Association of cumulative loneliness with all-cause mortality among middle-aged and older adults in the United States, 1996 to 2019.

Loneliness is a growing public health concern worldwide. We characterized the association between cumulative loneliness and subsequent all-cause mortality, using data from 9,032 participants aged 50+ in the population-based US Health and Retirement Study (HRS) from 1996 to 2019. Loneliness status (yes; no) was measured biennially from 1996 to 2004, and we categorized the experience of cumulative loneliness over the 8-y period as never, one time point, two time points, and ≥three time points. A multivariable-adjusted age-stratified Cox proportional hazards regression model was fitted to examine the association between cumulative loneliness from 1996 to 2004 and all-cause mortality from 2004 to 2019. Excess deaths due to each category of cumulative loneliness were calculated. Compared to those who never reported loneliness from 1996 to 2004, participants experiencing loneliness at one time point, two time points, and ≥three time points respectively had 1.05 (95% CI: 0.96 to 1.15), 1.06 (95% CI: 0.95 to 1.19), and 1.16 (95% CI: 1.02 to 1.33) times higher hazards of mortality from 2004 to 2019 (P trend = 0.01). These results correspond to 106 (95% CI: 68 to 144), 202 (95% CI: 146 to 259), and 288 (95% CI: 233 to 343) excess deaths per 10,000 person-years, for those experiencing loneliness at each of one, two, or ≥three time points from 1996 to 2004. Cumulative loneliness in mid-to-later life may thus be a mortality risk factor with a notable impact on excess mortality. Loneliness may be an important target for interventions to improve life expectancy in the United States.

Adjusting expected deaths for mortality displacement during the COVID-19 pandemic: a model based counterfactual approach at the level of individuals.

BACKGROUND: Near-real time surveillance of excess mortality has been an essential tool during the COVID-19 pandemic. It remains critical for monitoring mortality as the pandemic wanes, to detect fluctuations in the death rate associated both with the longer-term impact of the pandemic (e.g. infection, containment measures and reduced service provision by the health and other systems) and the responses that followed (e.g. curtailment of containment measures, vaccination and the response of health and other systems to backlogs). Following the relaxing of social distancing regimes and reduction in the availability of testing, across many countries, it becomes critical to measure the impact of COVID-19 infection. However, prolonged periods of mortality in excess of the expected across entire populations has raised doubts over the validity of using unadjusted historic estimates of mortality to calculate the expected numbers of deaths that form the baseline for computing numbers of excess deaths because many individuals died earlier than they would otherwise have done: i.e. their mortality was displaced earlier in time to occur during the pandemic rather than when historic rates predicted. This is also often termed "harvesting" in the literature. METHODS: We present a novel Cox-regression-based methodology using time-dependent covariates to estimate the profile of the increased risk of death across time in individuals who contracted COVID-19 among a population of hip fracture patients in England (N = 98,365). We use these hazards to simulate a distribution of survival times, in the presence of a COVID-19 positive test, and then calculate survival times based on hazard rates without a positive test and use the difference between the medians of these distributions to estimate the number of days a death has been displaced. This methodology is applied at the individual level, rather than the population level to provide a better understanding of the impact of a positive COVID-19 test on the mortality of groups with different vulnerabilities conferred by sociodemographic and health characteristics. Finally, we apply the mortality displacement estimates to adjust estimates of excess mortality using a "ball and urn" model. RESULTS: Among the exemplar population we present an end-to-end application of our methodology to estimate the extent of mortality displacement. A greater proportion of older, male and frailer individuals were subject to significant displacement while the magnitude of displacement was higher in younger females and in individuals with lower frailty: groups who, in the absence of COVID-19, should have had a substantial life expectancy. CONCLUSION: Our results indicate that calculating the expected number of deaths following the first wave of the pandemic in England based solely on historical trends results in an overestimate, and excess mortality will therefore be underestimated. Our findings, using this exemplar dataset are conditional on having experienced a hip fracture, which is not generalisable to the general population. Fractures that impede mobility in the weeks that follow the accident/surgery considerably shorten life expectancy and are in themselves markers of significant frailty. It is therefore important to apply these novel methods to the general population, among whom we anticipate strong patterns in mortality displacement - both in its length and prevalence - by age, sex, frailty and types of comorbidities. This counterfactual method may also be used to investigate a wider range of disruptive population health events. This has important implications for public health monitoring and the interpretation of public health data in England and globally.

Gender differences in estimated excess mortality during the COVID-19 pandemic in Thailand.

BACKGROUND: There is a limited body of research specifically examining gender inequality in excess mortality and its variations across age groups and geographical locations during the COVID-19 pandemic. This study aims to fill this gap by analyzing the patterns of gender inequality in excess all-cause mortality in Thailand during the COVID-19 pandemic. METHODS: Data pertaining to all-cause deaths and population between January 1, 2010, and December 31, 2021, were obtained from Thailand's Bureau of Registration Administration. A seasonal autoregressive integrated moving average (SARIMA) technique was used to estimate excess mortality during the pandemic between January 2020 to December 2021. Gender differential excess mortality was measured as the difference in age-standardized mortality rates between men and women. RESULTS: Our SARIMA-based estimate of all-cause mortality in Thailand during the COVID-19 pandemic amounted to 1,032,921 deaths, with COVID-19-related fatalities surpassing official figures by 1.64 times. The analysis revealed fluctuating patterns of excess and deficit in all-cause mortality rates across different phases of the pandemic, as well as among various age groups and regions. In 2020, the most pronounced gender disparity in excess all-cause mortality emerged in April, with 4.28 additional female deaths per 100,000, whereas in 2021, the peak gender gap transpired in August, with 7.52 more male deaths per 100,000. Individuals in the 80 + age group exhibited the largest gender gap for most of the observed period. Gender differences in excess mortality were uniform across regions and over the period observed. Bangkok showed the highest gender disparity during the peak of the fourth wave, with 24.18 more male deaths per 100,000. CONCLUSION: The findings indicate an overall presence of gender inequality in excess mortality during the COVID-19 pandemic in Thailand, observed across age groups and regions. These findings highlight the need for further attention to be paid to gender disparities in mortality and call for targeted interventions to address these disparities.

Pathways to Immunity: Patterns of Excess Death Across the United States and Within Closed Religious Communities.

Public health officials promoted COVID-19 vaccines to limit burdens placed on the U.S. healthcare system and end the pandemic. People in some closed religious communities refused to vaccinate and likely acquired temporary immunity through infection. This paper compares the death rates in Amish, Old Order Mennonites, and conservative Mennonite groups to a rate estimated for the U.S. population. Approximately two-thirds of the U.S. population was immunized against COVID-19, while few in the Amish/Mennonite community were. We find divergent patterns. Once vaccines became available, excess deaths declined in the general population and remained elevated among Amish and Mennonites. Vaccination campaigns must consider and value the cultural beliefs of closed religious communities to be effective.

Excess deaths from Alzheimer's disease and Parkinson's disease during the COVID-19 pandemic in the USA.

BACKGROUND: COVID-19 pandemic has indirect impacts on patients with chronic medical conditions, which may increase mortality risks for various non-COVID-19 causes. This study updates excess death statistics for Alzheimer's disease (AD) and Parkinson's disease (PD) up to 2022 and evaluates their demographic and spatial disparities in the USA. METHODS: This is an ecological time-series analysis of AD and PD mortality in the USA from January 2018 to March 2022. Poisson log-linear regressions were utilised to fit the weekly death data. Excess deaths were calculated with the difference between the observed and expected deaths under a counterfactual scenario of pandemic absence. RESULTS: From March 2020 to March 2022, we observed 41,115 and 10,328 excess deaths for AD and PD, respectively. The largest percentage increases in excess AD and PD deaths were found in the initial pandemic wave. For people aged ≥85 years, excess mortalities of AD and PD (per million persons) were 3946.0 (95% confidence interval [CI]: 2954.3, 4892.3) and 624.3 (95% CI: 369.4, 862.5), which were about 23 and 9 times higher than those aged 55-84 years, respectively. Females had a three-time higher excess mortality of AD than males (182.6 vs. 67.7 per million persons). The non-Hispanic Black people experienced larger increases in AD or PD deaths (excess percentage: 31.8% for AD and 34.6% for PD) than the non-Hispanic White population (17.1% for AD and 14.7% for PD). CONCLUSION: Under the continuing threats of COVID-19, efforts should be made to optimise health care capacity for patients with AD and PD.

Closed but Not Protected: Excess Deaths Among the Amish and Mennonites During the COVID-19 Pandemic.

"Excess deaths" is a means to estimate the lethality of COVID-19 (directly and indirectly). Assessing "excess death" in closed religious communities provides information on how COVID-19 impacted these communities. We use obituary information published in an Amish/Mennonite newspaper to examine excess death among the Amish/Mennonites in 2020. Our results indicate the Amish/Mennonite excess death rates are similar to the national trends in the USA. The excess death rate for Amish/Mennonites spiked with a 125% increase in November 2020. The impact of COVID-19 on this closed religious community highlights the need to consider religion to stop the spread of COVID-19.

Prenatal malnutrition and adult cognitive impairment: a natural experiment from the 1959-1961 Chinese famine.

The current measures of cognitive functioning in adulthood do not indicate a long-term association with prenatal exposure to the Dutch famine. However, whether such association emerges in China is poorly understood. We aimed to investigate the potential effect of prenatal exposure to the 1959-1961 Chinese famine on adult cognitive impairment. We obtained data from the Second National Sample Survey on Disability implemented in thirty-one provinces in 2006, and restricted our analysis to 387 093 individuals born in 1956-1965. Cognitive impairment was defined as intelligence quotient (IQ) score under 70 and IQ of adults was evaluated by the Wechsler Adult Intelligence Scale - China Revision. Famine severity was defined as excess death rate. The famine impact on adult cognitive impairment was estimated by difference-in-difference models, established by examining the variations of famine exposure across birth cohorts. Results show that compared with adults born in 1956-1958, those who were exposed to Chinese famine during gestation (born in 1959-1961) were at greater risk of cognitive impairment in the total sample. Stratified analyses showed that this effect was evident in males and females, but only in rural, not in urban areas. In conclusion, prenatal exposure to famine had an enduring deleterious effect on risk of cognitive impairment in rural adults.

The estimated change in the level and distribution of PM2.5-attributable health impacts in the United States: 2005-2014.

BACKGROUND: Photochemical modeling can predict the level and distribution of pollutant concentrations over time, but is resource-intensive. Partly for this reason, there are few studies exploring the multi-year trajectory of the historical change in fine particle (PM2.5) levels and associated health impacts in the U.S. OBJECTIVES: We used a unique dataset of Community Multi-Scale Air Quality (CMAQ) model simulations performed for a subset of years over a decade-long period fused with observations to estimate the change in ambient levels of PM2.5 across the contiguous U.S. We also quantified the change in PM2.5-attributable health risks and characterized the level of risk inequality over this period. METHODS: We estimated annual mean PM2.5 concentrations in 2005, 2011 and 2014. Using log-linear and logistic concentration-response coefficients we estimated changes in the numbers of deaths, hospital admissions and other morbidity outcomes. Calculating the Gini coefficient and Atkinson Index, we characterized the extent to which PM2.5 attributable risks were shared equally across the population or instead concentrated among certain subgroups. RESULTS: In 2005 the estimated fraction of deaths due to PM2.5 was 6.1%. This estimated value falls to 4.6% by 2014. Every portion of the contiguous U.S. experiences a decline in the risk of PM-related premature death over the 10-year period. As measured by the Gini coefficient and Atkinson index, the level of PM mortality risk is shared more equally in 2014 than in 2005 among all subgroups. CONCLUSIONS: Between 2005 and 2014, the level of PM2.5 concentrations fall, and the risk of premature death, declined and became more equitably distributed across the U.S.

Mortality Rates and Excess Death Rates for the Seriously Mentally Ill.

OBJECTIVES: -To compute mortality rates and excess death rates for patients with serious mental illness, specific to categories of gender, age and race/ethnicity. BACKGROUND: -People with serious mental illness are known to be at greatly increased risk of mortality across the lifespan. However, the measures of mortality reported for this high-risk population are typically only summary measures, which do not provide either the mortality rates or excess death rates needed to construct life tables for individuals with serious mental illness. METHODS: -Mortality rates were computed by dividing the number of deaths by the amount of life-years lived in strata specific to gender, age and race/ethnicity. Age-specific excess death rates were determined as the difference between the study population rate and the corresponding general population rate in each stratum. To compute excess death rates beyond observed ages in the cohort, a method with documented reliability and validity for chronic medical conditions was used. RESULTS: -For the cohort with mental illness, mortality rates for Black and White females were mostly equal, and consistently greater than those for Hispanic females; excess death rates for females displayed a similar pattern. Among males, mortality rates were highest for Whites, with Hispanics and Blacks close in magnitude at all ages. Excess death rates for males showed more divergence between the categories of race/ethnicity across the age range. CONCLUSIONS: -Mortality rates specific to categories of gender, age and race/ethnicity show sufficient differences as to make them the preferred way to construct life tables. This is especially true in contrast to broader summary measures such as risk ratios, standardized incidence rates, or life expectancy.

Mortality after shoulder arthroplasty.

One year post-operative mortality among patients with primary elective total shoulder arthroplasty (ETSA) and traumatic shoulder arthroplasty (TSA) were compared to the general population of a large healthcare system. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) were calculated. 614 ETSA patients, 1.0% one year mortality, and 168 TSA patients, 5.4% mortality rate, were evaluated. Patients with ETSA (SMR = 0.4, 95% CI 0.1-0.7) had lower odds of mortality than expected, while patients with TSA (SMR = 1.8, 95% CI 0.6-3.0) did not have higher than expected odds of mortality compared to the reference population. Understanding excess mortality following shoulder arthroplasty surgery allows providers to evaluate current practices and identify ways to optimize patients prior to surgery.

Global and Regional Cardiovascular Mortality Attributable to Nonoptimal Temperatures Over Time.

BACKGROUND: The association between nonoptimal temperatures and cardiovascular mortality risk is recognized. However, a comprehensive global assessment of this burden is lacking. OBJECTIVES: The goal of this study was to assess global cardiovascular mortality burden attributable to nonoptimal temperatures and investigate spatiotemporal trends. METHODS: Using daily cardiovascular deaths and temperature data from 32 countries, a 3-stage analytical approach was applied. First, location-specific temperature-mortality associations were estimated, considering nonlinearity and delayed effects. Second, a multivariate meta-regression model was developed between location-specific effect estimates and 5 meta-predictors. Third, cardiovascular deaths associated with nonoptimal, cold, and hot temperatures for each global grid (55 km × 55 km resolution) were estimated, and temporal trends from 2000 to 2019 were explored. RESULTS: Globally, 1,801,513 (95% empirical CI: 1,526,632-2,202,831) annual cardiovascular deaths were associated with nonoptimal temperatures, constituting 8.86% (95% empirical CI: 7.51%-12.32%) of total cardiovascular mortality corresponding to 26 deaths per 100,000 population. Cold-related deaths accounted for 8.20% (95% empirical CI: 6.74%-11.57%), whereas heat-related deaths accounted for 0.66% (95% empirical CI: 0.49%-0.98%). The mortality burden varied significantly across regions, with the highest excess mortality rates observed in Central Asia and Eastern Europe. From 2000 to 2019, cold-related excess death ratios decreased, while heat-related ratios increased, resulting in an overall decline in temperature-related deaths. Southeastern Asia, Sub-Saharan Africa, and Oceania observed the greatest reduction, while Southern Asia experienced an increase. The Americas and several regions in Asia and Europe displayed fluctuating temporal patterns. CONCLUSIONS: Nonoptimal temperatures substantially contribute to cardiovascular mortality, with heterogeneous spatiotemporal patterns. Effective mitigation and adaptation strategies are crucial, especially given the increasing heat-related cardiovascular deaths amid climate change.

Excess non-COVID-19-related mortality among inflammatory bowel disease decedents during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic disrupted healthcare in the United States. AIM: To investigate COVID-19-related and non-COVID-19-related death and characteristics associated with excess death among inflammatory bowel disease (IBD) decedents. METHODS: We performed a register-based study using data from the National Vital Statistics System, which reports death data from over 99% of the United States population, from January 1, 2006 through December 31, 2021. IBD-related deaths among adults 25 years and older were stratified by age, sex, race/ethnicity, place of death, and primary cause of death. Predicted and actual age-standardized mortality rates (ASMRs) per 100000 persons were compared. RESULTS: 49782 IBD-related deaths occurred during the study period. Non-COVID-19-related deaths increased by 13.14% in 2020 and 18.12% in 2021 [2020 ASMR: 1.55 actual vs 1.37 predicted, 95% confidence interval (CI): 1.26-1.49; 2021 ASMR: 1.63 actual vs 1.38 predicted, 95%CI: 1.26-1.49]. In 2020, non-COVID-19-related mortality increased by 17.65% in ulcerative colitis (UC) patients between the ages of 25 and 65 and 36.36% in non-Hispanic black (NHB) Crohn's disease (CD) patients. During the pandemic, deaths at home or on arrival and at medical facilities as well as deaths due to neoplasms also increased. CONCLUSION: IBD patients suffered excess non-COVID-19-related death during the pandemic. Excess death was associated with younger age among UC patients, and with NHB race among CD patients. Increased death at home or on arrival and due to neoplasms suggests that delayed presentation and difficulty accessing healthcare may have led to increased IBD mortality.

Forecast of peak infection and estimate of excess deaths in COVID-19 transmission and prevalence in Taiyuan City, 2022 to 2023.

In this paper, with the method of epidemic dynamics, we assess the spread and prevalence of COVID-19 after the policy adjustment of prevention and control measure in December 2022 in Taiyuan City in China, and estimate the excess population deaths caused by COVID-19. Based on the transmission mechanism of COVID-19 among individuals, a dynamic model with heterogeneous contacts is established to describe the change of control measures and the population's social behavior in Taiyuan city. The model is verified and simulated by basing on reported case data from November 8th to December 5th, 2022 in Taiyuan city and the statistical data of the questionnaire survey from December 1st to 23rd, 2022 in Neijiang city. Combining with reported numbers of permanent residents and deaths from 2017 to 2021 in Taiyuan city, we apply the dynamic model to estimate theoretical population of 2022 under the assumption that there is no effect of COVID-19. In addition, we carry out sensitivity analysis to determine the propagation character of the Omicron strain and the effect of the control measures. As a result of the study, it is concluded that after adjusting the epidemic policy on December 6th, 2022, three peaks of infection in Taiyuan are estimated to be from December 22nd to 31st, 2022, from May 10th to June 1st, 2023, and from September 5th to October 13th, 2023, and the corresponding daily peaks of new cases can reach 400 000, 44 000 and 22 000, respectively. By the end of 2022, excess deaths can range from 887 to 4887, and excess mortality rate can range from 3.06% to 14.82%. The threshold of the infectivity of the COVID-19 variant is estimated 0.0353, that is if the strain infectivity is above it, the epidemic cannot be control with the previous normalization measures.

The Effect of the COVID-19 Pandemic on Non-COVID-19 Deaths: Population-Wide Retrospective Cohort Study.

BACKGROUND: Health care avoidance in the COVID-19 pandemic has been widely reported. Yet few studies have investigated the dynamics of hospital avoidance behavior during pandemic waves and inferred its impact on excess non-COVID-19 deaths. OBJECTIVE: This study aimed to measure the impact of hospital avoidance on excess non-COVID-19 deaths in public hospitals in Hong Kong. METHODS: This was a retrospective cohort study involving 11,966,786 patients examined between January 1, 2016, and December 31, 2021, in Hong Kong. All data were linked to service, treatment, and outcomes. To estimate excess mortality, the 2-stage least squares method was used with daily tallies of emergency department (ED) visits and 28-day mortality. Records for older people were categorized by long-term care (LTC) home status, and comorbidities were used to explain the demographic and clinical attributes of excess 28-day mortality. The primary outcome was actual excess death in 2020 and 2021. The 2-stage least squares method was used to estimate the daily excess 28-day mortality by daily reduced visits. RESULTS: Compared with the prepandemic (2016-2019) average, there was a reduction in total ED visits in 2020 of 25.4% (548,116/2,142,609). During the same period, the 28-day mortality of non-COVID-19 ED deaths increased by 7.82% (2689/34,370) compared with 2016-2019. The actual excess deaths in 2020 and 2021 were 3143 and 4013, respectively. The estimated total excess non-COVID-19 28-day deaths among older people in 2020 to 2021 were 1958 (95% CI 1100-2820; no time lag). Deaths on arrival (DOAs) or deaths before arrival (DBAs) increased by 33.6% (1457/4336) in 2020, while non-DOA/DBAs increased only by a moderate 4.97% (1202/24,204). In both types of deaths, the increases were higher during wave periods than in nonwave periods. Moreover, non-LTC patients saw a greater reduction in ED visits than LTC patients across all waves, by more than 10% (non-LTC: 93,896/363,879, 25.8%; LTC: 7,956/67,090, 11.9%). Most of the comorbidity subsets demonstrated an annualized reduction in visits in 2020. Renal diseases and severe liver diseases saw notable increases in deaths. CONCLUSIONS: We demonstrated a statistical method to estimate hospital avoidance behavior during a pandemic and quantified the consequent excess 28-day mortality with a focus on older people, who had high frequencies of ED visits and deaths. This study serves as an informed alert and possible investigational guideline for health care professionals for hospital avoidance behavior and its consequences.

Assessment of mortality risks due to a strong cold spell in 2022 in China.

Background: With the intensification of global climate warming, extreme low temperature events such as cold spells have become an increasingly significant threat to public health. Few studies have examined the relationship between cold spells and mortality in multiple Chinese provinces. Methods: We employed health impact functions for temperature and mortality to quantify the health risks of the first winter cold spell in China on November 26th, 2022, and analyzed the reasons for the stronger development of the cold spell in terms of the circulation field. Results: This cold spell was a result of the continuous reinforcement of the blocking high-pressure system in the Ural Mountains, leading to the deepening of the cold vortex in front of it. Temperature changes associated with the movement of cold fronts produced additional mortality risks and mortality burdens. In general, the average excess risk (ER) of death during the cold spell in China was 2.75%, with a total cumulative excess of 369,056 deaths. The health risks associated with temperatures were unevenly distributed spatially in China, with the ER values ranging from a minimum of 0.14% to a maximum of 5.72%, and temperature drops disproportionately affect southern regions of China more than northern regions. The cumulative excess deaths exibited the highest in eastern and central China, with 87,655 and 80,230 respectively, and the lowest in northwest China with 27,474 deaths. Among the provinces, excess deaths pronounced the highest in Shandong with 29,492 and the lowest in Tibet with only 196. Conclusion: The study can provide some insight into the mortality burden of cold spells in China, while emphasising the importance of understanding the complex relationship between extreme low temperature events and human health. The outcomes could provide valuable revelations for informing pertinent public health policies.

SARS-CoV-2 infection as a potential risk factor for the development of cancer.

The COVID-19 pandemic has a significant impact on public health and the estimated number of excess deaths may be more than three times higher than documented in official statistics. Numerous studies have shown an increased risk of severe COVID-19 and death in patients with cancer. In addition, the role of SARS-CoV-2 as a potential risk factor for the development of cancer has been considered. Therefore, in this review, we summarise the available data on the potential effects of SARS-CoV-2 infection on oncogenesis, including but not limited to effects on host signal transduction pathways, immune surveillance, chronic inflammation, oxidative stress, cell cycle dysregulation, potential viral genome integration, epigenetic alterations and genetic mutations, oncolytic effects and reactivation of dormant cancer cells. We also investigated the potential long-term effects and impact of the antiviral therapy used in COVID-19 on cancer development and its progression.

Assessment of Excess Mortality in Italy in 2020-2021 as a Function of Selected Macro-Factors.

BACKGROUND: Excess mortality (EM) can reliably capture the impact of a pandemic, this study aims at assessing the numerous factors associated with EM during the COVID-19 pandemic in Italy. METHODS: Mortality records (ISTAT 2015-2021) aggregated in the 610 Italian Labour Market Areas (LMAs) were used to obtain the EM P-scores to associate EM with socioeconomic variables. A two-step analysis was implemented: (1) Functional representation of EM and clustering. (2) Distinct functional regression by cluster. RESULTS: The LMAs are divided into four clusters: 1 low EM; 2 moderate EM; 3 high EM; and 4 high EM-first wave. Low-Income showed a negative association with EM clusters 1 and 4. Population density and percentage of over 70 did not seem to affect EM significantly. Bed availability positively associates with EM during the first wave. The employment rate positively associates with EM during the first two waves, becoming negatively associated when the vaccination campaign began. CONCLUSIONS: The clustering shows diverse behaviours by geography and time, the impact of socioeconomic characteristics, and local governments and health services' responses. The LMAs allow to draw a clear picture of local characteristics associated with the spread of the virus. The employment rate trend confirmed that essential workers were at risk, especially during the first wave.

Effects of socioeconomic status on excess mortality in patients with multiple sclerosis in France: A retrospective observational cohort study.

Background: The effects of socio-economic status on mortality in patients with multiple sclerosis is not well known. The objective was to examine mortality due to multiple sclerosis according to socio-economic status. Methods: A retrospective observational cohort design was used with recruitment from 18 French multiple sclerosis expert centers participating in the Observatoire Français de la Sclérose en Plaques. All patients lived in metropolitan France and had a definite or probable diagnosis of multiple sclerosis according to either Poser or McDonald criteria with an onset of disease between 1960 and 2015. Initial phenotype was either relapsing-onset or primary progressive onset. Vital status was updated on January 1st 2016. Socio-economic status was measured by an ecological index, the European Deprivation Index and was attributed to each patient according to their home address. Excess death rates were studied according to socio-economic status using additive excess hazard models with multidimensional penalised splines. The initial hypothesis was a potential socio-economic gradient in excess mortality. Findings: A total of 34,169 multiple sclerosis patients were included (88% relapsing onset (n = 30,083), 12% progressive onset (n = 4086)), female/male sex ratio 2.7 for relapsing-onset and 1.3 for progressive-onset). Mean age at disease onset was 31.6 (SD = 9.8) for relapsing-onset and 42.7 (SD = 10.8) for progressive-onset. At the end of follow-up, 1849 patients had died (4.4% for relapsing-onset (n = 1311) and 13.2% for progressive-onset (n = 538)). A socio-economic gradient was found for relapsing-onset patients; more deprived patients had a greater excess death rate. At thirty years of disease duration and a year of onset of symptoms of 1980, survival probability difference (or deprivation gap) between less deprived relapsing-onset patients (EDI = -6) and more deprived relapsing-onset patients (EDI = 12) was 16.6% (95% confidence interval (CI) [10.3%-22.9%]) for men and 12.3% (95%CI [7.6%-17.0%]) for women. No clear socio-economic mortality gradient was found in progressive-onset patients. Interpretation: Socio-economic status was associated with mortality due to multiple sclerosis in relapsing-onset patients. Improvements in overall care of more socio-economically deprived patients with multiple sclerosis could help reduce these socio-economic inequalities in multiple sclerosis-related mortality. Funding: This study was funded by the ARSEP foundation "Fondation pour l'aide à la recherche sur la Sclérose en Plaques" (Grant Reference Number 1122). Data collection has been supported by a grant provided by the French State and handled by the "Agence Nationale de la Recherche," within the framework of the "Investments for the Future" programme, under the reference ANR-10-COHO-002, Observatoire Français de la Sclérose en Plaques (OFSEP).

Has a change in established care pathways during the first wave of the COVID-19 pandemic led to an excess death rate in the fragility fracture population? A longitudinal cohort study of 1846 patients.

OBJECTIVE: During the first wave of the COVID-19 pandemic, changes to established care pathways and discharge thresholds for patients with fragility fractures were made. This was to increase hospital bed capacity and minimise the inpatient risk of contracting COVID-19. This study aims to identify the excess death rate in this population during the first wave of the pandemic. DESIGN: A longitudinal cohort study of patients with fragility fractures identified by specific International Classification of Diseases (ICD)-10 codes. The first wave of the pandemic was defined as the 3-month period between 1 March and 1 June 2020. The control group presented between 1 March and 1 June 2019. SETTING: Two acute National Health Service hospitals within the East Midlands region of England. PARTICIPANTS: 1846 patients with fragility fractures over the aforementioned two specified matched time points. PRIMARY AND SECONDARY OUTCOME MEASURES: Four-month mortality of all patients with fragility fractures with a subanalysis of patients with fragility hip fractures. RESULTS: 832 patients with fragility fracture were admitted during the pandemic period (104 diagnosed with COVID-19). 1014 patients presented with fragility fractures in the control group. Mortality in patients with fragility fracture without COVID-19 was significantly higher among pandemic period admissions (14.7%) than the pre-pandemic cohort (10.2%) (HR=1.86; 95% CI 1.41 to 2.45; p<0.001) adjusted for age and sex. Length of stay was shorter during the pandemic period (effect size=-4.2 days; 95% CI -5.8 to -3.1, p<0.001). Subanalysis of patients with fragility hip fracture revealed a mortality of 8.4% in the pre-pandemic cohort, and 15.48% during pandemic admissions with no COVID-19 diagnosis (HR=2.08; 95% CI 1.11 to 3.90; p=0.021). CONCLUSIONS: There is a significant increase in excess death, not explained by confirmed COVID-19 infections. Altered care pathways and aggressive discharge criteria during the pandemic are likely responsible for the increase in excess deaths.

COVID-19 and drivers of excess death rate in Peru: A longitudinal ecological study.

Background: Peru has experienced unprecedented mortality and economic toll due to the COVID-19 (Coronavirus disease 2019) pandemic in 2020. We aimed to assess the association between socioeconomic factors and excess death rate, and to explore the relative contribution of these factors to the differences in excess death rate during January-December 2020. Methods: Different national secondary data sources were used to describe excess death rates and different determinants, from distal to proximal. A confounding-adjusted multilevel mixed-effects linear regression was used to assess the association between these variables and excess death rates. Their relative contributions to the differences in excess death rate between the periods with the highest and lowest excess death rates were analyzed through regression-based Oaxaca-Blinder decomposition methods. Findings: The excess death rate showed an increasing trend in all regions, with different slopes. The confounding-adjusted multilevel analysis showed that higher healthcare access was associated with lower excess death rates (difference (95%CI) -0.004 (-0.005, -0.002)), whereas COVID-19 incidence was associated with higher excess death rates (difference (95%CI) 0.052 (0.042, 0.063)). The decomposition analysis showed COVID-19 incidence (41.9%), per capita income (19.4%) and unemployment rate (14.6%) as the main risk factors, while the main protective factors included per capita health expenditure (44.7%), healthcare access (33.2%) and health insurance (12.1%). Interpretation: Our study suggests that the excess death rate during the COVID-19 pandemic in Peru may have been influenced by other factors besides COVID-19 incidence, from distal to proximal drivers, including socioeconomic determinants, factors outside and within the health sector, and susceptibility factors. Further studies at individual level are needed to corroborate our findings.