Mortality Incidence Rate Ratios Research Articles

Impaired survival of patients with non donor-specific anti-HLA antibodies before HLA-mismatched allogeneic stem cell transplantation

BackgroundWhile the detrimental role of donor-specific anti-HLA antibodies (DSAs) is well-described in the setting of hematopoietic stem cell transplantation (HSCT), few studies focus on non donor-specific ones and with controversial results. MethodsWe here report our monocenter experience on 64 adult patients receiving allogeneic HSCT from a HLA-mismatched donor between 2014 and 2022 who were tested for the presence of anti-HLA antibodies before transplant, focusing on fifteen patients with non donor-specific anti-HLA antibodies. ResultsThe survival of patients with non donor-specific anti-HLA antibodies was inferior with respect to patients without anti-HLA antibodies and similar to patients with DSAs. Median survival of patients with non donor-specific anti-HLA antibodies was 21 months (95 % CI: 9–42) vs. 61 months (95 % CI: 17–77) among the anti-HLA antibody-negative patients, with a significantly higher mortality incidence rate ratio (3.3 times-fold greater, p = 0.01). No pattern of death causes was found ConclusionsIn this monocenter series of HLA-mismatched HSCTs, impaired survival was observed in adult patients having non donor-specific anti-HLA antibodies before transplant, similar to those with DSAs. Our findings support those antibodies as a negative predictive factor even if they are not directed against the donor, thus warranting further investigation on larger cohorts.

Cancer Care Gap: Examining Cancer Mortality-Incidence Rate Ratio in Sub-Saharan Africa

PURPOSE The 2022 global burden of cancer estimate released by the International Agency for Research on Cancer (IARC) showed a huge burden of 20million new cancer cases and 9.7 million cancer deaths, a threat to the achievement of the 2030 Sustainable Development Goals target on Non-Communicable Diseases (NCDs). Africa accounts for only 5.9% of new global cases and 7.8% of cancer mortalities; however, these figures belie the enormous premature death that has made cancer a death sentence in Africa. A five-year survival rate measures cancer survival. However, due to the scarcity of follow-up data in Africa, the Mortality-Incidence Rate Ratio (MIR) which has an inverse relationship with survival has become a useful substitute for making comparisons on a global scale. The study's purpose is to compare the cancer MIR in Africa with other continents and disaggregate MIR in Sub-Saharan Africa across gender and major cancer sites. METHODS Data on Age Standardized Incidence Rate (World)-ASIR and Age Standardized Mortality Rate (World)-ASMR for six continents and the top five cancer sites in Africa (Breast, Prostrate, Cervix, Liver, and Colorectal) were extracted from the IARC Global Cancer Observatory (Cancer Today). MIR (calculated as the ratio of ASIR/ASMR) comparisons were done using Microsoft Excel 2021. RESULTS The average global cancer MIR is0.47. Africa has an estimated MIR of 0.67, which is more than double those of North America (0.23) and Oceania (0.23), and far above those of Europe (0.38), Latin America and the Caribbean (0.46). The high figure of Asia, 0.54, is well below the African Cancer MIR. Among the top five cancer sites in Sub-Sahara Africa, the liver has the highest MIR (0.95 compared to global MIR of 0.86) followed by the cervix (0.75 compared to global MIR of 0.50), Colorectal (0.73 compared to global MIR 0.44), prostrate (0.60 compare global MIR 0.38) and Breast (0.52 compare global MIR0.25). Disaggregated by gender, cancer MIR is higher in Sub-Saharan Africa for both sexes above the global average (Male 0.72 compared global MIR0.52; Female 0.67 compared global MIR 0.41). CONCLUSION The Mortality-Incidence rate ratio in Sub-Sahara Africa is alarmingly high compared to the global figure, reflecting a huge disparity in cancer care outcomes. A concerted effort to bridge the care gap in Sub-Sahara Africa is required to achieve the SDGs' NCD target, which aims to reduce premature death by a third.

Association of latent class analysis-derived multimorbidity clusters with adverse health outcomes in patients with multiple long-term conditions: comparative results across three UK cohorts

It remains unclear how to meaningfully classify people living with multimorbidity (multiple long-term conditions (MLTCs)), beyond counting the number of conditions. This paper aims to identify clusters of MLTCs in different age groups and associated risks of adverse health outcomes and service use. Latent class analysis was used to identify MLTCs clusters in different age groups in three cohorts: Secure Anonymised Information Linkage Databank (SAIL) (n=1,825,289), UK Biobank (n=502,363), and the UK Household Longitudinal Study (UKHLS) (n=49,186). Incidence rate ratios (IRR) for MLTC clusters were computed for: all-cause mortality, hospitalisations, and general practice (GP) use over 10 years, using <2 MLTCs as reference. Information on health outcomes and service use were extracted for a ten year follow up period (between 01st Jan 2010 and 31st Dec 2019 for UK Biobank and UKHLS, and between 01st Jan 2011 and 31st Dec 2020 for SAIL). Clustering MLTCs produced largely similar results across different age groups and cohorts. MLTC clusters had distinct associations with health outcomes and service use after accounting for LTC counts, in fully adjusted models. The largest associations with mortality, hospitalisations and GP use in SAIL were observed for the "Pain+" cluster in the age-group 18-36 years (mortality IRR=4.47, hospitalisation IRR=1.84; GP use IRR=2.87) and the "Hypertension, Diabetes & Heart disease" cluster in the age-group 37-54 years (mortality IRR=4.52, hospitalisation IRR=1.53, GP use IRR=2.36). In UK Biobank, the "Cancer, Thyroid disease & Rheumatoid arthritis" cluster in the age group 37-54 years had the largest association with mortality (IRR=2.47). Cardiometabolic clusters across all age groups, pain/mental health clusters in younger groups, and cancer and pulmonary related clusters in older age groups had higher risk for all outcomes. In UKHLS, MLTC clusters were not significantly associated with higher risk of adverse outcomes, except for the hospitalisation in the age-group 18-36 years. Personalising care around MLTC clusters that have higher risk of adverse outcomes may have important implications for practice (in relation to secondary prevention), policy (with allocation of health care resources), and research (intervention development and targeting), for people living with MLTCs. This study was funded by the National Institute for Health and Care Research (NIHR; Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (multimorbidity)-NIHR202020).

A novel approach for pharmacological substantiation of safety signals using plasma concentrations of medication and administrative/healthcare databases: A case study using Danish registries for an FDA warning on lamotrigine

PHARMACOM-EPI is a novel framework to predict plasma concentrations of drugs at the time of occurrence of clinical outcomes. In early 2021, the U.S. Food and Drug Administration (FDA) issued a warning on the antiseizure drug lamotrigine claiming that it has the potential to increase the risk of arrhythmias and related sudden cardiac death due to a pharmacological sodium channel-blocking effect. We hypothesized that the risk of arrhythmias and related death is due to toxicity. We used the PHARMACOM-EPI framework to investigate the relationship between lamotrigine’s plasma concentrations and the risk of death in older patients using real-world data. Danish nationwide administrative and healthcare registers were used as data sources and individuals aged 65 years or older during the period 1996 – 2018 were included in the study. According to the PHARMACOM-EPI framework, plasma concentrations of lamotrigine were predicted at the time of death and patients were categorized into non-toxic and toxic groups based on the therapeutic range of lamotrigine (3–15 mg/L). Over 1 year of treatment, the incidence rate ratio (IRR) of all-cause mortality was calculated between the propensities score matched toxic and non-toxic groups. In total, 7286 individuals were diagnosed with epilepsy and were exposed to lamotrigine, 432 of which had at least one plasma concentration measurement The pharmacometric model by Chavez et al. was used to predict lamotrigine’s plasma concentrations considering the lowest absolute percentage error among identified models (14.25 %, 95 % CI: 11.68–16.23). The majority of lamotrigine associated deaths were cardiovascular-related and occurred among individuals with plasma concentrations in the toxic range. The IRR of mortality between the toxic group and non-toxic group was 3.37 [95 % CI: 1.44–8.32] and the cumulative incidence of all-cause mortality exponentially increased in the toxic range. Application of our novel framework PHARMACOM-EPI provided strong evidence to support our hypothesis that the increased risk of all-cause and cardiovascular death was associated with a toxic plasma concentration level of lamotrigine among older lamotrigine users.

Estimating Associations Between Annual Concentrations of Particulate Matter and Mortality in the United States, Using Data Linkage and Bayesian Maximum Entropy.

Exposure to fine particulate matter (PM2.5) is an established risk factor for human mortality. However, previous US studies have been limited to select cities or regions or to population subsets (e.g., older adults). Here, we demonstrate how to use the novel geostatistical method Bayesian maximum entropy to obtain estimates of PM2.5 concentrations in all contiguous US counties, 2000-2016. We then demonstrate how one could use these estimates in a traditional epidemiologic analysis examining the association between PM2.5 and rates of all-cause, cardiovascular, respiratory, and (as a negative control outcome) accidental mortality. We estimated that, for a 1 log(μg/m3) increase in PM2.5 concentration, the conditional all-cause mortality incidence rate ratio (IRR) was 1.029 (95% confidence interval [CI]: 1.006, 1.053). This implies that the rate of all-cause mortality at 10 µg/m3 would be 1.020 times the rate at 5 µg/m3. IRRs were larger for cardiovascular mortality than for all-cause mortality in all gender and race-ethnicity groups. We observed larger IRRs for all-cause, nonaccidental, and respiratory mortality in Black non-Hispanic Americans than White non-Hispanic Americans. However, our negative control analysis indicated the possibility for unmeasured confounding. We used a novel method that allowed us to estimate PM2.5 concentrations in all contiguous US counties and obtained estimates of the association between PM2.5 and mortality comparable to previous studies. Our analysis provides one example of how Bayesian maximum entropy could be used in epidemiologic analyses; future work could explore other ways to use this approach to inform important public health questions.

Community predictors of COVID-19 cases and deaths in Massachusetts: Evaluating changes over time using geospatially refined data.

BackgroundThe COVID‐19 pandemic has highlighted the need for targeted local interventions given substantial heterogeneity within cities and counties. Publicly available case data are typically aggregated to the city or county level to protect patient privacy, but more granular data are necessary to identify and act upon community‐level risk factors that can change over time.MethodsIndividual COVID‐19 case and mortality data from Massachusetts were geocoded to residential addresses and aggregated into two time periods: “Phase 1” (March–June 2020) and “Phase 2” (September 2020 to February 2021). Institutional cases associated with long‐term care facilities, prisons, or homeless shelters were identified using address data and modeled separately. Census tract sociodemographic and occupational predictors were drawn from the 2015–2019 American Community Survey. We used mixed‐effects negative binomial regression to estimate incidence rate ratios (IRRs), accounting for town‐level spatial autocorrelation.ResultsCase incidence was elevated in census tracts with higher proportions of Black and Latinx residents, with larger associations in Phase 1 than Phase 2. Case incidence associated with proportion of essential workers was similarly elevated in both Phases. Mortality IRRs had differing patterns from case IRRs, decreasing less substantially between Phases for Black and Latinx populations and increasing between Phases for proportion of essential workers. Mortality models excluding institutional cases yielded stronger associations for age, race/ethnicity, and essential worker status.ConclusionsGeocoded home address data can allow for nuanced analyses of community disease patterns, identification of high‐risk subgroups, and exclusion of institutional cases to comprehensively reflect community risk.

Association between the Leukemia Mortality-to-Incidence Ratio and State Geographic Healthcare Disparities in the United States

INTRODUCTION: Leukemia is the seventh leading cause of cancer death in the United States (US) in 2021. The Mortality Incidence Rate Ratio, also known as Mortality-to-Incidence Ratio (MIR), is calculated by dividing the mortality rate by the incidence rate for selected cancers and population. The MIR provides a population-based indicator of cancer survival which has previously been used to assess healthcare disparities among different countries. Here weevaluated the potential association between leukemia MIR and state-based health disparities in the US.METHODS: Leukemia (AML, CML, ALL, CLL and other leukemias) MIRs for 2008-2017 were obtained from United States Cancer Statistics (USCS) database provided by the Centers for Disease Control and Prevention (CDC). America's Health Rankings (AHR), a partnership of the United Health Foundation and the American Public Health Association, evaluates the nation's health on a state-by-state basis by using weighted measures in 5 different categories (25% for Behaviors, 22.5% for Community & Environment, 12.5% for Policy, 15% for Clinical Care, and 25% for Outcomes). AHR then determines state health rankings and reflects state health disparities based on these specific factors. Here we analyzed the potential association between leukemia MIRs and state health rankings by linear regression.RESULTS: From 2008 to 2017, a total of 489,037 people were diagnosed with leukemia and 231,069 people died from leukemia in the US. The 10-year average of age-adjusted incidence rate and mortality rate were 14.2 and 6.7 per 100,000 population respectively. The average MIR between all states was calculated to be 0.470. As seen in Table 1, the lowest MIR (best survival) was found in Florida (0.374), New York (0.391), and New Jersey (0.412) with AHR 34, 19 and 11 respectively. The highest MIR (worst survival) was found in Mississippi (0.579), Wyoming (0.570), and Ohio (0.569) with AHR 50, 24 and 37 respectively. According to AHR, over the last decade, the states with the highest health rankings were reported in Vermont (No. 1), Hawaii (No. 2), and Massachusetts (No. 3) with MIR 0.508, 0.439 and 0.502 respectively. The states with the lowest health rankings were reported in Arkansas (No. 48), Louisiana (No. 49), and Mississippi (No. 50) with MIR 0.559, 0.503 and 0.579 respectively. In our analysis, states with better health rankings were significantly associated with lower MIRs (R 2=0.232, P<0.001), as seen in Figure 1.CONCLUSIONS: There is a remarkable geographic difference in leukemia MIRs in the US between 2008-2017. Leukemia MIR was significantly associated with state health rankings reported by the AHR. Although the quality of clinical care for leukemia patients remains to be an important predictor of mortality, our findings suggest that other aggregate determinants of health, including social, economic, and community and physical environment may also play a vital role in influencing leukemia survival. More in-depth analysis of these data focusing on specific leukemia subtypes as well as other factors (race, gender, age) may be helpful in identifying and addressing other non-medical issues negativity impacting on leukemia outcomes in different geographical regions in the United States. [Display omitted] DisclosuresWang: Kura Oncology: Consultancy, Honoraria, Other: Advisory board, steering committee, Speakers Bureau; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Stemline Therapeutics: Consultancy, Honoraria, Other: Advisory board, Speakers Bureau; Kite Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board; Takeda: Consultancy, Honoraria, Other: Advisory board; Pfizer: Consultancy, Honoraria, Other: Advisory Board, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: Advisory Board; Mana Therapeutics: Consultancy, Honoraria; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Honoraria, Other: Advisory Board; Jazz Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board; DAVA Oncology: Consultancy, Speakers Bureau; Rafael Pharmaceuticals: Other: Data safety monitoring committee; Gilead: Consultancy, Honoraria, Other: Advisory board; Daiichi Sankyo: Consultancy, Honoraria, Other: Advisory board; PTC Therapeutics: Consultancy, Honoraria, Other: Advisory board; Genentech: Consultancy; MacroGenics: Consultancy.

Characteristics and outcomes following motorized and non-motorized vehicular trauma in a resource-limited setting

IntroductionDespite the ubiquity of motorized vehicular transport, non-motorized transportation continues to be common in sub-Saharan Africa. MethodsWe performed a retrospective analysis of trauma patients presenting to Kamuzu Central Hospital in Malawi from February 2008 to May 2018. Demographic and clinical variables including injury characteristics and outcomes were collected. We performed bivariate and multivariate logistic regression to determine predictors of mortality following non-motorized vehicular trauma. ResultsThis study included 36,412 patients involved in vehicular road injuries. Patients in the non-motorized group had a preponderance of men (84% versus 73%, p<0.01). The proportion of patients with Glasgow Coma Scale > 8 was slightly higher in the non-motorized group (99% versus 98%, p<0.01), though injury severity did not differ significantly between the two groups. A higher proportion in the motorized group had the most severe injury of contusions and abrasions (56% versus 50%, p<0.01). In contrast, the non-motorized group had a higher proportion of orthopedic injuries (24% versus 16%, p<0.01). The crude mortality rate was 4.51% and 2.15% in the motorized and non-motorized groups, respectively. After controlling for demographic factors and injury severity, the incidence rate ratio of mortality did not differ significantly between motorized and non-motorized trauma groups (IRR 0.91, p=0.35). ConclusionsNon-motorized vehicular trauma remains a significant proportion of morbidity and mortality resulting from road traffic injuries. The injury severity and incidence rate ratio of mortality did not differ between motorized and non-motorized trauma groups. Health care providers should not underestimate the severity of injuries from non-motorized trauma.

A cross-sectional study of associations between herd-level calf mortality rates, compliance with legislation on calf welfare, and milk feeding management in Norwegian dairy herds

Our aim was to investigate the associations between management factors, compliance with current legislation, and herd-level calf mortality. In a national calf welfare audit, veterinary inspectors from the Norwegian Food Safety Authority assessed compliance with current legislation on calf welfare (n = 912 herds). Nine criteria were assessed and rated as satisfactory (1) or not satisfactory (0): housing, natural behavior, single pens, colostrum feeding, feeding, water, surveillance, illness/injuries, and <5% mortality rate. In addition, a short questionnaire on milk feeding management for 3-wk-old calves was distributed to all national calf welfare audit herds, and data on mortality and disease recordings were obtained from the Norwegian Dairy Herd Recording System (NDHRS). A herd welfare compliance score (WCS) for each farm was constructed, summarizing the results for the individual criteria. Most herds had a high WCS (median 9.0, range 2-9). Fifty-six percent of the national calf welfare audit herds (508/912) responded to the questionnaire. We performed a cross-sectional study using a data set from 431 herds with available data on recorded disease and mortality events from the NDHRS, recordings from the national calf welfare audit, and the questionnaire. A mixed-effects negative binomial model with Norwegian Food Safety Authority district as the random effect was fitted to the data. Of the 416 herds with available data on calf mortality, 108 (25.9%) reported no mortality in 2016, and the median 6-mo mortality rate was 0.064 (interquartile range 0-0.11) dead calves per 6 calf-months at risk, based on NDHRS recordings. Calf mortality rates were higher in herds whose calves did not have free access to water (incidence rate ratio 1.29; 95% confidence interval 1.02-1.64) and higher in herds that had reported calf disease events (incidence rate ratio 1.31; 95% confidence interval 1.09-1.54). Neither the WCS nor any of the calf milk feeding management factors were associated with mortality, but more than half of producers (59.6%) fed less milk than currently recommended for 3-wk-old calves (8 L/d first 3 to 4 wk). These results indicate that a lack of access to water was associated with higher calf mortality rates. Herds with registered calf disease events had a higher incidence rate ratio of mortality. This finding may be linked to suboptimal calf management, leading to more calf diseases and mortality; or it may be that veterinary consultancy occurs too late or only for the worst cases. There is room for improvement in Norwegian dairy calf management, and water should be provided to young calves.

Randomized Controlled Trial of Fixed Low-Vs Moderate-Dose Hydroxyurea for Primary Stroke Prevention in Sub-Saharan Africa: Final Results of the Spring Trial

Introduction: In children with sickle cell anemia (SCA) without transcranial Doppler (TCD) screening, the incidence rates of ischemic strokes is approximately the same among children living in low- and high- low-resource settings (Pediatr Neurol. 2019;95:73-78.) with a prevalence of ~ 11%. However, in high-income settings, the standard use of TCD ultrasonography, coupled initially with monthly blood transfusion therapy has dropped the stroke prevalence to &amp;lt; 1%. In a low-income setting, such as Nigeria, where 50% of children in the world with SCA are born (150,000 per year), initial monthly blood transfusion therapy is not practical for most children. In the Stroke Prevention in Nigeria (SPIN) Feasibility Trial (NCT01801423), fixed moderate-dose hydroxyurea was associated with a decreased rate of strokes in children with SCA and abnormal time-averaged mean of the maximum velocity (TAMMV) TCD measurements (≥200cm/sec) when compared to no treatment in the STOP Trial, 0.76 and 10.7 strokes per 100 person-years, repsectively (Am J Hematol. 2020). Based on the success of the SPIN trial, plus the challenges of real-world implementation of a government-supported primary stroke prevention programs for estimated 40,0000 children with SCA in three states in Nigeria, we tested the hypothesis that fixed-moderate dose (~20 mg/kg/day) hydroxyurea therapy for primary stroke prevention results in a 66% relative risk reduction (9 to 3 events per 100 person-years) when compared to fixed low-dose hydroxyurea (~10 mg/kg/day) therapy in a randomized controlled trial (The SPRING Trial; NCT02560935). Methods: In this partial-blind controlled phase III trial, we randomly assigned children between 5 and 12 years of age with SCA and a TCD time-averaged mean of the maximum velocity (TAMMV) ≥ 200 cm/sec measured independently twice or TAMMV ≥220 cm/sec once at study screening to receive fixed low-dose or fixed moderate-dose hydroxyurea. The primary endpoint was a clinical stroke or a transient ischemic attack (TIA). Myelosuppression was assessed with monthly complete blood counts (CBCs). Adherence to hydroxyurea was primarily based on an increase in MCV from baseline and monthly pill count return as a percent of dispensed pills. Hemoglobin F levels were measured at baseline, annually and upon trial exit. To evaluate the safety of hydroxyurea in the trial, children attending the same SCA clinics with TCD (TAMMV) &amp;lt;200 cm/sec at study screening were prospectively followed with biweekly phone calls and annual research visits. Results: A total of 220 children (mean age: 7.5 years, 51.8% female) were randomly assigned to fixed low- (10 mg/kg/day) or moderate- (20 mg/kg/day) dose hydroxyurea, and were followed for a median of 2.4 years (IQR 2.0-2.8). NINDS Clinical Trials leaders stopped the trial early because of futility for the primary outcome. In the fixed low- and moderate-dose hydroxyurea groups, the incidence rates of strokes per 100 person-years were 1.19 and 1.92 respectively, with an incidence rate ratio of 1.60 (95% CI: 0.31-10.34), p = 0.768. The incidence rate ratio of mortality when comparing the children treated with low- and moderate- fixed-dose hydroxyurea to the non-elevated TCD group (no hydroxyurea therapy, n= 211) was 1.97 (95% CI: 0.64-6.02) and 0.47 (95% CI: 0.05-2.38), p = 0.265 and 0.545, respectively. Returned pills during the trial was 5.4% and 4.8% in the fixed low- and moderate-dose groups, respectively, p= 0.144. MCV from baseline to endpoint increased 1.5fl and 7.2 fl in the fixed low- and moderate-dose groups, respectively, p&amp;lt;0.001. Upon exit from the trial 29.4% and 66.7% of the fixed- low and moderate -dose groups, respectively, had either hemoglobin level ≥ 9.0 g/dl, or a fetal hemoglobin level ≥ 20%. Conclusions: For primary stroke prevention in children with SCA, fixed low-dose, when compared to fixed moderate-dose hydroxyurea therapy, demonstrated no difference in the incidence rate of strokes. Both fixed low- and moderate -dose hydroxyurea doses are superior to no treatment for primary stroke prevention with abnormal TCD values. In partnership with Katsina, Kano, and Kaduna health department's leaders in Nigeria, 9 distinct SCA and primary stroke prevention clinics have been established, with the provision of free fixed low-dose hydroxyurea therapy (Bond Chemical, Nigeria; $0.15 per 500 mg) for abnormal TCD values, and biannual CBCs as standard care ,for over 40,000 children with SCA. Disclosures DeBaun: Global Blood Therapeutics (GBT): Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: fixed low and moderate dose hydroxyurea for primary stroke prevention in sickle cell

Risk Factors Associated With Mortality Among Residents With Coronavirus Disease 2019 (COVID-19) in Long-term Care Facilities in Ontario, Canada

The coronavirus disease 2019 (COVID-19) pandemic has been particularly severe among individuals residing in long-term care (LTC) facilities. As of April 10, 2020, half of Canada's COVID-19 deaths had occurred in LTC facilities. To better understand trends and risk factors associated with COVID-19 death in LTC facilities in Ontario, Canada. This cohort study of 627 LTC facilities included 269 total individuals who died of COVID-19 in Ontario to April 11, 2020, and 83 individuals who died of COVID-19 in Ontario LTC facilities to April 7, 2020. Because population denominators were not available for LTC residents, they were approximated as the total number of LTC facility beds in Ontario (79 498), assuming complete occupancy. Confirmed or suspected COVID-19 outbreaks; confirmed COVID-19 infection among residents and staff, diagnosed by real-time polymerase chain reaction testing. COVID-19-specific mortality incidence rate ratios (IRRs) for LTC residents were calculated with community-living Ontarians older than 69 years as the comparator group. Count-based regression methods were used to model temporal trends and to identify associations of infection risk among staff and residents with subsequent LTC resident death. Model-derived IRRs for COVID-19-specific mortality were generated through bootstrap resampling (1000 replicates) to generate median and 95% credible intervals for IRR over time. Of 627 LTC facilities, 272 (43.4%) reported COVID-19 infection in residents or staff. Of 1 731 315 total individuals older than 69 years living in Ontario during the study period, 229 (<0.1%) died; of 79 498 potential residents in LTC facilities, 83 (0.1%) died. The IRR for COVID-19-related death in LTC residents was 13.1 (95% CI, 9.9-17.3) compared with community-living adults older than 69 years. The IRR increased sharply over time and was 87.3 (95% credible interval, 6.4-769.8) by April 11, 2020. Infection among LTC staff was associated with death among residents with a 6-day lag (eg, adjusted IRR for death per infected staff member, 1.17; 95% CI, 1.11-1.26). In this cohort study of COVID-19-related deaths during the pandemic in Ontario, Canada, mortality risk was concentrated in LTC residents and increased during a short period. Early identification of risk requires a focus on testing, providing personal protective equipment to staff, and restructuring the LTC workforce to prevent the movement of COVID-19 between facilities.

Impact of the dialysate acid component on haemodialysis mortality rates.

No prospective study has evaluated the long-term effect on mortality of the new acid concentrates added to bicarbonate dialysate. The aim of this pharmacoepidemiological study was to evaluate the association between hydrochloric or citric acid-based dialysate and mortality on haemodialysis (HD). This study included 117 796 patients with 3 723 887 months on HD recorded in the national French Renal Epidemiology and Information Network registry. Dialysate acid components were retrospectively reconstructed for each facility. All patients on HD were associated each month with an exposure based on that at their facility of treatment. We took each patient's time-varying exposure into account to calculate the monthly mortality rates for each exposure. Incidence rate ratios (IRRs) for mortality were calculated with a Poisson regression, with acetic acid as the reference. Regressions were adjusted for initial clinical characteristics (age, gender, previous cardiovascular events, active malignancy, diabetes, pulmonary disease, mobility), dialysis technique and location (in-centre, outpatient centre, self-care unit) and ESRD vintage, updated monthly. The crude mortality rate per 1000 patient-months with citric acid {11.5 [95% confidence interval (CI) 11.1-12.0]} was lower than with either acetic acid [12.9 (95% CI 12.8-13.1)] or hydrochloric acid [12.8 (95% CI 12.2-13.5)]. For the 2014-17 period, the IRR for mortality with citric acid [adjusted IRR 0.94 (95% CI 0.90-0.99)] and with hydrochloric acid [adjusted IRR 0.86 (95% CI 0.79-0.94)] were significantly lower than with acetic acid. This post-marketing study of long-term exposure to dialysate acidifiers at the patient level found the use of citric and hydrochloric acid-based dialysates, compared with acetic acid, was associated with lower mortality.

The Relationship Between Air Pollution and All-Cause Mortality in Singapore

Ambient air pollution is a risk factor for both acute and chronic diseases and poses serious health threats to the world population. We aim to study the relationship between air pollution and all-cause mortality in the context of a city-state exposed to the Southeast Asian haze problem. The primary exposure was ambient air pollution, as measured by the Pollutants Standards Index (PSI). The outcome of interest was all-cause mortality from 2010–2015. A time-stratified case-crossover design was performed. A conditional Poisson regression model, including environmental variables such as PSI, temperature, wind speed, and rainfall, was fitted to the daily count of deaths to estimate the incidence rate ratio (IRR) of mortality per unit increase in PSI, accounting for overdispersion and autocorrelation. To account for intermediate exposure effects (maximum lag of 10 days), a distributed lag non-linear model was used. There were 105,504 deaths during the study period. Increment in PSI was significantly associated with an increased risk of mortality. The adjusted IRR of mortality per the 10-unit increase in PSI was 1.01 (95%CI = 1.00–1.01). The lag effect was stronger when PSI was in the unhealthy range compared to the good and moderate ranges. At lag = 7 days, PSI appeared to have an adverse effect on mortality, although the effect was not significant. These findings provide evidence on the general health hazard of exposure to air pollution and can potentially guide public health policies in the region.

Patient consultation rate and clinical and NHS outcomes: a cross-sectional analysis of English primary care data from 2.7 million patients in 238 practices

BackgroundPrimary care workload is high and increasing in the United Kingdom. We sought to examine the association between rates of primary care consultation and outcomes in England.MethodsCross sectional observational study of routine electronic health care records in 283 practices from the Clinical Practice Research Datalink from April 2013 to March 2014. Outcomes included mortality rate, hospital admission rate, Quality and Outcomes Framework (QOF) performance and patient satisfaction. Relationships between consultation rates (with a general practitioner (GP) or nurse) and outcomes were investigated using negative binomial and ordinal logistic regression models.ResultsRates of GP and nurse consultation (per patient person-year) were not associated with mortality or hospital admission rates: mortality incidence rate ratio (IRR) per unit change in GP/ nurse consultation rate = 1.01, 95% CI [0.98 to 1.04]/ 0.97, 95% CI [0.93 to 1.02]; hospital admission IRR per unit change in GP/ nurse consultation rate = 1.02, 95% CI [0.99 to 1.04]/ 0.98, 95% CI [0.94 to 1.032]. Higher rates of nurse but not GP consultation were associated with higher QOF achievement: OR = 1.91, 95% CI [1.39 to 2.62] per unit change in nurse consultation rate vs. OR = 1.04, 95% CI [0.87 to 1.24] per unit change in GP consultation rate. The association between the rates of GP/ nurse consultations and patient satisfaction was mixed.ConclusionThere are few associations between primary care consultation rates and outcomes. Previously identified demographic and staffing factors, rather than practice workload, appear to have the strongest relationships with mortality, admissions, performance and satisfaction. Studies with more detailed patient-level data would be required to explore these findings further.

Does ethnic diversity explain intra-UK variation in mortality? A longitudinal cohort study

ObjectivesIt has been proposed that part of the explanation for higher mortality in Scotland compared with England and Wales, and Glasgow compared with other UK cities, relates to greater ethnic...

Risk of stroke and transient ischaemic attack in patients with a diagnosis of resolved atrial fibrillation: retrospective cohort studies

ObjectivesTo determine rates of stroke or transient ischaemic attack (TIA) and all cause mortality in patients with a diagnosis of “resolved” atrial fibrillation compared to patients with unresolved atrial fibrillation...

Comorbidity, disability, and healthcare expenditure of ankylosing spondylitis in Korea: A population-based study.

BackgroundAnkylosing spondylitis (AS) is an inflammatory rheumatic disease typically diagnosed in young age and follows a chronic progressive course. Its impact on the patient is life-long and the burden that AS exerts on society is increasing cumulatively every year. We aimed to quantify the burden of AS and to identify the factors associated with comorbidity, disability, and healthcare expenditure in Korean AS patients.MethodsWe conducted a nationwide, population-based study using health insurance data (2003–2013). The analysis included individuals with incident AS (1,111 patients) and controls (5,555 patients) matched by age, sex, income, and geographic region. The incidence rates of extra-articular manifestations (EAMs), comorbidities, mortality, and disability (type and severity) were compared between AS patients and controls. Annual health expenditure per patient was also analyzed. Associations were expressed as odds ratios (ORs) with 95% confidence intervals (95%CIs).ResultsDuring the follow-up, 28% of AS patients experienced at least one EAM. AS diagnosis was significantly associated with Charlson comorbidity index ≥3 (OR 2.18, 95% CI 1.91–2.48). Disability rate was higher in AS patients than in controls regardless of cause and severity (OR 2.94, 95% CI 2.48–3.48), but crude incidence rate ratios for mortality were not significantly higher. On multivariate analysis, male sex (OR 3.18, 95% CI 2.13–4.75), presence of an EAM (OR 1.63, 95% CI 1.15–2.32), and older age at diagnosis (OR 1.27, 95% CI 1.20–1.35) were evidently associated with increased disability in AS. Presence of an EAM was also associated with increased AS-unrelated expenditures in biologic-naïve patients (median, 1112 vs. 877 USD per person, P < 0.05).ConclusionsIn patients with AS, demographic factors and systemic manifestations including EAMs and other comorbidities were associated with increased disability and healthcare expenditures.

Abstract WP193: Non-fatal Stroke and All-cause Mortality Among Community-dwelling Older Adults Living in Rural Ecuador. A Population-based, Prospective Cohort Study

Background: Stroke burden is a leading cause of disability on developing countries. However, there are no studies assessing the impact of previous non-fatal strokes on all-cause mortality in rural areas of Latin America, where living conditions and health care access are different than in urban centers. Using a population-based prospective cohort study (The Atahualpa Project), we aimed to assess the influence of non-fatal stroke on all-cause mortality in community-dwelling older adults living in a remote rural setting. Methods: Individuals aged ≥60 years with a non-fatal stroke were detected during yearly door-to-door surveys by the use of validated questionnaires and corroborated by a certified neurologist. Deaths occurring during the follow-up were identified from annual surveys, death certificates review, and other overlapping sources. Univariate tests for equality of survivor functions were used to estimate differences between observed and expected deaths for the presence of a non-fatal stroke. Survival analyses were conducted by the use of the mortality incidence rate ratio (IRR) and by Cox proportional hazard models with subsequent estimation of Kaplan Meier survival curves. Results: Of 437 individuals aged ≥60 years enrolled during a 5-year period, follow-up was achieved in 417 (95%), contributing 1,776 years of follow-up (average 4.3±1.3 years). Forty-five (10.8%) individuals were stroke survivors. Fifty-one deaths were detected, for an overall cumulative 5-year mortality rate of 12.2% (95% C.I.: 8.9 - 15.6). According to log-rank analysis, the ratio of observed versus expected deaths among stroke survivors was 14/5.12 (p=0.0001). Having history of a non-fatal stroke was significantly related to mortality (IRR: 3.38; 95% C.I.: 1.69 - 6.41; p=0.0005). A fully adjusted Cox proportional hazard model showed that non-fatal strokes independently predicted mortality (hazard ratio: 2.18, SE: 0.75; 95% C.I.: 1.11 - 4.28; p=0.024). Conclusions: This study shows the importance of a previous non-fatal stroke on the risk of all-cause mortality in inhabitants of a remote rural village. Epidemiological studies assessing the impact of region-specific factors influencing mortality may prove cost-effective for developing preventive strategies.

Can the New Global Lung Initiative Equations Better Stratify the Risk of Death in Elderly People with Chronic Obstructive Pulmonary Disease?

Background: The forced expiratory volume in the first second (FEV₁) is commonly expressed as percentage of its value predicted by equations. The most commonly used equations are poorly applicable to elderly people. Recently, a set of equations (Global Lung Initiative, GLI) has been released that is expected to be more appropriate in this population. Objectives: We evaluated the agreement of the GLI, European Respiratory Society (ERS), and National Health and Nutrition Examination Survey (NHANES) equations for prediction of FEV₁ and compared their discriminative capacity with respect to mortality, taking as reference the prediction equation developed in the population from which our sample was drawn (SARA). Methods: We studied 264 patients with chronic obstructive pulmonary disease aged ≥70 years. Agreement was evaluated using the Bland-Altman method, discriminative capacity using incidence rate ratios for mortality calculated across quartiles of each measure. Results: The mean age of the sample was 75.8 years (72.7% men). In women, the mean FEV1ERS/FEV1SARA, FEV1NHANES/ FEV1SARA, and FEV1GLI/FEV1SARA were 0.81, 0.91, and 0.966, respectively. The corresponding values in men were 0.959, 0.963, and 1.02, respectively. The overall discriminative capacity with respect to death was equally poor for all equations. Conclusion: The GLI equations for predicting FEV₁ provide similar estimates compared to an equation developed in a healthy subset of the population in which they are applied, and higher values compared to the ERS equation, especially in women. However, the use of the GLI equation does not improve the stratification of the risk of mortality in elderly people compared to ERS or NHANES equations.

Efficacy and Safety of Antiretroviral Therapy Initiated One Week after Tuberculosis Therapy in Patients with CD4 Counts < 200 Cells/μL: TB-HAART Study, a Randomized Clinical Trial.

BackgroundGiven the high death rate the first two months of tuberculosis (TB) therapy in HIV patients, it is critical defining the optimal time to initiate combination antiretroviral therapy (cART).MethodsA randomized, open-label, clinical trial comparing efficacy and safety of efavirenz-based cART initiated one week, four weeks, and eight weeks after TB therapy in patients with baseline CD4 count < 200 cells/μL was conducted. The primary endpoint was all-cause mortality rate at 48 weeks. The secondary endpoints were hepatotoxicity-requiring interruption of TB therapy, TB-associated immune reconstitution inflammatory syndrome, new AIDS defining illnesses, CD4 counts, HIV RNA levels, and AFB smear conversion rates. All analyses were intention-to-treat.ResultsWe studied 478 patients with median CD4 count of 73 cells/μL and 5.2 logs HIV RNA randomized to week one (n = 163), week four (n = 160), and week eight (n = 155). Sixty-four deaths (13.4%) occurred in 339.2 person-years. All-cause mortality rates at 48 weeks were 25 per 100 person-years in week one, 18 per 100 person-years in week four and 15 per 100 person-years in week eight (P = 0.2 by the log-rank test). All-cause mortality incidence rate ratios in subgroups with CD4 count below 50 cells/μL versus above were 2.8 in week one (95% CI 1.2–6.7), 3.1 in week four (95% CI 1.2–8.6) and 5.1 in week eight (95% CI 1.8–16). Serum albumin < 3gms/dL (adjusted HR, aHR = 2.3) and CD4 < 50 cells/μL (aHR = 2.7) were independent predictors of mortality. Compared with similar subgroups from weeks four and eight, first-line TB treatment interruption was high in week one deaths (P = 0.03) and in the CD4 subgroup <50 cells/μL (P = 0.02).ConclusionsAntiretroviral therapy one week after TB therapy doesn’t improve overall survival. Despite increased mortality with CD4 < 50 cells/μL, we recommend cART later than the first week of TB therapy to avoid serious hepatotoxicity and treatment interruption.Trial RegistrationClinicalTrials.gov NCT 01315301