Lower Death Research Articles

Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised, phase 2b study

Checkpoint inhibitors are standard adjuvant treatment for stage IIB-IV resected melanoma, but many patients recur. Our study aimed to evaluate whether mRNA-4157 (V940), a novel mRNA-based individualised neoantigen therapy, combined with pembrolizumab, improved recurrence-free survival and distant metastasis-free survival versus pembrolizumab monotherapy in resected high-risk melanoma. We did an open-label, randomised, phase 2b, adjuvant study of mRNA-4157 plus pembrolizumab versus pembrolizumab monotherapy in patients, enrolled from sites in the USA and Australia, with completely resected high-risk cutaneous melanoma. Patients with completely resected melanoma (stage IIIB-IV) were assigned 2:1 to receive open-label mRNA-4157 plus pembrolizumab or pembrolizumab monotherapy. mRNA-4157 was administered intramuscularly (maximum nine doses) and pembrolizumab intravenously (maximum 18 doses) in 3-week cycles. The primary endpoint was recurrence-free survival in the intention-to-treat population. This ongoing trial is registered at ClinicalTrials.gov, NCT03897881. From July 18, 2019, to Sept 30, 2021, 157 patients were assigned to mRNA-4157 plus pembrolizumab combination therapy (n=107) or pembrolizumab monotherapy (n=50); median follow-up was 23 months and 24 months, respectively. Recurrence-free survival was longer with combination versus monotherapy (hazard ratio [HR] for recurrence or death, 0·561 [95% CI 0·309-1·017]; two-sided p=0·053), with lower recurrence or death event rate (24 [22%] of 107 vs 20 [40%] of 50); 18-month recurrence-free survival was 79% (95% CI 69·0-85·6) versus 62% (46·9-74·3). Most treatment-related adverse events were grade 1-2. Grade ≥3 treatment-related adverse events occurred in 25% of patients in the combination group and 18% of patients in the monotherapy group, with no mRNA-4157-related grade 4-5 events. Immune-mediated adverse event frequency was similar for the combination (37 [36%]) and monotherapy (18 [36%]) groups. Adjuvant mRNA-4157 plus pembrolizumab prolonged recurrence-free survival versus pembrolizumab monotherapy in patients with resected high-risk melanoma and showed a manageable safety profile. These results provide evidence that an mRNA-based individualised neoantigen therapy might be beneficial in the adjuvant setting. Moderna in collaboration with Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.

Sperm Switch: A New Trend in Reducing Maternal Mortality

The study looked at the emerging practice of switching sperm to reduce maternal mortality in Ekiti State. Secondary data from the chosen health facilities in Ekiti State was used in the study. The major beneficiaries of family planning programs have historically been women, and men have been seen as the services' invisible partners. The study's ideas included male involvement in family planning, the effect caused by sperm switching on family planning, its difficulties, ways to use sperm switching to lower maternal death rates, and the responsibilities of midwives and the government in the process. The study's implications for nursing practice are that nurses and midwives undergoing training should be able to apply the sperm switch approach, and nurses should conduct additional research on new trends in family planning, particularly sperm switching, as well as the advantages of male involvement in family planning. The suggestion is that political commitment, priorities, effective governance, and enough financing should be given top priority. In addition, men should receive advice regarding the reversibility of the sperm switch method, and more awareness should be raised regarding the sperm switch strategy's positive effects on health when used with male contraceptives for family planning.

Exposure to Secondhand Smoke Extract Increases Cisplatin Resistance in Head and Neck Cancer Cells.

Chemotherapy and radiotherapy resistance are major obstacles in the long-term efficacy of head and neck squamous cell carcinoma (HNSCC) treatment. Secondhand smoke (SHS) exposure is common and has been proposed as an independent predictor of HNSCC recurrence and disease-free survival. However, the underlying mechanisms responsible for these negative patient outcomes are unknown. To assess the effects of SHS exposure on cisplatin efficacy in cancer cells, three distinct HNSCC cell lines were exposed to sidestream (SS) smoke, the main component of SHS, at concentrations mimicking the nicotine level seen in passive smokers' saliva and treated with cisplatin (0.01-100 µM) for 48 h. Compared to cisplatin treatment alone, cancer cells exposed to both cisplatin and SS smoke extract showed significantly lower cisplatin-induced cell death and higher cell viability, IC50, and indefinite survival capacity. However, SS smoke extract exposure alone did not change cancer cell viability, cell death, or cell proliferation compared to unexposed control cancer cells. Mechanistically, exposure to SS smoke extract significantly reduced the expression of cisplatin influx transporter CTR1, and increased the expression of multidrug-resistant proteins ABCG2 and ATP7A. Our study is the first to document that exposure to SHS can increase cisplatin resistance by altering the expression of several proteins involved in multidrug resistance, thus increasing the cells' capability to evade cisplatin-induced cell death. These findings emphasize the urgent need for clinicians to consider the potential role of SHS on treatment outcomes and to advise cancer patients and caregivers on the potential benefits of avoiding SHS exposure.

Gender differences, environmental pressures, tumor characteristics, and death rate in a lung cancer cohort: a seven-years Bayesian survival analysis using cancer registry data from a contaminated area in Italy.

In Taranto, Southern Italy, adverse impacts on the environment and human health due to industrial installations have been studied. In the literature, associations have been reported between gender, environmental factors, and lung cancer mortality in women and men. The aim of this study was to investigate the relationships between gender, residence in areas with high environmental pressures, bronchus/lung cancer characteristics, and death rate. Data from the Taranto Cancer Registry were used, including all women and men with invasive bronchus/lung cancer diagnosed between 1 January 2016 and 31 December 2020 and with follow-up to 31 December 2022. Bayesian mixed effects logistic and Cox regression models were fitted with the approach of integrated nested Laplace approximation, adjusting for patients and disease characteristics. A total of 2,535 person-years were observed. Male gender was associated with a higher prevalence of histological grade 3 (OR 2.45, 95% CrI 1.35-4.43) and lung squamous-cell carcinoma (OR 3.04, 95% CrI 1.97-4.69). Variables associated with higher death rate were male gender (HR 1.24, 95% CrI 1.07-1.43), pathological/clinical stage II (HR 2.49, 95% CrI 1.63-3.79), III (HR 3.40, 95% CrI 2.33-4.97), and IV (HR 8.21, 95% CrI 5.95-11.34), histological grade 3 (HR 1.80, 95% CrI 1.25-2.59), lung squamous-cell carcinoma (HR 1.18, 95% CrI 1.00-1.39), and small-cell lung cancer (HR 1.62, 95% CrI 1.31-1.99). Variables associated with lower death rate were other-type lung cancer (HR 0.65, 95% CrI 0.44-0.95), high immune checkpoint ligand expression (HR 0.75, 95% CrI 0.59-0.95), lung localization (HR 0.73, 95% CrI 0.62-0.86), and left localization (HR 0.85, 95% CrI 0.75-0.95). The results among patients with lung cancer did not show an association between residence in the contaminated site of national interest (SIN) and the prevalence of the above mentioned prognostic factors, nor between residence in SIN and death rate. The findings confirmed the independent prognostic values of different lung cancer characteristics. Even after adjusting for patients and disease characteristics, male gender appeared to be associated with a higher prevalence of poorly differentiated cancer and squamous-cell carcinoma, and with an increased death rate.

Environmental pressures, tumor characteristics, and death rate in a female breast cancer cohort: a seven-years Bayesian survival analysis using cancer registry data from a contaminated area in Italy.

In Taranto, Southern Italy, adverse impacts on the environment and human health due to industrial installations have been studied. In the literature, few associations have been reported between environmental factors and breast cancer mortality in women. The aim of this study was to investigate the relationships between residence in areas with high environmental pressures, female breast cancer characteristics, and death rate. Data from the Taranto Cancer Registry were used, including all women with invasive breast cancer diagnosed between 01 January 2015 and 31 December 2020 and with follow-up to 31 December 2021. Bayesian mixed effects logistic and Cox regression models were fitted with the approach of integrated nested Laplace approximation, adjusting for patients and disease characteristics. A total of 10,445 person-years were observed. Variables associated with higher death rate were residence in the contaminated site of national interest (SIN) (HR 1.22, 95% CrI 1.01-1.48), pathological/clinical stage III (HR 2.77, 95% CrI 1.93-3.97) and IV (HR 17.05, 95% CrI 11.94-24.34), histological grade 3 (HR 2.50, 95% CrI 1.20-5.23), Ki-67 proliferation index of 21-50% (HR 1.42, 95% CrI 1.10-1.83) and > 50% (HR 1.81, 95% CrI 1.29-2.55), and bilateral localization (HR 1.65, 95% CrI 1.01-2.68). Variables associated with lower death rate were estrogen and/or progesterone receptor positivity (HR 0.61, 95% CrI 0.45-0.81) and HER2/neu oncogene positivity (HR 0.59, 95% CrI 0.44-0.79). The findings confirmed the independent prognostic values of different female breast cancer characteristics. Even after adjusting for patients and disease characteristics, residence in the SIN of Taranto appeared to be associated with an increased death rate.

SARS-CoV-2 vaccination and risk of infectious diseases in hospitalized older patients.

Vaccinations, for example flu vaccine, may be a cause of cross-reactive immunostimulation that prevents a larger spectrum of infections. However, whether SARS-CoV-2 vaccinations may also determine this effect is unclear. This study aims, first, to assess the incidence of infections at hospital admission and during the hospitalization in older inpatients vaccinated and unvaccinated against SARS-CoV-2; second, to compare length of hospital stay and in-hospital mortality between vaccinated and unvaccinated individuals. This retrospective study included 754 older inpatients admitted to the Geriatrics and Orthogeriatrics Units of the University Hospital of Ferrara (Italy) between March 2021 and November 2021. Sociodemographic and health-related data, and the diagnosis of infections at hospital admission and during hospitalization were collected from medical records. The sample's mean age was 87.2years, 59.2% were females, and 75.5% were vaccinated against SARS-CoV-2. Vaccinated individuals had 36% lower odds of intra-hospital infections (OR = 0.64, 95%CI 0.44-0.94) and 39% lower in-hospital death (HR = 0.61, 95%CI 0.39-0.95), also after adjusting for potential confounders, while no significant results emerged about infections at hospital admission. Considering the hospitalization's endpoints, SARS-CoV-2 vaccination was associated with a lower probability of being transferred to long-term care or other hospital departments than returning home (OR = 0.63, 95%CI 0.40-0.99). In older inpatients, SARS-CoV-2 vaccination seems to be associated with a lower likelihood of intra-hospital infectious diseases not caused by SARS-CoV-2 and all-cause in-hospital mortality. The vaccination coverage in the older population could limit not only the onset and severity of COVID-19 but also the occurrence of other infectious diseases.

Effects of renin-angiotensin system inhibitor and beta-blocker use on mortality in older patients with heart failure with reduced ejection fraction in Japan.

Guideline-directed medical therapy with renin-angiotensin system (RAS) inhibitors and beta-blockers has improved the survival of patients with heart failure (HF) and reduced left ventricular ejection fraction (HFrEF). However, it is unclear whether RAS inhibitors and beta-blockers can be administered to older patients with HF. Therefore, this study aimed to investigate the effects of beta-blockers and RAS inhibitors on the prognosis of older patients with HFrEF. Demographic, clinical, and pharmacological data from 1,061 patients with acute decompensated HF, enrolled in the Kochi Registry of Subjects with Acute Decompensated Heart Failure (Kochi YOSACOI study), were analyzed to assess their impact on mortality. Additionally, a machine learning approach was applied to complement the conventional statistical model for analysis. Patients with HFrEF (n = 314) were divided into the all-cause mortality within 2 years group (n = 80) and the survivor group (n = 234). Overall, 41.1% (129/314) of the patients were aged ≥80, and 25.5% (80/314) experienced all-cause mortality within 2 years. Furthermore, 57.6% (181/314) and 79.0% (248/314) were prescribed RAS inhibitors and beta-blockers, respectively. Our analysis showed that RAS inhibitor use was associated with reduced all-cause mortality and cardiac death in patients with HFrEF of all ages (P < 0.001), and beta-blocker use had an interaction with age. Machine learning revealed that the use of beta-blockers altered the risk of mortality, with a threshold of approximately 80 years of age. Beta-blocker use was associated with lower all-cause mortality and cardiac death in patients with HFrEF aged <80 years (P < 0.001) but not in those aged ≥80 years (P = 0.319 and P = 0.246, respectively). These results suggest that beta blockers may differ in their all-cause mortality benefits according to age. RAS inhibitors prevented all-cause mortality and cardiac death at all ages, whereas beta-blockers had different effects depending on the patient's age. This study suggested that the choice of beta-blockers and RAS inhibitors is more important in older patients with HFrEF than in younger patients with the same condition.

Evaluation of an outreach programme for patients with COVID-19 in an integrated healthcare delivery system: a retrospective cohort study

ObjectivesIn the first year of the COVID-19 pandemic, health systems implemented programmes to manage outpatients with COVID-19. The goal was to expedite patients’ referral to acute care and prevent overcrowding...

EVALUATION OF ALVARADO SCORE IN DIAGNOSIS OF ACUTE APPENDICITIS

Background: Abdominal pain is frequently caused by acute appendicitis, which can be diagnosed early and result in a lower morbidity and death rate. Improved diagnostic procedures should minimize the progression to complicated appendicitis as well as reduce the number of unwanted surgical interventions. However, even with the advancements in diagnostic laboratory tests and contemporary radiographic imaging, appendicitis diagnosis is still primarily clinical. Different scoring methods were developed to reduce the negative appendectomy rate and raise the positive diagnosis rate of appendicitis such as Alvarado score. The present study aimed to evaluate the sensitivity and specificity of the Alvarado score as a method for the diagnosis of acute appendicitis. Methods: A total of 146 operated cases of appendectomy in Zawia Medical Center, Libya were studied. All patients presented during a period from July 2018 to July 2019 with symptoms and signs of acute appendicitis, and after that, they were operated on by the conventional method of open appendectomy. The relevant data was collected and analyzed, and the efficiency of the Alvarado scoring system was assessed by calculating sensitivity, positive predictive value, and negative appendectomy rate. Results: In this study, 100% of patients reported pain as their primary presenting symptom; presentations occurred between one and seven days, with a mean of two days; 100% of patients had surgery; and the overall negative appendectomy rate in Alvarado ≥7 was 5% and 72.5% was the positive predictive value (PPV).Conclusion: Our findings suggest that the Alvarado score has a very high positive predictive value, i.e., diagnostic accuracy. Also, with the help of the Alvarado score, we can reduce the number of negative appendectomies. Besides that, this scoring system is an easy, simple, cheap, reliable, safe, and fast tool in the preoperative diagnosis of acute appendicitis and can work effectively in routine practice.

Nirmatrelvir/ritonavir and remdesivir against symptomatic treatment in high-risk COVID-19 outpatients to prevent hospitalization or death during the Omicron era: a propensity score-matched study.

Even though worldwide death rates from coronavirus disease 2019 (COVID-19) have decreased, the threat of disease progression and death for high-risk groups continues. Few direct comparisons between the available severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antivirals have been made. We aimed to compare two SARS-CoV-2 antivirals (nirmatrelvir/ritonavir and remdesivir) against all-cause hospitalization or death. This is a propensity score-matched cohort study. We included all high-risk outpatients with COVID-19 in a tertiary referral center in Mexico City from 1 January 2022 to 31 July 2023. The primary outcome was all-cause hospitalization or death 28 days after symptom onset. The secondary outcome was COVID-19-associated hospitalization or death 28 days after symptom onset. Logistic regression analysis for characteristics associated with the primary outcome and a multi-group comparison with Kaplan-Meier survival estimates were performed. Of 1566 patients analyzed, 783 did not receive antiviral treatment, 451 received remdesivir, and 332 received nirmatrelvir/ritonavir. The median age was 60 years (interquartile range: 46-72), 62.5% were female and 97.8% had at least one comorbidity. The use of nirmatrelvir/ritonavir was associated with an absolute risk reduction of 8.8% and a relative risk reduction of 90% for all-cause hospitalization or death. The use of remdesivir was associated with an absolute risk reduction of 6.4% and a relative risk reduction of 66% for all-cause hospitalization or death. In multivariable analysis, both antivirals reduced the odds of 28-day all-cause hospitalization or death [nirmatrelvir/ritonavir odds ratio (OR) 0.08 - 95% confidence interval (CI): 0.03-0.19, remdesivir OR 0.29 - 95% CI: 0.18-0.45]. In high-risk COVID-19 outpatients, early antiviral treatment with nirmatrelvir/ritonavir or remdesivir was associated with lower 28-day all-cause hospitalization or death.

Mortality risk of Severe Acute Respiratory Syndrome cases classified as COVID-19: A longitudinal study.

The COVID-19 pandemic has significantly impacted global health, with diverse factors influencing the risk of death among reported cases. This study mainly analyzes the main characteristics that have contributed to the increase or decrease in the risk of death among Severe Acute Respiratory Syndrome (SARS) cases classified as COVID-19 reported in southeast Brazil from 2020 to 2023. This cohort study utilized COVID-19 notification data from the Sistema de Vigilância Epidemiológica (SIVEP) information system in the southeast region of Brazil from 2020 to 2023. Data included demographics, comorbidities, vaccination status, residence area, and survival outcomes. Classical Cox, Cox mixed effects, Prentice, Williams & Peterson (PWP), and PWP fragility models were used to assess the risk of dying over time. Across 987,534 cases, 956,961 hospitalizations, and 330,343 deaths were recorded over the period. Mortality peaked in 2021. The elderly, males, black individuals, lower-educated, and urban residents faced elevated risks. Vaccination reduced death risk by around 20% and 13% in 2021 and 2022, respectively. Hospitalized individuals had lower death risks, while comorbidities increased risks by 20-26%. The study identified demographic and comorbidity factors influencing COVID-19 mortality. Rio de Janeiro exhibited the highest risk, while São Paulo had the lowest. Vaccination significantly reduces death risk. Findings contribute to understanding regional mortality variations and guide public health policies, emphasizing the importance of targeted interventions for vulnerable groups.

Assessing Larval Toxicity of Sphaeranthus Indicus Linn Essential Oil Against Dengue and Filarial Vectors

This study focuses on a crucial objective: eradicating the formidable dengue and filarial vectors through larval toxicity using a novel essential oil derived from Sphaeranthus indicus Linn. The research encompasses several key methodologies, including pest rearing, homology modeling, and molecular docking. The G Power value is taken as 0.8, with two groups and each group carrying 5 sample sizes. Si-CVO is toxic to Aedes aegypti larvae, and it causes dose-dependent mortality in the II, III, and IV instar larvae, respectively. Maximum mortality rates for all instars were 500 ppm: 91.3% (II instar), 87.4% (III instar), and 83.2%. (IV instar). While the lowest dosage of 100 ppm had a lower death rate throughout all larval instars. It is observed that by using the novel essential oil from Sphaeranthus indicus Linn which is a plant derived product the baleful insects are killed and the agriculture efficiency is improved.

Higher Frequency of Healthcare Professionals is Associated With a Low Incidence of COVID-19-Related Death.

The COVID-19 pandemic has affected over 200 countries with varying levels of infection and mortality rates. To understand the impact of healthcare resources and cultural factors, a cross-sectional study was conducted on 76 countries. The study used K-means clustering to identify 2 distinct clusters and performed a Welch's test to compare different parameters. The countries were then plotted on the Inglehart-Welzel global cultural map. By incorporating this framework, researchers can systematically scrutinize the intricate interplay of cultural factors. This will provide valuable context for understanding individuals' behaviors, preferences, and decision-making as they pertain to the challenges posed by COVID-19 and its mitigation strategies. The results showed that countries with higher levels of healthcare professionals had a lower death rate, even with a relatively high rate of infection. These countries also had higher levels of individual self-expression. The study highlights the importance of adhering to recommended protocols, as neglect can result from a lack of self-expression, leading to an increase in the spread of communicable diseases. It also emphasizes crucial role of healthcare professionals in managing crisis related to the pandemic.

Investigating the Effectiveness of Care Delivery at an Acute Geriatric Community Hospital for Older Adults in the Netherlands: A Prospective Controlled Observational Study

ObjectivesHospital admission in older adults is associated with unwanted outcomes such as readmission, institutionalization, and functional decline. To reduce these outcomes, the Netherlands introduced an alternative to hospital-based care: the Acute Geriatric Community Hospital (AGCH). The AGCH is an acute care unit situated outside of a hospital focusing on early rehabilitation and comprehensive geriatric assessment. The objective of this study was to evaluate if AGCH care is associated with decreasing unplanned readmissions or death compared with hospital-based care. DesignProspective cohort study controlled with a historic cohort. Setting and ParticipantsA (sub)acute care unit (AGCH) and 6 hospitals in the Netherlands; participants were acutely ill older adults. MethodsWe used inverse propensity score weighting to account for baseline differences. The primary outcome was 90-day readmission or death. Secondary outcomes included 30-day readmission or death, time to death, admission to long-term residential care, occurrence of falls and functioning over time. Generalized logistic regression models and multilevel regression analyses were used to estimate effects. ResultsAGCH patients (n = 206) had lower 90-day readmission or death rates [odds ratio (OR) 0.39, 95% CI 0.23-0.67] compared to patients treated in hospital (n = 401). AGCH patients had a lower risk of 90-day readmission (OR 0.38, 95% CI 0.21-0.67) but did not differ on all-cause mortality (OR 0.89, 95% CI 0.44-1.79) compared with the hospital control group. AGCH patients had lower 30-day readmission or death rates. Secondary outcomes did not differ. Conclusions and ImplicationsAGCH patients had lower rates of readmission and/or death than patients treated in a hospital. Our results support further research on the implementation and cost-effectiveness of AGCH in the Netherlands and other countries seeking alternatives to hospital-based care.

COVID-19 vaccination outcomes in patients with a solid malignancy: Insights from extensive real-world data and propensity score matched analyses

This nationwide, multicentric, retrospective analysis of 1,126,946 COVID-19 cases (March 2020-June 2022) aims to elucidate the impact of COVID-19 vaccination on mortality in patients with a sole solid malignancy. Using data from the national digital medical record repository, outcomes were compared among fully vaccinated and nonvaccinated cohorts, factoring in gender, virus type, age, vaccination status, vaccine type, and cancer type. Logistic regression calculated odds ratios (OR) and their significance. Among 6,050 patients with both cancer and comorbidities, 1,797 had only solid malignancy. Vaccinated individuals in this group had reduced mortality rates, especially those >63 years (OR 0.169 [95% confidence interval [CI] 0.090-0.317]; P<.001). Lower deaths were observed in non-ICU (OR 0.193 [95% CI 0.097-0.382]; P<.001) and ICU cases (OR 0.224 [95% CI 0.077-0.646]; P=.003), with both vaccine types. No statistically significant benefits were observed against delta and omicron variants. Intrathoracic malignancies (OR 0.376 [95% CI 0.146-0.971]; P=.043) and palliative treatment (OR 0.384 [95% CI 0.192-0.766]; P=.006) showed vaccination benefits. Logistic regression revealed a higher fatal risk in nonvaccinated males >63. Propensity score matching supported these outcomes. Patients with sole solid malignancies face elevated COVID-19 mortality risk, particularly without active cytostatic therapy, with advanced disease on palliative treatment, or intrathoracic malignancies.

Risk of readmission and death after hospitalization for worsening heart failure: Role of post-discharge follow-up visits in a real-world study from the Grand Est Region of France.

Patients who experience hospitalizations due to heart failure (HF) face a significant risk of readmission and mortality. Our objective was to evaluate whether the risk of hospitalization and mortality following discharge from HF hospitalization differed based on adherence to the outpatient follow-up (FU) protocol comprising an appointment with a general practitioner (GP) within 15 days, a cardiologist within 2 months or both (termed combined FU). We studied all adults admitted for a first HF hospitalization from 2016 to 2020 in France's Grand Est region. Association between adherence to outpatient FU and outcomes were assessed with time-dependent survival analysis model. Among 67 476 admitted patients (mean age 80.3 ± 11.3 years, 53% women), 62 156 patients (92.2%) were discharged alive and followed for 723 (317-1276) days. Combined FU within 2 months was used in 21.1% of patients, with lower rates among >85 years, women, and those with higher comorbidity levels (p < 0.0001 for all). Combined FU was associated with a lower 1-year death or rehospitalization (adjusted hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.88-0.94, p < 0.0001) mostly related to lower mortality (adjusted HR 0.65, 95% CI 0.62-0.68, p < 0.0001) whereas HF readmission was higher (adjusted HR 1.19, 95% CI 1.15-1.24, p < 0.0001). When analysing components of combined FU separately, 1-year mortality was more related to cardiologist FU (HR 0.65, 95% CI 0.62-0.67, p < 0.0001), than GP FU (HR 0.87, 95% CI 0.85-0.90, p < 0.0001). Combined FU is carried out in a minority of patients following HF hospitalization, yet it is linked to a substantial reduction in 1-year mortality, albeit at the expense of an increase in HF hospitalizations.

Trends and projections of inflammatory bowel disease at the global, regional and national levels, 1990–2050: a bayesian age-period-cohort modeling study

BackgroundInflammatory bowel disease (IBD) is a global health concern with varying levels and trends across countries and regions. Understanding these differences is crucial for effective prevention and treatment strategies.MethodsUsing data from the 2019 Global Burden of Disease study, we examine IBD incidence, mortality, and disability-adjusted life years (DALYs) rates in 198 countries from 1990 to 2019. To assess changes in the burden of IBD, estimated annual percentage changes (EAPC) were calculated, and a Bayesian age-period-cohort model was used to predict the future 30-year trends of IBD.ResultsIn 2019, there were 405,000 new IBD cases globally (95% uncertainty interval (UI) 361,000 to 457,000), with 41,000 deaths (95% UI 35,000 to 45,000) and 1.62million DALYs (95% UI 1.36–1.92million). The global age-standardized incidence rate in 2019 was 4.97 per 100,000 person-years (95% UI 4.43 to 5.59), with a mortality rate of 0.54 (95% UI 0.46 to 0.59) and DALYs rate of 20.15 (95% UI 16.86 to 23.71). From 1990 to 2019, EAPC values for incidence, mortality, and DALYs rates were − 0.60 (95% UI − 0.73 to − 0.48), − 0.69 (95% UI − 0.81 to − 0.57), and − 1.04 (95% UI − 1.06 to − 1.01), respectively. Overall, the burden of IBD has shown a slow decline in recent years. In SDI stratification, regions with higher initial SDI (high-income North America and Central Europe) witnessed decreasing incidence and mortality rates with increasing SDI, while regions with lower initial SDI (South Asia, Oceania, and Latin America) experienced a rapid rise in incidence but a decrease in mortality with increasing SDI. Predictions using a Bayesian model showed lower new cases and deaths from 2020 to 2050 than reference values, while the slope of the predicted incidence-time curve closely paralleled that of the 2019 data.ConclusionIncreasing cases, deaths, and DALYs highlight the sustained burden of IBD on public health. Developed countries have stabilized or declining incidence rates but face high prevalence and societal burden. Emerging and developing countries experience rising incidence. Understanding these changes aids policymakers in effectively addressing IBD challenges in different regions and economic contexts.

Lives Versus Livelihoods: The Epidemiological, Social, And Economic Impact Of COVID-19 In Latin America And The Caribbean.

During the COVID-19 pandemic, Latin American and Caribbean countries implemented stringent public health and social measures that disrupted economic and social activities. This study used an integrated model to evaluate the epidemiological, economic, and social trade-offs in Argentina, Brazil, Jamaica, and Mexico throughout 2021. Argentina and Mexico displayed a higher gross domestic product (GDP) loss and lower deaths per million compared with Brazil. The magnitude of the trade-offs differed across countries. Reducing GDP loss at the margin by 1percent would have increased daily deaths by 0.5 per million in Argentina but only 0.3 per million in Brazil. We observed an increase in poverty rates related to the stringency of public health and social measures but no significant income-loss differences by sex. Our results indicate that the economic impact of COVID-19 was uneven across countries as a result of different pandemic trajectories, public health and social measures, and vaccination uptake, as well as socioeconomic differences and fiscal responses. Policy makers need to be informed about the trade-offs to make strategic decisions to save lives and livelihoods.

Cholesterol paradox in the community-living old adults: is higher better?

To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study. A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators. A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (Ptrend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%-4.43%) and 14.83% (95% CI: 13.79%-15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730-0.997), LDL-C (HR = 0.817, 95% CI: 0.680-0.982) and HDL-C (HR = 0.443, 95% CI: 0.271-0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501-0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010-1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death. In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.

Factors associated with unknown primary status in head and neck squamous cell carcinoma

ObjectivesHead and neck cancer of unknown primary (CUP) poses significant therapeutic challenges. We compare CUP and oropharyngeal primary (OP) cases to identify factors associated with tumor detection. MethodsThe 2004–2019 National Cancer Database was queried to identify CUP and OP cases based on clinical and pathologic TNM staging. Clinical and demographic characteristics were compared by primary detection and HPV status with descriptive statistics. Multivariable logistic regression models to characterize OP detection were constructed. Among HPV-positive and negative patients, respectively, OP and CUP patients were matched by clinical nodal disease. Cox proportional-hazards models were constructed using matched cohorts to characterize survival. Results81,053 CUP and OP cases were identified; 64.3 % were HPV-positive. OP detection increased over time in HPV-positive and negative disease. HPV-positive status had higher odds of OP detection (odds ratio (OR) = 1.77, p < 0.001), while females (OR = 0.95, p = 0.008), and black (OR = 0.82, p < 0.001) and Asian (OR = 0.7, p < 0.001) patients had lower odds compared to males and whites, respectively. In HPV-positive and negative disease, OP patients had higher 2 and 5-year survival rates than CUP (p < 0.001). Primary detection status conferred lower death risk in HPV-positive (hazard ratio (HR) = 0.85, p < 0.001) and negative disease (HR = 0.87, p < 0.001) when controlling for age, sex, race, comorbidities, insurance, treatment facility, and income. ConclusionIn the largest cohort of CUP to date, we report a survival benefit in primary tumor detection regardless of HPV status. Groups with higher persistent CUP rates, including non-white, female, HPV-negative, and low income patients, may benefit from increased diagnostic workup to improve detection and treatment.