Reduced Risk Of Mortality Research Articles

Duration of risk reduction in colorectal cancer incidence and mortality after a complete colonoscopy in Ontario, Canada: a population-based cohort study

Colorectal cancer guidelines recommend screening colonoscopy every 10 years after a negative procedure. If risk reduction extends past 10 years, the recommended interval could be extended, reducing the burden on the individual and health-care system. We aimed to estimate the duration that patients remain at reduced risk of colorectal cancer incidence and mortality after a complete colonoscopy. We did a population-based cohort study of individuals aged 50-65 years between Jan 1, 1994, to Dec 31, 2017. We excluded individuals with previous exposure to colonoscopy or colorectal surgery, those previously diagnosed with colorectal cancer, or a history of hereditary or other bowel disorders. We followed up participants until Dec 31, 2018, and identified all colonoscopies performed in this time period. We used a 9-level time-varying measure of exposure, capturing time since last complete colonoscopy (no complete colonoscopy, ≤5 years, >5-10 years, >10-15 years, and >15 years) and whether an intervention was performed (biopsy or polypectomy). A Cox proportional hazards regression model adjusting for age, sex, comorbidity, residential income quintile, and immigration status was used to estimate the association between exposure to a complete colonoscopy and colorectal cancer incidence and mortality. 5 298 033 individuals (2 609 060 [49·2%] female and 2 688 973 [50·8%] male; no data on ethnicity were available) were included in the cohort, with a median follow-up of 12·56 years (IQR 6·26-20·13). 90 532 (1·7%) individuals were diagnosed with colorectal cancer and 44 088 (0·8%) died from colorectal cancer. Compared with those who did not have a colonoscopy, the risk of colorectal cancer in those who had a complete negative colonoscopy was reduced at all timepoints, including when the procedure occurred more than 15 years earlier (hazard ratio [HR] 0·62 [95% CI 0·51-0·77] for female individuals and 0·57 [0·46-0·70] for male individuals. A similar finding was observed for colorectal cancer mortality, with lower risk at all timepoints, including when the procedure occurred more than 15 years earlier (HR 0·64 [95% CI 0·49-0·83] for female participants and 0·65 [0·50-0·83] for male participants). Those who had a colonoscopy with intervention had a significantly lower colorectal cancer incidence than those who did not undergo colonoscopy if the procedure occurred within 10 years for females (HR 0·70 [95% CI 0·63-0·77]) and up to 15 years for males (0·62 [(0·53-0·72]). Compared with those who do not receive colonoscopy, individuals who have a negative colonoscopy result remain at lower risk for colorectal cancer incidence and mortality more than 15 years after the procedure. The current recommendation of repeat screening at 10 years in these individuals should be reassessed. Canadian Institutes of Health Research.

Genetic Liability to Cardiovascular Disease, Physical Activity, and Mortality: Findings from the Finnish Twin Cohort.

We investigated whether longitudinally assessed physical activity (PA) and adherence specifically to World Health Organization PA guidelines mitigate or moderate mortality risk regardless of genetic liability to cardiovascular disease (CVD). We also estimated the causality of the PA-mortality association. The study used the older Finnish Twin Cohort with 4897 participants aged 33 to 60 yr (54.3% women). Genetic liability to coronary heart disease and systolic and diastolic blood pressure was estimated with polygenic risk scores (PRS) derived from the Pan-UK Biobank ( N ≈ 400,000; >1,000,000 genetic variants). Leisure-time PA was assessed with validated and structured questionnaires three times during 1975 to 1990. The main effects of adherence to PA guidelines and the PRS × PA interactions were evaluated with Cox proportional hazards models against all-cause and CVD mortality. A cotwin control design with 180 monozygotic twin pairs discordant for meeting the guidelines was used for causal inference. During the 17.4-yr (mean) follow-up (85,136 person-years), 1195 participants died, with 389 CVD deaths. PRS (per 1 SD increase) were associated with a 17% to 24% higher CVD mortality risk but not with all-cause mortality except for the PRS for diastolic blood pressure. Adherence to PA guidelines did not show significant independent main effects or interactions with all-cause or CVD mortality. Twins whose activity levels adhered to PA guidelines over a 15-yr period did not have statistically significantly reduced mortality risk compared with their less active identical twin sibling. The findings were similar among high, intermediate, and low genetic risk levels for CVD. The genetically informed Finnish Twin Cohort data could not confirm that adherence to PA guidelines either mitigates or moderates genetic CVD risk or causally reduces mortality risk.

Physical activity and mortality in patients with dementia: 2009-2015 National Health Insurance Sharing Service data.

The study aimed to investigate the survival rate of patients with dementia according to their level of physical activity and body mass index (BMI). A total of 5,789 patients with dementia were retrieved from the 2009-2015 National Health Insurance Sharing Service databases. Survival analysis was used to calculate the hazard ratio (HR) for physical activity and BMI. The study sample primarily comprised older adults (65-84 years old, 83.81%) and female (n = 3,865, 66.76%). Participants who engaged in physical activity had a lower mortality risk (HR = 0.91, p = 0.02). Compared to the underweight group, patients with dementia who had normal weight (HR = 0.86, p = 0.01), obesity (HR = 0.85, p = 0.03) and more than severe obesity (HR = 0.72, p = 0.02) demonstrated a lower mortality risk. This study emphasizes the significance of avoiding underweight and engaging in physical activity to reducing mortality risk in patients with dementia, highlighting the necessity for effective interventions.

Improved Early Outcomes With Off-Pump Coronary Artery Bypass Grafting in Patients With Left Ventricular Dysfunction: A Systematic Review and Meta-Analysis.

The ongoing debate surrounding coronary artery bypass grafting (CABG) with or without cardiopulmonary bypass persists, particularly in individuals with left ventricular dysfunction. The objective of this study was to evaluate the safety and efficacy of these 2 strategies through a comprehensive meta-analysis of existing studies. A systematic search of PubMed, EMBASE, Web of Science, and the Cochrane Central Registry was conducted from inception to July 2023. The primary focus was on studies comparing on-pump versus off-pump CABG as the primary treatment for multivessel coronary artery disease in patients with left ventricular dysfunction (ejection fraction ≤40%), with mortality as the primary outcome. The meta-analysis included 26 studies with a total of 35,863 patients. The results revealed a significant reduction in mortality risk [risk ratio (RR), 0.75; 95% confidence interval (CI), 0.60-0.93; P = 0.009] and other perioperative morbidities associated with off-pump CABG. These included stroke (RR, 0.67; 95% CI, 0.54-0.82; P = 0.0002), myocardial infarction (RR, 0.74; 95% CI, 0.56-0.97; P = 0.03), pulmonary complications (RR, 0.71; 95% CI, 0.55-0.92; P = 0.010), postoperative transfusion (RR, 0.70; 95% CI, 0.55-0.88; P = 0.002), neurological dysfunction (RR, 0.80; 95% CI, 0.64-1.00; P = 0.05), infection (RR, 0.74; 95% CI, 0.56-0.97; P = 0.03), renal failure (RR, 0.79; 95% CI, 0.67-0.95; P = 0.010), and reoperation for bleeding (RR, 0.66; 95% CI, 0.52-0.84; P = 0.0006). However, no significant difference was observed between the 2 groups regarding postoperative atrial fibrillation (RR, 0.97; 95% CI, 0.84-1.12; P = 0.69). In conclusion, off-pump CABG demonstrates a lower perioperative mortality risk and improved overall early outcomes compared with on-pump techniques in individuals with reduced left ventricular function.

Intensity-specific physical activity measured by accelerometer and the risk of mortality among individuals with cardiometabolic diseases: A prospective study from the UK Biobank

BackgroundWhile the health benefits of physical activity for general population are well-recognized, the prospective associations of physical activity volume and intensity with mortality among cardiometabolic disease individuals remain unclear. ObjectiveThe objective of this study was to investigate the associations of accelerometer-measured intensity-specific physical activity with mortality risk among population with cardiometabolic disease. DesignProspective cohort study. SettingParticipants were recruited from the United Kingdom (UK) across 22 assessment centers from 2006 to 2010. ParticipantsA total of 9524 participants from the UK Biobank (median: 67.00 years, interquartile range: 61.00–70.00 years) were included in final study. MethodsAccelerometer-measured total volume, moderate-to-vigorous and light intensity physical activity collecting from 2013 to 2015 were quantified using a machine learning model. Multivariable restricted cubic splines and Cox proportional hazard models with hazard ratios (HRs) and 95 % confidence intervals (CIs) were employed to examine the associations of interests. ResultsDuring the follow-up period (median: 6.87 years; interquartile range: 6.32–7.39 years), there were 659 (6.92 %) death events with 218 (2.29 %) cardiovascular disease-related deaths and 441 (4.63 %) non-cardiovascular disease-related deaths separately. In the fully adjusted models, compared with participants in the lowest quartiles of total volume, moderate-to-vigorous and light physical activities, the adjusted HRs (95 % CIs) of all-cause mortality for those in the highest quartiles were 0.40 (0.31, 0.52), 0.48 (0.37, 0.61), and 0.56 (0.44, 0.71) while those for cardiovascular diseases-related mortality were 0.35 (0.22, 0.55), 0.52 (0.35, 0.78) and 0.59 (0.39, 0.88), and for non-cardiovascular diseases-related mortality, they were 0.42 (0.30, 0.59), 0.40 (0.29, 0.54) and 0.54 (0.40, 0.73), separately. The optimal moderate-to-vigorous-intensity physical activity level for cardiovascular diseases-related mortality reduction was found to be in the third quartile (17.75–35.33 min/day). Furthermore, the observed inverse associations were mainly non-linear. ConclusionsPromoting physical activity, regardless of intensity, is essential for individuals with cardiometabolic disease to reduce mortality risk. For both all-cause and cardiovascular disease-related and non-cardiovascular disease-related mortality, the observed decrease in risk seems to level off at a moderate level. The current findings deriving from precise device-based physical activity data provide inference for secondary prevention of cardiometabolic disease.

Understanding Patterns of Adherence to Antifibrotic Treatment in Idiopathic Pulmonary Fibrosis: Insights from an Italian Prospective Cohort Study.

Background: Pirfenidone and Nintedanib have significantly improved the prognosis of patients with idiopathic pulmonary fibrosis (IPF), reducing mortality risk and exacerbations. This study aimed to analyze antifibrotic treatment utilization and its association with clinical outcomes (i.e., acute exacerbation or death) during 2014-2021 in newly diagnosed IPF patients, using Healthcare Utilization Databases of the Marche Region, Italy. Methods: The first 12-month adherence to antifibrotic was estimated using the Proportion of Days Covered (PDC), defining adherence as PDC ≥ 75%. State Sequence Analysis over the initial 52 weeks of treatment was used to identify adherence patterns. The role of adherence patterns on acute exacerbations/death, adjusted by demographic, clinical features, and monthly adherence after the 52-week period (time-dependent variable), was assessed with Cox regression. Results: Among 667 new IPF cases, 296 received antifibrotic prescriptions, with 62.8% being adherent in the first year. Three antifibrotic utilization patterns emerged-high adherence (37.2%), medium adherence (42.5%), and low adherence (20.3%)-with median PDCs of 95.3%, 79.5%, and 18.6%, respectively. These patterns did not directly influence three-year mortality/exacerbation probability, but sustained adherence reduced risk over time. Conclusions: Good adherence was observed in in this population-based study, emphasizing the importance of continuous antifibrotics therapy over time to mitigate adverse outcomes.

Changes in sleep score and leisure-time physical activity, their combination, and all-cause mortality in middle-aged and older Chinese adults: The Dongfeng-Tongji cohort study

ObjectivesTo prospectively investigate the associations of longitudinal changes in sleep score and LTPA and their combination with all-cause mortality. MethodsAmong 12,543 participants (mean age: 66.1 years) from the Dongfeng-Tongji cohort, we calculated sleep score (range, 0–4, integrating bedtime, sleep duration, sleep quality, and midday napping, higher score indicating healthier sleep) and LTPA at baseline (2008–2010) and the first follow-up (2013) surveys and their 5-year changes (defining stable sleep score as no change and stable LTPA as change within 150 min/week). We prospectively documented deaths from the first follow-up survey (2013) through December 31, 2018. ResultsDuring a mean 5.5-year follow-up, 792 deaths occurred. The 5-year changes in sleep score and LTPA were inversely associated with all-cause mortality risk, regardless of their initial values. When assessing 5-year changes in sleep score and LTPA jointly, compared with the stable sleep score-stable LTPA group, the decreased sleep score-decreased LTPA group had a 40 % (5–85 %) higher all-cause mortality risk, whereas the increased sleep score-increased LTPA group had a 34 % (9–52 %) lower risk. The direction of the joint association was mainly driven by sleep score change. Participants maintaining sleep scores ≥ 3 and LTPA ≥ 150 min/week over 5 years had a 44 % (28–56 %) lower all-cause mortality risk. ConclusionsPromoting sleep hygiene and LTPA together may benefit efforts in reducing mortality risk, with particular attention to monitoring long-term sleep health.

Association of lifestyles and multimorbidity with mortality among individuals aged 60 years or older: Two prospective cohort studies

Lifestyles are associated with all-cause mortality, yet limited research has explored the association in the elderly population with multimorbidity. We aim to investigate the impact of adopting a healthy lifestyle on reducing the risk of all-cause mortality in older individuals with or without multimorbidity in both China and UK. This prospective study included 29,451 and 173,503 older adults aged 60 and over from Chinese Longitudinal Healthy Longevity Survey (CLHLS) and UK Biobank. Lifestyles and multimorbidity were categorized into three groups, respectively. Cox proportional hazards regression was used to estimate the Hazard Ratios (HRs), 95% confidence intervals (95% CIs), and dose-response for all-cause mortality in relation to lifestyles and multimorbidity, as well as the combination of both factors. During a mean follow-up period of 4.7 years in CLHLS and 12.14 years in UK Biobank, we observed 21,540 and 20,720 deaths, respectively. For participants with two or more conditions, compared to those with an unhealthy lifestyle, adopting a healthy lifestyle was associated with a 27%–41% and 22%–42% reduction in mortality risk in the CLHLS and UK Biobank, respectively; Similarly, for individuals without multimorbidity, this reduction ranged from 18% to 41%. Among participants with multimorbidity, individuals with an unhealthy lifestyle had a higher mortality risk compared to those maintaining a healthy lifestyle, with HRs of 1.15 (95% CI: 1.00, 1.32) and 1.27 (95% CI: 1.16, 1.39) for two conditions, and 1.24 (95% CI: 1.06, 1.45) and 1.73 (95% CI: 1.56, 1.91) for three or more conditions in CLHLS and UK Biobank, respectively. Adherence to a healthy lifestyle can yield comparable mortality benefits for older individuals, regardless of their multimorbidity status. Furthermore, maintaining a healthy lifestyle can alleviate the mortality risks linked to a higher number of diseases.

Abstract PO1-17-07: Invasive disease-free survival as a surrogate for overall survival in patients with hormone receptor−positive/human epidermal growth factor receptor 2−negative early breast cancer: a real-world analysis

Abstract Background: Although the goal of treatment is to improve overall survival (OS), in the adjuvant setting, disease-free survival (DFS) is an important endpoint because DFS risk reduction may reduce mortality risk. After introduction of the STEEP criteria, invasive DFS (iDFS) was adopted as an objective, well accepted primary endpoint in early breast cancer (EBC) trials. This analysis evaluated iDFS as a surrogate for OS in the HR+/HER2− EBC adjuvant treatment setting using real-world data. Methods: This retrospective analysis of the ConcertAI Patient360 database contains deidentified electronic medical records of patients (pts) treated at US academic and community oncology clinics from Jan 1, 1995 to Apr 30, 2021. The cohort included pts with AJCC (8th ed.) stage II-III (if IIIB or IIIC, confirmation was required on residual tumor status; pathological and/or clinical staging [pathological stage was prioritized if both existed in the record]) HR+/HER2− EBC who had surgery and initiated adjuvant endocrine therapy (ET); ovarian function suppression was permitted. iDFS (disease recurrence, metastasis, second primary tumor, or death) and OS (death due to any cause) were defined as time between ET start and first qualifying event. Pts not experiencing an event were censored at data cutoff or maximum follow-up (whichever was first) for iDFS and maximum follow-up for OS. Correlation analyses between individual iDFS and OS times were performed using Pearson and Spearman correlations and an iterative multiple imputation (IMI) algorithm. Subgroup analyses were conducted by first ET, menopausal status (imputed as 50 years if missing), stage, nodal status, prior (neo)adjuvant chemotherapy, and prior radiation. Results: In total, 3133 pts were analyzed. Mean (SD) age (index or ET initiation date) was 58.4 (12.4) years; 98.8% of pts were female, 29.9% were premenopausal, 80.9% had stage II disease, 57.1% had nodal involvement, and 41.6% and 48.8% had received (neo)adjuvant chemotherapy and radiation therapy. Overall, 1854 and 653 pts received nonsteroidal aromatase inhibitors and tamoxifen only. The median follow-up time was 55.1 months for iDFS and 68.2 months for OS. The iDFS (1103 events [35.2%]) rates were 88.9% and 73.9% at 2 and 5 years. The OS (554 events [17.7%]) rates were 97.4% and 90.5% at 2 and 5 years. There was a significant and high correlation ( >0.85 based on IQWiG 2011 guidelines) between iDFS and OS in the overall cohort (Pearson 0.91, P< .001; Spearman 0.88, P< .001) with 82% of OS variation explained by iDFS (least square R2=0.82; Table). Results were confirmed by IMI rho (0.83, P< .001), which is interpreted as very strong ( >0.8). Results were consistent among all reported subgroups; Pearson and Spearman correlations exceeded 0.85 and IMI exceeded 0.8, except for pts with stage III disease where correlation remained high (Pearson 0.88, P< .001) or medium/strong (Spearman 0.84, P< .001; IMI 0.79, P< .001) and where most censoring was observed (38.2% of pts). Conclusions: This retrospective cohort analysis demonstrates a very strong pt-level surrogacy between iDFS and OS among pts with HR+/HER2− EBC treated in a real-world, US-based, academic and community setting. The findings complement the trial-level surrogacy from prior analyses using data from randomized controlled trials and support iDFS as a surrogate endpoint for OS in HR+/HER2− EBC trials. Citation Format: Stephanie Graff, Sara Tolaney, Lowell Hart, Pedram Razavi, Wolfgang Janni, Lee Schwartzberg, Andrii Danyliv, Juan Carlos Mora Payan, Ilia Ferrusi, Rishi Rajat Adhikary, Joyce O'Shaughnessy. Invasive disease-free survival as a surrogate for overall survival in patients with hormone receptor−positive/human epidermal growth factor receptor 2−negative early breast cancer: a real-world analysis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-17-07.

Statistical analysis plan for the replacing protein via enteral nutrition in a stepwise approach in critically ill patients (REPLENISH) randomized clinical trial

BackgroundThe optimal amount and timing of protein intake in critically ill patients are unknown. REPLENISH (Replacing Protein via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial evaluates whether supplemental enteral protein added to standard enteral nutrition to achieve a high amount of enteral protein given from ICU day five until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve a moderate amount of enteral protein would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients.MethodsIn this multicenter randomized trial, critically ill patients will be randomized to receive supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition to achieve a high amount of enteral protein (range of 2–2.4 g/kg/day) or no supplemental enteral protein to achieve a moderate amount of enteral protein (0.8–1.2 g/kg/day). The primary outcome is 90-day all-cause mortality; other outcomes include functional and health-related quality-of-life assessments at 90 days. The study sample size of 2502 patients will have 80% power to detect a 5% absolute risk reduction in 90-day mortality from 30 to 25%. Consistent with international guidelines, this statistical analysis plan specifies the methods for evaluating primary and secondary outcomes and subgroups. Applying this statistical analysis plan to the REPLENISH trial will facilitate unbiased analyses of clinical data.ConclusionEthics approval was obtained from the institutional review board, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia (RC19/414/R). Approvals were also obtained from the institutional review boards of each participating institution. Our findings will be disseminated in an international peer-reviewed journal and presented at relevant conferences and meetings.Trial registrationClinicalTrials.gov, NCT04475666. Registered on July 17, 2020.

Abstract PO5-11-08: Assessing practice patterns of antidepressant medication and tamoxifen use among patients with hormone receptor-positive breast cancer

Abstract Background: Treatment with endocrine therapy such as tamoxifen has been identified as one of the most important variables linked with survival among women with hormone receptor-positive breast cancer (BC). There is significant risk reduction of BC recurrence and BC mortality at 15 years among patients treated with tamoxifen for 5 years compared to no endocrine therapy. Tamoxifen is metabolized in the liver via multiple cytochrome P (CYP) isoforms. To ensure optimal efficacy of tamoxifen, consideration must be given to concomitant use of other commonly prescribed drugs such as antidepressants. Some selective serotonin reuptake inhibitors (SSRIs) are potent inhibitors of CYP2D6, an enzyme that metabolizes tamoxifen into its active metabolite, endoxifen, which has anti-tumor effect. Such inhibition can reduce the plasma concentration of endoxifen which could lead to higher rates of BC recurrence. This resulted in an FDA black box warning discouraging concurrent prescriptions of tamoxifen and SSRIs, yet clinical data to support this warning is lacking. Our aim is to describe the practice patterns of concomitant use of tamoxifen and antidepressant medication at our institution. Methods: This is a single institution retrospective study that included adult women, ages 18-99, with stage I-IV BC, who received adjuvant tamoxifen and were taking an antidepressant medication between years 2016-2021. Patients were identified from a tumor registry database. Patient demographics and tumor characteristics were collected via electronic medical record. Results: A total of 419 patients met the inclusion criteria. At the start of tamoxifen therapy, 348 women were on at least one antidepressant, mostly for Major Depressive Disorder (86%). Of those women, 22% were prescribed a strong/moderately potent CYP inhibitor (paroxetine, fluoxetine, duloxetine, or bupropion) and 43% were prescribed weak or non-CYP inhibiting SSRIs (citalopram, escitalopram, fluvoxamine, and sertraline). The most commonly prescribed antidepressants at the start of tamoxifen, alone or in combination with a second antidepressant, were: venlafaxine (30%), escitalopram (17%), sertraline (13%), citalopram (12%) and duloxetine (10%). Main prescribers of antidepressants were primary care physicians (70%), psychiatrists (10%) followed by academic medical oncologists (7%) and regional medical oncologists (6%). Interestingly, the majority of women continued taking the same antidepressant after starting tamoxifen (76%) while, at least 10% of patients changed anti-depressant classes prior to starting tamoxifen, due to concern for drug-drug interaction. When a different class of antidepressant was chosen after starting tamoxifen (22%), serotonin and norepinephrine reuptake inhibitors (SNRIs) were the most frequent class (48%), followed by a different SSRI (42%). The time in which the antidepressant change occurred was variable, but most commonly prior to initiating tamoxifen. Conclusion: Concurrent use of tamoxifen and antidepressant medications is common. Theoretical risk of reduced efficacy of tamoxifen with inhibitors of CYP leads to medication changes for some but not all patients requiring tamoxifen and an antidepressant medication. This can have clinical implications as stability on a specific antidepressant is important for patients and adjustment may impact control of their mood disorder. In some cases, even if a drug-drug interaction was identified, some patients chose to continue their current antidepressant due to concerns of mood de-stabilization, and in other cases, aromatase inhibitors were started as an alternative. These findings highlight differences in practice patterns for which additional guidance may be helpful in bringing awareness and standardization to care. Citation Format: Mariah Ondeck, Bennett Osantowski, Nerea Lopetegui-Lia, Wei Wei, Alexandra Murray, Amanda Maggiotto, Halle Moore, Erin Roesch. Assessing practice patterns of antidepressant medication and tamoxifen use among patients with hormone receptor-positive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-11-08.

Benefits of using SLGT2 Inhibitors for Patients with CDK and DM2 to Reduce Mortality Risks

Type 2 diabetes mellitus (T2DM) is the most common cause of chronic kidney disease (CKD). CKD is characterized by progressive liver tissue damage and is an important risk factor for mortality due to renal and cardiovascular outcomes. Thus, randomized clinical trials have investigated the use of sodium-glucose cotransporter 2 (SLGT2) inhibitors as a promising therapy for patients with CKD and T2DM. This study aimed to analyze the benefits of using SGLT2 inhibitors in patients with CKD and T2DM to reduce mortality risks. To this end, a qualitative, descriptive methodological approach was adopted using a literature review in the PubMed, Embase, and VHL databases. The inclusion criteria were clinical trial articles, randomized or non-randomized, cohort studies, case-control studies, and open access, published in Portuguese and English, between 2018 and 2023 with topics associated with SGLT2 inhibitors, CDK, and T2DM patients. In this context, it was observed that the risk of death from CKD in patients treated with Canaglifozin was 30% lower than in those treated with a placebo and that Dapaglifozin prolonged survival. In this context, when assessing the progression of kidney disease or death from cardiovascular causes in patients taking Empagliflozin, only 13.1% achieved the outcome compared to 16.9% on placebo, so the drug safely reduces the risk of mortality. Consequently, SGLT2 inhibitors have shown excellent results in the treatment of CDK and T2DM, with a reduction in the risk of mortality, positive effects on reducing renal and cardiovascular outcomes, as well as prolonging survival.

Cardiorespiratory fitness is a strong and consistent predictor of morbidity and mortality among adults: an overview of meta-analyses representing over 20.9 million observations from 199 unique cohort studies

ObjectiveTo examine and summarise evidence from meta-analyses of cohort studies that evaluated the predictive associations between baseline cardiorespiratory fitness (CRF) and health outcomes among adults.DesignOverview of systematic reviews.Data sourceFive bibliographic...

PERSPECTIVES OF PEOPLE WITH CHRONIC KIDNEY DISEASE REGARDING DIGITAL HEALTH INTERVENTIONS THAT PROMOTE A HEALTHY LIFESTYLE: QUALITATIVE SYSTEMATIC REVIEW

Chronic kidney disease (CKD) is a life-limiting condition that affects 1 in 10 adults and accounts for 12% of all deaths in Australia. Diet and physical activity are crucial to attenuate disease progression and reduce mortality risk. Digital health interventions have been proposed as a feasible model to deliver lifestyle interventions. Users’ perspectives are key to ensure the intervention is aligned with their needs and goals. As such, this systematic review aimed to synthesise the perspectives of people with CKD and develop higher order concepts that elucidate users’ preferences regarding digital health interventions that promote heathy lifestyle. This was a qualitative systematic review. A database search was conducted on CENTRAL, Scopus, MEDLINE, CINAHL and SPORTDiscus between 2000-2023. Eligibility criteria included primary research that reported the preferences of adults with CKD regarding digital lifestyle interventions. Two independent reviewers completed title, abstract and full text screening. Quotes were extracted verbatim, coded and categorised. Categories were then used to generate themes. Database search identified 5,761 records. One additional record was included following communication with a primary author. Fifteen papers were eligible, including 197 participants (age 51.0±7.2 years; 47% female). There were 83 people with CKD 1-5; 61 transplant recipients; and 53 people receiving maintenance dialysis. The overarching theme identified was that people with CKD considered digital interventions to be important platforms to access lifestyle interventions. There were five underlying themes that elucidated users’ preferences for digital interventions, including simple instruction and engaging design; individualised interventions; virtual communities of care; education and action plans; and timely reminders and automated behavioural monitoring. Digital health interventions were considered important platforms to deliver lifestyle interventions. Future research may apply users’ preferences in this review to inform the development and conduct of a digital lifestyle intervention for people with CKD.

Explanatory Role of Conversion Surgery as a Mediator of the Mortality Risk Difference Between Patients With Unresectable Metastatic Colorectal Cancer Treated With First-Line Anti-EGFR Agents Versus Bevacizumab

IntroductionBevacizumab and antiepidermal growth factor receptor-blocking (anti-EGFR) agents plus chemotherapy are first-line therapies for metastatic colorectal cancer (mCRC). Conversion surgery may improve outcomes; however, the extent to which it explains the difference in mortality rates among treatments is unclear. Herein, we aimed to assess the effects of conversion surgery on survival outcomes of patients with unresectable mCRC treated with bevacizumab and anti-EGFR agents. Materials and methodsThis retrospective cohort study included patients with mCRC treated with bevacizumab and anti-EGFR agents as first-line therapy. We estimated the direct and indirect effects of treatments by comparing the mortality risk associated with targeted therapy type. Hazard ratios (HR) and the corresponding confidence intervals (CI) were estimated. Mediation analysis was used to estimate hazard ratio differences, and the proportion mediated. ResultsA total of 5,106 patients were included. The natural indirect effect of conversion surgery reduced mortality risk (HR: 0.95; 95% CI, 0.93-0.97), with a mediated proportion of 42% after propensity score adjustment. In subgroup analyses, KRAS wild-type (HR: 0.94; 95% CI: 0.91-0.97), left tumor sidedness (HR: 0.94; 95% CI, 0.91-0.96), and liver resection (HR: 0.95; 95% CI, 0.93-0.98) were associated with reduced risks of mortality. The controlled and total direct effects of targeted therapy were associated with reduced mortality risk in the anti-EGFR-treated group compared to those in the bevacizumab-treated group; however, this effect was not statistically significant. ConclusionConversion surgery may account for the difference in survival outcomes between users of the anti-EGFR agents and bevacizumab.

Long-Term Survivability of Surgical and Non-Surgical Management of Spinal Epidural Abscess

Spinal epidural abscess (SEA) is a rare and life-threatening infection within the epidural space with significant functional impairment and morbidity. Active debate remains over whether to operate for SEAs, with limited existing data comparing the long-term survivability after surgical versus nonsurgical management. This study aims to determine the long-term survival of patients who underwent surgical and nonsurgical management for SEA. Retrospective cohort study. A total of 250 consecutive SEA patients. Survival and mortality rates, complications. All patients treated at a tertiary medical center for a primary SEA from January 2000 to June 2020 are identified. Data collection is by retrospective chart review. Cox proportional hazards regression models are used for all survival analyses while controlling for potential confounding variables and with multiple testing corrections. A total of 35 out of 250 patients died with an overall all-cause mortality of 14%. More than half of all deaths occurred within 90 days after treatment. The 90-day, 3-year, and 5-year survival rates are 92.8%, 89.2%, and 86.4%, respectively. Among surgery patients, the all-cause mortality was 13.07%, compared to 16.22% for medically-managed patients. Surgical treatment (decompression, fusion, debridement) significantly reduced the risk of death by 62.4% compared to medical therapy (p=.03), but surgery patients experienced a significantly longer mean length of stay (p=.01). Risk factors of short-term mortality included hypoalbuminemia (<3.5 g/dL), American Society of Anesthesiologists (ASA) 4+, and cardiac arrest. Risk factors of long-term mortality were immunocompromised state, elevated WBC count >12,000, sepsis, septic shock, ASA 4+, and cardiac arrest (p<.05). In terms of complications, surgically-managed patients experienced a higher proportion of deep vein thrombosis (p<.05). The overall long-term survivability of SEA treatment is relatively high at (86% at 5-year) in this study. The following SEA mortality risk factors were identified: hypoalbuminemia (short-term), immunocompromised state (long-term), leukocytosis (long-term), sepsis and septic shock (long-term), ASA 4+ and cardiac arrest (overall). For primary SEA patients, surgical management may reduce mortality risk compared to nonsurgical management.

Gender Differences in Patients with Gastric Adenocarcinoma.

Background: Gastric cancer (GC) epidemiology and outcomes vary by gender. Methods: We reviewed 18,436 GC patients from 2008 to 2018 and looked for gender differences in clinical characteristics and survival. Results: The gender proportion was 71% male and 29% female. Males had a significantly (p < 0.001) higher proportion of differentiated GC (66.3%) and a lower proportion of undifferentiated GC (26.3%). Diagnosis through medical check-ups was more common in males (30.0% vs. 26.4%, p < 0.001). Clinical staging revealed 54.6% of males and 52.9% of females had localized disease without lymph node metastasis (LNM), while distant metastasis occurred in 17.4% of males and 16.9% of females (p < 0.001). Kaplan-Meier survival curves indicated females had a significantly higher overall survival (p = 0.0018). The survival advantage for females was evident in the early stages, with a significant difference in localized disease without LNM (p < 0.001) and localized disease with LNM (p = 0.0026, log-rank test) but not in the advanced stages. Multivariate Cox regression analysis showed a significantly reduced mortality risk in females (p < 0.001). Conclusions: Significant gender differences exist with regard to pathological type, presentation, clinical stage, and overall survival. These findings suggest gender-specific strategies for screening, diagnosis, and treatment.

Real life experience on the use of Remdesivir in patients admitted to COVID-19 in two referral Italian hospital: a propensity score matched analysis

Remdesivir (RDV) was the first Food and Drug Administration (FDA)-approved medication for COVID-19, with discordant data on efficacy in reducing mortality risk and disease progression. In the context of a dynamic and rapidly changing pandemic landscape, the utilization of real-world evidence is of utmost importance. The objective of this study is to evaluate the impact of RDV on patients who have been admitted to two university referral hospitals in Italy due to COVID-19. All patients older than 18 years and hospitalized at two different universities (Bari and Palermo) were enrolled in this study. To minimize the effect of potential confounders, we used propensity score matching with one case (Remdesivir) and one control that never experienced this kind of intervention during hospitalization. Mortality was the primary outcome of our investigation, and it was recorded using death certificates and/or medical records. Severe COVID-19 was defined as admission to the intensive care unit or a qSOFAscore ≥ 2 or CURB65scores ≥ 3. After using propensity score matching, 365 patients taking Remdesivir and 365 controls were included. No significant differences emerged between the two groups in terms of mean age and percentage of females, while patients taking Remdesivir were less frequently active smokers (p < 0.0001). Moreover, the patients taking Remdesivir were less frequently vaccinated against COVID-19. All the other clinical, radiological, and pharmacological parameters were balanced between the two groups. The use of Remdesivir in our cohort was associated with a significantly lower risk of mortality during the follow-up period (HR 0.56; 95% CI 0.37–0.86; p = 0.007). Moreover, RDV was associated with a significantly lower incidence of non-invasive ventilation (OR 0.27; 95% CI 0.20–0.36). Furthermore, in the 365 patients taking Remdesivir, we observed two cases of mild renal failure requiring a reduction in the dosage of Remdesivir and two cases in which the physicians decided to interrupt Remdesivir for bradycardia and for QT elongation. Our study suggests that the use of Remdesivir in hospitalized COVID-19 patients is a safe therapy associated with improved clinical outcomes, including halving of mortality and with a reduction of around 75% of the risk of invasive ventilation. In a constantly changing COVID-19 scenario, ongoing research is necessary to tailor treatment decisions based on the latest scientific evidence and optimize patient outcomes.

Combining Spirometry and the ARISCAT Respiratory Risk Assessment Can Improve Postoperative Outcomes and Reduce Mortality Risk in Mexico

IntroductionAlthough a major goal of preoperative evaluation is to identify risk factors and improve postoperative outcomes, current clinical guidelines in Mexico indicate that preoperative spirometry should only be performed on patients with pulmonary disease. The aim of this study was to compare the incidence of postoperative complications (POC), mortality, and risk factors among adults who did or did not undergo preoperative spirometry, based on their Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) risk level. Material and methodsAn observational, retrospective and comparative study design was used to identify 2059 patients from the General Hospital of Mexico who had an ARISCAT assessment during 2013–2017. Patients were classified in two groups: ARISCAT with spirometry (n=1306) and ARISCAT without spirometry (n=753). Chi-square, Fisher's exact test and the Student's t-tests were used to compare groups. Logistic regression was used to identify factors associated with an increased risk of POC and mortality. ResultsIn the ARISCAT with spirometry group, 11% of patients had POC, compared with 48% of patients in the ARISCAT without spirometry group. High-risk ARISCAT patients who did not receive spirometry had higher mortality (18%), than those who underwent spirometry (0.4%). Logistic regression results indicate that not performing preoperative spirometry increases the probability of POC and mortality. ConclusionsOur findings suggest that the combined use of preoperative spirometry and ARISCAT is associated with reduced POC and mortality. Future clinical guidelines should recommend the use of preoperative spirometry for patients with a moderate or high ARISCAT level in Mexico.

The economic burden of obesity in 2024: a cost analysis using the value of a statistical life

ABSTRACT In 2024, the economic burden of obesity remains a paramount global concern due to its escalating prevalence, which imposes substantial pressures on healthcare systems, hampers productivity, and detracts from the quality of life. This paper explores the evolving obesity epidemic and its economic ramifications, emphasizing the necessity of precise measurement techniques to inform policy development and resource allocation. The study adopts the Value of a Statistical Life (VSL) methodology, which provides an innovative approach to quantifying the monetary value of mortality risk reductions associated with obesity-related health conditions. This approach surpasses traditional cost analyses that focus on direct medical expenses by incorporating a willingness-to-pay metric, reflecting societal preferences for risk mitigation. Our findings present a comprehensive cost analysis for the year 2024, utilizing both total deaths and Disability-Adjusted Life Years (DALYs) within the VSL framework, highlighting the importance of such an approach in understanding the full economic impact of obesity on a global scale.