Search

Background: The phase 3 NEURO-TTRansform trial showed eplontersen treatment for 65 weeks reduced transthyretin (TTR), halted progression of neuropathy impairment, and improved quality of life (QoL) in adult patients with hereditary TTR-mediated amyloidosis with polyneuropathy (ATTRv-PN), vs. historical placebo. Methods: NEURO-TTRansform enrolled patients with ATTRv-PN. A subset of patients were randomized to receive subcutaneous inotersen 300 mg weekly (Weeks 1–34) and subsequently switched to subcutaneous eplontersen 45 mg every 4 weeks (Weeks 37–81). Change in serum TTR and treatment-emergent adverse events (TEAEs) were evaluated through Week 85. Effects on neuropathy impairment, QoL, and nutritional status were also evaluated. Results: Of 24 patients randomized to inotersen, 20 (83%) switched to eplontersen at Week 37 and four discontinued due to AEs/investigator decision. Absolute change in serum TTR was greater after switching from inotersen (−74.3%; Week 35) to eplontersen (−80.6%; Week 85). From the end of inotersen treatment, neuropathy impairment and QoL were stable (i.e., did not progress) while on eplontersen, and there was no deterioration in nutritional status. TEAEs were fewer with eplontersen (Weeks 37–85; 19/20 [95%] patients) compared with inotersen (up to Week 35; 24/24 [100%] patients). Mean platelet counts decreased during inotersen treatment (mean nadir reduction ‒40.7%) and returned to baseline during eplontersen treatment (mean nadir reduction, ‒3.2%). Conclusions: Switching from inotersen to eplontersen further reduced serum TTR, halted disease progression, stabilized QoL, restored platelet count, and improved tolerability, without deterioration in nutritional status. This supports a positive benefit-risk profile for patients with ATTRv-PN who switch from inotersen to eplontersen. [ABSTRACT FROM AUTHOR]

Key Points: Question: Is the antisense oligonucleotide eplontersen associated with changes in serum transthyretin concentration and improvement in neuropathy symptoms among adults with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy? Findings: In this open-label study that enrolled 168 patients (144 assigned to subcutaneous eplontersen) and included 60 historical placebo patients, the eplontersen treatment group demonstrated changes from baseline to week 65/66 consistent with significantly lower serum transthyretin concentration (−81.7% vs −11.2%), less neuropathy impairment, and better quality of life compared with the historical placebo group. Meaning: Among adults with ATTRv polyneuropathy, the eplontersen treatment group had lower serum transthyretin concentration, less neuropathy impairment, and better quality of life compared with a historical placebo. Importance: Transthyretin gene silencing is an emerging treatment strategy for hereditary transthyretin (ATTRv) amyloidosis. Objective: To evaluate eplontersen, an investigational ligand-conjugated antisense oligonucleotide, in ATTRv polyneuropathy. Design, Setting, and Participants: NEURO-TTRansform was an open-label, single-group, phase 3 trial conducted at 40 sites across 15 countries (December 2019-April 2023) in 168 adults with Coutinho stage 1 or 2 ATTRv polyneuropathy, Neuropathy Impairment Score 10-130, and a documented TTR variant. Patients treated with placebo from NEURO-TTR (NCT01737398; March 2013–November 2017), an inotersen trial with similar eligibility criteria and end points, served as a historical placebo ("placebo") group. Interventions: Subcutaneous eplontersen (45 mg every 4 weeks; n = 144); a small reference group received subcutaneous inotersen (300 mg weekly; n = 24); subcutaneous placebo weekly (in NEURO-TTR; n = 60). Main Outcomes and Measures: Primary efficacy end points at week 65/66 were changes from baseline in serum transthyretin concentration, modified Neuropathy Impairment Score +7 (mNIS+7) composite score (scoring range, –22.3 to 346.3; higher scores indicate poorer function), and Norfolk Quality of Life Questionnaire–Diabetic Neuropathy (Norfolk QoL-DN) total score (scoring range, –4 to 136; higher scores indicate poorer quality of life). Analyses of efficacy end points were based on a mixed-effects model with repeated measures adjusted by propensity score weights. Results: Among 144 eplontersen-treated patients (mean age, 53.0 years; 69% male), 136 (94.4%) completed week-66 follow-up; among 60 placebo patients (mean age, 59.5 years; 68% male), 52 (86.7%) completed week-66 follow-up. At week 65, adjusted mean percentage reduction in serum transthyretin was −81.7% with eplontersen and −11.2% with placebo (difference, −70.4% [95% CI, −75.2% to −65.7%]; P <.001). Adjusted mean change from baseline to week 66 was lower (better) with eplontersen vs placebo for mNIS+7 composite score (0.3 vs 25.1; difference, −24.8 [95% CI, −31.0 to −18.6; P <.001) and for Norfolk QoL-DN (−5.5 vs 14.2; difference, −19.7 [95% CI, −25.6 to −13.8]; P <.001). Adverse events by week 66 that led to study drug discontinuation occurred in 6 patients (4%) in the eplontersen group vs 2 (3%) in the placebo group. Through week 66, there were 2 deaths in the eplontersen group consistent with known disease-related sequelae (cardiac arrhythmia; intracerebral hemorrhage); there were no deaths in the placebo group. Conclusions and Relevance: In patients with ATTRv polyneuropathy, the eplontersen treatment group demonstrated changes consistent with significantly lowered serum transthyretin concentration, less neuropathy impairment, and better quality of life compared with a historical placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT04136184; EU Clinical Trials Register: EudraCT 2019-001698-10 This open-label, single-group, phase 3 trial evaluates eplontersen, an investigational ligand-conjugated antisense oligonucleotide, in adults with hereditary amyloid transthyretin (ATTRv) polyneuropathy at 40 sites in 15 countries, compared with historical controls. [ABSTRACT FROM AUTHOR]

Aims: Heart failure (HF) substantially limits the ability of patients to engage in physical activities. A detailed understanding of how patients experience these limitations is required to develop valid and sensitive measures for use in clinical research. This qualitative study was designed to provide a thorough description of how HF patients experience physical activity limitations in their daily lives. Methods and results: Semi‐structured interviews were conducted with 40 HF patients. Interview transcripts were coded with the aim of identifying key aspects of physical activity. Patients were divided between HF with preserved ejection fraction (n = 21, 52.5%) and HF with reduced ejection fraction (n = 19, 47.5%); the majority of patients were New York Heart Association Class II (n = 22, 52.5%) or Class III (n = 16, 40.0%). Relevant physical activity themes, including mobility and broader daily function areas, were identified. The most frequently reported mobility limitations involved difficulty walking (up a steep incline, up steps, and long distances), limited walking speed, difficulty standing for long periods of time, and difficulty carrying and lifting objects. These limitations were principally related to three HF symptoms: dyspnoea, tiredness/fatigue, and peripheral oedema. Patients adapted to their symptoms and related mobility limitations in several ways, including taking rests during an activity, doing an activity more slowly, and avoiding/refraining from an activity altogether. The broader daily function areas most commonly impacted by the mobility limitations were housework, exercising or playing sports, and going shopping. Conclusions: Heart failure patients report numerous physical activity limitations. These specific mobility and daily function areas can be measured using clinical outcome assessments (e.g. patient‐reported outcomes and performance outcomes) in clinical trials and observational research. Accelerometry can be used to contribute to a holistic picture of patient functioning by passively collecting this type of data. [ABSTRACT FROM AUTHOR]

To evaluate how often trastuzumab therapy is ended early (i.e., early discontinuation) and how cardiovascular events and early discontinuation affect survival among older women with breast cancer. A population-based cohort of female Medicare beneficiaries with stage I-III breast cancer in 2005-2009 who received trastuzumab was assembled and followed through 2011. Completed trastuzumab treatment was defined as ≥11 months of continuous trastuzumab treatments with no delay between trastuzumab treatments >45 days. We identified trastuzumab-associated cardiovascular events as those occurring within 45 days before or after the last trastuzumab treatment. Using Cox proportional hazard models, we examined the association between early discontinuation of trastuzumab and cardiovascular events on all-cause mortality. Our cohort consisted of 585 women (mean age: 71.6 years). Approximately 41 % of women discontinued trastuzumab therapy early. Patients with early discontinuation of trastuzumab were more likely to have heart failure /cardiomyopathy, atrial fibrillation, and other cardiovascular events than women who completed trastuzumab. Cardiovascular events were strongly associated with an increased risk of all-cause mortality [adjusted hazard ratio (AHR) 3.54; 95 % confidence interval (CI) 1.87 to 6.68]. Women with early discontinuation of trastuzumab had a non-significant increase in risk of all-cause mortality (AHR: 1.74; 95 % CI 0.94 to 3.23), compared to women who completed trastuzumab. Early trastuzumab discontinuation was common among older patients, and often associated with adverse cardiovascular events. Development of cardiovascular events was associated with a higher mortality risk than early trastuzumab discontinuation, implying that reducing cardiovascular complications from trastuzumab therapy could likely have a substantive impact on overall survival in this population. [ABSTRACT FROM AUTHOR]

The Kaiser Permanente & Strategic Partners Patient Outcomes Research To Advance Learning (PORTAL) network engages four healthcare delivery systems (Kaiser Permanente, Group Health Cooperative, HealthPartners, and Denver Health) and their affiliated research centers to create a new national network infrastructure that builds on existing relationships among these institutions. PORTAL is enhancing its current capabilities by expanding the scope of the common data model, paying particular attention to incorporating patient-reported data more systematically, implementing new multi-site data governance procedures, and integrating the PCORnet PopMedNet platform across our research centers. PORTAL is partnering with clinical research and patient experts to create cohorts of patients with a common diagnosis (colorectal cancer), a rare diagnosis (adolescents and adults with severe congenital heart disease), and adults who are overweight or obese, including those with pre-diabetes or diabetes, to conduct large-scale observational comparative effectiveness research and pragmatic clinical trials across diverse clinical care settings. [ABSTRACT FROM AUTHOR]

The Kaiser Permanente & Strategic Partners Patient Outcomes Research To Advance Learning (PORTAL) network engages four healthcare delivery systems (Kaiser Permanente, Group Health Cooperative, HealthPartners, and Denver Health) and their affiliated research centers to create a new national network infrastructure that builds on existing relationships among these institutions. PORTAL is enhancing its current capabilities by expanding the scope of the common data model, paying particular attention to incorporating patient-reported data more systematically, implementing new multi-site data governance procedures, and integrating the PCORnet PopMedNet platform across our research centers. PORTAL is partnering with clinical research and patient experts to create cohorts of patients with a common diagnosis (colorectal cancer), a rare diagnosis (adolescents and adults with severe congenital heart disease), and adults who are overweight or obese, including those with pre-diabetes or diabetes, to conduct large-scale observational comparative effectiveness research and pragmatic clinical trials across diverse clinical care settings. [ABSTRACT FROM AUTHOR]

The article examines the association between hospital readmission and mortality rates for cardiac patients who were presented with clinical case of acute myocardial infarction, heart failure and pneumonia. It highlights the impact of quality of medical care provided by health care centers in resolving the risk associated with cardiac patients. The Centers for Medicare & Medicaid Services in the U.S. on the basis of a cohort analysis revealed that differences in performance of hospitals and diagnostic parameters implied by hospital were of immense use in determination of readmission rate and mortality rate of cardiac patients.

The article discusses a study which examined changes in the rate of hospitalization due to heart failure (HF) and one-year mortality rate in fee-for-service Medicare beneficiaries in the U.S. from 1998 to 2008. HF hospitalization and mortality rates were analyzed nationally and by state or territory. The study found that the age, sex and race-adjusted HF hospitalization rate decreased to 2007 per 100,000 person-years in 2008 from 2845 in 1998. The lowest rate of decline was observed in African American men. Risk-adjusted one-year mortality dropped to 29.6% in 2008 compared with 31.7% in 1999. The study showed an increase in some comorbidities such as hypertension and renal dysfunction in patients hospitalized for HF.

Objective: To determine population-based rates of the use of diagnostic imaging procedures with ionizing radiation in children, stratified by age and sex. Design: Retrospective cohort analysis. Setting: All settings using imaging procedures with ionizing radiation. Patients: Individuals younger than 18 years, alive, and continuously enrolled in United Health care between January 1, 2005, and December 31, 2007, in 5 large US health care markets. Main Outcome Measures: Number and type of diagnostic imaging procedures using ionizing radiation in children. Results: A total of 355 088 children were identified; 436 711 imaging procedures using ionizing radiation were performed in 150 930 patients (42.5%). The highest rates of use were in children older than 10 years, with frequent use in infants younger than 2 years as well. Plain radiography accounted for 84.7% of imaging procedures performed. Computed tomographic scans-associated with substantially higher doses of radiation-were commonly used, accounting for 11.9% of all procedures during the study period. Overall, 7.9% of children received at least 1 computed tomographic scan and 3.5% received 2 or more, with computed tomographic scans of the head being the most frequent. Conclusions: Exposure to ionizing radiation from medical diagnostic imaging procedures may occur frequently among children. Efforts to optimize and ensure appropriate use of these procedures in the pediatric population should be encouraged. [ABSTRACT FROM AUTHOR]

The article discusses a study which described the temporal changes in length of stay, discharge disposition, and short-term outcomes among older U.S. patients hospitalized for heart failure. The observational study examined 6,955,461 Medicare fee-for-service hospitalizations for heart failure between 1993 and 2006. The researchers found that the mean length of stay decreased from 8.81 days to 6.33 days between 1993 and 2006. The importance of examining an episode of acute care during a standardized period of assessment is also highlighted by the study.

The article presents a study which investigates the survival impact of regionalization of acute myocardial infarction (AMI) care on percutaneous coronary intervention (PCI) hospitals in the U.S. Risk-standardized mortality rates (RSMRs) between PCI hospitals and non-PCI hospitals within the same health care regions were analyzed. The study suggests that regionalizing AMI care to PCI hospitals can reduce mortality rates, however, survival outcomes varies across the regions.

Aims: To determine the relationship between admission systolic blood pressure (SBP) and mortality in older patients hospitalized for heart failure (HF) and among various subgroups. [ABSTRACT FROM PUBLISHER]

Context: During the last 2 decades, health care professional, consumer, and payer organizations have sought to improve outcomes for patients hospitalized with acute myocardial infarction (AMI). However, little has been reported about improvements in hospital short-term mortality rates or reductions in between-hospital variation in short-term mortality rates.Objective: To estimate hospital-level 30-day risk-standardized mortality rates (RSMRs) for patients discharged with AMI.Design, Setting, and Patients: Observational study using administrative data and a validated risk model to evaluate 3,195,672 discharges in 2,755,370 patients discharged from nonfederal acute care hospitals in the United States between January 1, 1995, and December 31, 2006. Patients were 65 years or older (mean, 78 years) and had at least a 12-month history of fee-for-service enrollment prior to the index hospitalization. Patients discharged alive within 1 day of an admission not against medical advice were excluded, because it is unlikely that these patients had sustained an AMI.Main Outcome Measure: Hospital-specific 30-day all-cause RSMR.Results: At the patient level, the odds of dying within 30 days of admission if treated at a hospital 1 SD above the national average relative to that if treated at a hospital 1 SD below the national average were 1.63 (95% CI, 1.60-1.65) in 1995 and 1.56 (95% CI, 1.53-1.60) in 2006. In terms of hospital-specific RSMRs, a decrease from 18.8% in 1995 to 15.8% in 2006 was observed (odds ratio, 0.76; 95% CI, 0.75-0.77). A reduction in between-hospital heterogeneity in the RSMRs was also observed: the coefficient of variation decreased from 11.2% in 1995 to 10.8%, the interquartile range from 2.8% to 2.1%, and the between-hospital variance from 4.4% to 2.9%.Conclusion: Between 1995 and 2006, the risk-standardized hospital mortality rate for Medicare patients discharged with AMI showed a significant decrease, as did between-hospital variation. [ABSTRACT FROM AUTHOR]

The article focuses on an observational study which estimated hospital-level 30-day risk-standardized mortality rates (RSMRs) for patients discharged with acute myocardial infarction (AMI). Administrative data and a validated risk model were used to evaluate 3,195,672 discharges in 2,755,370 patients discharged from nonfederal acute care hospitals in the U.S. between January 1, 1995 to December 31, 2006. A significant decrease was observed in the risk-standardized hospital mortality rate for Medicare patients discharged with AMI, as well as between-hospital variation.

Objective To evaluate the association between door-to- balloon time and mortality in hospital in patients undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction to assess the incremental mortality benefit of reductions in door-to- balloon times of less than 90 minutes. Design Prospective cohort study of patients enrolled in the American College of Cardiology National Cardiovascular Data Registry, 2005-6. Setting Acute care hospitals. Participants 43 801 patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention. Main outcome measure Mortality in hospital. Results Median door-to-balloon time was 83 minutes (interquartile range 6-109, 57.9% treated within 90 minutes). Overall mortality in hospital was 4.6%. Multivariable logistic regression models with fractional polynomial models indicated that longer door-to-balloon times were associated with a higher adjusted risk of mortality in hospital in a continuous non-linear fashion (30 minutes=3.0%, 60 minutes=3.5%, 90 minutes=4.3%, 120 minutes=5.6%, 150 minutes=7.0%, 180 minutes =8.4%, P<0.001). A reduction in door-to-balloon time from 90 minutes to 60 minutes was associated with 0.8% lower mortality, and a reduction from 60 minutes to 30 minutes with a 0.5% lower mortality. Conclusion Any delay in primary percutaneous coronary intervention after a patient arrives at hospital is associated with higher mortality in hospital in those admitted with ST elevation myocardial infarction. Time to treatment should be as short as possible, even in centres currently providing primary percutaneous coronary intervention within 90 minutes. [ABSTRACT FROM AUTHOR]

The article presents research assessing the association of implanting physician certification with outcomes following implantable cardioverter-defibrillator (ICD) procedures. The design and setting of the study involving cases submitted to the ICD Registry and analysis of certification status of the implanting physicians into categories of electrophysiologists, nonelectrophysiologists, cardiologists, and thoracic surgeons is explained. The medical outcomes measured were in-hospital procedural complication rates and the likelihood of receiving cardiac resynchronization therapy (CRT-D). Results indicate implantation by nonelectrophysiologists is associated with a higher risk of complications and a lower rate of CRT-D.

Background: Patients and purchasers prefer board-certified physicians, but whether these physicians provide better quality of care and outcomes for hospitalized patients is unclear.Objective: We evaluated whether care by board-certified physicians after acute myocardial infarction (AMI) was associated with higher use of clinical guideline recommended therapies and lower 30-day mortality.Subjects and Methods: We examined 101,251 Medicare patients hospitalized for AMI in the United States and compared use of aspirin, beta-blockers, and 30-day mortality according to the attending physicians' board certification in family practice, internal medicine, or cardiology.Results: Board-certified family practitioners had slightly higher use of aspirin (admission: 51.1% vs 46.0%; discharge: 72.2% vs 63.9%) and beta-blockers (admission: 44.1% vs 37.1%; discharge: 46.2% vs 38.7%) than nonboard-certified family practitioners. There was a similar pattern in board-certified Internists for aspirin (admission: 53.7% vs 49.6%; discharge: 78.2% vs 68.8%) and beta-blockers (admission: 48.9% vs 44.1%; discharge: 51.2% vs 47.1). Board-certified cardiologists had higher use of aspirin compared with cardiologists certified in internal medicine only or without any board certification (admission: 61.3% vs 53.1% vs 52.1%; discharge: 82.2% vs 71.8% vs 71.5%) and beta-blockers (admission: 52.9% vs 49.6% vs 41.5%; discharge: 54.7% vs 50.6% vs 42.5%). In multivariate regression analyses, board certification was not associated with differences in 30-day mortality.Conclusions: Treatment by a board-certified physician was associated with modestly higher quality of care for AMI, but not differences in mortality. Regardless of board certification, all physicians had opportunities to improve quality of care for AMI. [ABSTRACT FROM AUTHOR]

Context: Health care "report cards" have attracted significant consumer interest, particularly publicly available Internet health care quality rating systems. However, the ability of these ratings to discriminate between hospitals is not known. Objective: To determine whether hospital ratings for acute myocardial infarction (AMI) mortality from a prominent Internet hospital rating system accurately discriminate between hospitals' performance based on process of care and outcomes. Design, Setting, and Patients: Data from the Cooperative Cardiovascular Project, a retrospective systematic medical record review of 141 914 Medicare fee-for-service beneficiaries 65 years or older hospitalized with AMI at 3363 US acute care hospitals during a 4- to 8-month period between January 1994 and February 1996 were compared with ratings obtained from HealthGrades.com (1-star: worse outcomes than predicted, 5-star: better outcomes than predicted) based on 1994-1997 Medicare data. Main Outcome Measures: Quality indicators of AMI care, including use of acute reperfusion therapy, aspirin, β-blockers, angiotensin-converting enzyme inhibitors; 30-day mortality. Results: Patients treated at higher-rated hospitals were significantly more likely to receive aspirin (admission: 75.4% 5-star vs 66.4% 1-star, P for trend = .001; discharge: 79.7% 5-star vs 68.0% 1-star, P = .001) and β-blockers (admission: 54.8% 5-star vs 35.7% 1-star, P = .001; discharge: 63.3% 5-star vs 52.1% 1-star, P = .001), but not angiotensin-converting enzyme inhibitors (59.6% 5-star vs 57.4% 1-star, P = .40). Acute reperfusion therapy rates were highest for patients treated at 2-star hospitals (60.6%) and lowest for 5-star hospitals (53.6% 5-star, P = .008). Risk-standardized 30-day mortality rates were lower for patients treated at higher-rated than lower-rated hospitals (21.9% 1-star vs 15.9% 5-star, P = .001). However, there was marked heterogeneity within rating groups and substantial overlap o... [ABSTRACT FROM AUTHOR]

Reports on a study to investigate the relationship between patient sex, physician sex, and the use of cardiac procedures, specifically whether sex differences in cardiac catheterization after acute myocardial infarcation (AMI) were greater when patients were treated by male attending physicians compared with female physicians. Methods; Results; Conclusion suggesting that factors other than sexual bias by male physicians toward women account for sex differences in cardiac procedure use.

Focuses on the effectiveness of beta blocker therapy in reducing mortality among elderly patients who underwent coronary revascularization. Factors that contribute to the therapy's effectiveness; Findings suggesting that routine use of beta blockers is suitable for acute myocardial infarction patients.

Describes the contemporary national pattern of beta-blocker prescription at hospital discharge among patients aged 65 years or older with an acute myocardial infarction (AMI). Attempt to identify the most important predictors of the prescribed use of beta-blockers and to determine the independent association between beta-blockers at discharge and mortality in clinical practice; Design; Setting; Patients; Main outcome measures; Results; Conclusions.

The article reflects on the challenges of assessing the performance of hospitals with small volumes of patients. It discusses a study conducted by S. M. O'Brien and colleagues which examined the relationship between hospital performance and sample size using process-of-care measures of quality for acute myocardial infarction (AMI).

A personal narrative which explores the author's experience studying myocardial infarction is presented.