AIMS: Cardiac resynchronization therapy (CRT) is guideline recommended for the treatment of symptomatic heart failure (HF) with reduced left ventricular ejection fraction and prolonged QRS. However, patients with common comorbidities, such as persistent/permanent atrial fibrillation (AF), are often under-represented in clinical trials. METHODS: The Strategic Management to Optimize Response to Cardiac Resynchronization Therapy (SMART) registry (NCT03075215) was a global, multicentre, registry that enrolled de novo CRT implants, or upgrade from pacemaker or implantable cardioverter defibrillator to CRT-defibrillator (CRT-D), using a quadripolar left ventricular lead in real-world clinical practice. The primary endpoint was CRT response between baseline and 12 month follow-up defined as a clinical composite score (CCS) consisting of all-cause mortality, HF-associated hospitalization, New York Heart Association (NYHA) class and quality of life global assessment. RESULTS: The registry enrolled 2035 patients, of which 1558 had completed CCS outcomes at 12 months. The patient cohort was 33.0% female, mean age at enrolment was 67.5 ± 10.4 years and the mean left ventricular ejection fraction was 29.6 ± 7.9%. Notably, there was a high prevalence of mildly symptomatic patients (NYHA class I/II 51.3%), non-left bundle branch block (LBBB) morphology (38.0%), AF (37.2%) and diabetes mellitus (34.7%) at baseline. CCS at 12 months improved in 58.9% (n = 917) of patients; 20.1% (n = 313) of patients stabilized and 21.0% (n = 328) worsened. Several patient characteristics were associated with a lower likelihood of response to CRT including older age, ischaemic aetiology, renal dysfunction, AF, non-LBBB morphology and diabetes. Higher HF hospitalization (P < 0.001) and all-cause mortality (P < 0.001) were observed in patients with AF. These patients also had lower percentages of ventricular pacing than patients in sinus rhythm at baseline and follow-up (P < 0.001, both). A further association between AF and non-LBBB was observed with 81.4% of AF non-LBBB patients experiencing an HF hospitalization compared with 92.5% of non-AF LBBB patients (P < 0.001). Mortality between subgroups was also statistically significant (P = 0.019). CONCLUSIONS: This large, global registry enrolled a CRT-D population with higher incidence of comorbidities that have been historically underrepresented in clinical trials and provides new insight into factors influencing response to CRT. As defined by CCS, 58.9% of patients improved and 20.1% stabilized. Patients with AF had particularly worse clinical outcomes, higher HF hospitalization and mortality rates and lower percentages of ventricular pacing. High incidence of HF hospitalization in patients with AF and non-LBBB in this real-world cohort suggests that ablation may play an important role in increasing future CRT response rates.
- MeSH
- Global Health MeSH
- Ventricular Function, Left * physiology MeSH
- Quality of Life * MeSH
- Middle Aged MeSH
- Humans MeSH
- Follow-Up Studies MeSH
- Registries * MeSH
- Aged MeSH
- Cardiac Resynchronization Therapy * methods MeSH
- Heart Failure * therapy physiopathology mortality MeSH
- Stroke Volume * physiology MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
Introduction. Vagal nerve stimulation (VNS) is a therapeutical option for the treatment of drug-resistant epileptic patients. The response to VNS varies from patient to patient and is difficult to predict. The proposed study is based on our previous work, identifying relative mean power in pre-implantation EEG as a reliable marker for VNS efficacy prediction in adult patients. Our study has two main tasks. Firstly, to confirm the utility of relative mean power as a feature correlating with VNS efficacy in children. The second is to validate the applicability of our prediction classifier, Pre-X-Stim, in the pediatric population. Material and Methods. We identified a group of children with drug-resistant epilepsy. We included only children in whom EEG contained photic stimulation (Task 1) or was recorded based on the defined acquisition protocol used for development Pre-X-Stim (Task 2). Relative mean powers were calculated. VNS responders and non-responders were compared based on relative mean powers' values. In the next step, we evaluate the utility of our classifier, Pre-X-Stim, in the children population. Results: We identified 57 children treated with VNS - 17 patients were recruited for the Task 1 and 7 patients for the Task 2. When focusing on relative mean powers in EEG spectra, we observed statistically significant differences in theta range. The Pre-X-Stim algorithm was able to predict VNS efficacy correctly in 6 out of 7 patients (the accuracy 83.3%, the sensitivity 75%, the specificity 100%). Conclusions. Based on our results, it seems that children and adults share a similar pattern of EEG relative mean power changes. These changes can be used for pre-implantation prediction of VNS efficacy.
- MeSH
- Child MeSH
- Electroencephalography * methods MeSH
- Epilepsy * therapy physiopathology MeSH
- Humans MeSH
- Adolescent MeSH
- Child, Preschool MeSH
- Drug Resistant Epilepsy * therapy physiopathology MeSH
- Scalp MeSH
- Vagus Nerve Stimulation * methods MeSH
- Treatment Outcome MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
OBJECTIVES: In axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) patients initiating secukinumab, we aimed to assess retention rates and proportions of patients achieving remission and low disease activity (LDA), according to disease activity measures and patient-reported outcomes at 24 and 48 months. PATIENTS AND METHODS: Data on patients with axSpA and PsA who initiated secukinumab treatment were pooled from 13 European registries. Analyses were performed overall and stratified according to the number of previous biologic/targeted synthetic Disease-Modifying Antirheumatic Drugs (b/tsDMARDs, 0/1/≥2). Kaplan-Meier plots and Cox regression analyses were performed to assess and compare secukinumab retention rates. Comparisons of remission and LDA rates were performed by logistic regression analyses. RESULTS: The overall 24-/48-month secukinumab retention rates were 61%/51% in 767 axSpA patients, and 64%/49% in 975 PsA patients, respectively. Compared to b/tsDMARD naïve patients, a higher risk of withdrawal from secukinumab was found for those with≥2 prior b/tsDMARDs in axSpA and PsA, and 1 prior b/tsDMARD in axSpA. Generally, remission and LDA rates were numerically higher in b/tsDMARD naïve patients. After adjustment for confounders, statistically significantly higher remission and LDA rates were found for b/tsDMARD naïve patients compared to patients with≥ 2 prior b/tsDMARDs at 24 months in axSpA and PsA. CONCLUSION: This large European real-world study demonstrates that 4-year secukinumab retention rates were approximately 50% in both axSpA and PsA. b/tsDMARD naïve patients had higher retention, remission and LDA rates than patients with prior b/tsDMARD exposure.
- MeSH
- Antirheumatic Agents * therapeutic use MeSH
- Axial Spondyloarthritis * drug therapy diagnosis MeSH
- Time Factors MeSH
- Adult MeSH
- Patient Reported Outcome Measures MeSH
- Antibodies, Monoclonal, Humanized * therapeutic use MeSH
- Remission Induction MeSH
- Middle Aged MeSH
- Humans MeSH
- Follow-Up Studies MeSH
- Arthritis, Psoriatic * drug therapy diagnosis MeSH
- Registries MeSH
- Severity of Illness Index MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Observational Study MeSH
- Geographicals
- Europe MeSH
BACKGROUND: Postoperative nausea and vomiting (PONV) in pediatric patients is a common and clinically significant postoperative complication. The incidence of PONV has not been extensively studied in large pediatric cohorts. Furthermore, in 2020, the Fourth Consensus Guidelines for the management of PONV were published. However, the association between perioperative factors and adherence to these guidelines remains unclear. This study aims to assess both the incidence of PONV and guideline adherence within a large and diverse pediatric population. METHODS: We conducted a retrospective observational study at a large tertiary medical center, including pediatric patients (≤18 years) who underwent surgery between September 2020 and March 2023. We conducted a retrospective analysis of data from our electronic health records, focusing on patient demographics, surgical details, anesthesia details, and prophylaxis for PONV. We calculated the incidence of PONV and used multivariable logistic regression to identify the predictors of guideline adherence. RESULTS: The cohort included 3772 patients with a median (interquartile range [IQR]) age of 9.21 (3.55-14.68) years. The incidence (95% confidence intervals) of early PONV was 1.0% (0.7-1.4) and 3.8% (3.2-4.5) for delayed PONV. Adherence to the fourth consensus guidelines for PONV management was observed in 32.5% (31.0-34.0) of cases. A high risk of PONV was identified in 55.9% (54.3-57.5) of the patients. The most common number of PONV risk factors was 3, observed in 1151 patients (30.5% [29.1-32.0]). Significant predictors of guideline adherence included the intraoperative use of long-acting opioids (odds ratio [OR], 2.711, P < .001) and age ≥3 years (OR, 2.074, P < .001). Nonadherence was associated with a higher incidence of PONV at 24 hours postsurgery (4.4% (3.6-5.2) vs 2.7% (1.9-3.8), P = .012). Factors such as specific high PONV risk surgeries ( P = .001), maintenance with inhalational agents solely ( P = .017), and neostigmine use ( P < .001) were also all statistically significant. CONCLUSIONS: Our study revealed a lower-than-expected incidence of PONV in pediatric patients, highlighting the need for standardized definitions and improved reporting. Adherence to PONV guidelines was suboptimal, emphasizing the need for better implementation strategies.
- MeSH
- Antiemetics therapeutic use MeSH
- Child MeSH
- Guideline Adherence * standards MeSH
- Incidence MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Postoperative Nausea and Vomiting * epidemiology diagnosis prevention & control MeSH
- Child, Preschool MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Practice Guidelines as Topic standards MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
BACKGROUND AND OBJECTIVES: For thousands of years, betel nut has been used as a psychoactive agent in Asian and Oceanian populations. Betel nut chewing was associated with the alteration of human oral microbiome and with diseases such as oral cancer and periodontitis, but only in populations of Asian cultural background. We studied the influence of betel nut chewing on the oral microbiome in Papua New Guinea, where half of the population uses betel nut and the prevalence of these diseases is one of the highest in the world. METHODOLOGY: We characterized the oral microbiomes of 100 Papua New Guineans. We defined two cohorts of betel chewers (n = 50) and non-chewers (n = 50) based on a genetic approach to identify the presence of betel nut in saliva. We statistically compared the alpha and beta microbial diversities between the two cohorts. We performed linear discriminant analyses to identify bacterial species more prevalent in each cohort. RESULTS: We found that oral microbial diversity is significantly different between betel chewers and non-chewers. The dysbiosis observed in betel chewers, led to an increase of pathogenic bacterial species including Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, known to be in the aetiology of periodontal diseases. CONCLUSIONS AND IMPLICATIONS: Our study strongly supports the alteration of human oral microbiome by betel nut use, potentially leading to periodontal diseases. It also shows the need to consider local specificities (e.g. different habits, betel nut types, and oral microbial diversities) to better characterize the impact of betel nut chewing on health.
- Publication type
- Journal Article MeSH
One of the most common statistical analyses in experimental psychology concerns the comparison of two means using the frequentist t test. However, frequentist t tests do not quantify evidence and require various assumption tests. Recently, popularized Bayesian t tests do quantify evidence, but these were developed for scenarios where the two populations are assumed to have the same variance. As an alternative to both methods, we outline a comprehensive t test framework based on Bayesian model averaging. This new t test framework simultaneously takes into account models that assume equal and unequal variances, and models that use t-likelihoods to improve robustness to outliers. The resulting inference is based on a weighted average across the entire model ensemble, with higher weights assigned to models that predicted the observed data well. This new t test framework provides an integrated approach to assumption checks and inference by applying a series of pertinent models to the data simultaneously rather than sequentially. The integrated Bayesian model-averaged t tests achieve robustness without having to commit to a single model following a series of assumption checks. To facilitate practical applications, we provide user-friendly implementations in JASP and via the RoBTT package in R . A tutorial video is available at https://www.youtube.com/watch?v=EcuzGTIcorQ.
- MeSH
- Bayes Theorem MeSH
- Psychology, Experimental * methods MeSH
- Data Interpretation, Statistical MeSH
- Humans MeSH
- Models, Statistical * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND: Increased lung cancer risks for low socioeconomic status (SES) groups are only partially attributable to smoking habits. Little effort has been made to investigate the persistent risks related to low SES by quantification of potential biases. METHODS: Based on 12 case-control studies, including 18 centers of the international SYNERGY project (16,550 cases, 20,147 controls), we estimated controlled direct effects (CDE) of SES on lung cancer via multiple logistic regression, adjusted for age, study center, and smoking habits and stratified by sex. We conducted mediation analysis by inverse odds ratio weighting to estimate natural direct effects and natural indirect effects via smoking habits. We considered misclassification of smoking status, selection bias, and unmeasured mediator-outcome confounding by genetic risk, both separately and by multiple quantitative bias analyses, using bootstrap to create 95% simulation intervals (SI). RESULTS: Mediation analysis of lung cancer risks for SES estimated mean proportions of 43% in men and 33% in women attributable to smoking. Bias analyses decreased the direct effects of SES on lung cancer, with selection bias showing the strongest reduction in lung cancer risk in the multiple bias analysis. Lung cancer risks remained increased for lower SES groups, with higher risks in men (fourth vs. first [highest] SES quartile: CDE, 1.50 [SI, 1.32, 1.69]) than women (CDE: 1.20 [SI: 1.01, 1.45]). Natural direct effects were similar to CDE, particularly in men. CONCLUSIONS: Bias adjustment lowered direct lung cancer risk estimates of lower SES groups. However, risks for low SES remained elevated, likely attributable to occupational hazards or other environmental exposures.
- MeSH
- Mediation Analysis * MeSH
- Adult MeSH
- Smoking * epidemiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Logistic Models MeSH
- Lung Neoplasms * epidemiology MeSH
- Odds Ratio MeSH
- Risk Factors MeSH
- Aged MeSH
- Social Class * MeSH
- Case-Control Studies MeSH
- Bias * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a high recurrence rate after surgical therapy with curative intent. Adjuvant radiotherapy (RT) and mitotane therapy have been proposed as options following the adrenalectomy. However, the efficacy of adjuvant RT or mitotane therapy remains controversial. We aimed to evaluate the efficacy of adjuvant therapy in patients who underwent adrenalectomy for localised ACC. The PubMed, Scopus, and Web of Science databases were queried on March 2024 for studies evaluating adjuvant therapies in patients treated with surgery for localized ACC (PROSPERO: CRD42024512849). The endpoints of interest were overall survival (OS) and recurrence-free survival (RFS). Hazard ratios (HR) with 95% confidence intervals (95%CI) were pooled in a random-effects model meta-analysis. One randomized controlled trial (n = 91) and eleven retrospective studies (n = 4,515) were included. Adjuvant mitotane therapy was associated with improved RFS (HR: 0.63, 95%CI: 0.44-0.92, p = 0.016), while adjuvant RT did not reach conventional levels of statistical significance (HR:0.79, 95%CI:0.58-1.06, p = 0.11). Conversely, Adjuvant RT was associated with improved OS (HR:0.69, 95%CI:0.58-0.83, p<0.001), whereas adjuvant mitotane did not (HR: 0.76, 95%CI: 0.57-1.02, p = 0.07). In the subgroup analyses, adjuvant mitotane was associated with better OS (HR:0.46, 95%CI: 0.30-0.69, p < 0.001) and RFS (HR:0.56, 95%CI: 0.32-0.98, p = 0.04) in patients with negative surgical margin. Both adjuvant RT and mitotane were found to be associated with improved oncologic outcomes in patients treated with adrenalectomy for localised ACC. While adjuvant RT significantly improved OS in general population, mitotane appears as an especially promising treatment option in patients with negative surgical margin. These data can support the shared decision-making process, better understanding of the risks, benefits, and effectiveness of these therapies is still needed to guide tailored management of each individual patient.
- MeSH
- Chemotherapy, Adjuvant MeSH
- Radiotherapy, Adjuvant methods MeSH
- Adrenalectomy * methods MeSH
- Adrenocortical Carcinoma * therapy drug therapy radiotherapy MeSH
- Adrenal Cortex Neoplasms * therapy drug therapy surgery radiotherapy MeSH
- Antineoplastic Agents, Hormonal * therapeutic use MeSH
- Humans MeSH
- Mitotane * therapeutic use MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Meta-Analysis MeSH
- Review MeSH
- Systematic Review MeSH
AIM: Despite the high sensitivity of neonatal screening in detecting the classical form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, one of the unclear issues is identifying asymptomatic children with late onset forms. The aim of this nationwide study was to analyse the association between genotype and screened level of 17-hydroxyprogesterone in patients with the late onset form of 21-hydroxylase deficiency and to quantify false negativity. METHODS: In the Czech Republic, 1,866,129 neonates were screened (2006-2022). Among this cohort, 159 patients were confirmed to suffer from 21-hydroxylase deficiency, employing the 17-hydroxyprogesterone birthweight/gestational age-adjusted cut-off limits, and followed by the genetic confirmation. The screening prevalence was 1:11,737. Another 57 patients who were false negative in neonatal screening were added to this cohort based on later diagnosis by clinical suspicion. To our knowledge, such a huge nationwide cohort of false negative patients has not been documented before. RESULTS: Overall, 57 patients escaped from neonatal screening in the monitored period. All false negative patients had milder forms. Only one patient had simple virilising form and 56 patients had the late onset form. The probability of false negativity in the late onset form was 76.7%. The difference in 17-hydroxyprogesterone screening values was statistically significant (p<0.001) between severe forms (median 478.8 nmol/L) and milder (36.2 nmol/L) forms. Interestingly, the higher proportion of females with milder forms was statistically significant compared with the general population. CONCLUSIONS: A negative neonatal screening result does not exclude milder forms of 21-hydroxylase deficiency during the differential diagnostic procedure of children with precocious pseudopuberty.
- MeSH
- 17-alpha-Hydroxyprogesterone * blood MeSH
- False Negative Reactions MeSH
- Adrenal Hyperplasia, Congenital * diagnosis blood MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Neonatal Screening * methods MeSH
- Steroid 21-Hydroxylase genetics MeSH
- Age of Onset MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
Cíl: Cílem naší práce bylo popsat epidemiologickou situaci výskytu rotavirových gastroenteritid (RG) a vliv očkování na hospitalizaci pro RG v České republice (ČR) v letech 2018–2023. Metody: Byla provedena deskriptivní analýza anonymizovaných případů RG hlášených pod kódem A08.0 v systému pro hlášení infekčních onemocnění (ISIN) v České republice v letech 2018–2023. K analýze binárních proměnných byl použit chí-kvadrát test. Vliv očkování na hospitalizaci byl hodnocen pomocí logistické regrese s odds ratio (OR) a 95 % intervalu spolehlivosti. Použity byly programy Excel, STATA a Datawrapper GmbH. Incidence onemocnění byla přepočítána na 100 000 obyvatel. Výsledky: Ve sledovaném období bylo v ČR hlášeno celkem 26 303 případů RG (v rozmezí 1 811–7 483 ročně), což odpovídá průměrné roční incidenci 41,0 (rozmezí 16,9–69,6) na 100 000 obyvatel. Padesát jedna procent případů se vyskytlo u žen. Průměrná roční specifická incidence podle pohlaví byla srovnatelná. Případy se vyskytly u osob 0–101letých (medián 3 roky, mezikvartilové rozpětí [IQR] 1–8 let). Maximální počty případů byly zaznamenány v měsících březen až červen, přičemž v pandemických letech 2020 a 2021 byly celkové počty případů nižší, a tedy i sezonnost byla vyjádřena méně. Průměrná roční specifická incidence byla nejvyšší v krajích Vysočina, Jihočeském a Olomouckém. Hospitalizováno bylo 18 693 (71,1 %) případů RG, nejvíce případů ve věkové skupině 1–4 roky (34,7 %) a 5–9 let (11,9 %). Údaje o očkování byly dostupné pro 21 142 osob s RG, z nich 304 (1,4 %) osob bylo vykázáno jako očkováno. Riziko hospitalizace pro RG bylo u očkovaných osob statisticky významně nižší (p < 0,001) než u neočkovaných. Nahlášeno bylo celkem 27 epidemií RG, v největší bylo zaznamenáno 152 případů. Jako import bylo hlášeno 226 případů onemocnění. Závěr: Po zahájení očkování proti RG v ČR bylo očekáváno snížení počtu onemocnění, hospitalizací a úmrtí pro tato onemocnění. Nicméně významný dopad očkování na zátěž RG dosud v ČR pozorován není a domníváme se, že hlavním důvodem je nadále nízká proočkovanost proti RG v ČR. Doporučujeme proto zařadit toto dobrovolné očkování mezi očkování hrazená zdravotními pojišťovnami a zároveň apelujeme na časnou komunikaci vhodnosti očkování mezi praktickým lékařem pro děti a dorost a rodiči dětí.
Aim: To describe the epidemiological situation of rotavirus gastroenteritis (RVGE) and the impact of vaccination on hospitalization for RVGE in the Czech Republic in 2018–2023. Methods: A descriptive analysis was performed of anonymized RVGE cases reported under code A08.0 to the Infectious Diseases Reporting System (ISIN) in the Czech Republic in 2018–2023. The Chi-square test was used to analyse binary variables. The effect of vaccination on hospitalization was assessed using logistic regression with odds ratio (OR) and 95% confidence interval. Excel, STATA, and Datawrapper GmbH programs were used. The incidence of the disease was calculated per 100,000 population. Results: In the monitored period, a total of 26,303 RVGE cases were reported in the Czech Republic (range 1,811–7,483 per year), which corresponds to an average annual incidence of 41.0 (range 16.9–69.6) per 100,000 population. Fifty-one percent of cases occurred in women. The average annual sex-specific incidence rates were comparable. Patients were aged 0–101 years (median 3 years, interquartile range [IQR] 1–8 years). The maximum numbers of cases were recorded in the months of March to June. In the pandemic years 2020 and 2021, the overall numbers of cases were lower, and therefore the seasonality was less expressed. The average annual specific incidence was highest in the Vysočina, South Bohemian and Olomouc Regions. A total of 18,693 (71.1%) cases of RVGE were hospitalized, most of them in the age groups 1–4 years (34.7%) and 5–9 years (11.9%). Vaccination data were available for 21,142 individuals with RVGE, of whom 304 (1.4%) were reported as vaccinated. The risk of hospitalization for RVGE was statistically significantly lower (p < 0.001) in vaccinated than in unvaccinated individuals. A total of 27 RVGE outbreaks were reported, with the largest one involving 152 cases. Two hundred and twenty-six cases were classified as imported. Conclusions: After the introduction of RVGE vaccination in the Czech Republic, a reduction in RVGE cases, hospitalizations, and deaths was expected. However, a significant impact of vaccination on the RVGE burden has not yet been observed in the country. The main reason continues to be low RVGE vaccine coverage. We therefore recommend including this voluntary vaccination in the schedule covered by health insurance and also call for early communication of the appropriateness of such vaccination between the paediatric/adolescent medicine practitioners and children’s parents.