Burden Of Mortality Research Articles

Compound dry-hot-fire events connecting Central and Southeastern South America: an unapparent and deadly ripple effect

South America has experienced severe compound drought-heatwaves (CDHW), exacerbating fires. Recently, the unprecedented Pantanal 2020 fire season (P20F), burning a third of the biome, resulted in well-reported local impacts on the ecosystem, economy, and health. Nevertheless, the long-range ripple effects of this event remain unknown. We investigated the P20F-related cascading hazards, integrating models, observational and satellite-based data. P20F-related smoke elevated PM2.5 levels in the SA’s most populated area, exceeding WHO guidelines by up to 600%. Smoke-induced air pollution episodes coincided with widespread heatwaves, amplifying health risks. The mortality burden attributable to this multi-hazard short-term (14 days) exposure was estimated to be 2150 premature deaths (21% increase above expected levels). Our findings highlight that the impacts of CDHW-fires in SA are beyond the local level, implying growing challenges for risk management and public health and the need for governance based on telecoupled flows, linking different systems over multiple scales.

Burden of mortality and its predictors among TB-HIV co-infected patients in Ethiopia: Systematic review and meta-analysis

Burden of mortality and its predictors among TB-HIV co-infected patients in Ethiopia: Systematic review and meta-analysis

Delivery-Related Maternal Morbidity and Mortality Among Patients With Cardiac Disease

OBJECTIVE: To assess the risk of severe maternal morbidity (SMM) and mortality among pregnant patients with cardiovascular disease (CVD). METHODS: This was a retrospective cohort study of U.S. delivery hospitalizations from 2010 to 2020 using weighted population estimates from the National Inpatient Sample database. The primary objective was to evaluate the risk of SMM and maternal mortality among patients with CVD at delivery hospitalization. International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification codes were used to identify delivery hospitalizations, CVD, and SMM events. Multivariable logistic regression analyses were performed to compare SMM and mortality risk among patients with CVD and those without CVD. Given the substantial racial and ethnic disparities in SMM, mortality, and CVD burden, secondary objectives included evaluating SMM and mortality across racial and ethnic groups and assessing the population attributable fraction within each group. Lastly, subgroup analyses of SMM by underlying CVD diagnoses (eg, congenital heart disease, chronic heart failure) were performed. Variables used in the regression models included socioeconomic and demographic maternal characteristics, maternal comorbidities, and pregnancy-specific complications. RESULTS: Among 38,374,326 individuals with delivery hospitalizations, 203,448 (0.5%) had CVD. Patients with CVD had an increased risk of SMM (11.6 vs 0.7%, adjusted odds ratio [aOR] 12.5, 95% CI, 12.0–13.1) and maternal death (538 vs 5 per 100,000 delivery hospitalizations, aOR 44.1, 95% CI, 35.4–55.0) compared with those without CVD. Patients with chronic heart failure had the highest SMM risk (aOR 354.4, 95% CI, 301.0–417.3) among CVD categories. Black patients with CVD had a higher risk of SMM (aOR 15.9, 95% CI, 14.7–17.1) than those without CVD with an adjusted population attributable fraction of 10.5% (95% CI, 10.0–11.0%). CONCLUSION: CVD in pregnancy is associated with increased risk of SMM and mortality, with the highest risk of SMM among patients with chronic heart failure. Although CVD affects less than 1% of the pregnant population, it contributes to nearly 1 in 10 SMM events in the United States.

Growing burden of inflammatory bowel disease in China: Findings from the Global Burden of Diseases 2021 and predictions to 2035.

Inflammatory bowel disease (IBD) imposes a significant economic and social burden in China. We aim to assess the epidemiological trends of IBD in China, and to predict the burden in the near future. The incidence, mortality, prevalence, and disability-adjusted life year (DALYs) of IBD from 1990 to 2021 were obtained from Global Burden of Disease 2021. Estimated annual percentage change (EAPC), average annual percent change, total percent change, and age-period-cohort model were used to access trends. Bayesian age-period-cohort model was utilized to predict the risk of incidence and mortality. In 2021, IBD affected 168,077 people in China, with 24,941 new cases and 5640deaths. The age-standardized rate (ASR) of incidence and death was 1.4 and 0.3, respectively. The incidence and prevalence in China were lower than the global and high socio-demographic index (SDI) regions, but the ASR of incidence and prevalence (EAPC: 2.93 and 2.54, respectively) had rapidly increased from 1990 to 2021. The ASR of death and DALYs had significantly decreased (EAPC: -3.05 and -2.93, respectively). Middle-aged and elderly populations faced a severe burden of incidence and prevalence, while the elderly population faced a severe mortality burden. It is projected that by 2035, the ASR of incidence will continue to rise, whereas the death rate will continue to decline. The burden of IBD in China is serious and increasingly severe. Establishing a comprehensive disease management system in China will help better control the medical burden of IBD.

Hypertensive Disorders in Pregnancy: Differences by Hispanic Ethnicity and Black Race.

Black individuals carry the greatest burden of maternal mortality, with hypertensive disorders during pregnancy being a significant driving force to this disparity. However, research on maternal health disparities predominantly groups Hispanic Black individuals with all other individuals of Hispanic ethnicity. We hypothesized that this aggregation might obscure the risk patterns of hypertensive disorders in pregnancy for Hispanic-Black and non-Hispanic Black individuals. We analyzed a California statewide dataset of vital records linked to hospitalization discharge data for births from 2007 to 2018. Using multivariable logistic regression models adjusted for age, pre-pregnancy BMI, parity, smoking status, diabetes, and chronic renal disease, we compared the odds of hypertensive disorders in pregnancy between Hispanic Black, non-Hispanic Black, and non-Black Hispanic racial-ethnic groups. Hypertensive disorders were categorized into two groups: (1) any hypertensive disorder and (2) chronic hypertension alone, non-severe hypertensive disorders, and severe hypertensive disorders in pregnancy. Non-Hispanic Black people had 75% increased odds of developing a hypertensive disorder during pregnancy (adjusted odds ratio (aOR); 95% confidence interval (CI): 1.74, 1.78) and Hispanic-Black individuals had a 31% increased odds (95% CI: 1.24, 1.38) as compared with non-Black Hispanic individuals. When considering hypertensive disorders separately, the race-associated differences were largest for chronic hypertension alone, with non-Hispanic Black individuals showing an aOR of 2.35 (95% CI: 2.32, 2.38) and Hispanic-Black individuals an aOR of 1.80 (95% CI: 1.66, 1.95). Compared with non-Black Hispanic individuals, the prevalence of hypertensive disorders in pregnancy was higher in Black-Hispanic individuals and highest in non-Hispanic Black individuals. Racial/ethnic differences were larger for chronic hypertension alone than for preeclampsia.

The burden of all-cause mortality following influenza-associated hospitalizations, FluSurv-NET, 2010-2019.

While the estimated number of U.S. influenza-associated deaths is reported annually, detailed data on the epidemiology of influenza-associated deaths, including the burden of in-hospital versus post-hospital discharge deaths are limited. Using data from the 2010-11 through 2018-19 seasons from the Influenza Hospitalization Surveillance Network, we linked cases to death certificates to identify patients who died from any cause during their influenza hospital stay or within 30 days post discharge. We described demographic and clinical characteristics of patients who died in hospital versus post discharge and characterized locations and causes of death (COD). Among 121,390 cases hospitalized with laboratory-confirmed influenza over 9 seasons, 5.5% died; 76% of deaths were in patients ≥65 years, 71% were non-Hispanic White, and 34% had ≥4 underlying medical conditions. Among all patients with an influenza-associated hospitalization who died, 48% of deaths occurred after hospital discharge; the median days from discharge to death was 9 days (IQR 3-19 days). Post-discharge deaths more often occurred in older patients and among those with underlying medical conditions. Only 37% of patients who died had "influenza" as a COD on their death certificate. Influenza was more frequently listed as a COD among persons who died in-hospital compared with cardiovascular disease among those who died after discharge. All-cause mortality burden is substantial among patients hospitalized with influenza, with almost 50% of deaths occurring within 30 days after hospital discharge. Surveillance systems should consider capture of post-discharge outcomes to better characterize the impact of influenza on all-cause mortality.

Using normalisation process theory (NPT) to explore implementation of the maternal perinatal death surveillance and response (MPDSR) policy in Uganda: a reflection

BackgroundThe implementation of the maternal perinatal death surveillance and response (MPDSR) policy is among the envisaged strategies to reduce the high global burden of maternal and perinatal mortality and morbidity. However, implementation of this policy across various contexts is inconsistent. Theoretically informed approaches to process evaluation can support assessment the implementation of policy interventions such as MPDSR, particularly in understanding what the actors involved actually do. In this article, we reflect on how the normalisation process theory (NPT) was used to explore implementation of the MPDSR policy in Uganda. NPT is a sociological theory concerned with the social organisation of the work (implementation) of making practices routine elements of everyday life (embedding) and of sustaining embedded practices in their social contexts (integration).MethodsThis qualitative multiple case study conducted across eight districts in Uganda and among 10 health facilities (cases) representing four out of the seven levels of the Uganda health care system. NPT was utilised in several ways including informing the study design, structuring the data collection tools (semi-structured interview guides), providing an organising framework for analysis, interpreting and reporting of study findings as well as making recommendations. Study participants were purposely selected to reflect the range of actors involved in the policy implementation process. This included direct care providers located at each of the cases, the Ministry of Health and from agencies and professional associations. Data were collected using semi-structured, in-depth interviews and were inductively and deductively analysed using NPT constructs and subconstructs.Results and conclusionNPT served useful for process evaluation, particularly in identifying factors that contribute to variations in policy implementation. Considering the NPT focus on the agency of people involved in implementation, additional efforts are required to understand how recipients of the policy intervention influence how the intervention becomes embedded within the various contexts.

Spatiotemporal patterns and factors contributing to neonatal mortality in Ethiopia: Data from EDHS 2000 to 2019.

Although Ethiopia has substantial improvements in various health indicators such as maternal and child mortality, the burden of neonatal mortality remains high. Between 2016 and 2019, neonatal mortality increased from 29 deaths per 1,000 live births to 33 deaths per 1,000 live births. This study aimed to explore the spatial patterns and factors contributing to neonatal mortality in Ethiopia. Data from the Ethiopian Demographic and Health Surveys (EDHS) for the years 2000, 2005, 2011, 2016, and 2019 were analyzed. The EDHS sampling design uses a two-stage cluster sampling technique, considering census enumeration areas as primary sampling units and households as secondary sampling units. We used the Spatial Scan analysis in SaTScan and Getis-Ord Gi* statistic in Geographic Information System (GIS), to analyse the spatiotemporal patterns of neonatal mortality. Maternal, newborn and health service-related factors contributing to neonatal mortality were also analyzed using a multilevel logistic regression model. Adjusted Odds Rios (AOR) with corresponding 95% CI were presented as a measure of association and a P-value of 0.05 was used to declare statistical significance. During the initial three consecutive surveys, there was a consistent pattern of hot spot clusters in the Amhara and Benshangul Gumuz regions, along with certain parts of the Oromia region. However, in later surveys, these clusters shifted to the eastern parts of the country, notably including the Somali region. Early initiation of breast feeding was associated with reduced chances of neonatal death (Adjusted Odds Ratio [AOR]) = 0.27; 95% Confidence Interval [CI]: 0.23, 0.32). Neonates born at home (AOR = 1.46; 95% CI: 1.16, 1.82) and male babies had a higher likelihood of mortality during the neonatal period compared to their counterparts (AOR = 1.36; 95% CI: 1.24, 1.51). The odds of neonatal mortality increased with the number of children a mother had ever given birth to (AOR = 1.36; 95% CI: 1.24, 1.51). In contrast, longer birth intervals were associated with a reduced risk of neonatal mortality (AOR = 0.76; 95% CI: 0.68, 0.83). The central southern, central-western, north-western, and northern parts of Ethiopia had most of the neonatal death clusters in the first three rounds of DHS while eastern Ethiopia had the highest neonatal mortality clusters in the latest two surveys. Our results underscore the importance for policymakers and health administrators to reassess intervention approaches and reallocate resources to regions identified as hot spots for neonatal mortality. Enhancing the initiation of breastfeeding within the first hour of birth would improve newborn survival rates. Special attention and care need to be given to babies born of smaller sizes.

Maternal and Fetal Outcomes of Aplastic Anemia During Pregnancy and Delivery: Systematic Review and Meta-Analysis.

Little scientific evidence exists on maternal and fetal outcomes in aplastic anemia (AA) during pregnancy. The review was conducted to assess the maternal and fetal outcomes due to AA during pregnancy. Web of Science, EMBASE, PubMed, Scopus, Cochrane CENTRAL, and registries until May 5, 2024. Studies (prospective, retrospective cohort, cross-sectional, one arm, survey, follow-up studies) evaluating AA during pregnancy were searched as per PROSPERO registered protocol (CRD42024506668). Case reports, case series, expert opinion letters, and studies assessing less than or equal to 10 pregnant women were not considered. The primary outcome was the prevalence of preeclampsia in AA pregnancies. The secondary outcomes included spontaneous abortion, preterm premature rupture of membranes, premature rupture of membranes, fetal growth restriction, type of delivery, intrauterine fetal death, maternal and neonatal mortality, and pre and post-pregnancy remission status comparison. The quality of research was checked using the New Castle-Ottawa risk-of-bias tool. A meta-analysis model with a random effect distribution, coupled with meta-regression, sensitivity analysis, and publication bias assessment, was used in the statistical software R. Standard Equator network study reporting guidelines were followed. Seven (one prospective and six retrospective cohort) studies included patients with confirmed AA diagnosis in 248 pregnancies. The pooled prevalence of preeclampsia was 13% (95% CI, 8%-20%). Heterogeneity was low in the present meta-analysis (I2 = 26%). The secondary outcome evaluation showed a pooled prevalence of 5% (95% CI, 3%-11%) for spontaneous abortion, 4% (95% CI, 1%-11%) for preterm premature rupture of membranes, 10% (95% CI, 3%-28%) for premature rupture of membranes, 6% (95% CI, 3%-11%) for fetal growth restriction, 5% (95% CI, 2%-13%) for intrauterine fetal death, 12% (95% CI, 5%-26%) for post-partum hemorrhage, 74% (95% CI, 45%-91%) for intrapartum transfusion requirement, and 55% (95% CI, 27%-80%) for the cesarean delivery opting. The maternal mortality in pregnancies with AA was 4% (95% CI, 0.01-0.14), whereas neonatal mortality was 7% (95% CI, 0.03-0.18). The odds of AA complete remission were better in pre-pregnancy than post-pregnancy (OR = 0.36; 95% CI = 0.08-1.66), although the results remain insignificant. The leave-one-out sensitivity analysis did not change the pooled estimates for the primary outcome. A risk of developing preeclampsia was observed in every eighth pregnant woman with an AA diagnosis. AA remission status might worsen after undergoing pregnancy, considering the significant obstetric morbidity and mortality burden.

Non-optimal temperature-attributable mortality and morbidity burden by cause, age and sex under climate and population change scenarios: a nationwide modelling study in Japan

Future temperature effects on mortality and morbidity may differ. However, studies comparing projected future temperature-attributable mortality and morbidity in the same setting are limited. Moreover, these studies did not consider future population change, human adaptation, and the variations in subpopulation susceptibility. Thus, we simultaneously projected the temperature-related mortality and morbidity by cause, age, and sex under population change, and human adaptation scenarios in Japan, a super-ageing society. We used daily mean temperatures, mortality, and emergency ambulance dispatch (a sensitive indicator for morbidity) in 47 prefectures of Japan from 2015 to 2019 as the reference for future projections. Future mortality and morbidity were generated at prefecture level using four shared socioeconomic pathway (SSP) scenarios considering population changes. We calculated future temperature-related mortality and morbidity by combining baseline values with future temperatures and existing temperature risk functions by cause (all-cause, circulatory, respiratory), age (<65 years, ≥65 years), and sex under various climate change and SSP scenarios (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). Full human adaptation was simulated based on empirical evidence using a fixed percentile of minimum mortality or morbidity temperature (MMT), while no adaptation was simulated with a fixed absolute MMT. A future temporal decline in mortality burden attributable to non-optimal temperatures was observed, driven by greater cold-related deaths than heat-related deaths. In contrast, temperature-related morbidity increased over time, which was primarily driven by heat. In the 2050s and 2090s, under a moderate scenario, there are 83.69 (95% empirical confidence interval [eCI] 38.32-124.97) and 77.31 (95% eCI 36.84-114.47) all-cause deaths per 100,000 population, while there are 345.07 (95% eCI 258.31-438.66) and 379.62 (95% eCI 271.45-509.05) all-cause morbidity associated with non-optimal temperatures. These trends were largely consistent across causes, age, and sex groups. Future heat-attributable health burden is projected to increase substantially, with spatiotemporal variations and is particularly pronounced among individuals ≥65y and males. Full human adaptation could yield a decreasing temperature-attributable mortality and morbidity in line with a decreasing population. Our findings could support the development of targeted mitigation and adaptation strategies to address future heat-related impacts effectively. This includes improved healthcare allocations for ambulance dispatch and hospital preventive measures during heat periods, particularly custom-tailored to address specific health outcomes and vulnerable subpopulations. Japan Science and Technology Agency and Environmental Restoration and Conservation Agency and Ministry of the Environment of Japan.

Projecting future minimum mortality temperature in China

Minimum mortality temperature (MMT) increases with global warming due to climate adaptation, which is crucial for the precise assessment of mortality burden attributed to climate change. Nevertheless, forecasting future MMT poses a challenge given the unavailability of future mortality data. Here, we attempted to develop a novel approach to project future MMT. First, we estimated the MMT of 334 locations in China using a distributed lag nonlinear model. Then, meta regression models were applied to investigate the associations between MMT and several temperature variables(Most Frequent Temperature(MFT), average daily mean temperature, average daily minimum temperature, average daily maximum temperature and percentiles of temperature from 1st to 100th). A generalized linear regression model was employed to investigate whether significant differences existed in the relationships between MMT and temperature from the 1st to the 100th percentile. Finally, an optional indicator of MMT for projecting future values was identified. Our results indicated that temperatures in the 85th to 89th percentiles were closely associated with MMT, with the 88th percentile temperature serving as the most effective indicator, as confirmed by meta-regression models. Using the 88th percentile of temperature as alternative indicator of MMT, compared with the period of 2006-2015, the projected MMT in most districts and counties in China tended to rise under three representative concentration pathways (RCPs) in the 2030s (2030-2039), 2060s (2060-2069), and 2090s (2090-2099). Our findings provide some insight to project future MMT for assessing mortality burden related to temperature change driven by global warming.

Behavioral Interventions for Tobacco Cessation in Low and Middle-Income Countries: A Systematic Review and Meta-analysis.

An estimated 78% of the total deaths attributable to smoking tobacco use occurred in low- and middle-income countries (LMICs) in 2019. In addition, smokeless tobacco increases the risk of all-cause mortality, all cancers including upper aero-digestive tract cancer, stomach cancer, ischaemic heart disease (IHD) and stroke; with 88% of the mortality burden being borne by the South-East Asian region. Evidence-based interventions from high income countries (HICs) are not easily transferable to LMICs, as patterns of tobacco use, health beliefs associated with tobacco use, and awareness of specific health risks vary substantially. We synthesised the effectiveness of behavioural interventions for tobacco cessation in LMICs through a systematic review and meta-analysis. Interventional studies which delivered individual behavioural intervention and assessed abstinence from tobacco use were included. We examined the pooled intervention effect at six months post-intervention follow up. For continuous abstinence at six months, the intervention was superior to active comparator (RR 2.32; 95% CI 1.78-3.02), and usual care (RR 4.39; 95% CI 2.38-8.11). For point prevalence abstinence at six months, the intervention was superior to active comparator (RR 1.76; 95% CI 1.28-2.44), and usual care (RR 2.37; 95% CI 1.47-3.81). The statistical heterogeneity was substantial to considerable for all comparisons. Only six studies had an overall low risk of bias. Publication bias was observed for all comparisons, except for 6-month continuous outcomes. Implementation research is needed to understand factors for programme sustainability and equity of impact of behavioural interventions in reducing tobacco use in LMICs. Our review is an important step towards the understanding of effectiveness of behaviour interventions for tobacco cessation suited for low- and middle-income countries and which are responsive to the contextual needs of such countries.

Mortality burden attributed to anthropogenic warming during Europe’s 2022 record-breaking summer

The record-breaking temperatures in Europe during the 2022 summer were associated with over 60,000 heat-related deaths. By combining epidemiological models with detection and attribution techniques, we attribute half of this mortality burden (~56% [95% CI 39–77%]) to anthropogenic warming. Likewise, this applies to all sexes, ages, and heat-related mortality burdens during previous years (2015–2021). Our results urgently call for increasing ambition in adaptation and mitigation.

Chest Wall Hydatid Disease: Surgical management and risk Factors for Recurrence and Mortality

Background Hydatidosis of the thoracic wall differs from other hydatid localizations in its pathophysiology, diagnostic, and therapeutic management. It is a little-studied entity. The objectives of our work were to describe its surgical management and to analyze the factors that may influence recurrence and mortality. Methods A retrospective, descriptive, longitudinal, and multicenter study on four university hospital surgical centers of Tunis, from January 1995 to December 2022 including operated hydatid cysts of the thoracic wall. Overall survival (OS) and cumulative recurrence rates were calculated. Univariate and multivariable Cox regression analyses were performed to identify recurrence and mortality risk factors. Results Forty-nine patients were included. The mean age was 41 ± 17 years [8-76]. The main presenting sign was thoracic parietal swelling (n=22). Chest ultrasound and CT scan showed multivesicular formation in 17 and 33 cases, respectively. Muscle involvement was in the intercostal (n=4), paravertebral (n=13), and pectoralis major (n=3) muscles. Bone involvement was vertebral (n=11), costal (n=12), costo-vertebral (n=21) and sternal (n=2). A posterolateral thoracotomy was performed (n=20). Surgical excision at various levels of the chest wall with spinal stabilization (n=15) was performed. Sixty-three percent of the patients received antiparasitic medical treatment. Recurrence occurred in 37% of cases. Four patients died from hydatidosis-related complications. Factors could be independently associated with recurrence such as male gender, and vertebral involvement. The presence of a visceral hydatid cyst located at a distance from the parietal lesion at the time of diagnosis and the occurrence of postoperative infectious complications could increase mortality. Conclusions Chest wall hydatidosis represents a rare medical condition where surgery remains the preferred treatment modality. However, it carries a substantial burden of morbidity and mortality, influenced by various factors. Further large-scale studies are necessary to gain a deeper understanding of these factors and to optimize management strategies accordingly.

Excess mortality and hospitalizations associated with seasonal influenza in patients with heart failure

Abstract Background Influenza virus may cause severe infection in patients with heart failure. It is accepted that influenza infection is associated with increased morbidity and mortality in patients with heart failure. However, less is known about the excess burden of morbidity and mortality caused by influenza infection in patients with heart failure at a population level. Purpose To estimate the excess burden of morbidity and mortality as determined by annual excess number of deaths and hospitalizations associated with influenza infection in patients with heart failure. Methods We collected nationwide data on weekly number of deaths and hospitalizations among patents with heart failure in Denmark and weekly estimates of influenza circulation as determined by the proportion of positive influenza samples analyzed at all Danish Hospitals. These data were correlated in a time series linear regression model and this model was used to estimate the annual excess number of deaths and hospitalizations attributable to influenza circulation among patients with heart failure in Denmark. Results Data were available from 2010 to 2018 encompassing 8 influenza seasons with an annual mean of 25180 samples tested for influenza. Among an annual mean of 70570 patients with heart failure, our model estimated that influenza activity was associated with an annual excess of 250 all cause deaths (95%CI 144-489) corresponding to 2.6% of all all-cause deaths (95%CI 1.5% - 5.1%). Similarly, influenza activity was associated with an annual excess of 115 cardiovascular deaths (95%CI 62-244) corresponding to 2.9% of all cardiovascular deaths (95%CI 1.5% - 6.1%) among patients with heart failure. Influenza activity was also associated with an annual excess of 251 hospitalizations for pneumonia or influenza (95%CI 107-533) corresponding to 5.0% of all hospitalizations for pneumonia or influenza. Conclusion Our results indicate that influenza activity likely causes substantial morbidity and mortality among patients with heart failure. Notably, our study suggests that approximately 2.6% of all deaths and 5.0% of all hospitalizations with influenza or pneumonia may be attributed to influenza in patients with heart failure.

Alcohol-related premature mortality in Northern Dimension partnership countries 2003-2021

Abstract Background Potential Years Life Lost (PYLL) is an established method to measure, follow trends and compare disease burden within and between countries. Northern Dimension Partnership in Health and Social wellbeing (NDPHS) network was established in 2003 and includes the following countries: Estonia, Finland, Germany, Iceland, Latvia, Lithuania, Norway, Poland, Russia, and Sweden. Due to the Russian invasion to Ukraine, Russia is now excluded from the collaboration. Iceland is not included in the analyses due to too small number of events. Methods Premature mortality was defined as a death before the age of 70 years. Alcohol-related deaths included the following ICD-codes: E24.4, F10, G31.2, G62.1, G72.1, I42.6, K29.2, K70, K85.2, K86.0, Q86.0, R78.0, X45, X65, Y15, K73, K74.0-K74.2, K74.6, O354, P043 and G4051. PYLL-rates per 100,000 population are presented separately for men and women in four time points: 2003, 2013, 2017 and 2021. Data were obtained from Eurostat and analyses are standardized to EU standard population. Results In the whole NDPHS area, alcohol related PYLL-rates declined between 2003 and 2017: from 527 to 458 in men, and from 159 to 134 in women. However, between 2017 and 2021 the rates increased: to 509 in men and to 154 in women. In 2021, the highest alcohol-related PYLL-rates were in Latvia (1696 in men and 530 in women) and the lowest in Norway (94 in men and 43 in women). Thus, the differences between countries in alcohol-related PYLL-rates were 20-fold in meles and 10-fold in females. In all countries the rates were 2-3 times higher in men compared to women. Conclusions Alcohol use is an important cause of premature mortality and disease burden in NDPHS area. There are marked differences in alcohol-related PYLL-rates between sexes and countries. The increase in alcohol-related PYLL-rates between 2017 and 2021 may be related to the Covid-pandemic. Key messages • Alcohol use is an important cause of premature mortality and disease burden in NDPHS countries, and there are marked differences in alcohol-related mortality between sexes and countries. • Reduction of total alcohol consumption is an evidence-based most effective public health measure to reduce alcohol-related health harms.

Performance of an automated echocardiographic artificial intelligence model. to detect subclinical heart failure with preserved ejection fraction (HFpEF) in community-dwelling older adults

Abstract Background Heart failure (HF) with preserved Ejection Fraction (HFpEF) is common among older adults and associated with a high burden of morbidity and mortality. Early identification of subclinical HFpEF, defined by abnormalities in cardiac structure and function without symptoms of HF, can prompt early initiation of evidence-based therapies to prevent HFpEF. However, scalable strategies for the identification of subclinical HFpEF are lacking. Purpose To evaluate the performance of a validated, automated echocardiographic artificial Intelligence algorithm (Ultromics, UK) to identify subclinical HFpEF among community-dwelling individuals without HF. Methods The study included participants of the Dallas Hearts and Minds Study without HF who underwent cardiovascular phenotyping with resting and exercise echocardiography and maximal cardiopulmonary exercise testing. The resting apical 4C echocardiographic images were analyzed by the AI echo algorithm to identify the HFpEF phenotype (AI-HFpEF). Subclinical HFpEF was defined by E/e’ &amp;gt;14 and Peak exercise oxygen uptake (VO2peak) &amp;lt;25th percentile for the cohort. The performance of the AI algorithm to detect subclinical HFpEF was determined using the area under the receiver operating curve and decision curve analysis and was compared with the previously validated H2FpEF score. The association between the AI-HFpEF phenotype and the presence of subclinical HFpEF, VO2peak, exercise E/e’, left ventricular strain, and left atrial strain was assessed using multivariable-adjusted logistic and linear regression models. Results The study included 511 participants (mean age: 61 y, 57% women, mean VO2peak = 16.9 ml/kg/min). Using the AI echo algorithm, subclinical HFpEF was detected in 10% of participants (n=76), and 10% were non-diagnostic. The participants with (vs. without) AI-HFpEF phenotype were older and had a higher burden of CVD risk factors, left ventricular hypertrophy, and left atrial dilation. Subclinical HFpEF, as defined by the gold standard criteria, was present in 5.3% of participants. The AUROC for diagnosis of subclinical HFpEF using the AI-HFpEF algorithm was 0.85 vs. 0.78 by the H2FpEF score (see Figure). In the adjusted analysis, the AI-HFpEF phenotype was significantly associated with greater odds of subclinical HFpEF by exercise and echocardiographic phenotyping criteria, higher E/e’ with exercise, lower VO2 peak, and worse LV and LA strain (see Table). In decision curve analysis, the AI-HFpEF algorithm identified 23 additional cases of subclinical HFpEF per 1000 screened participants compared with the H2FpEF score. Conclusion The AI-HFpEF algorithm can reliably identify community-dwelling individuals with subclinical HFpEF characterized by diastolic dysfunction at rest or exercise and impaired exercise capacity. Future studies are needed to assess the utility of the AI-HFpEF algorithm in screening for subclinical HFpEF in health systems.

Diagnostic and prognostic evaluation of an echocardiography-based artificial intelligence algorithm for detecting HFpEF: a case-control analysis

Abstract Background Heart failure (HF) with preserved Ejection Fraction (HFpEF) is common among older adults and is associated with a high burden of morbidity and mortality. Despite its increasing prevalence, the diagnosis of HFpEF remains challenging. Recently, the FDA cleared an echocardiography-based AI HFpEF model that utilizes a 3-dimensional convolutional neural network to detect HFpEF using a single 4-chamber clip from a resting echocardiogram. However, the external validation of this algorithm against clinically adjudicated and confirmed HFpEF is limited. Purpose To evaluate the diagnostic and prognostic performance of the echocardiography-based AI HFpEF model in a cohort of HFpEF patients and matched controls. Methods The study included patients with clinically adjudicated HFpEF based on clinical history, normal ejection fraction (&amp;gt;45%), and evidence of elevated filling pressure by resting (PCWP &amp;gt; 15 mm Hg) or exercise invasive hemodynamics (PCWP &amp;gt; 25 mm Hg) or echocardiogram (E/e’ &amp;gt;14). The controls were age, sex, and BMI-matched patients without HF and a normal echocardiogram. The performance of the AI HFpEF model was evaluated using receiver operator curves. In patients with HFpEF, the association of the AI-HFpEF phenotype with elevated resting/exercise PCWP and peak exercise oxygen uptake (VO2peak) was assessed using multivariable logistic and linear regression models adjusting for age, sex, race, BMI, and comorbidities (diabetes, hypertension, kidney disease, atrial fibrillation). Results Of the 166 patients referred for evaluation of HFpEF, 82% had clinically adjudicated HFpEF, and 69.8% had elevated LV filling pressure at rest or exercise. In the matched cohorts of patients with clinically adjudicated HFpEF and matched control individuals (N = 122 each), the AI algorithm-based probability of HFpEF demonstrated good performance in identifying clinically adjudicated and hemodynamically confirmed HFpEF (AUROC: 0.75 for each) that was greater than the widely used H2FpEF score (0.69 and 0.70, Figure). In the HFpEF referral cohort, a higher probability of HFpEF based on the AI-algorithm phenotype was significantly associated with lower VO2peak (b [95% CI] per 5% higher probability: -0.11 [-0.21 to -0.01, P-value: 0.03] and greater odds of elevated PCWP (Odds ratio [95% CI] per 5% higher probability: 1.07 [1.01 – 1.15, P-value: 0.04] at rest or exercise after accounting for other confounders. Based on Youden’s index, the AI algorithm-based probability threshold of &amp;gt;0.75 was identified as the optimal cutoff for detecting HFpEF by the AI algorithm, with high sensitivity (0.85) and accuracy (0.74) and, adequate specificity (0.66). Conclusion The echocardiography-based AI HFpEF model demonstrated excellent sensitivity and discrimination in identifying patients with vs. without clinical HFpEF. Furthermore, the AI HFpEF model also had prognostic utility such that individuals with a higher probability of AI-HFpEF phenotype had more severe HFpEF.

Proteome-wide associations of pulse pressure in the UK Biobank

Abstract Introduction Large artery stiffness (LAS) significantly contributes to the burden of cardiovascular morbidity and mortality, and is marked by an increased pulse pressure (PP)(1). Therapeutically targeting LAS may help in mitigating cardiovascular disease and other comorbidities. Purpose We aimed to investigate the proteomic associations of PP, and their putative causal role using Mendelian randomization (MR). Methods We first investigated associations between baseline circulating protein levels for 2,941 protein analytes measured using Olink technology, and PP in the UK Biobank (N=54,219). Regression analyses were adjusted for age, sex, mean arterial pressure, body mass index and stroke volume. Next, we conducted two-sample MR analyses to evaluate associations between genetically-predicted plasma protein levels and PP, for 1,820 proteins with available genetic instruments. We conducted inverse-variance weighted MR as our main analysis, and genetic colocalization analyses as sensitivity. We used a 5% false discovery rate (FDR) threshold to account for multiple comparisons. Results After correction for multiple comparisons, measured levels of 61 out of 2,923 proteins were significantly associated with PP (Figure 1). Genetically-predicted levels for 58 proteins were significantly associated with PP after FDR correction (Figure 2). At nominal significance, 31 proteins were concordantly associated with PP in both analyses, and 19 had consistent directions of effect, including natriuretic peptide B (NPPB, βobservational=0.04, Standard Error (SE)=0.009, PFDR&amp;lt;0.001), thrombospondin-2 (THBS2, βobservational=0.05, SE=0.009, PFDR&amp;lt;0.001), paraoxonase-2 (PON2, βobservational=-0.03, SE=0.008, PFDR&amp;lt;0.001), and sclerostin (SOST, βobservational=-0.03, SE=0.009, PFDR&amp;lt;0.001). NPPB was concordant in direction of effect and met an FDR-corrected significance threshold. Conclusions Our study identifies multiple novel proteins with a putative causal effect on PP. Our findings identify NPPB with a high level of statistical confidence, which could have important implications given the current availability of FDA-approved medications to boost NPPB effects. Our findings will lead to further investigations regarding the biology and clinical role of the identified candidate therapeutic targets.

Paediatric iGAS Morbidity and Mortality in Ireland 2022-2023 episodic upsurge

Abstract There was an unseasonal upsurge in invasive Group A Streptococcal (iGAS) activity in Ireland during the 2022/2023 winter period. In particular, there was an increase in the proportion of paediatric infections and a rise in the age specific death rate for those under the age of 18, from 0.10 to 1.43 per 100,000. This review aimed to describe the demographic and clinical factors associated with paediatric iGAS infection during this upsurge. All iGAS cases under the age of 16 years, notified to Public Health between 1st October and 30th June 2023, were included. A review of hospital records for each case was conducted using a standardised electronic data collection proforma. Descriptive, univariate and multivariate analysis was conducted using SPSS statistical package. There was a total of 183 cases of iGAS notified during this upsurge in Ireland. A hospital chart review was conducted for 169 of these cases, giving a response rate of 92.3%. The median age was 4 years (range 0-15,) with 44.4% (75) having a previous healthcare attendance during their illness. Varicella coinfection occurred in 27.8% (47) of cases. There was respiratory viral coinfection in 40.8% (69) of cases, and this was significantly associated with an increased risk of death RR 6.49 (95% CI 4.45 - 29.08) p &amp;lt; 0.05. A respiratory site of infection was also significantly associated with an increased risk of death RR 10.13 (95% CI 2.23 - 45.95) p &amp;lt; 0.001. However, both factors did not remain significant once adjusted for age, sex, ethnicity and deprivation index. This national review demonstrated the significant burden of paediatric iGAS morbidity and mortality during this upsurge. A significant proportion of cases, 37.9% (64) were associated with vaccine preventable illness, with respiratory viral infections and a respiratory site of infection both being significantly associated with an increased risk of death. Key messages • A significant proportion of iGAS cases were associated with a vaccine preventable illness. • A respiratory site of iGAS infection was significantly associated with an increased risk of death in paediatric cases.