing close to peak viral load, the average sensitivity for Delta was 80.4% and for Omicron 81.4% (p < 0.05). Sensitivity in vaccinated individuals was lower for Omicron (OR = 0.94; 95% confidence interval (CI): 0.87-1.03), particularly in reinfections (OR = 0.83; 95% CI: 0.75-0.92). Saliva AG-RDT sensitivity was below average for both Delta (74.4%) and Omicron (78.4%). Tests on the European Union Category A list had higher sensitivity than tests in Category B. The highest sensitivity for Omicron (88.5%) was recorded for patients with loss of smell or taste, however, these symptoms were almost 10-fold less common than for Delta. The sensitivity of AG-RDTs performed on initially asymptomatic individuals done 1, 2 or 3 days before a positive PCR test was consistently lower for Omicron compared with Delta.ConclusionSensitivity for Omicron was lower in subgroups that may become more common if SARS-CoV-2 becomes an endemic virus.

Nonprocedural bleeding after left atrial appendage closure versus direct oral anticoagulants: A subanalysis of the randomized PRAGUE-17 trial.

INTRODUCTION: Observational studies have shown low bleeding rates in patients with atrial fibrillation (AF) treated by left atrial appendage closure (LAAC); however, data from randomized studies are lacking. This study compared bleeding events among patients with AF treated by LAAC and nonvitamin K anticoagulants (NOAC). METHODS: The Prague-17 trial was a prospective, multicenter, randomized trial that compared LAAC to NOAC in high-risk AF patients. The primary endpoint was a composite of a cardioembolic event, cardiovascular death, and major and clinically relevant nonmajor bleeding (CRNMB) defined according to the International Society on Thrombosis and Hemostasis (ISTH). RESULTS: The trial enrolled 402 patients (201 per arm), and the median follow-up was 3.5 (IQR 2.6-4.2) years. Bleeding occurred in 24 patients (29 events) and 32 patients (40 events) in the LAAC and NOAC groups, respectively. Six of the LAAC bleeding events were procedure/device-related. In the primary intention-to-treat analysis, LAAC was associated with similar rates of ISTH major or CRNMB (sHR 0.75, 95% CI 0.44-1.27, p = 0.28), but with a reduction in nonprocedural major or CRNMB (sHR 0.55, 95% CI 0.31-0.97, p = 0.039). This reduction for nonprocedural bleeding with LAAC was mainly driven by a reduced rate of CRNMB (sHR for major bleeding 0.69, 95% CI 0.34-1.39, p = .30; sHR for CRNMB 0.43, 95% CI 0.18-1.03, p = 0.059). History of bleeding was a predictor of bleeding during follow-up. Gastrointestinal bleeding was the most common bleeding site in both groups. CONCLUSION: During the 4-year follow-up, LAAC was associated with less nonprocedural bleeding. The reduction is mainly driven by a decrease in CRNMB.

Statistical analysis plan for a randomized controlled trial examining pedometer-based walking intervention in patients with heart failure with reduced ejection fraction: the WATCHFUL trial.

BACKGROUND: Physical activity is an effective management strategy for heart failure with reduced ejection fraction, but patients' compliance is challenging. Walking is a suitable form of physical activity due to its convenience and sustainability, and it can potentially improve functional capacity in heart failure patients. OBJECTIVES: The WATCHFUL trial aims to determine whether a pedometer-based walking intervention combined with face-to-face sessions and regular telephone contact improves functional capacity in heart failure patients. METHODS: The WATCHFUL trial is a 6-month multicenter, parallel-group, randomized, controlled, superiority trial with a 6-month follow-up. A total of 202 patients were recruited for the trial. The primary analysis will evaluate the change in distance walked during the 6-min walk test from baseline to 6 months based on the intention-to-treat population; the analysis will be performed using a linear mixed-effect model adjusted for baseline values. Missing data will be imputed using multiple imputations, and the impact of missing data will be assessed using a sensitivity analysis. Adverse events are monitored and recorded throughout the trial period. DISCUSSION: The trial has been designed as a pragmatic trial with a scalable intervention that could be easily translated into routine clinical care. The trial has been affected by the COVID-19 pandemic, which slowed patients' recruitment and impacted their physical activity patterns. CONCLUSIONS: The present publication provides details of the planned statistical analyses for the WATCHFUL trial to reduce the risks of reporting bias and erroneous data-driven results. TRIAL REGISTRATION: ClinicalTrials.gov (identifier: NCT03041610, registered: 3/2/2017).

Using real-time ascertainment rate estimate from infection and hospitalization dataset for modeling the spread of infectious disease: COVID-19 case study in the Czech Republic.

We present a novel approach to estimate the time-varying ascertainment rate in almost real-time, based on the surveillance of positively tested infectious and hospital admission data. We also address the age dependence of the estimate. The ascertainment rate estimation is based on the Bayes theorem. It can be easily calculated and used (i) as part of a mechanistic model of the disease spread or (ii) to estimate the unreported infections or changes in their proportion in almost real-time as one of the early-warning signals in case of undetected outbreak emergence. The paper also contains a case study of the COVID-19 epidemic in the Czech Republic. The case study demonstrates the usage of the ascertainment rate estimate in retrospective analysis, epidemic monitoring, explanations of differences between waves, usage in the national Anti-epidemic system, and monitoring of the effectiveness of non-pharmaceutical interventions on Czech nationwide surveillance datasets. The Czech data reveal that the probability of hospitalization due to SARS-CoV-2 infection for the senior population was 12 times higher than for the non-senior population in the monitored period from the beginning of March 2020 to the end of May 2021. In a mechanistic model of COVID-19 spread in the Czech Republic, the ascertainment rate enables us to explain the links between all basic compartments, including new cases, hospitalizations, and deaths.

Mortality related to pressure ulcers in Czech Republic - Analyses of national health registries.

BACKGROUND: Pressure ulcers/pressure injuries (PUs/PIs) relate to decreasing quality of life, prolonged hospitalisation, the increased economic cost of care, and increased mortality. That's why this study focused on one of the mentioned factors - mortality. OBJECTIVES: The study analyses national data in the Czech Republic to map the mortality phenomenon comprehensively based on data from national health registries. METHOD: The retrospective, nationwide cross-sectional data analysis of data collected by the National Health Information System (NHIS) has been provided in the period 2010-2019 with a special focus on 2019. Hospitalisations with PUs/PIs were identified by reporting L89.0-L89.9 diagnosis as a primary or secondary hospitalisation diagnosis. We also included all the patients who died in the given year with an L89 diagnosis reported in 365 days prior the death. RESULTS: In 2019, 52.1% of patients with reported PUs/PIs were hospitalised, and 40.8% were treated on an outpatient basis. The most common underlying cause of death mortality diagnosis (43.7%) in these patients was the diseases of the circulatory system. Patients who die in a healthcare facility while hospitalised with an L89 diagnosis generally have a higher category of PUs/PIs than persons who die outside a healthcare facility. CONCLUSION: The proportion of patients dying in a health facility is directly proportional to the increasing PUs/PIs category. In 2019, 57% of patients with PUs/PIs died in a healthcare facility, and 19% died in the community. In 24% of patients who died in the healthcare facility, PUs/PIs were reported 365 days before the death.