Significant Reduction In Mortality Risk Research Articles

The Prognosis and Outcomes of Acutely Ill Patients Admitted to “Hospital-at-home” Programs Versus Patients with Similar Attributes Admitted to Internal Hospital Wards

Hospital-at-home programs have shown clinical and economic benefits globally but are still in the early stages in Israel for acute care. This study evaluated hospital-at-home units’ clinical, safety, and economic outcomes compared to internal wards. The study assesses hospital-at-home units’ clinical, safety, and economic outcomes versus internal wards for acutely ill patients. This retrospective matched cohort study assessed the impact of at-home hospitalization on patient survival. Patients admitted from the emergency room to at-home hospitalization were matched 2:1 with patients admitted to internal wards based on demographic and clinical characteristics using propensity score matching. The primary outcome was the rate of readmissions at 30 days. After matching, 645 individuals were included: 215 in the hospital-at-home group and 430 in the control group. Baseline characteristics were well-balanced. After 30 days, 6 individuals in the study group and 38 in the control group had died. The study group’s overall mortality rate was significantly lower (2.79% vs 8.84%, p = .0043). The hazard ratio for the control group compared to the study group was 1.907 (95% CI 1.227-2.963), indicating a 90% increased risk of death. The primary outcome of readmissions at 30 days did not differ significantly between groups. Secondary outcomes showed substantially lower healthcare resource use in the study group. Hospital-at-home units are a safe alternative to internal wards, offering significant mortality risk reduction and lower healthcare resource use. These findings support the feasibility of implementing hospital-at-home units for acute care in Israel.

Modeling mortality prediction in older adults with dementia receiving COVID-19 vaccination

ObjectiveThis study compared COVID-19 outcomes between vaccinated and unvaccinated older adults with and without cognitive impairment.MethodElectronic health records from Israel from March 2020-February 2022 were analyzed for a large cohort (N = 85,288) aged 65 + . Machine learning constructed models to predict mortality risk from patient factors. Outcomes examined were COVID-19 mortality and hospitalization post-vaccination.ResultsOur study highlights the significant reduction in mortality risk among older adults with cognitive disorders following COVID-19 vaccination, showcasing a survival rate improvement to 93%. Utilizing machine learning for mortality prediction, we found the XGBoost model, enhanced with inverse probability of treatment weighting, to be the most effective, achieving an AUC-PR value of 0.89. This underscores the importance of predictive analytics in identifying high-risk individuals, emphasizing the critical role of vaccination in mitigating mortality and supporting targeted healthcare interventions.ConclusionsCOVID-19 vaccination strongly reduced poor outcomes in older adults with cognitive impairment. Predictive analytics can help identify highest-risk cases requiring targeted 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.

Abstract CT252: Nicotinamide in combination with EGFR-TKIs for the treatment of stage IV lung adenocarcinoma with EGFR mutations: A randomized double-blind (Phase IIb) trial

Abstract Background: RUNX3 is a tumor suppressor gene, which is inactivated in approximately 70% of lung adenocarcinomas. Nicotinamide, a sirtuin inhibitor, has demonstrated potential in re-activating epigenetically silenced RUNX3 in cancer cells. This study assessed the therapeutic benefits of combining nicotinamide with first-generation EGFR-TKIs for patients with stage IV lung cancer carrying EGFR mutations. Patients and Methods: We assessed the impact of nicotinamide on carcinogen-induced lung adenocarcinomas in mice and observed that nicotinamide increased RUNX3 levels and inhibited lung cancer growth. Subsequently, 110 consecutive patients with stage IV lung cancer who had EGFR mutations were recruited: 70 females (63.6%) and 84 never-smokers (76.4%). The patients were randomly assigned to receive either nicotinamide (1 g/day, n = 55) or placebo (n = 55). The primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS), respectively. Results: After a median follow-up of 54.3 months, the nicotinamide group exhibited a median PFS of 12.7 months (95% CI, 10.4-18.3), while the placebo group had a PFS of 10.9 months (9.0-13.2; p = 0.2). The median OS was similar in the two groups (31.0 months with nicotinamide vs. 29.4 months with placebo; p = 0.2). Notably, subgroup analyses revealed a significant reduction in mortality risk for females (p = 0.01) and never-smokers (p = 0.03) treated with nicotinamide. Conclusion: The addition of nicotinamide with EGFR-TKIs demonstrated potential improvements in PFS and OS, with notable survival benefits for female patients and those who had never smoked. (ClinicalTrials.gov Identifier: NCT02416739) Citation Format: Cheol-Kyu Park, Hyung-Joo Oh, Suk-Chul Bae, In-Jae Oh, Kyoung-Mi Jung, Da-Mi Kim, Jung-Won Lee, Chang Kyun Kang, Il Yeong Park, Young-Chul Kim. Nicotinamide in combination with EGFR-TKIs for the treatment of stage IV lung adenocarcinoma with EGFR mutations: A randomized double-blind (Phase IIb) trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT252.

Impact of Pre-Infection COVID-19 Vaccination on the Incidence and Severity of Post-COVID Syndrome: A Systematic Review and Meta-Analysis.

This systematic review critically evaluated the impact of a pre-infection COVID-19 vaccination on the incidence and severity of post-COVID-19 syndrome and aimed to assess the potential protective effect across different vaccines and patient demographics. This study hypothesized that vaccination before infection substantially reduces the risk and severity of post-COVID-19 syndrome. In October 2023, a comprehensive literature search was conducted across three databases, PubMed, Embase, and Scopus, focusing on studies published up to that date. Utilizing a wide array of keywords, the search strategy adhered to the PRISMA guidelines and was registered in the Open Science Framework. The inclusion criteria comprised studies focusing on patients with a breakthrough SARS-CoV-2 infection who developed post-COVID-19 syndrome. We included a total of 13 articles that met the inclusion criteria, analyzing more than 10 million patients with a mean age of 50.6 years, showing that the incidence of intensive care unit (ICU) admissions post-vaccination was as low as 2.4%, with a significant reduction in mortality risk (OR 0.66, 95% CI 0.58-0.74). The prevalence of post-COVID-19 syndrome symptoms was lower in vaccinated individuals (9.5%) compared to unvaccinated (14.6%), with a notable decrease in activity-limiting symptoms (adjusted OR 0.59, 95% CI 0.48-0.73). Vaccinated patients also showed a quicker recovery and return to work (HR 1.37, 95% CI 1.04-1.79). The pooled odds ratio of 0.77 indicates that vaccination is associated with a 23% reduction in the risk of developing post-COVID-19 syndrome (95% CI 0.75-0.79). Despite the protective effects observed, a substantial heterogeneity among the studies was noted. In conclusion, a pre-infection COVID-19 vaccination is associated with a significant reduction in the risk and severity of post-COVID-19 syndrome. However, the observed heterogeneity across studies suggests a need for further research with standardized methods to fully comprehend vaccine efficacy against long COVID.

Real-world progression in the survival of de novo Metastatic prostate cancer over the past decade

BackgroundThe impact of evolving treatment strategies for metastatic prostate cancer (mPCa) on real-world survival is not well understood. We analyzed changes in mPCa survival over the past decade and discussed the potential driving factors behind these changes. MethodsOur study involved 43,228 mPCa patients (2004–2020) from the SEER database, divided into 4 diagnostic periods. We used a multivariate Cox proportional hazards model to evaluate diagnostic periods' influence on overall mortality (OM) and prostate cancer-specific mortality (PSM), and calculated relative median survival improvements between adjacent periods. Subgroup analyses based on age and distant metastasis sites were conducted. ResultsPatients diagnosed in 2016 to 2020 experienced significantly reduced mortality risk compared to those in 2004 to 2007 (HR 0.64 for OM, HR 0.62 for CSM, both P < 0.001). The study period witnessed an absolute improvement in median overall survival (OS) and prostate cancer-specific survival (PCSS), 17 months (54.8%) and 25 months (67.6%) respectively. The most rapid relative survival improvement occurred post-2016, with a 29.7% increase in median OS and a 37.8% increase in PCSS compared to 2012 to 2015. There was a significant reduction in mortality risk throughout the study period in both age groups (age <75 and ≥75), but absolute survival gains were smaller in the older group (24 months [68.6%] vs. 8 months [32%] for OS, 36 months [90.0%] vs. 11 months [33.3%] for PCSS), with lower relative survival improvements after 2016 (37.2% vs. 17.9% for OS, 49% vs. 22.2% for PCSS). All metastasis site subgroups (except M1a) exhibited a significant reduction in mortality risk (all P < 0.001). Absolute survival improvements were 58 months (134.9%) for M1a, 16 months (50.0%) for M1b, and 17 months (54.8%) for M1c. ConclusionThe survival of mPCa have significantly improved over the past decade, although the progress is slower in elderly patients. Investigating the underlying reasons for survival differences among various patient profiles can further refine mPCa treatment strategies.

Abstract 18349: The Impact of Concomitant Mitral Regurgitation on Aortic Valve Intervention Outcomes in Paradoxical Low-Flow Low-Gradient Severe Aortic Stenosis

Background: Patients with paradoxical low flow low gradient severe aortic stenosis (LFLGAS) exhibit low transvalvular flow rates due to reduced stroke volumes, while maintaining preserved left ventricular ejection fraction (LVEF). The presence of mitral regurgitation (MR) adds complexity to this already challenging diagnosis, by further lowering flow rate. However, the impact of aortic valve intervention in this patient population remains uncertain. Methods: A total of 1178 patients were included from an institutional echo database with adjudicated aortic valve area (AVA &lt;1.0 cm2), transaortic gradients (mean gradient&lt; 40 mmHg) and low flow rate (Q ≤210 ml/sec), to confirm the diagnosis of LFLGAS and preserved LVEF (&gt;50%). Subgroups were formed based on the presence of severe MR and subsequent surgical and transcatheter aortic valve intervention (SAVR/TAVR). Patients who underwent mitral valve intervention were censored. All-cause mortality was assessed as the primary outcome. Results: Patients with severe MR had significantly lower flow rates compared to patients w/o severe MR (166.5 ± 26.3 vs 174.7 ± 25, p=0.006). During a median follow up of 1.3 years, 745 deaths (62.2%) were identified, with a cumulative incidence significantly lower in the intervention groups (Figure). After multivariate propensity adjustment for age, sex, aortic valve area and comorbidities, aortic valve intervention showed a significant reduction in mortality risk in both intervention groups, which was more pronounced in the severe MR group compared to patients w/o severe MR (AdjHR 0.334, p=0.015 vs 0.436, p&lt;0.001, p for interaction =0.24). Conclusions: In paradoxical low-flow low-gradient severe aortic stenosis, aortic valve intervention results in a survival benefit, especially among patients with concomitant severe MR. Our findings highlight the importance of recognizing severe MR as a flow-diverting lesion that can impact outcomes in LFLGAS.

The outcomes of three different techniques of coronary artery bypass grafting: On-pump arrested heart, on-pump beating heart, and off-pump.

Conventional coronary artery bypass grafting (CABG) or on-pump arrested heart CABG (ONCAB) is a standard and simple technique. However, adverse effects can occur due to the use of aortic cross-clamp and cardiopulmonary bypass. Performing off-pump CABG (OPCAB) aims to avoid these adverse effects but may result in incomplete revascularization. On-pump beating heart CABG (ONBHCAB) combines the benefits of both ONCAB and OPCAB. This study focuses on comparing the short- and long-term outcomes of different CABG techniques. Retrospective observational cohort included 2,028 patients who underwent ONCAB, OPCAB, and ONBHCAB. The short-term outcomes including postoperative ischemic injury, hemodynamic functions, and adverse events were compared. The long-term outcomes were overall survival and the occurrence of major adverse cardiovascular events (MACE). Propensity score matching ensured comparability among the three patient groups. After matching, there were no differences in baseline characteristics. Regarding ischemic injury, OPCAB showed the lowest peak cardiac enzyme levels (all p≤0.001). There were no statistically significant differences in the change of hemodynamic function (cardiac index) between the three groups (p = 0.158). Ten-year survival for OPCAB, ONBHCAB, and ONCAB were 80.5%, 75.9%, and 73.7%, respectively. OPCAB was associated with a significant reduction in mortality risk and MACE when compared to others (Mortality HR = 0.33, p = 0.001, MACE HR = 0.52, p = 0.004). OPCAB implementation resulted in a lower occurrence of postoperative ischemic injury than ONCAB and ONBHCAB. No differences in postoperative hemodynamic function in all three techniques were observed. OPCAB respectively were preferable techniques beneficial for long-term outcomes.

Conventional Biological versus Sutureless Aortic Valve Prostheses in Combined Aortic and Mitral Valve Replacement.

Sutureless aortic valve prostheses have proven to provide a significant decrease in procedural, cardiopulmonary bypass and cross-clamp time, leading to a significant reduction in mortality risk in elderly high-risk cohorts. In this study, we sought to review our institutional experience on the sutureless aortic valve replacement (SU-AVR) and the concomitant mitral valve replacement (SMVR), comparing the combined conventional surgical aortic valve replacement (SAVR) with SMVR. Between March 2018 and July 2022, 114 consecutive patients underwent a combined aortic and mitral valve replacement at our institution. We stratified the patients according to the operative procedures into two groups and matched them 1:2: Group 1 underwent a combined conventional SAVR and SMVR (n = 46), and Group 2 included combined SU-AVR with Perceval prosthesis and SMVR (n = 23). No significant differences in the preoperative characteristics were present. SU-AVR combined with SMVR demonstrated excellent haemodynamic performance, comparable to that of SAVR plus SMVR, with median postoperative gradients over the aortic valve of 4 mmHg (IQR 3.0-4.0) in Group 1 and 4 mmHg (IQR 3.0-4.0) in Group 2 (p = 0.67). There was no significant difference in the occurrence of postoperative major adverse events such as death, stroke, myocardial infarction and kidney failure between the groups. There was also no significant difference in the permanent pacemaker implantation rate, paravalvular leakage or valve dislocation. We also could not detect any significant difference in postoperative mortality between the groups. SU-AVR has proven to be a reliable alternative to conventional valve prostheses in patients with multivalve disease undergoing combined aortic and mitral valve replacement, offering shorter procedural time and outstanding hemodynamic performance compared to the conventional surgical method.

Dose–response association of aerobic and muscle-strengthening physical activity with mortality: a national cohort study of 416 420 US adults

ObjectivesTo investigate the dose–response association of aerobic physical activity (PA) and muscle-strengthening exercise (MSE) with all-cause mortality.MethodsNational Health Interview Survey data (1997–2014) were linked to the National Death Index through...

Examining the Gradient of All-Cause Mortality Risk in Women across the Cardiorespiratory Fitness Continuum.

Although cardiorespiratory fitness (CRF) is inversely associated with all-cause mortality in women, less is known regarding the gradient of mortality risk in women, particularly at the lower end of the CRF continuum. A total of 17,901 healthy women (mean age, 45.9 yr) completed a baseline clinical examination, including a maximal treadmill exercise test at the Cooper Clinic in Dallas, TX, between 1971 and 2016. Participants were placed into CRF quintiles based on age and treadmill time. After a mean follow-up period of 17.9 yr, 1198 all-cause deaths occurred. More favorable cardiometabolic risk factors, smoking status, and physical activity levels were observed across ordered CRF quintiles ( P < 0.001 for all). Adjusted all-cause mortality hazard ratios with 95% confidence intervals were 1.71 (1.40-2.09), 1.55 (1.29-1.87), 1.25 (1.03-1.51), 1.16 (0.97-1.38), and 1.0 (referent), respectively, across CRF quintiles ( P trend ≤ 0.001). When utilizing CRF as a continuous variable in a spline analysis and using 4.5 METs as the referent, we estimate a 10% reduction in mortality risk per 1-MET increment in CRF ( P < 0.001) until a threshold of approximately 11 METs. Mortality risk was approximately 50% lower at the 11-MET threshold when compared with the referent. No further significant reduction in mortality risk was observed beyond the 11-MET threshold. In addition, age-adjusted hemodynamic variables including resting and maximal double product, heart rate reserve, double-product reserve, and 1-min recovery heart rate were more favorable across CRF quintiles ( P < 0.001 for all). Beginning at a referent value of 4.5 METs, a significant decreasing gradient of all-cause mortality exists across the CRF continuum, until a threshold of approximately 11 METs is reached. Although all women should be encouraged to work toward meeting public health guidelines for physical activity, it is especially important to target those at the low end of the CRF continuum.

Renin-angiotensin system modulation and outcomes in patients hospitalized for interstitial SARS-CoV2 pneumonia: a cohort study.

AimThe role of cardiovascular (CV) pharmacotherapies in patients with severe COVID-19 pneumonia remains controversial. This study aims to assess the impact of renin–angiotensin system modulation (RASi) (either angiotensin-converting enzymes (ACEIs) or angiotensin-receptor blockers (ARBs)) on COVID-19 outcome.MethodsWe performed a cohort study on consecutive patients admitted for COVID-19 pneumonia at the Internal Medicine Unit of Sant'Orsola-Malpighi Hospital in Bologna, Italy. Patients with a possible alternative cause of respiratory failure other than COVID-19 were excluded. Clinical, pharmacological and laboratory data at admission and during the hospitalization were collected. Patients were treated with intravenous dexamethasone, low molecular weight heparin and nasal flow or Venturi mask oxygen. Subjects were followed until discharge, Intensive Care Unit (ICU) admission or death. Severe cases were defined by acute respiratory distress syndrome (arterial oxygen partial pressure and the fraction of inhaled oxygen ratio (P/F) ≤ 100 mmHg/%, or P/F ≤ 150 mmHg/% and respiratory rate ≥ 26/min). Patients with chronic use of RAS modulation were compared with those without for the composite outcome of in-hospital mortality or ICU admission. Hazard ratios (HR) were obtained by Cox regression, adjusted for several clinical factors.ResultsOf the 268 patients enrolled in the study, 93 (35%, mean age 68 ± 13 years, 67% males) were treated with RASi (58% ACEIs and 42% ARBs). There were no meaningful differences between the RASI and no RASI group regarding clinical and laboratory parameters at admission. As expected, patients in the RASi group had a higher prevalence of hypertension, diabetes mellitus, atrial fibrillation, and ischemic heart disease. One hundred eight patients (40%) were admitted to ICU during hospitalization due to severe respiratory failure, and 24 (9%) died. The risk of in-hospital death or ICU admission was lower in the RASI group than in the non-RASI group (age and sex-adjusted HR 0.57, 95% CI 0.37–0.8), even after adjustment for several comorbidities (fully adjusted HR 0.44, 95% CI 0.26–0.74). Seven (7.5%) patients died in the RASi group vs 17 (9.7%) in the non-RASi group, leading to a non-statistically significant mortality risk reduction (fully adjusted HR 0.69, 95% CI 0.18–1.90). The lower risk in the RASi group was primarily related to ARBs use compared to ACEIs (HR 0.5, 95% CI 0.28–0.92 and HR 0.82, 95% CI 0.51–1.32, respectively).ConclusionsOur study showed an inverse association between the chronic use of RASi and COVID-19 pneumonia severity (either ICU admissions or in-hospital death), even when significant comorbidities are considered.

Effectiveness of clinical pathway in subjects with heart failure: A real-world study from Italian health claims

&#x0D; Background: Several process-of-care indicators have been developed and implemented to improve the quality of heart failure (HF) patients care. The aim of this study is to assess the relationship between a set of recommendations for HF care with measurable clinical outcomes, also in terms of outcomes that could be avoided.&#x0D; Methods: A retrospective cohort study was carried out on subjects with at least one hospitalization with a primary diagnosis of HF in 2007. Data were retrieved from healthcare utilization databases of Lombardy region (Italy). Exposure to selected recommendations (periodic control of echocardiogram and use of blockers of the renin-angiotensin system and beta-blockers) was recorded. All cause mortality and hospitalization with primary diagnosis of HF were considered as outcomes. Multivariable Cox models and Poisson model were fitted to estimate the exposure-outcome association.&#x0D; Results: Among 8207 cases of HF, those who adhered to none, one or all recommendations during the first year after diagnosis were 11%, 60% and 30%, respectively. Compared to patients who adhered to no recommendation, a significant mortality risk reduction of 24% (95% CI 17-31%) and 44% (36 52%) were observed for those who adhered to one and all recommendations, respectively. A significant reduction in the rate of re-hospitalizations in subjects adhered to at least one recommendation was also observed. A decreased trend in Population Attributable Fraction for death cases according to follow-up time was observed.&#x0D; Conclusion: A strict control of patients with HF through regular clinical examinations must be considered as fundamental for the reduction of mortality and re-hospitalizations.&#x0D;

Reduced Bone Loss Is Associated With Reduced Mortality Risk in Subjects Exposed to Nitrogen Bisphosphonates: A Mediation Analysis.

Bisphosphonates, potent antiresorptive agents, have been found to be associated with mortality reduction. Accelerated bone loss is, in itself, an independent predictor of mortality risk, but the relationship between bisphosphonates, bone loss, and mortality is unknown. This study aimed to determine whether the association between bisphosphonates and mortality is mediated by a reduction in the rate of bone loss. Participants from the population-based Canadian Multicentre Osteoporosis Study were followed prospectively between1996 and 2011. Comorbidities and lifestyle factors were collected at baseline and bone mineral density (BMD) at baseline and at years 3 (for those aged 40 to 60 years), 5, and 10. Rate of bone loss was calculated using linear regression. Information on medication use was obtained yearly. Bisphosphonate users grouped into nitrogen bisphosphonates (nBP; alendronate or risedronate) and etidronate and non-users (NoRx) were matched by propensity score, including all baseline factors as well as time of treatment. Cox's proportional hazards models, unadjusted and adjusted for annual rate of bone loss, were used to determine the association between nBP and etidronate versus NoRx. For the treatment groups with significant mortality risk reduction, the percent of mortality reduction mediated by a reduction in the rate of bone loss was estimated using a causal mediation analysis. There were 271 pairs of nBP and matched NoRx and 327 pairs of etidronate and matched NoRx. nBP but not etidronate use was associated with significant mortality risk reduction (hazard ratios [HR] = 0.61 [95% confidence interval 0.39-0.96] and 1.35 [95% CI 0.86-2.11] for nBP and etidronate, respectively). Rapid bone loss was associated with more than 2-fold increased mortality risk compared with no loss. Mediation analysis indicated that 39% (95% CI 7%-84%) of the nBP association with mortality was related to a reduction in the rate of bone loss. This finding provides an insight into the mechanism of the relationship between nBP and survival benefit in osteoporotic patients. © 2019 American Society for Bone and Mineral Research.

Real-World Treatment Patterns and Comparative Effectiveness Among a Population of Elderly Patients with Acute Myeloid Leukemia (AML)

Introduction: Conventional intensive chemotherapy remains the standard of care for younger, functionally fit patients with AML, whereas patients with advanced age, poor performance indicators (PPIs), and/or increased comorbidity burden are often untreated or treated with less intensive chemotherapy and DNA hypomethylating agents (HMAs). Survival outcomes among these patients have not improved over several decades, and there is a scarcity of data on the comparative effectiveness of AML chemotherapies at the population level. We sought to describe the treatment patterns and associated survival outcomes of older AML patients in a real-world setting.Methods: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to obtain a cohort of elderly patients diagnosed with AML. Patients included in the study fulfilled the following eligibility criteria: diagnosed with a first primary AML between January 1, 2000 and December 31, 2013, aged > 66 years, and continuously enrolled in Medicare Part A and B in the year prior to diagnosis. The data set included Medicare claims data available up to the year 2015, which allowed a minimum 2 years of follow-up time. The study included 11,142 patients, of which 6,370 (57%) did not receive treatment within 3 months of diagnosis. Of those initiating treatment, 936 (8%) were treated with azacitidine and/or decitabine (HMA), 153 (1%) were treated with a cytarabine combination regimen (Intensive), 433 (4%) received another type of agent (Other) and 3,250 (29%) received an unidentified agent (Unknown). The Unknown group received their treatment during an inpatient stay, and claims for inpatient stays are paid based on International Classification of Diseases, Ninth Revision (ICD-9) diagnosis or procedures codes and not chemotherapy J codes. It is possible that these “Unknown” therapies are indicative of an intensive regimen that needed to be administered in a controlled inpatient setting. To compare patient characteristics by treatment type, the chi-square test for categorical variables and analysis of variance (ANOVA) or t-test for continuous variables were used. Unadjusted Kaplan-Meier survival plots and corresponding log-rank test were used to compare overall survival by treatment type. Cox proportional hazards regression modeling estimated the relative risk of death adjusting for demographic and clinical factors.Results: Use of HMA therapies significantly increased from 2% in 2005 to 22% in 2013, whereas the untreated rate significantly decreased during that same time period, from 63% in 2005 down to 45% in 2013. Rates of Intensive therapy remained fairly consistent throughout the entire study period. There were similarities in demographic and clinical characteristics between patients receiving Intensive and Unknown therapies and between patients receiving HMA and Other therapies (Table 1). Patients receiving Intensive chemotherapy and Unknown therapy were younger, had lower comorbidity burden, and were less likely to have prior myelodysplastic syndromes (MDS) or PPIs. The median unadjusted overall survival was longest for patients receiving Intensive therapy (16.7 months), followed by HMA therapy (7.3 months), Unknown therapy (4.5 months), Other therapy (3.5 months), and was shortest for Untreated patients (1.6 months; log-rank P < 0.0001). After adjusting for age, sex, race, MDS, PPIs, comorbidity score, marital status, income, education, geographic region, and year of diagnosis in the survival model, receipt of all types of antileukemic therapy showed a significant mortality risk reduction compared with palliative care or no treatment. The largest reduction in mortality risk was noted in the Intensive therapy group (hazard ratio [HR] 0.32; 95% CI 0.25-0.40), followed by HMA (HR 0.47; 95% CI 0.43-0.52), Other (HR 0.49; 95% CI 0.43-0.56), and Unknown (HR 0.66; 95% CI 0.62-0.70) compared with the Untreated group.Conclusions: There was a significant survival benefit for patients who received all types of antileukemic therapy, even among the HMA and Other therapy groups who had similar characteristics to the Untreated group of patients. The findings from this study provide a rationale to strongly consider therapy rather than best supportive care in older patients who do not fit the criteria for more intensive regimens. DisclosuresSatram-Hoang:Celgene Corp.: Research Funding; Genentech: Research Funding. Parisi:Celgene Corp.: Employment, Equity Ownership.

Mortality Risk Reductions for Replacing Sedentary Time with Physical Activities

BACKGROUND: Insufficient physical activity is a well-established risk factor for chronic disease and early mortality. More recent evidence suggests that excess sitting time may be an additional risk factor, independent of physical inactivity. This may be due, at least in part, to the displacement of physical activities with sedentary behaviors. PURPOSE: To examine the mortality risk reductions associated with replacing thirty minutes of daily sitting time for an equivalent duration of physical activity. METHODS: Participants included 40,866 men and 60,891 women in the Cancer Prevention Study-II Nutrition Cohort. An isotemporal substitution approach to Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (HR, 95% CI) for all-cause mortality associated with the substitution of thirty minutes of daily sitting time with an equal duration of light or moderate-to-vigorous intensity physical activity (LPA, MVPA). RESULTS: During 14 years (1999-2013) of follow-up, 16,163 men and 15,638 women died. Overall, reallocation of 30 min[BULLET OPERATOR]day-1 of sitting to LPA (HR=0.94, 0.92-0.97) or MVPA (HR=0.91, 0.88-0.93) was associated with significant reductions in mortality risk. Among the least active participants, the replacement of 30 min[BULLET OPERATOR]day-1 of sitting time with 30 min[BULLET OPERATOR]day-1 LPA was associated with a 14% mortality risk reduction (HR=0.86, 0.83-0.89) and replacement with MVPA was associated with a 50% mortality risk reduction (HR=0.50, 0.44-0.58). Similar associations were seen among the moderately active group (HR=0.91, 0.89-0.96 for LPA replacement, HR=0.65, 0.56-0.79 for MVPA replacement). However, among the most active participants, substitution of sitting time with LPA or MVPA was not associated with a significant reduction in mortality risk (HR=1.00, 0.97-1.02, HR=0.97, 0.95-1.01, respectively). CONCLUSIONS: Among the least active and moderately active, the replacement of modest amounts of sitting time with either LPA or MVPA was associated with longevity, although the associations were strongest when sitting time was replaced with MVPA.

A meta-analysis of cyclosporine treatment for Stevens-Johnson syndrome/toxic epidermal necrolysis.

BackgroundStevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are dermatologic emergencies with high morbidity and mortality risk. Cyclosporine, an immunomodulatory agent, is sometimes used off-label, and its role continues to be debated. This meta-analysis aimed to provide an update of current evidence and to clarify the role of cyclosporine in SJS/TEN treatment better.MethodsUsing the keywords [cyclosporine OR cyclosporine OR ciclosporin OR CsA] AND [Steven-Johnson OR SJS OR toxic epidermal OR epidermal necrolysis OR TEN OR hypersensitivity OR dermatologic OR burns], a preliminary search on the PubMed, Ovid, Web of Science, and Google Scholar Database yielded 615 papers published in English between January1, 1960 and July 1, 2017. The inclusion criteria for this review were: 1) published retrospective or prospective study (excluding single case reports); 2) patients with clinical diagnosis of SJS or TEN; 3) trial of cyclosporine treatment; and 4) available survival/mortality data.ResultsA total of 12 studies, with a total of 358 SJS/TEN patients were reviewed. Two studies were excluded from the meta-analysis as they did not report SCORe of toxic epidermal necrosis/predicted mortality data; one was excluded because of possible data irregularities. Meta-analysis of nine studies revealed a significant reduction in mortality risk with cyclosporine therapy (standardized mortality ratio 0.320; 95% CI: 0.119–0.522; P=0.002). Cyclosporine was also generally well tolerated with little adverse effects or increased infection, albeit the patients tended to be critically ill. Publication bias was observed in the funnel plot and Egger test (P=0.0467).ConclusionCurrently available evidence are predominantly open trials and retrospective studies with a significant risk of bias, perhaps owing to the rarity and life-threatening nature of the condition. Given its immunomodulatory actions, cyclosporine could be a potential treatment option for SJS/TEN in addition to best supportive measures. Further confirmation with robust randomized, controlled trials or larger case series is necessary and should be encouraged.

Smoking behavioral changes and subsequent mortality during a 18-year follow-up in Kinmen, Taiwan

BackgroundThe aim of this study was to examine the changes in smoking behavior over 6 years and to relate these changes to mortality risk during 18 years’ follow-up. MethodsWe followed a cohort for 6 years (1991–1997) to assess changes in smoking behavior and then for an additional 12 years (1997–2008) to relate these findings to mortality in 4986 Chinese individuals. Participants were classified as never smokers, long-term quitters, new smokers, new quitters, and continuing smokers. Mortality was ascertained by linkage with the nationwide death registry. ResultsCompared with never smokers, continuing smokers had the highest risk of 1.84 [95% confidence interval (CI): 1.38, 2.45] for all-cause mortality, new quitters had a risk of 1.49 (95% CI: 1.04, 2.15), new smokers had a risk of 1.26 (95% CI: 0.59, 2.68), and long-term quitters had a risk of 1.11 (95% CI: 0.64, 1.91). There was a significant 19% risk reduction in all-cause mortality for new quitters. ConclusionSmoking cessation was associated with a significant reduction in mortality risk within approximately 6 years, while no significantly increased risk was observed for long-term quitters.

Submaximal fitness and mortality risk reduction in coronary heart disease: a retrospective cohort study of community-based exercise rehabilitation

ObjectivesTo examine the association between submaximal cardiorespiratory fitness (sCRF) and all-cause mortality in a cardiac rehabilitation (CR) cohort.DesignRetrospective cohort study of participants entering CR between 26 May 1993 and 16...

Association between Objectively Measured Physical Activity and Mortality in NHANES.

We examined total activity, light activity, and moderate-to-vigorous physical activity (MVPA) as predictors of mortality in a nationally representative sample of older adults. Then we explored the theoretical consequences of replacing sedentary time with the same duration of light activity or MVPA. Using accelerometer-measured activity, the associations between total activity, light activity (100-2019 counts per minute), and MVPA (>2019 counts per minute) counts and mortality were examined in adults age 50 to 79 yr in the National Health and Nutrition Examination Survey, 2003-2006 (n = 3029), with mortality follow-up through December 2011. Cox proportional hazard models were fitted to estimate mortality risks. An isotemporal substitution model was used to examine the theoretical consequences of replacing sedentary time with light activity or MVPA on mortality. After adjusting for potential confounders, including age, sex, race/ethnicity, education, BMI, and the presence of comorbid conditions, those in the highest tertile of total activity counts had one fifth the risk of death of those in the lowest tertile (hazard ratio [HR] = 0.21, 95% confidence interval [CI] = 0.12-0.38), and those in the middle tertile had one third the risk of death (HR = 0.36, 95% CI = 0.30-0.44). In addition, replacing 30 min of sedentary time with light activity was associated with significant reduction in mortality risk (after 5 yr of follow-up: HR = 0.80, 95% CI = 0.75-0.85). Replacing 30 min of sedentary time with MVPA was also associated with reduction in mortality risk (HR = 0.49, 95% CI = 0.25-0.97). Greater total activity is associated with lower all-cause mortality risk. Replacing sedentary time with light activity or MVPA may reduce mortality risk for older adults.