Adjusted Incidence Rate Research Articles

Participation in the National Bowel Cancer Screening Program by people with severe mental illness, Australia, 2006-2019: a national data linkage study.

To compare rates of participation in the National Bowel Cancer Screening Program (NBCSP) and follow-up for people with severe mental illness with those for people without severe mental illness or not prescribed antidepressants. Retrospective cohort study; analysis of de-identified linked NBCSP, Pharmaceutical Benefits Scheme (PBS), and Medicare Benefits Schedule (MBS) data. Australia, 2006-2019. People aged 50-74 years (NBCSP-eligible) with severe mental illness, defined as those dispensed two or more prescriptions for second generation antipsychotics or for lithium (PBS data), and a random sample of people aged 50-74 years eligible for Medicare-subsidised services but never prescribed psychotropic medications (antipsychotics, lithium, antidepressants). NBCSP participation (returned faecal occult blood test sample), valid test result, positive test result, and follow-up colonoscopy rates. A total of 119 475 people with severe mental illness and 1 090 574 control group people were included in our analyses. The proportion of women was larger in the severe mental illness group (51.3%) than the control group (48.7%), as were the proportions who lived in inner regional areas (23.5% v 19.1%) or in areas in the lowest socio-economic quintile (21.8% v 14.7%). The NBCSP participation rate was lower among people with severe mental illness (adjusted incidence rate ratio [IRR], 0.70; 95% confidence interval [CI], 0.69-0.84). The proportion of valid test results was smaller for people with severe mental illness (95.9% v 98.7%; adjusted IRR, 0.97; 95% CI, 0.96-0.99), and the positive test result proportion larger (12.3% v 6.6%; adjusted IRR, 2.01; 95%CI, 1.94-2.09). The proportion of positive test results followed by colonoscopy was smaller for people with severe mental illness (71.7% v 82.6%; adjusted IRR, 0.88; 95% CI, 0.85-0.92). People with severe mental illness were less likely to participate in the NBCSP or to undergo colonoscopy after a positive test result than other Australians. These differences may contribute to higher colorectal cancer mortality among people with severe mental illness. The contributions of differences in cancer stage at diagnosis and subsequent treatment to higher colorectal cancer mortality require further study.

Abstract 4138570: The Hidden Killer in Patients with Sepsis Spectra Disorders: Systolic Heart Failure

Introduction: Sepsis and systolic heart failure (sHF) often prompt hospitalization and require near diametrically opposite treatment strategies. We, therefore, studied whether sHF would impact outcomes in patients with sepsis spectra. Methods: We examined the National Inpatient Sample 2021 for adults admitted with sepsis spectra (sepsis, severe sepsis, and septic shock). We compared patients with sHF vs those without. STATA 18 th edition was used for analyses. Age, gender, race, hypertension, diabetes, obesity, dyslipidemia, and Elixhauser comorbidity index were identified as confounders by univariate analyses and tested further with multivariate logistic regression models. The primary outcome was mortality. Secondary outcomes were the need for intubation, cardiac arrest, length of stay (LOS), and total hospital charges. Results: In 2021, nationwide, 3,030,351 adults were admitted for sepsis spectra, and 209,134 (6.9%) had concomitant sHF. Patients with sHF and sepsis spectra (as compared to those without sHF) were less likely female (35.5% vs. 48%), had a substantially higher likelihood of a prior MI, and nearly 50% were diabetic and hyperlipidemic with a higher comorbidity index. Baseline characteristics are in the Table. Sepsis and sHF resulted in substantially higher mortality (22.7%) as compared to patients with sepsis alone (14.9%) adjusted odds ratio (aOR) of 1.11 (CI 1.08-1.14; p-value < 0.001). Patients with sepsis and sHF were more likely to require intubation 22.2% vs. 14.0% aOR 1.21 (CI 1.18-1.25; p-value < 0.001), had more cardiac arrest 7.7% vs. 4.0% aOR 1.38 (CI 1.32-1.44; p-value < 0.001), and a longer LOS (11.9 vs 9.4 days adjusted incidence rate ratio (aIRR) 1.06; CI 1.05 – 1.08; p-value < 0.001). Consequently, total hospital charges were also higher, $189,415 vs $133,720, aIRR 1.15 (CI 1.13-1.18; p-value < 0.001). Conclusion: In 2021, nationwide, sepsis spectra remain a major cause of in-patient mortality. We demonstrate that the coexistence of systolic heart failure and sepsis dramatically worsens complications, mortality, and total hospital costs. This study is a call to action for the in-depth analyses of this very high-risk group of patients.

Abstract 4134320: Integrated safety and tolerability of mavacamten treatment over 5 years in patients with obstructive hypertrophic cardiomyopathy

Background: Mavacamten, a cardiac myosin inhibitor, is approved across 5 continents for the treatment of obstructive hypertrophic cardiomyopathy (HCM). Long-term data of mavacamten are available from multiple studies, providing the opportunity to further understand mavacamten long term safety, including adverse events (AEs) of clinical interest. Aim: To present integrated safety data of patients who received mavacamten treatment for obstructive HCM across 5 studies. Methods: The pooled population included all patients who received ≥1 dose of mavacamten in PIONEER-HCM, PIONEER-Open Label Extension (data cut-off: May 31, 2022), EXPLORER-HCM, MAVA-Long-Term Extension (EXPLORER cohort; data cut-off: August 31, 2023) and VALOR-HCM including long-term extension (data cut-off: November 11, 2022). Results: The population consisted of 368 patients (mean [SD] age: 59.4 [12.2] years; male: 57.1%; White: 90.8%), including 350 patients who continued onto an extension study after completing a parent study. The majority of patients (57.6%) had a cumulative time on study of ≥3 years. Forty (10.9%) patients permanently discontinued treatment (13 due to AEs). In total, 20.7% of patients had a treatment emergent AE (TEAE) of Grade ≥3 and 14.7% had a TEAE leading to drug interruption. Overall, 4.3% of patients had drug-related serious TEAEs and 1.6% had a TEAE leading to death. The cumulative exposure adjusted incidence rates (EAIR) of all TEAEs, including AEs of clinical interest (atrial fibrillation [AF], ejection fraction [EF] decreased and heart failure [HF]), decreased as exposure increased over time, from 347.1/100 patient-years (P-Y) at Week 60 (~year 1) to 271.8/100 P-Y at Week 252 (~year 5). The EAIR of AF decreased over time from 13.3/100 P-Y at Week 60 (~year 1) to 6.2/100 P-Y at Week 252 (~year 5) ( Figure ). The EAIR for EF decreased and HF also decreased over time ( Figure ). Conclusions: This integrated analysis of all patients with obstructive HCM treated with mavacamten across the 5 clinical studies over 5 years demonstrated that mavacamten treatment is generally well tolerated and that the EAIRs of selected TEAEs of clinical interest (AF, EF decreased and HF) decreased as exposure increased over time.

Resuscitation of adult shocked trauma patients using major haemorrhage protocol guided by viscoelastic haemostatic assays versus formulaic approach.

The resuscitation of trauma patients with critical bleeding may follow a formulaic approach using high ratios of blood components or a viscoelastic haemostatic assay (VHA) guided approach. The aim of this study was to compare the two strategies for resuscitation of shocked trauma patients. This was a registry-based cohort study including shocked trauma patients from two trauma centres-one practising a formulaic approach, with VHA unavailable during trauma resuscitation and the other practicing a VHA-guided resuscitation strategy. The primary outcome was the total units of blood components transfused in 24 h after adjusting for differences in baseline characteristics and time to death. Between 01 Jan 2020 and 31 Dec 2022, 152 eligible patients were categorised to the formulaic group and 40 to the VHA group. Prehospital times were longer in the formulaic group (2.0 vs. 1.4 h), and more patients in the VHA group (38% vs. 17%) were transfused prehospital blood components. Formulaic resuscitation was associated with significantly more blood components transfused (adjusted incidence rate ratio 1.5; 95%CI: 1.4-1.7, p < 0.001). Using a formulaic approach, patients were administered more red blood cells, plasma and platelets, but fewer cryoprecipitate. There was no significant association of the formulaic approach with in-hospital mortality (adjusted odds ratio 2.4; 95%CI: 0.7-8.0, p = 0.17). Given the cost and potential adverse effects of blood component transfusions, VHA-guided transfusion strategies present an attractive option, particularly among centres managing high volumes of shocked patients. Further trials, enrolling the population most likely to benefit from precision transfusion strategies, are indicated.

Cannabis Vaping Among US Adults With Disabilities: Findings From the 2022 Behavioral Risk Factor Surveillance System.

Studies have demonstrated that people with disabilities are more likely to use cannabis than people without disabilities. However, less is known about novel forms of use, such as cannabis vaping, in this population. We examined the correlates of cannabis vaping among people with disabilities and the association between cannabis vaping and the frequency of cannabis use in any form. We used data from the 2022 Behavioral Risk Factor Surveillance System to examine the association between disabilities and past-month cannabis vaping, as well as the number of days that cannabis was used in the past month, among US adults. We used weighted multivariable logistic and modified Poisson regression models with incidence rate ratios to examine the associations. The prevalence of cannabis vaping was higher among adults with any disability (4.6%) than among adults without disabilities (2.8%); adults with only cognitive disabilities had the highest prevalence (8.2%). Daily nicotine vaping (adjusted odds ratio [AOR] = 6.04; 95% CI, 4.14-8.80), former cigarette smoking status (AOR = 1.67; 95% CI, 1.25-2.25), and being aged 18-24 years (vs ≥65 y) (AOR = 11.07; 95% CI, 7.05-17.38) were associated with higher odds of cannabis vaping among adults with any disability. Disability status modified the relationship between cigarette smoking and cannabis vaping (P < .001). Additionally, among adults with disabilities, the rate of cannabis-use days was higher among adults who vaped cannabis (adjusted incidence rate ratio = 1.28; 95% CI, 1.19-1.36) than among adults who did not vape cannabis. Among adults with disabilities, nicotine consumption by vaping was associated with cannabis vaping. Our findings highlight the need for interventions that reduce the risk of polysubstance use (ie, nicotine and cannabis) in this population.

Differentiation of Providencia species bloodstream infections: A population-based analysis

BackgroundAlthough Providencia species are recognised as important causes of bloodstream infections (BSI), their epidemiology is not well defined due to their infrequent occurrence. Our objective was to determine the overall incidence, determinants, and outcomes of Providencia species BSI, and compare the epidemiology of P. stuartii and P. rettgeri in a large population. MethodsAll patients within Queensland, Australia with Providencia species BSI between 2000-2019 were included with clinical and outcome data collected from state-wide datasets. ResultsAmong 268 residents, there was 273 incident episodes of Providencia species BSI; with 118 cases (43.2%) due to P. rettgeri, 150 cases (55.0%) due to P. stuartii, for age and sex adjusted incidence rates of 1.5, and 2.1 per million respectively. Five cases (<2.0%) were due to other Providencia species. The median age was 73.9 years, 80% were male, and most episodes were of community onset. As compared to P. rettgeri, patients with P. stuartii BSI were more likely to have dementia, peptic ulcer disease, and hemiplegia but less likely to have comorbid liver disease. The overall distribution of infection foci were different with P. stuartii more commonly associated with lower respiratory tract source and P. rettgeri with urinary source. All cause 30-day case fatality was significantly higher for P. rettgeri versus P. stuartii (35; 29.7% vs. 24; 16%; p=0.007). ConclusionsProvidencia species are important causes of community onset BSI especially in older males. Although they share similar incidence, P. stuartii and P. rettgeri BSI differ on many clinical aspects.

Long-term physical and mental health outcomes of Ebola Virus Disease survivors in Kenema District, Sierra Leone: A cross-sectional survey.

The 2013-2016 Ebola Virus Disease (EVD) epidemic in West Africa was the deadliest in history, with over 28,000 cases. Numerous physical and mental health symptoms have been reported in EVD survivors, although there is limited prior research on how the health of survivors compares to the general population. We conducted a survey of EVD survivors in Kenema District, Sierra Leone and a population-based sample of community members who lived in EVD-affected areas but were not diagnosed with EVD, and compared resulting data about self-reported symptoms, duration, and severity between EVD survivors and community members through multivariate regression models. This study found that more than six years after the epidemic, survivors were significantly more likely to experience both physical and mental health symptoms than community members, with respective adjusted incidence rate ratios (IRRs) of 2.65 (95% CI, 2.28-3.09), p < 0.001, and 11.95 (95% CI, 6.58-21.71), p < 0.001. The most highly reported physical health symptoms experienced by EVD survivors were joint pain (75.5%), headaches (67.3%), and vision problems (44.5%), and the most prevalent psychological symptoms were spells of terror and panic (25.5%) and difficulty falling asleep or staying asleep (20.0%). EVD survivors were significantly more likely than community members to report the symptoms as lasting for a longer period, a median of 6.0 (3.0-7.0) years, and with higher severity. The results indicated that six years after the epidemic, EVD survivors in Kenema District, Sierra Leone are experiencing worse physical and mental health than their peers. These findings of the long-term, debilitating health issues following EVD infection should be considered when designing and implementing future epidemic responses.

Risk of incident cancer in patients with Inflammatory Bowel Disease with prior breast cancer: a multicenter cohort study

Background and AimsBreast cancer is the most common malignancy observed in patients with inflammatory bowel diseases (IBD). The aim of our study was to evaluate incident cancer rate (recurrence or new-onset cancer) in a cohort of IBD patients with a history of breast cancer according to the subsequent IBD treatment provided. MethodsA multicenter retrospective study included consecutive IBD patients with prior breast cancer. The inclusion date corresponded to the diagnosis of index malignancy. Follow-up lasted from cancer diagnosis until the occurrence of incident cancer. ResultsAmong 207 patients included (median disease duration: 13 years [IQR 6 - 21]), first line treatment (median interval of 28 months [IQR 7 - 64]) was a conventional immunosuppressant in 19.3 % of patients, anti-TNF in 19.8 %, vedolizumab in 7.2 % and ustekinumab in 1.9 %.After a median follow-up of 71 months [IQR, 34 - 148], 42 (20%) incident cancers were observed (34 breast cancer recurrences). Adjusted incidence rates per 1000 person-years were 10.2 (95%CI 6.0- 16.4) for the untreated arm and 28.9 (95%CI 11.6-59.6) for exposed patients (p= 0.0519). There was no significant difference between treated patients and controls regarding incident-cancer free survival rates (p=0.4796). In multivariable analysis, factors associated with incident cancer were stage T4d (p=0.036), triple negative tumor (p=0.016) and follow-up of less than 71 months (p=0.005). ConclusionWe did not find a statistically significant increase in incident breast cancer related to IBD treatment beyond the already known poor prognostic factors of breast cancer.

Burden of infant group B Streptococcus disease and impact of maternal screening and antibiotic prophylaxis in Ontario, Canada: a population-based cohort study

Group B Streptococcus (GBS) significantly contributes to neonatal sepsis and meningitis, with varying disease rates reported globally and limited population-based data. We estimated infant GBS disease burden in Ontario, Canada and assessed the association of maternal GBS screening (35-37 weeks' gestation) and intrapartum antibiotic prophylaxis (IAP) provision with infant disease rates. Our population-based cohort study included pregnant individuals and their offspring from April 2012 to March 2018, utilising the provincial birth registry linked to health administrative data. GBS cases were ascertained through culture results and diagnostic codes. We calculated incidence rates for early-onset disease (EOD: 0-6 days), late-onset disease (LOD: 7-89 days), and ultra-LOD (ULOD: 90-365 days). Adjusted incidence rate ratios (aIRR) were derived via log-binomial regression to compare infant GBS rates according to screening and IAP-receipt. Among 776,148 liveborn infants, we identified 803 with GBS, with multiples exhibiting a threefold incidence increase. Incidence rates of EOD, LOD and ULOD were 0.49, 0.46 and 0.07 per 1000 livebirths, respectively. Of eligible pregnancies, 94% were screened; 23% screened positive, and 81% of them received IAP. Nearly 12% of term EOD infants had mothers who missed IAP despite screening positive. Maternal screening was associated with lower rates of any infant GBS disease (aIRR: 0.60; 95% CI: 0.45, 0.80). Among screen-positive births, IAP-receipt was associated with reduced rates of EOD (aIRR: 0.72, 95% CI: 0.48, 1.29) and LOD/ULOD (aIRR: 0.69; 95% CI: 0.46, 1.05), but confidence intervals included 1.0. Our study, the largest Canadian investigation into infant GBS disease, highlights both widespread adoption and ongoing challenges of the current prevention strategy. Canadian Institutes of Health Research.

Intrapartum antibiotic exposure and infectious diseases in childhood – a population-based cohort study

Intrapartum antibiotics are used to prevent group B streptococcus disease in newborn infants. We hypothesised that intrapartum antibiotic exposure is associated with the occurrence of childhood infectious diseases because it influences the development of the gut microbiome. The cohort for this population-based study comprised vaginally delivered children born in Northern Finland in 2007-2018. We used structured electronic medical records linked to comprehensive national registers. Primary outcome was the number of infectious disease episodes leading to an emergency room visit, outpatient hospital visit, or hospitalisation from birth until five years of age. Analyses were performed on 9733 children (48.8% girls) exposed to intrapartum antibiotics and on 35,842 unexposed children (49.9% girls). Exposure to intrapartum antibiotics was associated with increased risk of any infectious disease episode at the ages 7-28 days (adjusted incidence rate ratio [aIRR] 1.30, 95% CI 1.10-1.54) and 1-2 years (aIRR 1.10, 95% CI 1.02-1.18). The occurrence of urinary tract infections was associated with the exposure to intrapartum antibiotics whereas the occurrence of severe infections caused by pathogens susceptible to penicillin was reversely associated with the exposure to intrapartum antibiotics. Maternal intrapartum antibiotics were associated with the occurrence of infectious diseases in the offspring. The observed associations appeared to depend on bacterial pathogens and their antimicrobial susceptibility to penicillin. Pediatric Research Foundation, Alma och K.A. Snellman Foundation, Orion Research Foundation, Päivikki and Sakari Sohlberg Foundation, Finnish Medical Foundation, Academy of Finland, Finland.

Ambient particulate matter and frequency of outpatient visits for chronic rhinosinusitis in the United States.

Emerging evidence has underscored the harmful effects of air pollution on the upper airway. We investigated the relationship between ambient particulate matter (PM) level and the frequency of outpatient visits for chronic rhinosinusitis (CRS). We conducted an ecological cohort study of US adults enrolled in The Merative MarketScan outpatient database from 2007 to 2020. For each geographical subunit (core-based statistical area [CBSA]), we calculated the annual rate of CRS-related outpatient visits per 1000 well-patient checkup visits (CRS-OV). Using data from the Environmental Protection Agency's Air Quality System, we mapped the rolling statistical average of daily PM2.5 and PM10 over the preceding year onto each CBSA×year combination. We employed multivariable negative binomial regression modeling to estimate the association between PM levels and subsequent CRS-OV. Across 3933 observations (CBSA×year combinations), encompassing ∼4 billion visits, the median CRS-OV was 164 (interquartile range 110-267). The mean PM2.5 level was 8.9µg/m3 (SD 2.6) and the mean PM10 level was 20.2µg/m3 (SD 7.2). Adjusting for patient demographics and respiratory comorbidities, a compounded rise in subsequent CRS-OV was observed with increasing PM levels. Each µg/m3 rise in PM2.5 independently predicted a 10% increase in CRS-OV (adjusted incidence rate ratio [aIRR]) 1.10, 95% confidence interval [CI] 1.08-1.13) and each µg/m3 rise in PM10 independently predicted a 3% increase in CRS-OV (aIRR 1.03, 95% CI 1.02-1.04). Elevated ambient PM2.5 and PM10 levels are associated with a subsequent compounded increase in the frequency of CRS-OV, with PM2.5 predicting a more pronounced rise compared to PM10.

Healthcare utilization in general practice and hospitals preceding a diagnosis of systemic sclerosis: a nationwide registry study.

Irreversible tissue damage is frequently present at the time of diagnosis in systemic sclerosis (SSc), which calls for earlier diagnosis. This study estimated healthcare utilization three years before the diagnosis of SSc. We conducted a population-based cohort study using data from Danish national registries. Incident patients diagnosed with SSc between January 1, 2005, and December 31, 2018, were matched by age and gender with 10 references without SSc. The date of diagnosis was the index date. We estimated quarterly rates and adjusted incidence rate ratios (IRRs) with 95% confidence intervals (CI) of healthcare utilization in the three years preceding the diagnosis for patients with SSc and their references. A total of 1,650 SSc patients (1,255 women and 395 men) and 16 500 non-SSc references were included. The mean age was 58 years (interquartile range 48-68). Three years before diagnosis, patients with SSc had more contacts with general practice (IRRwomen= 1.43 [95% CI: 1.33; 1.53], IRRmen= 1.47 [95% CI: 1.26; 1.71]) and hospitals (IRRwomen= 1.86 [95% CI: 1.62; 2.14], IRRmen= 2.70 [95% CI: 2.04; 3.58]) compared with their references. In the last three months before diagnosis, patients with SSc had significantly more contacts with general practice (IRRwomen= 2.30 [95% CI: 2.16; 2.44], IRRmen= 2.98 [95% CI: 2.64; 3.35]) and hospitals (IRRwomen= 5.62 [95% CI: 5.08; 6.20], IRRmen= 9.53 [95% CI: 7.81; 11.63]). The higher use of healthcare services in general practice and hospitals in the three years before diagnosis suggests an opportunity to facilitate earlier diagnosis and treatment of SSc.

Community Paramedicine Program in Social Housing and Health Service Utilization

Community Paramedicine at Clinic (CP@clinic) is a chronic disease prevention program that decreases 911 calls for emergency medical services, but its wider system effects are unknown. To evaluate the effects of CP@clinic vs usual care on individual-level health service utilization outcomes. This open-label, pragmatic cluster randomized clinical trial evaluated all residents 55 years or older in 30 social housing buildings in Ontario, Canada, that had (1) a unique postal code, (2) at least 50 apartments, (3) 60% or more residents 55 years or older, and (4) a similar building for pairing (15 intervention and 15 control buildings, pair-matched randomization). The 12-month intervention had a staggered start date from January 1, 2015, to December 1, 2015, and ended between December 31, 2015, and November 30, 2016. Administrative health data analysis was conducted in May 2022. CP@clinic was a health promotion and disease prevention program led by specially trained community paramedics who held weekly drop-in sessions in social housing buildings. These paramedics conducted 1-on-1 risk assessments, provided health education and referrals to relevant community resources, and, with consent, sent assessments to family physicians. Control buildings received usual care (universal health care, including free primary and specialty medical care). Individual-level health service utilization was measured from administrative health data, with ED visits via ambulance as the primary outcome; secondary outcomes included ED visits for any reason, primary care visits, hospitalizations, length of hospital stay, laboratory tests, receipt of home care, transfer to long-term care, and medication initiation. Generalized estimating equations were used to estimate intervention effects on individual-level health service utilization, accounting for trial design and individual-level baselines. The 30 social housing buildings had 3695 residents (1846 control and 1849 intervention participants; mean [SD] age, 72.8 [9.1] years; 2400 [65.0%] female). Intention-to-treat analysis found no significant difference in ED visits by ambulance (445 of 1849 [24.1%] vs 463 of 1846 [25.1%]; adjusted odds ratio [AOR], 0.97; 95% CI, 0.89-1.05) but found higher antihypertensive medication initiation (74 of 500 [14.8%] vs 47 of 552 [8.5%]; AOR, 1.74; 95% CI, 1.19-2.53) and lower anticoagulant initiation (48 of 1481 [3.2%] vs 69 of 1442 [4.8%]; AOR, 0.68; 95% CI, 0.53-0.86) in the intervention arm vs the control arm. CP@clinic attendance was associated with higher incidence of primary care visits (adjusted incidence rate ratio, 1.10; 95% CI, 1.03-1.17), higher odds of receiving home care (AOR, 1.07; 95% CI, 1.01-1.13), and lower odds of long-term care transfers (AOR, 0.32; 95% CI, 0.13-0.81). In this cluster randomized clinical trial of CP@clinic, the intervention did not affect the rate of ED visits by ambulance; however, there were increased primary care visits and connections to home care services, which may have increased antihypertensive medication initiation and reduced long-term care transfers from social housing. Health policymakers should consider CP@clinic's impact as an upstream approach to improve care for older adults with low income. ClinicalTrials.gov Identifier: NCT02152891.

Aficamten in patients with obstructive hypertrophic cardiomyopathy: an integrated safety analysis

Abstract Background Aficamten is a next-in-class, oral, selective cardiac myosin inhibitor targeting the hypercontractility underlying hypertrophic cardiomyopathy (HCM). It relieves left ventricular outflow tract obstruction, improves exercise capacity, symptoms, quality of life, and cardiac biomarkers with a modest effect on left ventricular ejection fraction (LVEF). Purpose To present an integrated safety analysis from all aficamten trials to date. Methods Patients with obstructive HCM (oHCM) who received ≥1 dose of aficamten or placebo [PBO] in the phase 2 REDWOOD-HCM trial, phase 3 SEQUOIA-HCM trial, or the open-label extension FOREST-HCM were included. Results In the PBO-controlled pool of REDWOOD-HCM and SEQUOIA-HCM, 170 patients received aficamten and 153 PBO. In the cumulative (parent+extension) aficamten treated pool, 283 patients were analyzed from initial dose of aficamten or after enrollment in FOREST-HCM (100 PBO-to-aficamten). Overall, mean age was 59 years, 42% were female. In the PBO-controlled pool the mean cumulative follow up was 70.8 patient-years (py) on aficamten, and 66.3 py on PBO, and the total cumulative exposure period to aficamten was 205.2 py. The mean dose of aficamten in the cumulative pool was 12.6 mg/day. Treatment emergent serious adverse events (TESAE) occurred in 10 (5.9%) aficamten patients vs 14 (9.2%) PBO patients in the PBO-controlled pool, and in 24 (8.5%) aficamten patients in the cumulative pool. In the blinded phase, reported AEs were dizziness in 11 (6.5%) aficamten vs 3 (2%) PBO patients, syncope in 3 (1.8%) vs 4 (2.6%), dyspnea in 11 (6.5%) vs 8 (5.2%) and hypertension in 11 (6.5%) vs 4 (2.6%). Site-read LVEF &amp;lt;50%, all resulting in down-titration occurred in 9 (5.3%) aficamten patients [exposure adjusted incidence rate (EAIR) 11.2 per 100 py] and 1 (0.7%) PBO patient (EAIR: 1.3 per 100 py), and in 11 (3.9%) aficamten patients in the cumulative pool (EAIR: 5.3 per 100 py). None of the LVEF &amp;lt;50% events in aficamten patients were associated with heart failure symptoms; 1 PBO patient with a low LVEF had an AE of peripheral edema. During the maintenance phase of the cumulative exposure pool, 1588 echocardiograms were performed, of which 11 (0.7%) led to dose reduction due to LVEF &amp;lt;50%, none resulted in discontinuation or treatment interruption. In the cumulative pool, 6 (2.1%) patients terminated treatment early, none due to aficamten-related AEs. New onset atrial fibrillation occurred in 4 (2.4%) aficamten (EAIR: 4.9 per 100 py) and 5 (3.3%) PBO patients (EAIR: 6.5 per 100 py). There were no deaths during the study period. Conclusions In this integrated safety analysis, aficamten had a safety profile similar to PBO and was consistent over an extended treatment period. There was a low incidence of LVEF &amp;lt;50%, none of which were associated with clinical sequalae, and all were successfully managed by dose reduction. Monitoring echocardiography in the maintenance phase yielded very few actionable results.

Recurrence of internet gaming disorder in Korean adolescents: a 24-month follow-up study.

Many adolescents use internet games, and some of them experience psychological and social difficulties due to excessive gaming. Although there have been many studies on the onset and associated factors of internet gaming disorder (IGD) , research focusing specifically on its relapse is scarce. Considering that addictive disorders often have a chronic course with frequent relapse, this study prospectively observed adolescents from the general population to explore IGD recurrence rate and associated factors of recurrence. In this prospective cohort study, from 1587 middle school gaming users, 1452 (91.5%) were followed up at 12months and 24months. The results showed that the cumulative recurrence rate of IGD was 16.1%, which was higher than the initial incidence rate of 3.6%; the adjusted incidence rate ratio was 2.43 with 95% CI 1.21-4.87 (P = 0.012). In addition, starting internet gaming before entering primary school was associated with a higher risk of relapse (P = 0.004). Limiting internet gaming for children before they enter primary school may reduce the risk of relapse of IGD that they may encounter during their adolescent years.

How much does elective cardioversion increase the risk of ischaemic stroke compared to the baseline risk in atrial fibrillation? A nationwide study

Abstract Background Patients with atrial fibrillation (AF) undergoing cardioversion (CV) are exposed to an increased risk for stroke during the post-cardioversion period, but the exact magnitude of this risk after elective CV with preceding appropriate oral anticoagulant (OAC) therapy is unknown. Purpose We explored the rate of ischaemic stroke (IS) after elective CV and compared the IS rate during the post-cardioversion period with the long-term stroke rate in patients with AF using guideline-recommended OAC therapy. Methods This is a nationwide register-based study, including all AF patients undergoing their first-ever elective CV between 2012-18 in Finland. Data were collected from the Finnish health care registers covering uniquely all levels of care. Visual assessment of the survival curve identified a cut-off point in IS rate at 1 week after CV. Therefore, the follow-up time was split into two intervals, the 1-week post-cardioversion period and the subsequent period up to 360 days. Stroke rates were calculated separately for these periods. Unadjusted and adjusted incidence rate ratios were estimated with Poisson regression. Moreover, interaction between the two follow-up periods and conventional IS risk factors as well as OAC treatment was assessed. Results A total of 9625 AF patients undergoing their first elective CV were identified (mean age 67.7±9.9 years, 61.2% men, mean CHA2DS2-VASc score 2.6±1.6). Warfarin was used in 6 245 (64.9%) and non-vitamin K oral anticoagulants in 3 380 (35.1%) patients. Overall, 92 (1.0%) patients suffered an IS during the year after CV. The survival plot displayed a higher incidence of IS within the first week after CV, stabilizing thereafter to a consistent level (Figure). In the adjusted regression analyses, IS rate within the first week after elective CV was 13.6-fold (95% confidence interval [CI]: 8.6-21.5) compared the subsequent rate of IS (Table). We observed no significant interaction between any of the conventional IS risk factors or OAC treatment and the two follow-up time periods, indicating that their association with IS rate did not differ during the post-cardioversion period compared to the subsequent time period. Conclusions In this nationwide study, the rate of IS was roughly 14 times higher during the first week after elective CV compared to the subsequent follow-up time.Cumulative risk of IS after elective CVIncidence rates of IS after elective CV

Predictors and number of antenatal care visits among reproductive age women in Sub-Saharan Africa further analysis of recent demographic and health survey from 2017-2023: Zero-inflated negative binomial regression.

Antenatal care (ANC) is an important component of maternal and child health care. To reduce perinatal mortality and improve women's experience of care, the World Health Organization (WHO) recommends pregnant women should attend at least eight ANC visits. However, in Sub-Saharan Africa (SSA), the mean number of ANC visits among reproductive-age women using Demographic and Health Surveys (DHS) data following the new WHO recommendation is so far limited. Therefore, the study aimed to determine the mean number of ANC visits and its predictors among reproductive-age women in SSA. Community-based cross-sectional study was conducted among 188,880 weighted reproductive-age women in SSA using a recent round of DHS data from 2017-2023. Zero-inflated negative binomial regression (ZINB) was conducted and statistical significance was declared at p-value <0.05 and adjusted incidence rate ratio(AIRR) for count model part and adjusted odds ratio for logit model inflated part of ZINBR with 95% confidence interval (CI) were reported. The mean number of ANC visits among reproductive-age women in SSA was 4.08 with 95%CI [4.07, 4.09]. Among reproductive-age women who gave birth in the last five years before the survey, 7.3% had eight or more ANC visits during pregnancy. Age of women, maternal and husband educational status, types of pregnancy, birth order, household size, number of under-five children, and wealth index were associated with the numbers of ANC visits among reproductive-age women in Sub-Saharan. The mean number of ANC visits among reproductive-age women in SSA is too lower than the new WHO recommendation of ANC visits for a positive pregnancy experience. This study also highlights that the proportion of at least eight ANC visits is low and there are still disparities in the mean of ANC visits across different regions of SSA. The increasing maternal age, higher maternal and husband educational status, wanted pregnancy, the number of household members, the number of under-five children, and higher wealth index increase the number of ANC visits. Unwanted pregnancy, no more fertility desire, and rural residences were contributed for zero ANC visits in SSA. Therefore, efforts should be geared towards improving maternal and husband's educational status. We strongly recommend that the governments of SSA countries should empower women economically and educationally to achieve the goals of ANC as recommended by the WHO.

The association between glucose-dependent insulinotropic polypeptide and/or glucagon-like peptide-1 receptor agonist prescriptions and substance-related outcomes in patients with opioid and alcohol use disorders: A real-world data analysis.

This study aimed to estimate the strength of association between prescriptions of glucose-dependent insulinotropic polypeptide (GIP) and/or glucagon-like peptide-1 receptor agonists (GLP-1 RA) and the incidence of opioid overdose and alcohol intoxication in patients with opioid use disorder (OUD) and alcohol use disorder (AUD), respectively. This study also aimed to compare the strength of the GIP/GLP-1 RA and substance use-outcome association among patients with comorbid type 2 diabetes and obesity. A retrospective cohort study analyzing de-identified electronic health record data from the Oracle Cerner Real-World Data. About 136 United States of America health systems, covering over 100 million patients, spanning January 2014 to September 2022. The study included 503 747 patients with a history of OUD and 817 309 patients with a history of AUD, aged 18 years or older. The exposure indicated the presence (one or more) or absence of GIP/GLP-1 RA prescriptions. The outcomes were the incidence rates of opioid overdose in the OUD cohort and alcohol intoxication in the AUD cohort. Potential confounders included comorbidities and demographic factors. Patients with GIP/GLP-1 RA prescriptions demonstrated statistically significantly lower rates of opioid overdose [adjusted incidence rate ratio (aIRR) in OUD patients: 0.60; 95% confidence interval (CI) = 0.43-0.83] and alcohol intoxication (aIRR in AUD patients: 0.50; 95% CI = 0.40-0.63) compared to those without such prescriptions. When stratified by comorbid conditions, the rate of incident opioid overdose and alcohol intoxication remained similarly protective for those prescribed GIP/GLP-1 RA among patients with OUD and AUD. Prescriptions of glucose-dependent insulinotropic polypeptide and/or glucagon-like peptide-1 receptor agonists appear to be associated with lower rates of opioid overdose and alcohol intoxication in patients with opioid use disorder and alcohol use disorder. The protective effects are consistent across various subgroups, including patients with comorbid type 2 diabetes and obesity.

Impact of GLP-1RA on the Risk of Adverse Liver Outcomes Among Patients With Alcohol-Associated Liver Disease and Type 2 Diabetes.

We sought to characterise the impact of GLP-1RA on adverse liver outcomes (ALO) among patients with alcohol-associated liver disease (ALD) and Type 2 diabetes mellitus (T2DM). Patients with T2DM newly diagnosed with ALD between 2013 and 2020 were identified using IBM MarketScan database and were categorised by GLP-1RA exposure. Overlap propensity score weighting (OPSW) followed by Poisson regression models was used to analyse adjusted risk of ALO, a composite endpoint defined by first occurrence of hepatic decompensation (HD), portal hypertension (PH), hepatocellular carcinoma (HCC) or liver transplantation (LT) relative to GLP-1RA. Among 14 730 patients, most individuals were male (n = 9752, 66.2%) with median age of 57 (IQR 52-61) years; 2.2% (n = 317) of patients had GLP-1RA exposure. Overall, 32.0% (n = 4717) of patients experienced HD, 15.9% (n = 2345) had PH, 3.8% (n = 563) developed HCC, while 2.5% (n = 374) underwent transplantation. Non-GLP-1RA patients had higher incidence of HD (32.2% vs. 22.4%) and HCC (3.9% vs. 0.3%) versus patients taking GLP-1RA (both p < 0.001); in contrast, there was no difference in incidence of PH (14.5% vs. 16.0%) and LT (1.3% vs. 2.6%) (both p > 0.05). After OPSW, overall incidence of ALO was lower in GLP-1RA cohort (GLP-1RA: 12.0%, 95%CI 9.0-16.0 vs. non-GLP-1RA: 21.0%, 95%CI 20.0-22.0) with an absolute incidence risk reduction of 9.0% (95%CI 3.0%-15.0%) associated with GLP-1RA. GLP-1RA was most strongly associated with lower likelihood of HD with reduced adjusted incidence rate of 0.56 (95%CI 0.36-0.86) relative to non-GLP-1RA individuals. GLP-1RA may have a hepatoprotective impact among patients with ALD and T2DM.

Association of Periodontal Condition With Impaired Glucose Tolerance: Results of a 15-Year Follow-Up Study.

The aim of this study was to investigate whether periodontal condition is associated with the development of impaired glucose tolerance (IGT). This study was based on a subpopulation of a cohort of persons born in 1935 and living in Oulu, Finland, on October 1, 1990. The participants were normoglycemic (no previously diagnosed diabetes mellitus and a 2-h oral glucose tolerance test [OGTT] blood glucose < 7.8 mmol/L) in the baseline examinations (1990-1992) and had fasting blood glucose < 7.0 mmol/L in the follow-up examinations (2007-2008) (n = 225). The outcome was IGT on follow-up, measured by a blood glucose level of ≥ 7.8 mmol/L after OGTT. The exposure was the periodontal condition at baseline categorized into four groups: 0, 1-6, ≥ 7 sites with deepened (≥ 4 mm) periodontal pockets, and edentulousness. A total of 23% of the participants developed IGT. The adjusted incidence rate ratios with 95% confidence intervals (CI) for dentate participants with 1-6 sites and ≥ 7 sites with deepened periodontal pockets, and edentate participants (reference category dentate participants without deepened periodontal pockets) were 1.5 (95% CI, 0.6-4.0), 1.8 (95% CI, 0.7-4.4), and 1.6 (95% CI, 0.6-4.0), respectively. Poor periodontal condition may predispose individuals to IGT; however, further studies on this matter are warranted.