Significant Reduction In Risk Research Articles

Dairy Foods, Weight Change, and Risk of Obesity During the Menopausal Transition

BackgroundWeight gain during the menopausal transition is common. Dairy consumption may impact weight change during this critical period, and different dairy foods may have different effects. ObjectivesThis study aimed to investigate the associations of different types of dairy foods with weight gain and risk of obesity in perimenopausal women from the Nurses’ Health Study II cohort. MethodsThe examination at menopause was selected as the exam closest to the reported age at menopause. Weight change during 12 y surrounding menopause was derived from self-reported weight data for 3 exams before and 3 after menopause. The mean age of the first weight measure was 45.8 y and the average BMI was 25.0 kg/m2. Dairy food intakes were estimated as mean intakes over the same 12 y. Generalized linear models were used to assess the association between dairy foods and annualized weight change. Cox proportional hazard models were used to estimate the adjusted relative risks for becoming obese over 12 y surrounding menopause. ResultsIn longitudinal analyses, those with the highest yogurt intakes had the lowest weight gain at every exam. This was not the case for other forms of dairy. After adjusting for potential covariates, those consuming ≥2.0 servings/wk of yogurt (compared with <1.0 serving/month) had a 31% (RR: 0.69; 95% CI: 0.64, 0.74) lower risk of obesity. The highest total dairy intake (≥2.0 servings/d compared with <1.0) was associated with only a 12% (RR: 0.88; 95% CI: 0.82, 0.95) reduction in obesity risk. Higher activity levels and alternative healthy eating index scores were independently associated with statistically significant reductions in risk of obesity, but higher intakes of yogurt strengthened these beneficial associations. ConclusionYogurt intake was associated with less weight gain and lower obesity risk in women during the menopausal transition.

The effectiveness and cost-effectiveness of clinical fracture-risk assessment tools in reducing future osteoporotic fractures among older adults: a structured scoping review.

We aim to provide a synopsis of the evidence about the use of clinical fracture-risk assessment tools to influence health outcomes, including reducing future osteoporotic fractures and their cost-effectiveness. We followed the guidelines of Arksey and O'Malleyand their modifications. A comprehensive search strategy was created to search CINAHL, Medline, and Embase databases until June 29, 2021, with no restrictions. We critically appraised the quality of all included studies. Fourteen studies were included in the review after screening 2484 titles and 68 full-text articles. Four randomized controlled trials investigated the effectiveness of clinical fracture-risk assessment tools in reducing all fractures among older women. Using those assessment tools did not show a statistically significant reduction in osteoporotic fracture risk compared to usual care; however, additional analyses of two of these trials showed a trend toward reducing hip fractures, and the results might be clinically significant. Four studies tested the impact of screening programs on other health outcomes, and participants reported positive results. Eight simulation studies estimated the cost-effectiveness of using these tools to screen for fractures, with the majority showing significant potential savings. According to the available evidenceto date, using clinical fracture-risk assessment screening tools was not more effective than usual care in preventing all osteoporosis-related fractures. However, using those screening tools positively influenced women's perspectives on osteoporosis, may have reduced hip fracture risk, and could potentially be cost-effective. This is a relatively new research area where additional studies are needed.

Exercise-based cardiac rehabilitation for coronary heart disease: a meta-analysis.

Coronary heart disease is the most common reason for referral to exercise-based cardiac rehabilitation (CR) globally. However, the generalizability of previous meta-analyses of randomized controlled trials (RCTs) is questioned. Therefore, a contemporary updated meta-analysis was undertaken. Database and trial registry searches were conducted to September 2020, seeking RCTs of exercise-based interventions with ≥6-month follow-up, compared with no-exercise control for adults with myocardial infarction, angina pectoris, or following coronary artery bypass graft, or percutaneous coronary intervention. The outcomes of mortality, recurrent clinical events, and health-related quality of life (HRQoL) were pooled using random-effects meta-analysis, and cost-effectiveness data were narratively synthesized. Meta-regression was used to examine effect modification. Study quality was assessed using the Cochrane risk of bias tool. A total of 85 RCTs involving 23 430 participants with a median 12-month follow-up were included. Overall, exercise-based CR was associated with significant risk reductions in cardiovascular mortality [risk ratio (RR): 0.74, 95% confidence interval (CI): 0.64-0.86, number needed to treat (NNT): 37], hospitalizations (RR: 0.77, 95% CI: 0.67-0.89, NNT: 37), and myocardial infarction (RR: 0.82, 95% CI: 0.70-0.96, NNT: 100). There was some evidence of significantly improved HRQoL with CR participation, and CR is cost-effective. There was no significant impact on overall mortality (RR: 0.96, 95% CI: 0.89-1.04), coronary artery bypass graft (RR: 0.96, 95% CI: 0.80-1.15), or percutaneous coronary intervention (RR: 0.84, 95% CI: 0.69-1.02). No significant difference in effects was found across different patient groups, CR delivery models, doses, follow-up, or risk of bias. This review confirms that participation in exercise-based CR by patients with coronary heart disease receiving contemporary medical management reduces cardiovascular mortality, recurrent cardiac events, and hospitalizations and provides additional evidence supporting the improvement in HRQoL and the cost-effectiveness of CR.

Gestational weight gain and neonatal outcomes in different zygosity twins: a cohort study in Wuhan, China

ObjectiveTo evaluate whether twin zygosity influences the association between neonatal outcomes and gestational weight gain (GWG) based on the Chinese guidelines in twin-pregnancy women.DesignA retrospective cohort study. And it is...

Effect of Local Antibiotic Prophylaxis on Postoperative Deep Infection in Fracture Surgery: A Systematic Review and Meta-Analysis.

Despite the use of systemic antibiotic prophylaxis, postoperative infection after fracture surgery remains an issue. The purpose of this systematic review and meta-analysis was to evaluate the effect of locally applied antibiotics on deep infection in fracture surgery in both the open and closed fractures. A comprehensive search of MEDLINE, Embase, and PubMed was performed from the date of inception to April 15, 2021, and included studies in all languages. Cohort studies were eligible if they investigated the effect on the infection rate of local antibiotic prophylaxis on deep infection after fracture surgery. This study was conducted according to the Cochrane Handbook for Systematic Reviews and reported as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias was assessed using version 2 of the Cochrane risk-of-bias tool for randomized trials and the Methodological Index for Nonrandomized Studies tool where applicable. An inverse variance random-effects model was the primary analysis model because of the anticipated diversity in the evaluated populations. Univariate models were used when a single outcome was of interest. The risk of deep infection was significantly reduced when local antibiotics were applied compared with the control group receiving systemic prophylaxis only. This beneficial effect was observed in open fractures but failed to reach statistical significance in closed fractures. This meta-analysis suggests that there may be a significant risk reduction in deep infection rate after fracture surgery when local antibiotics are added to standard systemic prophylaxis, particularly in open fractures. Further high-powered Level I studies are needed to support these findings. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

The effect of icosapent ethyl on left atrial and left ventricular morphology.

Atrial fibrillation (AF) is a common arrhythmia associated with poor outcomes. N-3 fatty acids have been shown to provide significant cardiovascular risk reduction, but they may exacerbate the risk of AF. The pathway by which N-3 fatty acids may be arrhythmogenic is unknown. One possible mechanism involves cardiac chamber morphology alteration. The purpose of this study was to investigate the effect of icosapent ethyl (IPE) on left atrial (LA) size and left ventricular (LV) mass. This study used coronary computed tomographic angiography images gathered from the Effect of Icosapent Ethyl on Progression of Coronary Atherosclerosis (EVAPORATE) trial. EVAPORATE was a randomised, double-blind, placebo-controlled study finding a significant reduction in coronary atherosclerosis progression in patients with residually elevated triglycerides despite statin therapy on 4 g IPE daily versus 4 g placebo daily. Computed tomography images were used to measure LA size and LV mass at 0 and 18 months. Of 80 enrolled patients, 68 were included in the final analysis. Baseline demographics and risk factors were similar between IPE and placebo cohorts. LA anterior- posterior diameter measured on axial (p=0.51) and sagittal (p=0.52) orientations were not different over time. Also, there was no difference between groups in the change in LA volume (p=0.84). Change in LV mass was similar between groups (p=0.13). In conclusion, this study did not detect differences in LA size or LV mass over 18 months between patients on 4 g daily IPE versus placebo.

Reduced risk of serious pneumococcal infections up to 10years after a dose of pneumococcal conjugate vaccine in established arthritis.

To examine rates of serious pneumococcal infections up to 10years after vaccination with 7-valent conjugated pneumococcal vaccine (PCV7) in patients with arthritis compared to non-vaccinated arthritis patients. In total, 595 adult arthritis patients (rheumatoid arthritis; RA=342, 80% women and spondylarthropathy; SpA=253, 45% women) received one dose of PCV7. Mean age/disease duration were 62/16 and 51/14years, respectively. For each patient, 4 matched reference subjects were identified. At vaccination, 420 patients received bDMARDs (anti-TNF=330, tocilizumab=15, abatacept=18, anakinra=1, rituximab=56). Methotrexate was given as monotherapy (n=86) or in combination with bDMARD (n=220). 89 SpA patients received NSAIDs without DMARD. The Skåne Healthcare Register was searched for ICD-10 diagnostic codes for pneumococcal infections (pneumonia, lower respiratory tract infection, septicemia, meningitis, septic arthritis) between January 2000 and December 2018. Frequency of infections after vs before vaccination were calculated (relative risks). Relative risk ratio (RRR) and relative risk reduction (1-RRR) were calculated comparing patients vs non-vaccinated references. Kaplan-Meier and Cox regression were used to investigate time to first event and predictors of infections. Among vaccinated RA and SpA patients, there was a significant relative risk reduction of pneumonia and all serious infections; 53% and 46%, respectively. There was no significant difference in time to first pneumonia or all serious infections after vaccination between patients and references. Higher age, RA diagnosis and concomitant prednisolone were associated with infections. One dose of pneumococcal conjugate vaccine may decrease risk of serious pneumococcal infection up to 10years in patients with arthritis receiving immunomodulating treatment.

Evaluation of the Incidence of the Esophagogastric Pre-Cancerous Mucosal Lesions after Bariatric Surgery.

Bariatric surgery is associated with significant risk reduction for obesity-related and hormone-mediated cancers; however, few studies report gastric or esophageal cancer development after bariatric surgery. This study evaluates the incidence of pre-cancerous mucosal lesions one year after bariatric surgery. Eligible patients for omega-loop gastric bypass and classic Roux-en-Y gastric bypass (RYGB) underwent upper endoscopy before bariatric surgery and one year after the procedure. Several biopsies were obtained from esophagogastric mucosa, all of which were evaluated by pathologists regarding the development of any pre-cancerous lesion. A total of 108 patients were included in the study. Seventy-one underwent omega bypass and 37 classic RYGB. Follow-up endoscopy indicated no dysplastic changes in esophagogastric mucosa one year after the surgery. The number of patients with gastric intestinal metaplasia was 22 and 25 before and after the surgery, respectively, which was not a statistically significant increase. Bariatric surgeries might not increase the risk of developing pre-cancerous lesions in the esophagogastric mucosa. Further epidemiological studies may help to establish this finding.

Adherence to the Atrial Fibrillation Better Care (ABC) pathway and the risk of major outcomes in patients with atrial fibrillation: A post-hoc analysis from the prospective GLORIA-AF Registry.

The 'Atrial fibrillation Better Care' (ABC) pathway has been proposed to streamline a more holistic or integrated care approach to atrial fibrillation (AF) management. We aimed to analyse the impact of adherence to the ABC pathway on the risk of major adverse outcomes in a contemporary prospective global cohort of patients with AF. Patients enrolled Phase II and III of the GLORIA-AF Registry with complete data on ABC pathway adherence and follow-up were included in this post-hoc analysis between November 2011 and December 2014 for Phase II, and between January 2014 and December 2016 for Phase III. The primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACEs). Multivariable Cox-regression and delay of event (DoE) analyses were used to evaluate the association between adherence to the ABC pathway and the risk of outcomes. We included 24,608 patients in this analysis (mean age: 70.2 (10.3) years, 10,938 (44.4%) females). Adherence to the ABC pathway was associated with a significant risk reduction for the primary outcome, with greatest magnitude observed for full ABC pathway adherence (adjusted Hazard Ratio [aHR] 0.54, 95% Confidence Interval [CI]: 0.44-0.67, p<0.0001). ABC pathway adherence was also associated with reduced risk of mortality (aHR: 0.89, 95% CI: 0.79-1.00, p=0.048), thromboembolism (aHR: 0.78, 95% CI: 0.65-0.94, p=0.0078), and MACE (aHR: 0.82, 95% CI: 0.71-0.95, p=0.0071). An increasing number of ABC criteria attained was associated with longer event-free survival in the DoE analysis. Adherence to the ABC pathway in patients with AF was associated with a reduced risk of major adverse events, including mortality, thromboembolism and MACE. This underlines the importance of using the ABC pathway in the clinical care of patients with AF. This study was funded by Boehringer Ingelheim.

Did the coronavirus vaccination program in a rural and regional area work? Health outcomes of the vaccination program in Wide Bay.

The objective of this case study is to evaluate the effectiveness of the Wide Bay region coronavirus vaccination program in preventing hospitalisation for coronavirus disease 2019 (COVID-19). Population vaccination data and the vaccination status of patients hospitalised with confirmed COVID-19 have been used to evaluate preventable hospitalisations and risk reduction during and after a 2 month period following the outbreak of COVID-19 in Wide Bay after removal of public health measures in Queensland in December 2021. Wide Bay is a rural region of Queensland including K'Gari (formerly Fraser Island) to the east, the North Burnett farming region in the west and extending from the Fraser Coast to the Discovery Coast. Two local regional hospitals received and managed hospitalised COVID-19 patients. The region had, at this time, 171 365 people 20 years and older eligible for coronavirus vaccination. The risk reduction for hospitalisation of those receiving fewer than two vaccinations, two vaccinations and three vaccinations was calculated to determine the vaccination program effectiveness. The program achieved 90% effectiveness for people with two or more vaccinations (those with two vaccinations and those receiving boosters of third or more vaccination), and 97% effectiveness for those having received three vaccinations, in preventing hospitalisation for COVID-19 during the period. This translated into a significant risk reduction for hospitalisation for those receiving two or more vaccinations, preserving capacity to enable the health service to manage all cases locally.

Abstract P021: Association of social determinants of health and healthcare-related factors with delayed total neoadjuvant therapy among rectal cancer patients from the national cancer database

Abstract Total neoadjuvant therapy (TNT) is a treatment strategy for rectal cancer that includes a course of chemotherapy and a separate course of chemoradiation before definitive surgery. The use of TNT has increased in recent years and carries the potential for improved sphincter preservation and a significant risk reduction of locoregional recurrence. One criterion of the National Accreditation Program for Rectal Cancer is to begin definitive treatment within 60 days of a patient’s diagnosis of rectal cancer. The objective of this study was to evaluate the association of social determinants of health and healthcare-related factors with starting TNT 60 days or more after diagnosis using data from the National Cancer Database (NCDB). Patients aged 18 years and older diagnosed with primary rectal cancer between 2016 and 2019, who underwent NCCN recommended TNT regimen followed by definitive surgery at a Commission on Cancer (CoC)-accredited facility and did not die before receiving surgery were eligible for the current study. We included 3,210 patients in the analytic sample who did not have the following conditions: clinical stage IV, clinical stage T1N0 or lower, non-adenocarcinoma histology, and adjuvant therapy use. Logistic regression models were used to estimate the odds ratio (OR) and 95% confidence intervals (CI) for factors potentially associated with starting TNT more than 60 days after a cancer diagnosis. The median age of patients included in the study was 57 years old, with a majority of them starting TNT within 60 days (87.5%), were males (62.3%), and reported as Non-Hispanic White race and ethnicity (76.7%). Furthermore, 35.0% had a median household income of $63,333 or more, 57.7% had private insurance/managed care, 65.0% traveled within 30 miles to their treatment facility, and 49.1% lived in a zip code where less than 10.9% of adults age 25 or older did not graduate from high school. In multivariable models, factors positively associated with starting TNT after 60 days or more were uninsured status (OR 2.93, CI: 1.84, 4.67), living in a zip code with more than 10.8% of adults age 25 or older not graduating from high school (OR 1.66, CI: 1.22, 2.25), traveling more than 30 miles to the treatment facility (OR 1.63, CI: 1.20, 2.20), treatment with an academic/research program (OR 1.51, CI: 1.13, 2.02), Medicaid as primary insurance (OR 1.50, CI: 1.03, 2.19), Hispanic ethnicity (OR 1.44, CI: 1.00, 2.07), male (OR 1.28, CI: 1.00, 1.65) and age (1.02, CI: 1.01, 1.04). In conclusion, results from this study show that social determinants of health and other healthcare-related factors are significantly associated with those who started TNT more than 60 days after a rectal cancer diagnosis. Further investigation is ongoing to understand the impact of delays in TNT and other treatment regimens for rectal cancer. Citation Format: Megan T. Mai, Zheng Shi, Duke Appiah. Association of social determinants of health and healthcare-related factors with delayed total neoadjuvant therapy among rectal cancer patients from the national cancer database. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P021.

Impact of type of dialyzable beta-blockers on subsequent risk of mortality in patients receiving dialysis: A systematic review and meta-analysis.

Beta-blockers has been reported to improve all-cause mortality and cardiovascular mortality in patients receiving dialysis, but type of beta-blockers (i.e., high vs. low dialyzable) on patient outcomes remains unknown. This study aimed at assessing the outcomes of patients receiving dialyzable beta-blockers (DBBs) compared to those receiving non-dialyzable beta-blockers (NDBBs). We searched the databases including PubMed, Embase, Cochrane, and ClinicalTrials.gov until 28 February 2022 to identify articles investigating the impact of DBBs/NDBBs among patients with renal failure receiving hemodialysis/peritoneal dialysis (HD/PD). The primary outcome was risks of all-cause mortality, while the secondary outcomes included risk of overall major adverse cardiac event (MACE), acute myocardial infarction (AMI) and heart failure (HF). We rated the certainty of evidence (COE) by Cochrane methods and the GRADE approach. Analysis of four observational studies including 75,193 individuals undergoing dialysis in hospital and community settings after a follow-up from 180 days to six years showed an overall all-cause mortality rate of 11.56% (DBBs and NDBBs: 12.32% and 10.7%, respectively) without significant differences in risks of mortality between the two groups [random effect, aHR 0.91 (95% CI, 0.81-1.02), p = 0.11], overall MACE [OR 1.03 (95% CI, 0.78-1.38), p = 0.82], and AMI [OR 1.02 (95% CI, 0.94-1.1), p = 0.66]. Nevertheless, the pooled odds ratio of HF among patients receiving DBBs was lower than those receiving NDBB [random effect, OR 0.87 (95% CI, 0.82-0.93), p<0.001]. The COE was considered low for overall MACE, AMI and HF, while it was deemed moderate for all-cause mortality. The use of dialyzable and non-dialyzable beta-blockers had no impact on the risk of all-cause mortality, overall MACE, and AMI among dialysis patients. However, DBBs were associated with significant reduction in risk of HF compared with NDBBs. The limited number of available studies warranted further large-scale clinical investigations to support our findings.

Effectiveness of Vitamin D Supplementation on Disease Course in Inflammatory Bowel Disease Patients: Systematic Review With Meta-Analysis.

The vitamin D role in bone metabolism is well known; however, recent evidence suggests the impact of vitamin D in immune modulation and its implications in immune-mediated diseases, including inflammatory bowel disease (IBD). We performed a systematic review with meta-analysis by a specific protocol (PROSPERO: CRD42022311184; March 2022, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=311184). Randomized clinical trials involving IBD patients treated with vitamin D supplementation, compared with placebo, that evaluated the risk of clinical relapse and disease activity were included. Literature search was performed using Medline, Scopus, and Cochrane CENTRAL through January 2022. Out of 1448 articles, 12 (11 full-texts and 1 abstract) were included. Seven randomized clinical trials reported data on the clinical relapse as dichotomous outcome, while 7 studies reported data on disease activity expressed as continuous variables. The pooled risk ratio of clinical relapse was 0.64 (95% confidence interval, 0.46-0.89; I2 = 25%) among 458 IBD patients. However, this seems to be solid only in Crohn's disease (CD) patients. In fact, only 2 studies, involving 67 patients with ulcerative colitis, were included in the analysis. CD patients in clinical remission had a strong significant risk reduction in clinical relapse (risk ratio, 0.47; 95% confidence interval, 0.27-0.82; I2 = 0%), suggesting that it could be a specific subgroup with maximum clinical benefit of vitamin D supplementation. This meta-analysis shows that vitamin D supplementation can reduce the risk of clinical relapse in IBD patients, especially in CD patients in clinical remission. In a subgroup analysis, it was not significant (due to small number of studies and low number of patients), and well-powered studies are needed, in particular for ulcerative colitis patients.

Risk Reduction Assessment of Vibrio parahaemolyticus on Shrimp by a Chinese Eating Habit

In China, a traditional perspective recommended that consuming seafood should be mixed or matched with vinegar, because people thought this traditional Chinese eating habit could reduce the risk of pathogenic microorganism infection, such as Vibrio parahaemolyticus induced diarrhea. However, this empirical viewpoint has not yet been evaluated scientifically. This study conducted a simplified quantitative microbiological risk assessment (QMRA) model, which was employed to estimate the risk reduction of V. parahaemolyticus on ready-to-eat (RTE) shrimp by consuming with vinegars (white vinegar, aromatic vinegar, or mature vinegar). Results showed the reduction of V. parahaemolyticus density on RTE shrimp after consuming with white vinegar, aromatic vinegar and mature vinegar was respectively 0.9953 log CFU/g (90% confidence interval 0.23 to 1.76), 0.7018 log CFU/g (90% confidence interval 0.3430 to 1.060) and 0.6538 log CFU/g (90% confidence interval 0.346 to 0.9620). The infection risk of V. parahaemolyticus per meal in this QMRA model was quantified by a mean of 0.1250 with the standard deviation of 0.2437. After consuming with white vinegar, aromatic vinegar, and mature vinegar, the mean infection risk of V. parahaemolyticus on shrimp decreased to 0.0478, 0.0652, and 0.0686. The QMRA scenarios indicated significant reductions in infection risk when eating RTE shrimp by the Chinese eating habit (consuming with vinegar). This good eating habit should be recommended to promote the spread of around the world.

Clival Chordomas in the Endoscopic Endonasal Era: Clinical Management, Outcomes, and Complications.

Surgical management of skull base chordomas has changed significantly in the past 2 decades, most notably with use of the endoscopic endonasal approach (EEA), although high quality outcome data using these modern approaches remain scarce. To evaluate outcomes in a large series of patients treated by a single surgeon, using primarily the EEA. Between 2006 and 2020, 68 patients with skull base chordoma underwent resection using mostly the EEA. Complications, outcomes, and potential contributing factors were evaluated using Kaplan-Meier survival analysis and univariable and multivariable Cox proportional hazards models. Overall 5-year survival was 76.3% (95% CI 61.5%-86.0%), and 5-year progression-free survival was 55.9% (95% CI 40.0%-69.0%). In multivariable analysis, radical resection was associated with significant reduction in risk of death (hazard ratio [HR] 0.04, 95% CI 0.005-0.33, P = .003) and disease progression (HR 0.05, 95% CI 0.01-0.18, P < .001). Better preoperative function status reduced risk of death (HR 0.42 per 10-point increase in Karnofsky Performance Scale, 95% CI 0.28-0.63, P < .001) and progression (HR 0.60 per 10-point increase in Karnofsky Performance Scale, 95% CI 0.45-0.78, P < .001). Localization at the clivus reduced risk of death (HR 0.02, 95% CI 0.002-0.15, P < .001) and progression (HR 0.24, 95% CI 0.09-0.68, P = .007) compared with tumors at the craniovertebral junction. In multivariable analysis, overall survival and progression-free survival of chordoma resection was most positively affected by radical resection, better preoperative functional status, and tumor location at the clivus rather than craniovertebral junction.

Impact of first-line use of caplacizumab on treatment outcomes in immune thrombotic thrombocytopenic purpura

BackgroundThe von Willebrand factor–directed nanobody caplacizumab has greatly changed the treatment of immune thrombotic thrombocytopenic purpura (iTTP) in recent years. Data from randomized controlled trials established efficacy and safety. ObjectivesThis study aims to address open questions regarding patient selection, tailoring of therapy duration, obstacles in prescribing caplacizumab in iTTP, effect on adjunct treatment, and outcomes in the real-world setting. MethodsWe report retrospective, observational cohorts of 113 iTTP episodes treated with caplacizumab and 119 historical control episodes treated without caplacizumab. We aggregated data from the caplacizumab phase II/III trials and real-world data from France, the United Kingdom, Germany, and Austria (846 episodes, 396 treated with caplacizumab, and 450 historical controls). ResultsCaplacizumab was efficacious in iTTP, independent of the timing of therapy initiation, but curtailed the time of active iTTP only when used in the first-line therapy within 72 hours after diagnosis and until at least partial ADAMTS13-activity remission. Aggregated data from multiple study populations showed that caplacizumab use resulted in significant absolute risk reduction of 2.87% for iTTP-related mortality (number needed to treat 35) and a relative risk reduction of 59%. ConclusionCaplacizumab should be used in first line and until ADAMTS13-remission, lowers iTTP-related mortality and refractoriness, and decreases the number of daily plasma exchange and hospital stay. This trial is registered at www.clinicaltrials.gov as #NCT04985318.

Breast cancer risk for women with diabetes and the impact of metformin: A meta-analysis.

Diabetes mellitus has been associated with increased breast cancer (BC) risk; however, the magnitude of this effect is uncertain. This study focused on BC risk for women with type 2 diabetes mellitus (T2DM). Two separate meta-analyses were conducted (1) to estimate the relative risk (RR) of BC for women with T2DM and (2) to evaluate the risk of BC for women with T2DM associated with the use of metformin, a common diabetes treatment. In addition, subgroup analyses adjusting for obesity as measured by body mass index (BMI) and menopausal status were also performed. Studies were identified via PubMed/Scopus database and manual search through April 2021. A total of 30 and 15 studies were included in the first and second meta-analyses, respectively. The summary RR of BC for women with T2DM was 1.15 (95% confidence interval [CI], 1.09-1.21). The subgroup analyses adjusting BMI and adjusting BMI and menopause resulted in a summary RR of 1.22 (95% CI, 1.15-1.30) and 1.20 (95% CI, 1.05-1.36), respectively. For women with T2DM, the summary RR of BC was 0.82 (95% CI, 0.60-1.12) for metformin users compared with nonmetformin users. Women with T2DM were more likely to be diagnosed with BC and this association was strengthened by adjusting for BMI and menopausal status. No statistically significant reduction of BC risk was observed among metformin users. These two meta-analyses can inform decision-making for women with type 2 diabetes regarding their use of metformin and the use of screening mammography for early detection of breast cancer.

1066 THE USEFULNESS OF CEREBRAL PROTECTION DURING TAVR: A METANALYSIS

Abstract Introduction although transcatheter aortic valve replacement (TAVR) represents a milestone in the treatment of degenerative aortic stenosis, stroke remains an important complication compared to surgical aortic valve replacement (SAVR). Multiple magnetic resonance imaging (MRI) studies demonstrated a substantial rate of new cerebral ischemic lesions after TAVR. In order to avoid debris passage into the circulation and to prevent procedure-related embolic stroke, cerebral embolic protection (CEP) devices were developed. However, their safety and efficacy remain controversial. Very recently, new studies provided additional evidence on this topic. Aim to assess the entire body of evidence from randomized controlled studies about neurological outcomes after TAVR. Materials and Methods a systematic meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched MEDLINE, Scopus, and Google Scholar for randomized controlled studies. The following keywords were used for the search: “transcatheter aortic valve implantation” or “stroke prevention” or “embolic protection” and “cerebral protection”. Study groups were defined as a the “CEP group” and the “control group”. Non-randomized studies reporting outcomes with cerebral embolic protection (CEP) during TAVR were excluded to reduce the selection and confounding bias of observational pilot studies. The primary outcome was post-procedural stroke. Secondary outcomes included total lesion volume on MRI and new ischemic lesions on MRI. Results nine trials including 4077 patients were eligible for analysis and included to the meta-analysis. Of those, 2203 patients were randomized to cerebral embolic protection and 1874 patients to control group. Despite the rate of post-procedural stroke was higher in the CEP arm (2.27%) compared to the control arm (2.87%, p&amp;lt;0.001), the use of cerebral embolic protection was not associated with a significantly lower risk of stroke (OR=0.82, 95% CI 0.59-1.15; p=0.255). Cumulative meta-analysis revealed a trend towards a lower impact on stroke prevention with more recent trials. Conclusions use of cerebral embolic protection devices during TAVR is a safe procedure. However, the current outline of results from all randomized controlled trials available does not support its routine use, as no significant reduction of stroke risk was evident. The use of these devices might be considered in selected high-risk patients, such as in the setting of heavy calcified cusps or atherosclerotic aortic lesions.

1918. Impact of the SARS-CoV-2–Neutralizing Antibody Combination AZD7442 (Tixagevimab/Cilgavimab) on the Severity and Progression of COVID-19 Symptoms in the Phase 3 TACKLE Trial

Abstract Background Outpatient treatment with SARS-CoV-2–neutralizing antibody combination AZD7442 (tixagevimab/cilgavimab) in adults with mild to moderate COVID-19 significantly reduced progression to severe disease or death through Day 29 and was well-tolerated in the Phase 3 TACKLE study (NCT04723394). We report a post hoc analysis of the impact of AZD7442 in reducing self-reported COVID-19 symptom severity and time to symptom resolution through Day 29 in TACKLE. Methods In TACKLE, non-hospitalized adults with mild to moderate COVID-19 were randomized 1:1 and dosed ≤7 days from symptom onset with a single 600mg AZD7442 dose (2 consecutive intramuscular (IM) injections, 300 mg of each antibody; n=452) or placebo (n=451). Symptom occurrence and severity were self-reported daily by participants through study Day 29. Participants rated each symptom as not experienced, mild, moderate, severe, or emergency room (ER) or hospital visit. Symptom progression was compared between AZD7442 and placebo using a stratified Cochran-Mantel-Haenszel test. Change from baseline in symptom severity was compared using a mixed model for repeated measures. Time to symptom resolution was compared using Kaplan-Meier and Cox proportional hazards methods. Missing symptom data for those who were hospitalized or died were imputed as either failures or as severity scores of ER or hospital visit. Results Progression of ≥1 symptoms to a worse severity score occurred in 170 (55.7%) AZD7442- versus 204 (63.4%) placebo-treated participants, translating to a nominally significant relative risk reduction of 12.5% (95% confidence interval 0.5–23.0; P=0.041). Over 29 days, the overall mean improvement from baseline in severity of body aches, chills, cough, diarrhea, fatigue, headache, muscle aches, nausea, and runny nose was significantly greater with AZD7442 versus placebo (Figure). The greatest improvements were observed with cough, fatigue, and muscle aches. Significant differences were observed for most symptoms within 1 and 2 weeks post AZD7442 dosing. Figure. Forest plot for LS difference in severity of COVID-19 symptoms between AZD7442 and placebo through Day 29 CI, confidence interval; LS, least squares. The overall P value is calculated using a mixed model for repeated measures, including terms for symptom severity baseline value, time from symptom onset (≤5 vs &amp;gt;5 days), risk of progression to severe COVID-19 (high vs low), treatment, visit, and treatment by visit interaction. Conclusion For the treatment of mild to moderate COVID-19, a single IM 600-mg AZD7442 dose was associated with reductions in progression of COVID-19 symptom severity and may hasten symptom improvement through Day 29. Disclosures Jesus Abraham Simón Campos, MD, AstraZeneca: Board Member|AstraZeneca: Speaker|Eli Lilly: Board Member|Pfizer: Board Member|Roche: Board Member|Roche: Speaker Douglas Arbetter, MPH, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Hugh Montgomery, MD, AstraZeneca: Advisor/Consultant|Millfield Medical Ltd: Advisor/Consultant|UK National Institute for Health Research's Comprehensive Biomedical Research Centre at University College London Hospitals: Grant/Research Support F.D. Richard Hobbs, FMedSci, AstraZeneca: Grant/Research Support|AstraZeneca: Principal investigator|NIHR Applied Research Collaboration, Oxford Thames Valley: Director|Oxford BRC and NIHR MedTech: Investigator|UKRI and NIHR: Grant/Research Support Francisco Padilla, MD, Amgen: Grant/Research Support|Amgen: Personal fees|AstraZeneca: Grant/Research Support|AstraZeneca: Personal fees|Boehringer Ingelheim: Grant/Research Support|Boehringer Ingelheim: Personal fees|Ferrer: Grant/Research Support|Ferrer: Personal fees|Kowa: Grant/Research Support|Kowa: Personal fees|Medix: Grant/Research Support|Medix: Personal fees|Merck Sharp and Dohme: Grant/Research Support|Merck Sharp and Dohme: Personal fees|Novartis: Grant/Research Support|Novartis: Personal fees|Pfizer: Grant/Research Support|Pfizer: Personal fees|Sanofi: Grant/Research Support|Sanofi: Personal fees|Servier: Grant/Research Support|Servier: Personal fees|Silanes: Grant/Research Support|Silanes: Personal fees Kenneth Kim, MD, Adagio: Funding|Eli Lilly: Funding|Merck: Funding|Pfizer: Funding|Regeneron: Speaker|Regeneron: Funding Katie Streicher, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Alison Templeton, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Rolando M. Viani, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Mark T. Esser, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds.

1127. Effectiveness of Remdesivir as Treatment for COVID-19 Positive US Veterans

Abstract Background The COVID 19 disease has claimed over 6.3 million lives, globally. Despite such high casualties, the treatment options are limited. Although the FDA issued emergency use authorizations for oral antivirals to treat mild-to-moderate COVID 19 disease, intravenous Remdesivir treatment remains the only fully FDA-approved antiviral. However, many early studies questioned its efficacy. Accordingly, the WHO initially recommended against its use in COVID 19 positive patients. Based on the newly emerging data, as of 22 April 2022, WHO suggests that Remdesivir can be effectively used in mild or moderate COVID 19 cases. This retrospective cohort data analysis was undertaken to evaluate and clarify the effectiveness of Remdesivir use in older US veterans. Methods The deidentified veterans' data were accessed from the VA COVID 19 Shared Data Resources with local ethical approvals. Propensity matched cohorts with and without Remdesivir treatment were analyzed using Cox regression models, constructed in a way to avoid immortal time and calendar time biases. Limited to hospitalized veterans, patients were followed for 60 days to the outcomes of mechanical ventilation (MV) and death in separate models. The cohort was also limited to those who received low flow without high flow oxygen and a combination of low and high flow oxygen in another set of models. Results A total of 3,372 veterans were included in this study who were hospitalized between 01 January to 31 December 2021 for COVID 19 disease. Of those, 1,686 received Remdesivir treatment, while their matches never received it. After propensity score matching that included demography, vaccination status, comorbidities, medication use, lab tests, Remdesivir recipients and controls were similar in age (66.8±14.1 vs. 67.0±13.8 years). Relative risk reductions (1-HR), 53% for MV, and 42% for death (Fig. 1) were observed with low flow oxygen and Remdesivir therapy. In veterans who received high and low flow oxygen, although there was a significant 18% reduction in risk for death, progression to MV was not significant (P=0.22). Figure 1A forest plot showing the hazard ratios (HRs) for death and mechanical ventilator use in hospitalized US veterans with COVID-19 positivity between 01st of January to 31st of December 2021. Conclusion The data showed significant risk reductions of disease progression to MV/death when Remdesivir was used in COVID 19 positive patients with low supplementary oxygen flow, supporting the current NIH recommendation. Disclosures Sujee Jeyapalina, PhD, Dr. Jeyapalina received funding from Gilead Sciences, Inc. for COVID-19 data research: Grant/Research Support Gregory Stoddard, Mstat, Greg Stoddard received funding from Gilead Sciences, Inc. for COVID-19 data research: Grant/Research Support Jay Agarwal, MD, Dr. Agarwal received funding from Gilead Sciences, Inc. for COVID-19 data research: Grant/Research Support.