Standardized Mortality Ratio Research Articles

Excess mortality among people in homelessness with substance use disorders: a Swedish cohort study

BackgroundPeople in homelessness have an increased risk of substance use disorders (SUDs) and poor health outcomes. This cohort study aimed to investigate the association between homelessness and mortality in people...

Epidemiology, linkage to care and natural history of women of childbearing age with chronic hepatitis B: A population-based study.

Pregnant women with chronic hepatitis B (CHB) are a priority population for hepatitis B care. Identification of HBV status prior to pregnancy would facilitate timely maternal interventions and perinatal care. In our study, we aimed to study the epidemiology of CHB among women of childbearing age (WoCBA, 18-49 years) in Alberta, Canada. We retrospectively analysed Alberta Analytics databases to study CHB epidemiology, natural history and care linkage among WoCBA in Alberta, between April 2012 and March 2021. A Poisson regression was conducted to estimate incidence of newly identified CHB cases and prevalence trends, whereas predictors of care linkage were determined using logistic regression. Age/sex-adjusted incidence of newly identified CHB among WoCBA between 2015 and 2020 was 36.2/100,000 person/years, highest among individuals aged 30-39 years. Incidence of newly identified CHB decreased from 52.6 to 18.2/100,000 between 2015 and 2020, but prevalence increased from 131.7 to 248.6/100,000 in the same period. Newly identified CHB incident cases (n = 2124) had lower survival rates than age/sex-matched Canadians, with a standardized mortality ratio of 5.7 (95% CI 2.6-11.0). Increasing age (years) at diagnosis (HR, 1.2; 95% CI 1.1-1.3) was independently associated with mortality. Comorbid hepatocellular carcinoma, anti-HBV treatment and year of diagnosis were not significantly associated with mortality. Of the 1927 women with 2436 hepatitis B surface antigen-positive pregnancies from 2012 to 2020, only 27.6% had recommended HBV assessment during pregnancy. Of those women meeting criteria for antiviral therapy to prevent mother-to-child transmission (MTCT), only 66.4% received treatment. Suboptimal management during pregnancy and overall lower survival rates highlight the need to address care linkage barriers in women of childbearing age living with CHB.

Unveiling sex-based geographical disparities in myelodysplastic syndrome mortality trends in Spain (1999-2022).

To comprehensively analyze trends in myelodysplastic neoplasm (MDS) mortality across Spain (1999-2022), examining sex and regional differences. We analyzed nationwide death records and population data, calculating age-standardized mortality rates (ASMRs) and standardized mortality ratios (SMRs) stratified by sex and Autonomous Community (AC). Joinpoint regression identified significant shifts in trends. Across Spain, MDS mortality risk varied among men, with rates ranging from 1.08 to 4.38 per 100,000 across regions, while women's rates ranged from 1.23 to 2.02. Five regions had higher risks than the national average, while six had lower risks. Joinpoint analysis revealed three periods nationally: a decline until 2008, and an increase until 2017, followed by a significant decrease. Despite the overall stable national trend (-0.5% annual change), significant regional variations emerged. Andalusia stood out with a worrying increase in MDS mortality, while Aragon and Murcia demonstrated promising declines. Extremadura displayed a unique trajectory with an initial rise followed by stabilization, while Galicia exhibited a contrasting trend with an initial decline and subsequent increase. Notably, men consistently faced a higher risk of MDS mortality compared to women, with significant disparities across regions. Extremadura, in particular, showed a marked difference in risk between genders. MDS mortality trends in Spain are complex, and influenced by gender, region, and time. Further research is needed to understand regional disparities, recent national decline, and higher risk in specific demographics. Tailored interventions based on local factors and targeted research are crucial to address these complexities and improve patient outcomes.

Degenerative mitral regurgitation due to flail leaflet: sex-related differences in presentation, management, and outcomes.

Presentation, outcome, and management of females with degenerative mitral regurgitation (DMR) are undefined. We analysed sex-specific baseline clinical and echocardiographic characteristics at referral for DMR due to flail leaflets and subsequent management and outcomes. In the Mitral Regurgitation International Database (MIDA) international registry, females were compared with males regarding presentation at referral, management, and outcome (survival/heart failure), under medical treatment, post-operatively, and encompassing all follow-up. At referral, females (n = 650) vs. males (n = 1660) were older with more severe symptoms and higher MIDA score. Smaller cavity diameters belied higher cardiac dimension indexed to body surface area. Under conservative management, excess mortality vs. expected was observed in males [standardized mortality ratio (SMR) 1.45 (1.27-1.65), P < .001] but was higher in females [SMR 2.00 (1.67-2.38), P < .001]. Female sex was independently associated with mortality [adjusted hazard ratio (HR) 1.29 (1.04-1.61), P = .02], cardiovascular mortality [adjusted HR 1.58 (1.14-2.18), P = .007], and heart failure [adjusted HR 1.36 (1.02-1.81), P = .04] under medical management. Females vs. males were less offered surgical correction (72% vs. 80%, P < .001); however, surgical outcome, adjusted for more severe presentation in females, was similar (P ≥ .09). Ultimately, overall outcome throughout follow-up was worse in females who displayed persistent excess mortality vs. expected [SMR 1.31 (1.16-1.47), P < .001], whereas males enjoyed normal life expectancy restoration [SMR 0.92 (0.85-0.99), P = .036]. Females with severe DMR were referred to tertiary centers at a more advanced stage, incurred higher mortality and morbidity under conservative management, and were offered surgery less and later after referral. Ultimately, these sex-related differences yielded persistent excess mortality despite surgery in females with DMR, while males enjoyed restoration of life expectancy, warranting imperative re-evaluation of sex-specific DMR management.

Share of Adult Suicides After Recent Jail Release

Although people released from jail have an elevated suicide risk, the potentially large proportion of this population in all adult suicides is unknown. To estimate what percentage of adults who died by suicide within 1 year or 2 years after jail release could be reached if the jail release triggered community suicide risk screening and prevention efforts. This cohort modeling study used estimates from meta-analyses and jail census counts instead of unit record data. The cohort included all adults who were released from US jails in 2019. Data analysis and calculations were performed between June 2021 and February 2024. The outcomes were percentage of total adult suicides within years 1 and 2 after jail release and associated crude mortality rates (CMRs), standardized mortality ratios (SMRs), and relative risks (RRs) of suicide in incarcerated vs not recently incarcerated adults. Taylor expansion formulas were used to calculate the variances of CMRs, SMRs, and other ratios. Random-effects restricted maximum likelihood meta-analyses were used to estimate suicide SMRs in postrelease years 1 and 2 from 10 jurisdictions. Alternate estimate was computed using the ratio of suicides after release to suicides while incarcerated. Included in the analysis were 2019 estimates for 7 091 897 adults (2.8% of US adult population; 76.7% males and 23.3% females) who were released from incarceration at least once, typically after brief pretrial stays. The RR of suicide was 8.95 (95% CI, 7.21-10.69) within 1 year after jail release and 6.98 (95% CI, 4.21-9.76) across 2 years after release. A total of 27.2% (95% CI, 18.0%-41.7%) of all adult suicide deaths occurred in formerly incarcerated individuals within 2 years of jail release, and 19.9% (95% CI, 16.2%-24.1%) of all adult suicides occurred within 1 year of release (males: 23.3% [95% CI, 20.8%-25.6%]; females: 24.0% [95% CI, 19.7%-36.8%]). The alternate method yielded slightly larger estimates. Another 0.8% of adult suicide deaths occurred during jail stays. This cohort modeling study found that adults who were released from incarceration at least once make up a large, concentrated population at greatly elevated risk for death by suicide; therefore, suicide prevention efforts focused on return to the community after jail release could reach many adults within 1 to 2 years of jail release, when suicide is likely to occur. Health systems could develop infrastructure to identify these high-risk adults and provide community-based suicide screening and prevention.

Surveillance for metachronous cancers after endoscopic resection of esophageal squamous cell carcinoma.

The literature pertaining to surveillance following treatment for esophageal squamous cell carcinoma (SCC) was reviewed and summarized, encompassing the current status and future perspectives. Analysis of the standardized mortality and incidence ratios for these cancers indicates an elevated risk of cancer in the oral cavity, pharynx, larynx, and lungs among patients with esophageal SCC compared to the general population. To enhance the efficacy of surveillance for these metachronous cancers, risk stratification is needed. Various factors, including multiple Lugol-voiding lesions, multiple foci of dilated vascular areas, young age, and high mean corpuscular volume, have been identified as predictors of metachronous SCCs. Current practice involves stratifying the risk of metachronous esophageal and head/neck SCCs based on the presence of multiple Lugol-voiding lesions. Endoscopic surveillance, scheduled 6-12 months post-endoscopic resection, has demonstrated effectiveness, with over 90% of metachronous esophageal SCCs treatable through minimally invasive modalities. Narrow-band imaging emerges as the preferred surveillance method for esophageal and head/neck SCC based on comparative studies of various imaging techniques. Innovative approaches, such as artificial intelligence-assisted detection systems and radiofrequency ablation of high-risk background mucosa, may improve outcomes in patients following endoscopic resection.

Incidence of cardiovascular mortality among head and neck cancer patients.

While treatment advancements have prolonged the lives of patients with head and neck cancer, the subgroups of these patients at higher risk for cardiovascular disease (CVD) mortality remain unclear. We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with head and neck cancer from 2000 to 2019. We compared their CVD mortality against the general US population using standardized mortality ratios (SMRs). Our analysis included 474,366 patients, identifying that 14% of deaths were due to CVD, with an SMR of 1.19. Notably, patients under the age of 39 had a CVD SMR increase of over 100-fold. Those with distant tumor stages showed the highest CVD SMR of 1.52 (95% CI 1.50-1.54). An upward trend in SMR to 2.53 (95% CI 2.51-2.56) was observed from 2011 to 2019. Within the initial 5-year post-diagnosis, the SMR for CVD was 3.17 (95% CI 3.14-3.20), which exceeded the general population's rates but declined in the 5-20-year range after diagnosis. Patients who did not any therapy had the greatest CVD SMR of 2.26 (95% CI 2.24-2.28). Hypopharyngeal cancer patients exhibited the highest CVD SMR of 1.54 (95% CI 1.52-1.56). The study highlights that head and neck cancer patients, especially younger individuals and those with advanced disease stages, face substantial CVD mortality risks. The CVD SMR peaks within 5years following diagnosis. Patients abstaining from treatment bear the highest risk of CVD mortality. Cardioprotective measures should be considered critical for this patient population.

Long-Term Risks of Cardiovascular Death among Older Patients with Major Hematological Malignancies: A Population-Based Cohort Study from SEER Database.

The objective of this study was to identify the risk of cardiovascular disease (CVD)-related death in older patients with major hematological malignancies (HM). This study included 103,102 older patients diagnosed with seven major types of HM between 1975 and 2018 (median follow-up: 2.7 years) from the Surveillance, Epidemiology, and End Result database. The proportion of deaths, Fine-Gray subdistribution hazards regression model, standardized mortality ratios (SMR), and absolute excess risk (AER) were used to evaluate the risk of CVD-related death. For older patients with HM, CVD-related death ranked as the second leading cause of death, surpassed only by primary malignancy. Compared to the general older population, older patients with HM had higher SMR and AER of CVD-related deaths (SMR: 1.16-1.81; AER: 41.24-308.99), heart disease-related deaths (SMR: 1.19-1.90; AER: 39.23-274.69), and cerebrovascular disease-related deaths (SMR: 0.99-1.66; AER: -0.35 to 24.15). The proportion of deaths and cumulative mortality increased with the passage of survival time, especially in patients with Hodgkin lymphoma with stage I/II and those aged ≥85 years with chronic lymphocytic leukemia, surpassing primary malignancy. The risk of CVD-related death varied among different HM types. For older patients with HM, long-term cardiovascular risk management needs to be focused on while addressing the primary malignancy. Our results emphasize the need to manage long-term cardiovascular risk in older patients with hematological malignancies, especially in those identified as high-risk cases.

Air pollution and mortality for cancer of the respiratory system in Italy: an explainable artificial intelligence approach.

Respiratory system cancer, encompassing lung, trachea and bronchus cancer, constitute a substantial and evolving public health challenge. Since pollution plays a prominent cause in the development of this disease, identifying which substances are most harmful is fundamental for implementing policies aimed at reducing exposure to these substances. We propose an approach based on explainable artificial intelligence (XAI) based on remote sensing data to identify the factors that most influence the prediction of the standard mortality ratio (SMR) for respiratory system cancer in the Italian provinces using environment and socio-economic data. First of all, we identified 10 clusters of provinces through the study of the SMR variogram. Then, a Random Forest regressor is used for learning a compact representation of data. Finally, we used XAI to identify which features were most important in predicting SMR values. Our machine learning analysis shows that NO, income and O3 are the first three relevant features for the mortality of this type of cancer, and provides a guideline on intervention priorities in reducing risk factors.

Association of nirmatrelvir–ritonavir with post-acute sequelae and mortality in patients admitted to hospital with COVID-19: a retrospective cohort study

Studies have established the short-term efficacy of nirmatrelvir-ritonavir in managing COVID-19, yet its effect on post-COVID-19 condition, especially in patients admitted to hospital, remains understudied. This study aimed to examine the effect of nirmatrelvir-ritonavir on post-COVID-19 condition among patients admitted to hospital in Hong Kong. This retrospective cohort study used real-world, territory-wide inpatient records, vaccination records, and confirmed COVID-19 case data from the Hong Kong Hospital Authority and Department of Health, The Government of the Hong Kong Special Administrative Region. Patients aged 18 years and older who tested positive for SARS-CoV-2 between March 11, 2022, and Oct 10, 2023, and who were admitted to hospital with COVID-19 were included. The treatment group included patients prescribed nirmatrelvir-ritonavir within 5 days of symptom onset, excluding those prescribed molnupiravir within 21 days, and the control group had no exposure to either nirmatrelvir-ritonavir or molnupiravir. The outcomes were post-acute inpatient death and 13 sequelae (congestive heart failure, atrial fibrillation, coronary artery disease, deep vein thrombosis, chronic pulmonary disease, acute respiratory distress syndrome, interstitial lung disease, seizure, anxiety, post-traumatic stress disorder, end-stage renal disease, acute kidney injury, and pancreatitis). These outcomes were evaluated starting at 21 days after the positive RT-PCR date in each respective cohort constructed for the outcome. Standardised mortality ratio weights were applied to balance covariates, and Cox proportional hazards regression was used to investigate the relationship between nirmatrelvir-ritonavir and outcomes. 136 973 patients were screened for inclusion, among whom 50 055 were eligible and included in the analysis (24 873 [49·7%] were female and 25 182 [50·3%] were male). 15 242 patients were prescribed nirmatrelvir-ritonavir during acute COVID-19 and 23 756 patients were included in the control group; 11 057 patients did not meet our definition for the exposed and unexposed groups. Patients were followed up for a median of 393 days (IQR 317-489). In the nirmatrelvir-ritonavir group compared with the control group, there was a significantly lower hazard of post-acute inpatient death (hazard ratio 0·62 [95% CI 0·57-0·68]; p<0·0001), congestive heart failure (0·70 [0·58-0·85]; p=0·0002), atrial fibrillation (0·63 [0·52-0·76]; p<0·0001), coronary artery disease (0·71 [0·59-0·85]; p=0·0002), chronic pulmonary disease (0·68 [0·54-0·86]; p=0·0011), acute respiratory distress syndrome (0·71 [0·58-0·86]; p=0·0007), interstitial lung disease (0·17 [0·04-0·75]; p=0·020), and end-stage renal disease (0·37 [0·18-0·74]; p=0·0049). There was no evidence indicating difference between the groups in deep vein thrombosis, seizure, anxiety, post-traumatic stress disorder, acute kidney injury, and pancreatitis. This study showed extended benefits of nirmatrelvir-ritonavir for reducing the risk of post-acute inpatient death as well as cardiovascular and respiratory complications among patients admitted to hospital with COVID-19. Further research is essential to uncover the underlying mechanisms responsible for these observed negative associations and to devise effective strategies for preventing the onset of post-acute sequelae. Health and Medical Research Fund, Research Grants Council theme-based research schemes, and Research Grants Council Collaborative Research Fund.

Longer Interval Between First Colonoscopy With Negative Findings for Colorectal Cancer and Repeat Colonoscopy

For individuals without a family history of colorectal cancer (CRC), colonoscopy screening every 10 years is recommended to reduce CRC incidence and mortality. However, debate exists about whether and for how long this 10-year interval could be safely expanded. To assess how many years after a first colonoscopy with findings negative for CRC a second colonoscopy can be performed. This cohort study leveraged Swedish nationwide register-based data to examine CRC diagnoses and CRC-specific mortality among individuals without a family history of CRC. The exposed group included individuals who had a first colonoscopy with findings negative for CRC at age 45 to 69 years between 1990 and 2016. The control group included individuals matched by sex, birth year, and baseline age (ie, the age of their matched exposed individual when the exposed individual's first colonoscopy with findings negative for CRC was performed). Individuals in the control group either did not have a colonoscopy during the follow-up or underwent colonoscopy that resulted in a CRC diagnosis. Up to 18 controls were matched with each exposed individual. Individuals were followed up from 1990 to 2018, and data were analyzed from November 2022 to November 2023. A first colonoscopy with findings negative for CRC, defined as a first colonoscopy without a diagnosis of colorectal polyp, adenoma, carcinoma in situ, or CRC before or within 6 months after screening. The primary outcomes were CRC diagnosis and CRC-specific death. The 10-year standardized incidence ratio and standardized mortality ratio were calculated to compare risks of CRC and CRC-specific death in the exposed and control groups based on different follow-up screening intervals. The sample included 110 074 individuals (65 147 females [59.2%]) in the exposed group and 1 981 332 (1 172 646 females [59.2%]) in the control group. The median (IQR) age for individuals in both groups was 59 (52-64) years. During up to 29 years of follow-up of individuals with a first colonoscopy with findings negative for CRC, 484 incident CRCs and 112 CRC-specific deaths occurred. After a first colonoscopy with findings negative for CRC, the risks of CRC and CRC-specific death in the exposed group were significantly lower than those in their matched controls for 15 years. At 15 years after a first colonoscopy with findings negative for CRC, the 10-year standardized incidence ratio was 0.72 (95% CI, 0.54-0.94) and the 10-year standardized mortality ratio was 0.55 (95% CI, 0.29-0.94). In other words, the 10-year cumulative risk of CRC in year 15 in the exposed group was 72% that of the 10-year cumulative risk of CRC in the control group. Extending the colonoscopy screening interval from 10 to 15 years in individuals with a first colonoscopy with findings negative for CRC could miss the early detection of only 2 CRC cases and the prevention of 1 CRC-specific death per 1000 individuals, while potentially avoiding 1000 colonoscopies. This cohort study found that for the population without a family history of CRC, the 10-year interval between colonoscopy screenings for individuals with a first colonoscopy with findings negative for CRC could potentially be extended to 15 years. A longer interval between colonoscopy screenings could be beneficial in avoiding unnecessary invasive examinations.

Depressive symptoms and smoking: Effect on mortality in a primary care cohort

ObjectiveDepressive symptoms have been suggested to increase mortality risk but causality remains unproven. Depressive symptoms increase likelihood of smoking which is thus a potential factor modifying the effect of depressive symptoms on mortality. This study aims to assess if the association of depressive symptoms and all-cause mortality is affected by smoking. MethodsA prospective cohort study in Finnish primary care setting was conducted among 2557 middle-aged cardiovascular disease (CVD) risk persons identified in a population survey. Baseline depressive symptoms were assessed by Beck's Depression Inventory (BDI) and current smoking by self-report. Data on mortality was obtained from the official statistics. Effect of depressive symptoms and smoking on all-cause mortality after 14-year follow-up was estimated. ResultsCompared to non-depressive non-smokers, the adjusted hazard ratio (HR) for all-cause mortality was 3.10 (95% CI 2.02 to 4.73) and 1.60 (95% CI 1.15 to 2.22) among smoking subjects with and without depressive symptoms, respectively. Compared to the general population, relative survival was higher among non-depressive non-smokers and lower among depressive smokers. Relative standardized mortality ratio (SMR) for all-cause mortality was 1.78 (95% CI 1.31 to 2.44) and 3.79 (95% CI 2.54 to 6.66) among non-depressive and depressive smokers, respectively, compared to non-depressive non-smokers. The HR for all-cause mortality and relative SMR of depressive non-smokers were not increased compared to non-depressive non-smokers. ConclusionCurrent smoking and increased depressive symptoms seem to additively contribute to excess mortality.

P055 Prevalence, incidence, and mortality of Raynaud’s phenomenon, scleroderma, Sjogren’s syndrome and systemic lupus erythematosus: an overview of systematic reviews and meta-analyses

Abstract Background/Aims To comprehensively review any existing systematic reviews and/or meta-analysis on the prevalence, incidence, and mortality rates of Raynaud’s Phenomenon (RP), Sjögren’s Syndrome (SS), Scleroderma and Systematic Lupus Erythematosus (SLE). Methods An umbrella review of systematic reviews and/or meta-analysis was undertaken using two electronic databases - PubMed and Embase (OVID). The searches were limited to English language and a publication period of 2000-2023. Any systematic reviews and/or meta-analysis reporting the prevalence, incidence, or all-cause/cause-specific mortality of the studied diseases were collected. The number of included and excluded studies were reported through the PRISMA checklist. The pooled estimate and its corresponding 95% confidence intervals and P-values were reported from each included study. If there were no pooled estimates reported in the study, a narrative synthesis of their results was reported. Results In this umbrella review, a total of 43 systematic reviews and/or meta-analysis were reported, of which 1 was RP, 5 SS, 11 scleroderma and 26 SLE. The pooled prevalence and incidence rates for RP was 4.85% (95% CI: 2.08-8.71%) and 0.25% (95% CI: 0.19-0.32%), respectively. There was a lack of mortality findings for RP. The global prevalence rate for SS was reported to be 60.82 per 100,000 (95% CI: 43.79-77.94). The pooled incidence rate and cardiovascular mortality risk ratio were reported to be 6.92 (95% CI: 4.98-8.86) per 100,000 person-years and 1.48 (0.77-2.85), respectively. The pooled prevalence and incidence rates for scleroderma were found to be 17.6 (95% CI 15.1, 20.5) and 1.4 (1.1-1.9) per 100,000 person-years-at-risk. The pooled standardised mortality ratio (SMR) for Scleroderma ranged from 2.82 to 3.4. The global prevalence rate for SLE was found to be 43.7 (15.87-108.92) per 100,000. Incidence rates for SLE were found to be 5.14 (95% CI: 1.4-15.13) per 100,000. SMR of SLE ranged from 1.35-4.60. Conclusion Included studies reported varying values for the prevalence, incidence, all-cause/cause-specific findings of SS, scleroderma, and SLE. This could be due to differences in study populations, diagnostic criteria, case definitions, and included studies’ design. Although there were number of systematic reviews and/or meta-analysis investigating the epidemiology of scleroderma and SLE, there were few in RP and SS. Disclosure A. Chen: None. S. Lax: None. M. Grainge: None. P. Lanyon: None. F. Pearce: None.

Updated Analysis of Radon Exposure and Lung Cancer Mortality in the Cohort of Newfoundland Fluorspar Miners (1950-2016).

The commercial mining of fluorspar in St. Lawrence Newfoundland began in 1933. Miners who worked underground were exposed to high levels of radon progeny, especially before ventilation was introduced into the mines in 1960. The mean cumulative radon exposure for underground miners in this cohort was 380.9 working level months (WLM). A series of studies of this cohort have characterized the increased risks of lung cancer mortality due to radon. We have extended the follow-up of this cohort an additional 15 years to provide additional insights on the risks of low levels of radon exposure, and the modifying effects of time since exposure, age at first exposure, attained age, duration of exposure, and cigarette smoking. The cohort consisted of 1,735 underground and 315 male surface miners who, combined, accrued 81,650 person-years of follow-up. The mortality experience of the cohort was determined from 1950-2016 through record linkage to Canadian national death data. Individual-level estimates of exposure to radon progeny, in WLMs, were determined for each year of employment. We compared the mortality experience of the underground miners to Newfoundland men using the standardized mortality ratio (SMR). Poisson regression models were fit to estimate excess relative risks (ERR) per 100 WLM. There were 236 lung cancer deaths identified, and of these, 221 occurred among underground workers. The SMR for lung cancer among underground miners compared to Newfoundland men was 2.67 (95% CI: 2.33, 3.04). The ERR per 100 WLM for lung cancer mortality, assuming a 5-year exposure lag, was 0.41 (95% CI: 0.23, 0.59). Attained age and time since exposure were important modifiers to the radon-lung cancer relationship. The joint relationship between smoking and radon on lung cancer risk was sub-additive, however, the smoking data were limited and available for only half of the cohort.

Reducing suicides in mental healthcare: results from a 4-year follow-up implementation study in the Netherlands (SUPRANET).

In 2016, the SUicide PRevention Action NETwork (SUPRANET) was launched. The SUPRANET intervention aims at better implementing the suicide prevention guideline. An implementation study was developed to evaluate the impact of SUPRANET over time on three outcomes: 1) suicides, 2) registration of suicide attempts, and 3) professionals' knowledge and adherence to the guideline. This study included 13 institutions, and used an uncontrolled longitudinal prospective design, collecting biannual data on a 2-level structure (institutional and team level). Suicides and suicide attempts were extracted from data systems. Professionals' knowledge and adherence were measured using a self-report questionnaire. A three-step interrupted time series analysis (ITSA) was performed for the first two outcomes. Step 1 assessed whether institutions executed the SUPRANET intervention as intended. Step 2 examined if institutions complied with the four guideline recommendations. Based on steps 1 and 2, institutions were classified as below or above average and after that, included as moderators in step 3 to examine the effect of SUPRANET over time compared to the baseline. The third outcome was analyzed with a longitudinal multilevel regression analysis, and tested for moderation. After institutions were labeled based on their efforts and investments made (below average vs above average), we found no statistically significant difference in suicides (standardized mortality ratio) between the two groups relative to the baseline. Institutions labeled as above average did register significantly more suicide attempts directly after the start of the intervention (78.8 per 100,000 patients, p<0.001, 95%CI=(51.3 per 100,000, 106.4 per 100,000)), and as the study progressed, they continued to report a significantly greater improvement in the number of registered attempts compared with institutions assigned as below average (8.7 per 100,000 patients per half year, p=0.004, 95%CI=(3.3 per 100,000, 14.1 per 100,000)). Professionals working at institutions that invested more in the SUPRANET activities adhered significantly better to the guideline over time (b=1.39, 95%CI=(0.12,2.65), p=0.032). Institutions labeled as above average registered significantly more suicide attempts and also better adhered to the guideline compared with institutions that had performed less well. Although no convincing intervention effect on suicides was found within the study period, we do think that this network is potentially able to reduce suicides. Continuous investments and fully implementing as many guideline recommendations as possible are essential to achieve the biggest drop in suicides.

All-cause, cardiovascular disease and cancer mortality in the population of a large Italian area contaminated by perfluoroalkyl and polyfluoroalkyl substances (1980–2018)

BackgroundPer- and polyfluoroalkyl substances (PFAS) are associated with many adverse health conditions. Among the main effects is carcinogenicity in humans, which deserves to be further clarified. An evident association has been reported for kidney cancer and testicular cancer. In 2013, a large episode of surface, ground and drinking water contamination with PFAS was uncovered in three provinces of the Veneto Region (northern Italy) involving 30 municipalities and a population of about 150,000. We report on the temporal evolution of all-cause mortality and selected cause-specific mortality by calendar period and birth cohort in the local population between 1980 and 2018.MethodsThe Italian National Institute of Health pre-processed and made available anonymous data from the Italian National Institute of Statistics death certificate archives for residents of the provinces of Vicenza, Padua and Verona (males, n = 29,629; females, n = 29,518) who died between 1980 and 2018. Calendar period analysis was done by calculating standardised mortality ratios using the total population of the three provinces in the same calendar period as reference. The birth cohort analysis was performed using 20–84 years cumulative standardised mortality ratios. Exposure was defined as being resident in one of the 30 municipalities of the Red area, where the aqueduct supplying drinking water was fed by the contaminated groundwater.ResultsDuring the 34 years between 1985 (assumed as beginning date of water contamination) and 2018 (last year of availability of cause-specific mortality data), in the resident population of the Red area we observed 51,621 deaths vs. 47,731 expected (age- and sex-SMR: 108; 90% CI: 107–109). We found evidence of raised mortality from cardiovascular disease (in particular, heart diseases and ischemic heart disease) and malignant neoplastic diseases, including kidney cancer and testicular cancer.ConclusionsFor the first time, an association of PFAS exposure with mortality from cardiovascular disease was formally demonstrated. The evidence regarding kidney cancer and testicular cancer is consistent with previously reported data.

A population-based study of COVID-19 mortality risk in US cancer patients.

In this study, we provide the largest analysis to date of a US-based cancer cohort to characterize death from COVID-19. A total of 4 020 669 patients across 15 subtypes living with cancer in 2020 and included in the National Cancer Institute's Surveillance, Epidemiology, and End Results database were abstracted. We investigated prognostic factors for death due to COVID-19 using a Cox proportional hazards model and calculated hazard ratios (HRs). Standardized mortality ratios were calculated using observed mortality counts from Surveillance, Epidemiology, and End Results and expected mortality based on US mortality rates. A total of 291 323 patients died, with 14 821 (5.1%) deaths attributed to COVID-19 infection. The COVID-19 disease-specific mortality rate was 11.81/10 000-persons years, and the standardized mortality ratio of COVID-19 was 2.30 (95% confidence interval [CI] = 2.26 to 2.34; P < .0001). COVID-19 ranked as the second leading cause of death following ischemic heart disease (5.2%) among 26 noncancer causes of death. Patients who are older (80 years and older vs 49 years and younger: HR = 21.47, 95% CI = 19.34 to 23.83), male (vs female: HR = 1.46, 95% CI = 1.40 to 1.51), unmarried (vs married: HR = 1.47, 95% CI = 1.42 to 1.53), and Hispanic or non-Hispanic African American (vs non-Hispanic White: HR = 2.04, 95% CI = 1.94 to 2.14 and HR = 2.03, 95% CI = 1.94 to 2.14, respectively) were at greatest risk of COVID-19 mortality. We observed that people living with cancer are at 2 times greater risk of dying from COVID-19 compared with the general US population. This work may be used by physicians and public health officials in the creation of survivorship programs that mitigate the risk of COVID-19 mortality.

Effects of the COVID-19 pandemic on short-term postoperative outcomes of emergency surgery for gastroduodenal perforation: A nationwide study in Japan based on the National Clinical Database.

To examine the potential negative effects of the COVID-19 pandemic on short-term postoperative outcomes of emergency surgery for gastroduodenal perforation in Japan. A total of 7973 cases of gastroduodenal perforation from 2019 to 2021 were retrieved from the National Clinical Database (NCD), which includes >95% of surgical cases in Japan. Data were analyzed nationally and in subgroups for subjects in areas with high infection levels (HILs). Postoperative 30-d mortality, surgical mortality, and complications (Clavien-Dindo (CD) grade ≥3) were examined. Months were considered to have significantly high or low mortality or complication rates, if the 95% confidence interval (CI) of the standardized mortality (morbidity) ratio (SMR) does not contain 1. Nationally, data from 2019 vs 2020 and 2021 showed 30-d mortality of 175 (6.7%) vs 398 (7.4%), surgical mortality of 250 (9.5%) vs 537 (10.1%), and complications (CD ≥3) of 558 (21.2%) vs 1163 (21.8%). Among these data, the only significantly high SMR was found for complications in July 2020 (1.36 [95% CI: 1.001-1.80]). In areas with HILs, data from 2019 vs 2020 and 2021 indicated 30-d mortality of 91 (6.3%) vs 215 (7.3%), surgical mortality of 135 (9.4%) vs 294 (10.0%), and complications (CD ≥3) of 304 (21.1%) vs (23.1%). In these data, no month had a significantly high SMR. The COVID-19 pandemic had few negative effects on outcomes after surgery for gastroduodenal perforation. These findings suggest that the emergency system for gastroduodenal perforation in Japan was generally maintained during the pandemic.

Comparative Effectiveness of Valoctocogene Roxaparvovec and Prophylactic FactorVIII Replacement in Severe HemophiliaA.

A prospective, non-interventional study (270-902) followed 294 adults with severe hemophiliaA (SHA) receiving prophylactic factorVIII (FVIII). From these participants, 112 rolled over into a single-arm, multicenter, phase3 trial (GENEr8-1; NCT03370913) that evaluated efficacy and safety of valoctocogene roxaparvovec, a gene therapy that provides endogenous FVIII in individuals with SHA. Participants from 270-902 who did not roll over provide an opportunity for a contemporaneous external control. Therefore, the comparative effectiveness of valoctocogene roxaparvovec vs FVIII prophylaxis was evaluated using propensity scoring (PS). This posthoc analysis compared 112 participants from GENEr8-1 (treated cohort) to 73 participants in 270-902 who did not enroll in GENEr8-1 (control cohort). The primary analysis used standardized mortality ratio weighting to re-weight baseline characteristics of the control cohort to better match the treated cohort. Mean annualized bleeding rates (ABR) for treated and all bleeds were compared between cohorts along with the proportion of participants with zero bleeds (treated and all bleeds). Sensitivity and scenario analyses were also conducted. PS adjustments reduced differences in baseline characteristics between cohorts. Mean treated (4.40 vs 0.85; P < 0.001) and all (5.01 vs 1.54; P < 0.001) ABR were significantly lower, and the proportions of participants with zero treated bleeds (82.1% vs 32.9%; P < 0.001) and all bleeds (58.0% vs 28.5%; P < 0.001) were significantly higher in GENEr8-1. PS-adjusted analyses were consistent with prior intra-individual comparisons. Compared with participants receiving prophylactic FVIII, the participants receiving valoctocogene roxaparvovec experienced lower ABR, and a higher proportion had zero bleeds. ClinicalTrials.gov identifier, NCT03370913.

A retrospective study of morbidity and mortality of chronic acid sphingomyelinase deficiency in Germany

BackgroundAcid sphingomyelinase deficiency (ASMD) is a rare, progressive, potentially fatal lysosomal storage disease that exhibits a broad spectrum of clinical phenotypes. There is a need to expand the knowledge of disease mortality and morbidity in Germany because of limited information on survival analysis in patients with chronic ASMD (type B or type A/B).MethodsThis observational, multicentre, retrospective cohort study was conducted using medical records of patients with the first symptom onset/diagnosis of ASMD type B or type A/B between 1st January 1990 and 31st July 2021 from four German medical centres. Eligible medical records were abstracted to collect data on demographic characteristics, medical history, hospitalisation, mortality, and causes of death from disease onset to the last follow-up/death. Survival outcomes were estimated using the Kaplan–Meier analysis. Standardised mortality ratio (SMR) was also explored.ResultsThis study included 33 chart records of patients with ASMD type B (n = 24) and type A/B (n = 9), with a median (interquartile range [IQR]) age of 8.0 [3.0–20.0] years and 1.0 [1.0–2.0] years, respectively, at diagnosis. The commonly reported manifestations were related to spleen (100.0%), liver (93.9%), and respiratory (77.4%) abnormalities. Nine deaths were reported at a median [IQR] age of 17.0 [5.0–25.0] years, with 66.7% of overall patients deceased at less than 18 years of age; the median [IQR] age at death for patients with ASMD type B (n = 4) and type A/B (n = 5) was 31.0 [11.0–55.0] and 9.0 [4.0–18.0] years, respectively. All deaths were ASMD-related and primarily caused by liver or respiratory failures or severe progressive neurodegeneration (two patients with ASMD type A/B). The median (95% confidence interval [CI]) overall survival age since birth was 45.4 (17.5–65.0) years. Additionally, an SMR [95% CI] analysis (21.6 [9.8–38.0]) showed that age-specific deaths in the ASMD population were 21.6 times more frequent than that in the general German population.ConclusionsThis study highlights considerable morbidity and mortality associated with ASMD type B and type A/B in Germany. It further emphasises the importance of effective therapy for chronic ASMD to reduce disease complications.