Calendar Period Research Articles

Incidence and predictors of clinical failure after early treatment for mild-to-moderate COVID-19 in high-risk individuals: A multicentric cohort study.

To estimate the risk of COVID-19-related hospitalization and death (CovH/D), among high-risk individuals early treated for COVID-19 and to identify associated factors. A multicenter cohort of 12,475 high-risk outpatients (female 50.2%, median age 70 years [IQR 57-80], fully vaccinated 79.1%, immunocompromised 23.2%) treated with monoclonal antibodies or antivirals for mild-to-moderate COVID-19 (March 2021-May 2023) in the Lazio region, Italy. The unadjusted risk of CovH/D by Day 30 was 3.08% (95% CI 2.7%-3.4%). By means of logistic regression models, which included a specific set of potential confounders for each exposure of interest, we observed a higher risk for the elderly, unvaccinated and immunocompromised participants. Using the "Delta period" as a reference, a decreased risk was observed for Omicron waves. Despite the administration of COVID-19 early treatment and the decreasing risk of CovH/D across the calendar periods, the elderly, the unvaccinated and the immunocompromised people remain at high risk of clinical progression.

Outcomes with intensive treatment for acute myeloid leukemia: an analysis of two decades of data from the HARMONY Alliance.

Since 2017, targeted therapies combined with conventional intensive chemotherapy have started to improve outcome of patients with acute myeloid leukemia (AML). However, even before these innovations outcomes with intensive chemotherapy have improved, which has not yet been extensively studied. Thus, we used a large pan-European multicenter dataset of the HARMONY Alliance to evaluate treatment-time dependent outcomes over two decades. In 5359 AML patients, we compared the impact of intensive induction therapy on outcome over four consecutive 5-year calendar periods from 1997 to 2016. During that time, the 5- year survival of AML patients improved significantly, also across different genetic risk groups. In particular, the 60-day mortality rate has dropped from 13.0% to 4.7% over time. The independent effect of calendar periods on outcome was confirmed in multivariate models. Improvements were documented both for patients.

Patient characteristics and mortality trends among octogenarians with heart failure over two decades - a Danish nationwide study

Abstract Background Mortality rates among octogenarians with heart failure (HF) have changed little despite significant advancements in care over recent decades. Investigating the factors contributing to this trend may offer valuable insights for devising targeted management strategies for the oldest HF patients. Purpose We aimed to examine different patient characteristics associated with mortality among octogenarians with HF over the past 20 years. Methods From nationwide Danish healthcare registries, we included all patients with new-onset HF between 2001-2020 who were ≥ 80 years old at the time of diagnosis. The patients were categorized into 5-year calendar periods depending on the time of their diagnosis, the first period being between 2001-2005 and the last 2016-2020. The Kaplan-Meier estimator was used to assess the mortality risk. Mortality rates were examined with multivariable Cox regression models, comparing the first (reference) and the last calendar period and adjusting for predefined covariables. Results We included 47,754 octogenarian patients with new-onset HF, of whom 13,293 (51%) were diagnosed between 2001-2005 and 12,813 (49%) between 2016-2020. The distribution of males and females changed between the two calendar periods, with 5696 (43%) males in the first period and 6631 (52%) in the last period. The 3-year absolute mortality risk decreased by 8% [95% CI, 7.9-8.0] from 2001-2005 (64% [95% CI, 63.9-64.7]) to 2016-2020 (56% [95% CI, 55.3-56.7]) (p-value <0.001) (Figure 1). After adjustment for covariables, patients diagnosed in the last period exhibited a mortality hazard ratio (HR) of 0.94 [CI 95% 0.90-0.99] (p-value 0.02) compared to those diagnosed in the first period. An interaction was observed between the first and the last calendar periods among patients with a history of myocardial infarction and those aged <85 years. The survival rates improved over time for patients with a history of myocardial infarction (HR 0.80 [95% CI, 0.72-0.90], p-value for interaction<0.001), as well as for those aged between 80 and 85 years (HR 0.86 [95% CI, 0.80-0.91], p-value for interaction<0.001) (Figure 2). Conclusion Over two decades the mortality risk among octogenarians with HF has improved slightly, however it remains high. Patients with a history of myocardial infarction and those aged 80 to 85 years emerge as subgroups experiencing the most improved survival rates over time.3-year mortality riskMortality rates in selected subgroups

Temporal trends in mitral valve surgery in Denmark: changes in patient characteristics and outcomes from 1996 to 2021

Abstract Background Mitral valve regurgitation (MR) is associated with increased morbidity and mortality. Mitral valve surgery (MVS) is recommended in severe MR, which is the second most common cause of heart valve surgery in the Western world. Data on national practice patterns are lacking and are essential for the continuous epidemiologic surveillance of the disease. Purpose To investigate temporal trends in patient characteristics, incidence and mortality in patients undergoing MVS for MR in Denmark from 1996 to 2021. Methods Using Danish nationwide registries, we identified all patients ≥18 years undergoing MVS for MR. Patients operated due to infective endocarditis were excluded. The study population was grouped into one 6-year and four 5-year calendar bands and type of MVS (mitral valve repair, mechanical or biological valve replacement and transcatheter-edge-to-edge repair (TEER)). Temporal trends in patient characteristics were computed. Annual incidence rates were calculated while considering the total Danish population ≥18 years at risk. For one-year postoperative mortality analysis, the reverse Kaplan-Meier estimator and a multivariable Cox proportional hazard analysis were used. Results We identified 7,813 patients (median age 67.3 years, 65.6% males) undergoing MVS. Over calendar time, burden of comorbidities decreased while median age increased, Table 1. From 1996 to 2021, a stepwise increase was seen in the overall incidence rate for MVS from 3.87 [95% CI 3.32-4.51] to 7.06 [95% CI 6.34-7.58] per 100,000 person-years (p<0.001). The incidence of mechanical valve replacement statistically significantly decreased (p<0.001), while the incidence of mitral valve repair (p=0.004), biological replacement (p≤0.001) and TEER statistically increased (p=0.015), Figure 1. For the overall study period, one-year mortality was 5.0% for mitral valve repair, 12.7% for mechanical valve replacement, 15.7% for biological valve replacement and 19.0% for TEER. Demographics and one-year mortality stratified by calendar period are shown in Table 1. In the mitral valve repair group, adjusted analysis showed a stepwise statistically significant decrease in one-year mortality with HR 0.30 (95% CI 0.17-0.53, p≤0.001) in 2017-2021 as compared to 1996-2001. In the remaining surgical groups, trends were towards decreasing one-year mortality over calendar periods but did not reach statistical significance. Conclusion(s) In this Danish nationwide cohort study, we observed an increase in the incidence of overall mitral valve surgery from 1996 to 2021. The incidence of mechanical valve replacement decreased, while the incidence of mitral valve repair, biological replacement and TEER increased. Mortality rates significantly improved for mitral valve repair patients over calendar time. Continuous epidemiological surveillance of this patient group is required in an era of development in treatment guidelines, surgical methods and patient demographics.Table 1Figure 1

Prescription time trends in patients with high-impact chronic pain: A National Patient Registry Study.

High-impact chronic pain (HICP), defined as chronic pain with a significant impact on daily function, affects approximately 8% of the Western population. In Denmark, HICP still remains to be described at the population level. Some patients with HICP are referred to the Danish pain centres, where they are registered with a procedural code. We conducted a nationwide registry-based study of all Danish patients registered with a visit to a pain centre from January 2005 to March 2022, to explore time trends in the prescription of analgesics and sedatives in this HICP subpopulation. Furthermore, data on socioeconomics and hospital diagnoses are reported. We used data from the Central Person Registry, the Danish National Patient Registry, the Danish National Prescription Registry, combined with data on socioeconomic information from Statistics Denmark. Data was collected on prescriptions 3 months before the first visit to a pain centre. Prescriptions were stratified into five calendar periods: before 2011, 2011-2013, 2014-2016, 2017-2019, and 2020-2022. We identified 66,577 patients referred to a pain centre. Over 15 years, prescriptions before referral declined for opioids (from 53.2% to 31.7%), NSAIDs (from 28.3% to 23.5%), antidepressants (from 20.5% to 16.8%), anxiolytics (from 12.3% to 3.2%), and sleep medication (from 15.8% to 7.6%). In contrast, prescriptions increased for paracetamol (from 31.1% to 48.9%) and gabapentinoids (from 19.2% to 27.7%). In patients with HICP visiting Danish pain centres, prescriptions before referral decreased for opioids over 15 years, with a simultaneously increased prescription of gabapentinoids (gabapentin and pregabalin). This nationwide study of 66,577 Danish patients with high-impact chronic pain reveals a significant decrease in filled opioid prescriptions over the past 15 years, with a simultaneous rise in gabapentinoid use before referral to pain centres. These findings suggest a shift in clinical practice towards alternative pain management strategies. The study underscores the need for continued research into the long-term effects of these changes and their impact on patient outcomes.

Temporal trends in major bleeding after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction from 2003 to 2017: the Western Denmark Heart Registry

Abstract Background Management of patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) has changed during the last two decades. Introduction of more potent platelet inhibitors may carry an increased risk of bleeding complications, while other therapeutic options, such as use of radial artery access and proton pump inhibitors may reduce bleeding risk. The combined impact of these treatment changes on bleeding risk in patients with STEMI remains unknown. Purpose To examine temporal trends in 1-year risk of major bleeding after STEMI treated with primary PCI from 2003 to 2017. Methods We used the Western Denmark Heart Registry to identify first-time PCI-treated patients undergoing primary PCI for STEMI from 2003 to 2017. Patients were divided into 4 calendar periods based on the time of STEMI. The main outcome was 1-year risk of major bleeding defined as a hospital admission for bleeding using a validated definition with high accuracy. Additionally, the 1-year risk of major bleeding in STEMI patients was compared with the risk in an age- and sex-matched general population cohort without prior coronary artery disease. Results From 2003 to 2017, we identified 18,540 patients treated with primary PCI for STEMI (median age 64 years, 75% men)and 92,700 age- and sex-matched individuals. The 1-year risk of major bleeding after STEMI was similar across the different time periods; 4.1% in 2003-2006, 3.8% in 2007-2010, 3.8% in 2011-2014, and 4.5% in 2015-2017. The adjusted HR for bleeding in STEMI patients was 1.03 (95% CI 0.83-1.26) when comparing the latest period with the earliest period. The age- and sex-matched general population exhibited a 1-year risk of major bleeding of around 1% in all time periods (Figure 1). Conclusions Despite changes in management, the 1-year risk of major bleeding remained stable around 4% after primary PCI-treated STEMI from 2003 to 2017. This risk was approximately 4 times higher than the bleeding risk observed in an age- and sex-matched general population.

Changes in length of hospital stay for infective endocarditis - data from before and after the POET trial

Abstract Background The results from the Partial Oral Treatment of left-sided Endocarditis (POET) trial was published in August 2018 and established non-inferiority of a switch to oral step-down antibiotic treatment in stabilized patients with infective endocarditis (IE). However, data on length of hospital stay and safety following the POET trial are warranted. Purpose To examine the changes in length of hospital stay before and after POET publication. Further, to assess safety (relapse of bacteremia and 180 days of mortality) before and after POET publication. Methods By cross-linkage of Danish nationwide registries, patients with first-time IE caused by Streptococcus spp., Enterococcus faecalis, Staphylococcus aureus, or coagulase negative staphylococci from 2012-2021 were identified. Immediately following the publication of the POET trial, the POET criteria was implemented and used in Denmark. The study period was categorized according to publication date (before and after September 2018). Median length of hospital stay was examined according to calendar period. Mortality (from admission date) and relapse of bacteremia (after discharge) at 180 days of follow-up were examined with the Kaplan-Meier estimator and the Cumulative Incidence Function, respectively. Results We identified 3,008 patients before publication of the POET trial (median age 72.8 years) and 1,740 after the publication (median age 75.2 years) (p<0.0001). The burden of comorbidities was comparable between groups. The median length of hospital stay decreased by 8 days: 41 days (IQR: 29-49) before POET publication and 33 days (IQR: 21-44) after POET publication (p<0.0001 for difference), Figure 1. Similar reductions in length of hospital stay were seen across different microbiological etiologies and age groups. The reduction in length of hospital stay was most pronounced in non-surgically treated patients. The mortality from IE admission with a maximum of 180 days follow-up was 27.5% before POET publication and 28.3% after POET publication (p-value=0.41 for difference). The bacteremia relapse rate within 180 days was 3.5% before POET publication and 1.6% after POET publication (p-value=0.0002 for difference), Figure 2. Conclusion Following the POET trial, we found an 8 days reduction in median length of hospital stay with no change in mortality and an associated lower rate of relapse of bacteremia.

Twenty-year trends in peripheral artery disease, lower extremity revascularization, and lower extremity amputation in newly diagnosed type 2 diabetes

Abstract Background Trends in risk of lower extremity complications in patients with newly diagnosed type 2 diabetes (T2DM) are largely unexplored. Purpose To examine the 5-year risk trends of peripheral artery disease (PAD), lower extremity revascularization (LER), and lower extremity amputation (LEA) in patients with newly diagnosed T2DM over a 25-year study period. Methods We conducted a cohort study that included all patients in Denmark diagnosed with T2DM from 1996 to 2015, who had no prior hospital diagnosis of atherosclerotic cardiovascular disease. These patients were age- and sex-matched with up to three comparisons from the general population. Individuals were assigned to 5-year calendar periods based on their year of inclusion and were followed for 5 years. The primary outcomes were the 5-year risks of PAD, LER, and LEA. Age- and sex-adjusted hazard ratios (aHR) were computed using Cox regression analysis. Results The study cohort consisted of 288,825 newly diagnosed T2DM patients (52% males; median age 61 years) and 782,232 comparisons from the general population. From 1996-2000 to 2015-2020, the 5-year risk of PAD decreased from 2.2% to 1.2% (aHR 0.56 [95% CI 0.52-0.61]), LER from 0.7% to 0.5% (aHR 0.73 [95% CI 0.63-0.84]), and LEA from 1.0% to 0.4% (aHR 0.44 [95% CI 0.38-0.50]) in T2DM patients (Figure). Compared with the general population, the 5-year risk differences decreased from 1.4% to 0.5% for PAD, from 0.4% to 0.2% for LER, and from 0.8% to 0.3% for LEA. The distribution of LEA types (hip/thigh, knee/lower leg, or ankle/foot/toe amputation) remained largely stable over time in T2DM patients. Use of prophylactic cardiovascular medications in T2DM patients increased notably during the study period, especially use of statins (5% to 50%) and multiple antihypertensive drugs (18% to 33%). Conclusions Over recent decades, the risks of PAD, LER, and LEA have decreased in patients with newly diagnosed T2DM, approaching the risk levels observed in the general population. This coincided with a great increase in use of prophylactic cardiovascular medications among T2DM patients.Trends in lower extremity complications.

Temporal changes in characteristics, incidence, and mortality in patients undergoing surgical intervention for mitral stenosis

To examine temporal changes in patient characteristics, the incidence rate of surgical intervention, and the three-year mortality rate for patients undergoing surgical intervention for mitral valve stenosis (MS) from 2001 to 2021 in Denmark. Utilizing Danish nationwide registries, we identified all adult patients undergoing first-time surgical intervention for MS (2001–2021). Temporal changes in the incidence rate of surgical intervention across calendar periods were investigated (2001–2005, 2006–2010, 2011–2015, and 2016–2021). Using Kaplan-Meier estimates, we computed temporal changes in three-year all-cause mortality across calendar periods. With multivariable Cox regression analysis, we assessed the adjusted rates of mortality. We included 256 patients (median age 60.3 years, 31.3% males). A stepwise decrease in the burden of chronic heart failure was identified (2001–2005: 54%, and 2016–2021: 20%, p-value < 0.001 for trend), while the burden of atrial fibrillation seemed stable (2001–2005: 51%, and 2016–2021: 46%, p-value = 0.27 for trend). The proportion of patients with rheumatic MS was 64% in 2001–2005 and 33% in 2016–2021, p-value < 0.001 for trend. 28 patients (10.9%) had mitral valve surgery prior to the first-time surgical intervention for MS. A stepwise decrease in the incidence rate of surgical intervention was observed: 3.3 cases per million person-years in 2001–2005 and 2.2 in 2016–2021. The incidence of patients diagnosed with first-time MS remained stable over calendar periods (2001–2005: 54.5 incidences per million person-years, and 2016–2021: 41.9, p-value = 0.46 for trend). The in-hospital mortality was 8.6% and the three-year mortality after surgical discharge was 9.0%, and we found no difference over calendar periods in either crude estimates or adjusted analysis. From nationwide data across three decades, we identified that the incidence of surgical interventiondecreased significantly within the past 20 years, while all-cause mortality remained stable. The burden of heart failure decreased, while the burden of atrial fibrillation remained stable over the study period.

Impact of a tubeless, disposable insulin pump on emergency department visits and inpatient admissions among a Medicare population.

A tubeless, disposable insulin pump (Omnipod DASH Insulin Management System, Insulet Corporation) has demonstrated improved glycemic outcomes for people with diabetes who require insulin. The impact of the system on downstream health care events has not been studied. To assess health care resource utilization for a Medicare population before and after starting tubeless, disposable insulin pump therapy. This retrospective, observational analysis used data from the Centers for Medicare & Medicaid Services 100% Research Identifiable Files. Study outcomes included change in event rates for diabetes-related emergency department (DRED) visits, all-cause emergency department (ACED) visits, diabetes-related inpatient (DRIP) admissions, and all-cause inpatient (ACIP) admissions among Medicare beneficiaries who started the tubeless, disposable insulin pump in 2020 (postpump observation period) as compared with the same duration and calendar period in 2019 (prepump observation period) with no pump use. Subgroup analyses were performed based on Medicare entitlement reason, diabetes type, and diagnosis status for depressive disorder. A total of 811 users met the criteria for analysis: 46.2% had type 2 diabetes, a majority (59.2%) were aged 65 years or older, and 37.0% had a diagnosis for depressive disorder. Significant reductions were observed for DRED of -46.9% (95% CI = -63% to -23%); ACED of -29.0% (95% CI = -37% to -20%); ACIP of -19.9% (95% CI = -32% to -6%). DRIP rates declined notably (-36.6%; 95% CI = -61% to 4%). Event rates observed across subgroups demonstrated consistent downward trends; however, not all were statistically significant. These findings demonstrate that use of the tubeless, disposable insulin pump was associated with reductions in DRED, ACED, and ACIP. Our results provide real-world evidence to support the use of the tubeless, disposable insulin pump among Medicare beneficiaries who require insulin, regardless of diabetes type or Medicare entitlement reason. Additional studies are recommended to further evaluate the effect of insulin pumps on health care utilization among the Medicare population and other insurance populations.

Estimated impact of a tobacco-elimination strategy on lung-cancer mortality in 185 countries: a population-based birth-cohort simulation study

The tobacco-free generation aims to prevent the sale of tobacco to people born after a specific year. We aimed to estimate the impact of eliminating tobacco smoking on lung-cancer mortality in people born during 2006-10 in 185 countries. For this population-based birth-cohort simulation study, we proposed a scenario in which tobacco sales were banned for people born between Jan 1, 2006, and Dec 31, 2010, and in which this intervention was perfectly enforced, quantified until Dec 31, 2095. To predict future lung-cancer mortality rates, we extracted lung-cancer mortality data by sex, 5-year age group, and 5-year calendar period for countries with at least 15 years of data from the WHO Mortality Database. For countries for which mortality data were not available, we extracted data on lung-cancer incidence from the Cancer Incidence in Five Continents. To establish the number of lung-cancer deaths that could be prevented in the birth cohort if tobacco smoking was eliminated, we subtracted reported age-specific rate of deaths in people who had never smoked tobacco (hereafter referred to as never smokers) from a previous study from the expected rate of lung-cancer deaths in our birth cohort and applied this difference to the size of the population. We computed population impact fractions (PIFs), the percentage of lung-cancer deaths that could be prevented, by dividing the number of preventable lung-cancer deaths by the expected lung-cancer deaths in the birth cohort. We also aggregated expected and prevented deaths into the four World Bank income groups (ie, high-income, upper-middle-income, lower-middle-income, and low-income). The primary outcome was the impact on lung-cancer mortality of implementing a tobacco-free generation. Our birth cohort included a total population of 650 525 800 people. Globally, we predicted that 2 951 400 lung-cancer deaths could occur in the population born during 2006-10 if lung-cancer rates continue to follow trends observed during the past 15 years. Of these deaths, 1 842 900 (62·4%) were predicted to occur in male individuals and 1 108 500 (37·6%) were expected to occur in female individuals. We estimated that 1 186 500 (40·2%) of 2 951 400 lung-cancer deaths in people born during 2006-10 could be prevented if tobacco elimination (ie, a tobacco-free generation) was achieved. We estimated that more lung-cancer deaths could be prevented in male individuals (844 200 [45·8%] of 1 842 900 deaths) than in female individuals (342 400 [30·9%] of 1 108 500 deaths). In male individuals, central and eastern Europe had the highest PIF (48 900 [74·3%] of 65 800 deaths) whereas in female individuals, western Europe had the highest PIF (56 200 [77·7%] of 72 300 deaths). Middle Africa was the region with the lowest PIF in both male individuals (180 [2·1%] of 8600 deaths) and female individuals (60 [0·9%] of 6400 deaths). In both sexes combined, PIF was 17 400 (13·5%) of 128 900 deaths in low-income countries, 104 900 (15·8%) of 662 800 deaths in lower-middle-income countries, 650 100 (43·9%) of 1 482 200 deaths in upper-middle-income countries, and 414 100 (61·1%) of 677 600 deaths in high-income countries. The implementation of a tobacco-free generation could substantially reduce global lung-cancer mortality. However, data from low-income countries were scarce and our estimates should be interpreted with caution. Spanish Society of Pneumology and Thoracic Surgery.

Risk of central nervous system tumors in the offspring of individuals exposed to production radiation

Aim. To assess the risk of malignant central nervous system (CNS) tumors among the first-generation offspring of workers from the Mayak Production Association.Materials and Methods. A retrospective epidemiological analysis was conducted in a cohort of the offspring of workers from Russia's first nuclear power plant (n = 8890), born between 1949 and 1973. The comparison group consisted of 4345 offspring born during the same period to non-exposed parents. The observation period covered 72 years (1949−2020), with a total of 818,208 person-years of follow-up. The analysis focused on the frequency, dynamics, and structure of CNS malignancies. The relative risk of CNS tumors and the excess relative risk per unit dose of parental occupational radiation exposure were calculated with 95% confidence intervals.Results. Overall, the frequency of CNS tumors in both groups over the entire observation period did not differ significantly (3.4 per 1000 in the main group, 1.8 per 1000 in the comparison group). Analysis of CNS tumor incidence dynamics across calendar periods showed no significant differences, with the peak in the main group occurring during 2001−2010. No significant differences were found in the age of CNS tumor onset or the average age of parents at the time of offspring birth. Histological structure and localization of CNS tumors varied across groups. The relative risk assessment for CNS tumors showed a statistically insignificant increase in risk among the offspring in the main group when considering total observations and sex-specific analyses. Among the offspring of mothers with confirmed preconceptional and intrauterine occupational radiation exposure, the relative risk of CNS tumors was higher for males and both sexes combined (3.6 [1.06−12.28] and 2.74 [1.08−6.93]; 4.34 [1.27−14.77] and 3.3 [1.31−8.36], respectively). However, the analysis of excess relative risk did not indicate significant risk estimates for maternal radiation exposure, neither in general nor across different dose intervals.Conclusion. The study did not confirm the hypothesis that parental occupational radiation exposure influences the risk of CNS tumors in offspring. Given the relatively young age of the cohort and the low number of CNS tumor cases, issues related to maternal radiation exposure require further observation.

Solving problems of volume scheduling for shipbuilding enterprises in conditions of limited resources

The shipbuilding industry development strategy for the period up to 2035 and beyond is aimed at creating a new competitive shipbuilding industry based on the development of scientific, technical and personnel potential, optimization of production capacities, their modernization and technical re-equipment [1]. The paper is devoted to solving problems of volume-calendar production planning for shipbuilding enterprises when coordinating the production capacity of the enterprise with the resource needs to fulfill obligations determined by the generated order portfolio. Shipbuilding and ship repair enterprises are typical representatives of enterprises with single and small-scale production and a long production cycle of the main products [2-4]. The problem is solved at the stage of forming a portfolio of orders, which is based on the limited volumes of resources available to the production system. It is required to determine the amount of missing resources by calendar periods that are necessary for the effective functioning of the production system. Non-stored resources such as labor resources, equipment operating time, are usually taken into account when solving the problems of volumetric or volume-scheduling planning. Such resources being unused in a certain planning cycle cannot be used in subsequent cycles. The procedure for finding missing volumes of resources is formulated as the problem of reducing an incompatible system of linear two-sided algebraic inequalities to a compatible one. To do this, it is proposed to “expand” the initial parameters of the system, taking into account the costs of expansion, so that the system becomes compatible. In the general case, formally, the problem under consideration is close to the problem of finding a Chebyshev point [5] for an incompatible system of linear algebraic equations, i.e. a point that is geometrically the least deviating from all hyperplanes formed by the system constraints. The paper proposes statements and solutions of volume-scheduling problems for the case when the structure of the problem constraints is modeled by a root-oriented weighted tree. This hierarchical structure is typical for shipbuilding enterprises [6].

Courier delivery of antiretroviral therapy: a cohort study of a South African private-sector HIV programme.

Courier delivery has become a popular antiretroviral therapy (ART) distribution method in some HIV care settings, yet data on ART courier delivery and how it relates to ART outcomes are scarce. We studied the differences in viral suppression rates between individuals from a South African private sector HIV programme receiving ART by courier delivery and those receiving ART through traditional retail dispensing. Individuals aged 15 years or older who were actively enrolled in the Aid for AIDS programme between January 2011 and July 2022 were eligible for the analysis. The outcome of interest was viral suppression defined as a viral load (VL) <400 copies per ml. We calculated adjusted odds ratios (OR) for the association between the ART distribution method and viral suppression, comparing those receiving refills through courier pharmacies versus retail dispensing at the time of the VL testing. We used generalized estimating equations to account for repeated VL testing of the same individual. The models were adjusted for age, sex, calendar year, ART regimen, history of mental illness and medical insurance scheme. We computed adjusted ORs for the calendar periods 2011-2013, 2014-2016, 2017-2019, 2020-2022 and overall. We extracted 442,619 VL measurements from 68,720 eligible individuals, 39,406 (57.3%) were women. The median number of VL measurements per individual was 6 (IQR 3-10). VL suppression was detected in 398,901 (90.1%) tests, and 185,701 (42.0%) of the tests were taken while the individual was receiving ART by courier delivery. Overall, courier delivery was associated with 5% higher odds of viral suppression than retail dispensing (adjusted OR 1.05, 95% CI 1.02-1.08). The strength and direction of this association varied by calendar period, with an adjusted OR of 1.37 (95% CI 1.27-1.48) in 2011-2013 and 1.02 (95% CI 0.97-1.07) in 2020-2022. Courier delivery of ART is a viable alternative to retail dispensing in the South African private sector, as it was associated with higher viral suppression until 2016 and similar suppression rates in recent years. Further research is needed to investigate the potential benefits and drawbacks of courier delivery of ART in both private and public healthcare settings.

Sacred journeys and pilgrimages: health risks associated with travels for religious purposes.

Pilgrimages and travel to religious Mass Gatherings (MGs) are part of all major religions. This narrative review aims to describe some characteristics, including health risks, of the more well known and frequently undertaken ones. A literature search was conducted using keywords related to the characteristics (frequency of occurrence, duration, calendar period, reasons behind their undertaking and the common health risks) of Christian, Muslim, Hindu, Buddhist and Jewish religious MGs. About 600 million trips are undertaken to religious sites annually. The characteristics varies between religions and between pilgrimages. However, religious MGs share common health risks, but these are reported in a heterogenous manner. European Christian pilgrimages reported both communicable diseases, such as norovirus outbreaks linked to the Marian Shrine of Lourdes in France, and noncommunicable diseases (NCD). NCD predominated at the Catholic pilgrimage to the Basilica of Our Lady of Guadalupe in Mexico, which documented 11 million attendees in one week. The Zion Christian Church Easter gathering in South Africa, attended by about 10 million pilgrims, reported mostly motor vehicles accidents. Muslim pilgrimages, such as the Arbaeen (20 million pilgrims) and Hajj documented a high incidence of respiratory tract infections, up to 80% during Hajj. Heat injuries and stampedes have been associated with Hajj. The Hindu Kumbh Mela pilgrimage, which attracted 100 million pilgrims in 2013, documented respiratory conditions in 70% of consultations. A deadly stampede occurred at the 2021 Jewish Lag BaOmer MG. Communicable and NCD differ among the different religious MGs. Gaps exists in the surveillance, reporting, and data accessibility of health risks associated with religious MGs. A need exists for the uniform implementation of a system of real-time monitoring of diseases and morbidity patterns, utilising standardised modern information-sharing platforms. The health needs of pilgrims can then be prioritised by developing specific and appropriate guidelines.

Locoregional recurrence in studies of primary systemic therapy in early invasive breast cancer

IntroductionThe use of primary systemic therapy (PST) in early invasive breast cancer is routine but there are concerns about risk of locoregional recurrence. MethodsWe conducted a systematic literature review to identify studies of locoregional treatment and recurrence in patients with early invasive breast cancer who received non-endocrine PST. ResultsWe identified 112 studies (18 prospective trials and 94 non-interventional studies). The use of surgery and radiotherapy after PST was recorded in 65 (58 %) and 50 (45 %) of studies respectively. 66 (59 %) studies reported locoregional recurrence. Cumulative 5-year locoregional recurrence risks varied from 1 % to 23 %. Locoregional recurrence was higher in patients under the age of 40, those who did not achieve a pathological complete remission after PST, had ER-negative or HER2 negative tumours, were recorded to have inoperable disease before PST, and did not have radiotherapy. LRR rates in these studies have not fallen over the overall calendar period of patient enrollment (1999–2016). ConclusionThe recording of locoregional treatments and outcomes is suboptimal in studies of PST and efforts to improve this are required. In the absence of randomised evidence, our findings may help to inform care and guideline development. We were unable to exclude concern that the use of PST is associated with a higher than desired risk of locoregional recurrence.

Epidemiology and clinical correlates of hidradenitis suppurativa in primary care in Italy.

Hidradenitis suppurativa (HS) is a persistent skin disorder that is characterized by painful lesions or pus-filled lumps, mostly occurring in areas where the skin flexes. It is a disfiguring condition that significantly reduces the quality of life of those affected. Developing new, effective treatments for HS is crucial, but it is important that it be recognized and diagnosed early, especially in primary care settings. To assess the epidemiology and clinical correlates of HS in a primary care setting. The study utilized the Italian Health Search Database (HSD). A case-control design was adopted to investigate the clinical correlates of HS. Cases were classified as either "definite" or "probable" using an operational algorithm. Up to 10 controls were matched to each case based on factors such as calendar period, age, sex, and duration of follow-up. Cumulative prevalence of HS increased from 0.06% in 2002 to 0.46% in 2021. When only "definite" cases were considered, the prevalence was almost 10 times lower (0%-0.02%). Several clinical correlates were found to be positively associated with HS, including obesity, dyslipidemia, hypertension, autoimmune/inflammatory diseases, and depression. This study found that correct diagnoses of HS were made, as demonstrated by the expected relationship with clinical correlates. These associations were consistent when probable cases were included in the analysis. This evidence could serve as a foundation for proposing a decision support system for general practitioners to help identify HS in individuals with certain coexisting conditions.

Comparison of the Number of Dog Adoptions in a Pilot Program That Restored Limited Visitor Access to Kennels: A Community Case Report

In the 2020–2022 pandemic period, the Orange County (California) animal shelter used an appointment-based adoption system in which visitors did not have access to the kennels. In a 2023 pilot program, visitors were allowed to view some large dogs in their kennels for a limited portion of the shelter’s hours of operation. More adoptions than expected were observed during viewing hours compared to other days and times during the pilot period. Compared to the same calendar period in the preceding year, kennel viewing periods showed an 82% increase in adoptions while appointment-only periods showed only a 4% increase. A higher proportion of large dogs were adopted from the viewable kennels than from the general inventory of large dogs. This was not a randomized controlled study, and these estimates are based solely on retrospective comparisons. It is not known how these increased adoption levels scale if access is available to more kennels or for a substantial portion of the hours of operation.

Coccidioidomycosis seasonality in California: a longitudinal surveillance study of the climate determinants and spatiotemporal variability of seasonal dynamics, 2000–2021

Coccidioidomycosis, an emerging fungal disease in the western USA, exhibits seasonal patterns that are poorly understood, including periods of strong cyclicity, aseasonal intervals, and variation in seasonal timing that have been minimally characterized, and unexplained as to their causal factors. Coccidioidomycosis incidence has increased markedly in recent years, and our limited understanding of intra- and inter-annual seasonality has hindered the identification of important drivers of disease transmission, including climate conditions. In this study, we aim to characterize coccidioidomycosis seasonality in endemic regions of California and to estimate the relationship between drought conditions and coccidioidomycosis seasonal periodicity and timing. We analysed data on all reported incident cases of coccidioidomycosis in California from 2000 to 2021 to characterize seasonal patterns in incidence, and conducted wavelet analyses to assess the dominant periodicity, power, and timing of incidence for 17 counties with consistently high incidence rates. We assessed associations between seasonality parameters and measures of drought in California using a distributed lag nonlinear modelling framework. All counties exhibited annual cyclicity in incidence (i.e., a dominant wavelet periodicity of 12 months), but there was considerable heterogeneity in seasonal strength and timing across regions and years. On average, 12-month periodicity was most pronounced in the Southern San Joaquin Valley and Central Coast. Further, the annual seasonal cycles in the Southern San Joaquin Valley and the Southern Inland regions occurred earlier than those in coastal and northern counties, yet the timing of annual cycles became more aligned among counties by the end of the study period. Drought conditions were associated with a strong attenuation of the annual seasonal cycle, and seasonal peaks became more pronounced in the 1-2 years after a drought ended. We conclude that drought conditions do not increase the risk of coccidioidomycosis onset uniformly across the year, but instead promote increased risk concentrated within a specific calendar period (September to December). The findings have important implications for public health preparedness, and for how future shifts in seasonal climate patterns and extreme events may impact spatial and temporal coccidioidomycosis risk. National Institutes of Health.

Deciphering the Sex gap in global life expectancy: the impact of female-specific cancers 1990-2019.

Females live longer than males, which results in a sex gap in life expectancy. This study examines the contribution of female cancers to this differential by world region and country 1990-2019 with special focus to the 15-69 age group. Cause-specific mortality data for 30 cancers, including four female-specific cancers from 238 countries and territories was retrieved from the Global Burden of Disease Study 2019. Using life table techniques and demographic decomposition analysis, we estimated the contribution of cancer deaths to the sex gap in life expectancy by age and calendar period. At ages 15-69, females had a higher life expectancy than males in 2019. Countries with the largest sex gaps or the largest female advantage in life expectancy were in Eastern Europe and Northern Asia, Latin America and Southern Africa. In contrast, countries with the smallest sex gaps were mainly located in Northern Africa, Northern America, and Northern Europe. The contribution of female-specific cancers to sex gaps in life expectancy were largely negative, ranging from -0.15 years in the Western Pacific to -0.26 years in the Eastern Mediterranean Region, implying that the disproportionately higher premature cancer mortality among females contributed to a reduction in the female life expectancy advantage. Female-specific cancers are important determinants of sex gaps in life expectancy. Their negative impact on life expectancy at working and reproductive age groups has far-reaching consequences for society. Increasing the availability and access to prevention, screening, timely diagnosis, and effective treatment can reduce this gap.