Significant Reduction In Risk Research Articles

Development of an Improved LASER-Resistant Endotracheal Tube.

Surgical fires, particularly within Otolaryngology, remain a surprisingly frequent and devastating complication of laser-related surgery in the oropharynx and airway; Current estimates suggest anywhere from 200 to 600 surgical fires per year in the United States, with 20%-30% of these occurring as a complication of laser surgery and 90%-95% of these occurring in the head and neck region. Unfortunately, the complications of laser surgery in the airway may include respiratory failure, airway burns with stenosis, and may result in mortality. The most commonly utilized endotracheal tube for protection against inadvertent laser strikes, the Laser-Shield II tube (Medtronic), was removed from the commercial marketplace in 2016 after cases of airway fires were reported as a result of feature deficiencies in the product (FDA MAUDE Database review). Since the demise of the Laser-Shield II tube, alternatives such as the Mallinckrodt laser tube and handmade reinforced tubes have been utilized, although shortcomings in design and features have made these options less appealing to practicing Otolaryngologists. Creating a laser-safe endotracheal tube is critical for safe upper airway surgery. This paper evaluates new technologies, materials, and technical innovations in endotracheal tubes that may advance patient safety in laser-assisted Otolaryngology procedures. This paper evaluates new technologies, materials, and technical innovations in endotracheal tubes that may advance patient safety in laser-assisted Otolaryngology procedures. First, this article reviews the background of laser surgery in Otolaryngology and the consequent risk of surgical fire with resultant development of laser-resistant endotracheal tubes and commercial availability. Next, a review of claims and national database review of product failures related to previous laser-resistant endotracheal tubes is performed through the FDA MAUDE database. This includes an evaluation of cases: review of techniques in laser airway surgery including spontaneous ventilation, decreased O2 concentration, currently available endotracheal tubes including "handmade" fixes for perceived safety risks, and determination of failure points for previous laser-resistant endotracheal tubes. Third, the paper reviews the requested features of an "ideal" laser-resistant endotracheal tube. Finally, the paper reviews failure testing from an initial, unsuccessful attempt at material development and the consequent development of alternative technologies that address failure points from previous endotracheal tubes and addresses requested features with a detailed analysis of FDA-approval required testing. Extensive lab testing of the new tube predicts a significant reduction of risk in vivo with inability to perforate the shaft or cuff of the tubes under standard working conditions. While no iteration of a laser-resistant endotracheal tube is entirely laser safe, advances in technology can improve the safety profile of these devices. The new tube contains a double cuff, a soft and flexible shaft to minimize laryngeal insertion trauma, a smooth external surface, a tight-to-shaft balloon, and methylene blue dye in the cuff to alert the user to inadvertent penetration. These characteristics were the most requested by laryngologists in the development of a new laser-resistant tube. The newest endotracheal tube brings the features most requested by Otolaryngologists in a laser-resistant tube, and improves the safety profile over previous tubes. Development of a new endotracheal tube represents an advancement in safety for the Otolaryngologist in laser airway surgery. Understanding the previous history and the science behind surgical fire formation is essential in advancing safety for patients in the future. N/A Laryngoscope, 134:S1-S12, 2024.

Tiotropium reduces clinically important deterioration in patients with mild-to-moderate chronic obstructive pulmonary disease: A post hoc analysis of the Tie-COPD study

BackgroundClinically important deterioration (CID) is a composite endpoint used to holistically assess the complex progression of chronic obstructive pulmonary disease (COPD). Tiotropium improves lung function and reduces the rate of COPD exacerbations in patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 (mild) or 2 (moderate). However, whether tiotropium reduces CID risk in patients with mild-to-moderate COPD remains unclear. MethodsThis was a post hoc analysis of the 24-month Tie-COPD study comparing 18 μg tiotropium with placebo in patients with mild-to-moderate COPD. CID was defined as a decrease of ≥100 mL in trough forced expiratory volume in 1 s, an increase of ≥2 unit in COPD Assessment Test (CAT) score, or moderate-to-severe exacerbation. The time to the first occurrence of one of these events was recorded as the time to the first CID. Subgroup analyses were conducted among patients stratified by CAT score, modified Medical Research Council (mMRC) dyspnea score, and GOLD stage at baseline. ResultsOf the 841 randomized patients, 771 were included in the full analysis set. Overall, 643 patients (83.4 %) experienced at least one CID event. Tiotropium significantly reduced the CID risk and delayed the time to first CID compared with placebo (adjusted hazard ratio = 0.58, 95 % confidence interval = 0.49–0.68, P < 0.001). Significant reductions in CID risk were also observed in various subgroups, including patients with a CAT score <10, mMRC score <2, and mild COPD. ConclusionsTiotropium reduced CID risk in patients with mild-to-moderate COPD, even in patients with fewer respiratory symptoms or mild disease, which highlights tiotropium's effectiveness in treating COPD patients with mild disease. Trial registrationThis study is registered at ClinicalTrials.gov (Tie-COPD, NCT01455129).

Meta-Analysis of Randomized Trials: Efficacy and Safety of Colchicine for Secondary Prevention of Cardiovascular Disease.

Colchicine has shown potential cardioprotective effects owing to its broad anti-inflammatory properties. We performed a meta-analysis to assess its safety and efficacy in secondary prevention in patients with established coronary artery disease (CAD). We searched Ovid Healthstar, MEDLINE, and Embase (inception to May 2022) for randomized controlled trials (RCTs) evaluating the cardiovascular effects of colchicine compared with placebo or usual care in patients with CAD. Study-level data on efficacy and safety outcomes were pooled using the Peto method. The primary outcome was the composite of cardiovascular (CV) death, myocardial infarction (MI), or stroke. A total of 8 RCTs were included with a follow-up duration of ≥1 month, comprising a total of 12,151 patients. Compared with placebo or usual care, colchicine was associated with a significant risk reduction in the primary outcome (odds ratio (OR) 0.70, 95% CI 0.60 to 0.83, P < 0.0001; I2 = 52%). Risks of MI (OR 0.75, 95% CI 0.62 to 0.91, P = 0.003; I2 = 33%), stroke (OR 0.47, 95% CI 0.30 to 0.74, P = 0.001; I2 = 0%), and unplanned coronary revascularization (OR 0.67, 95% CI 0.55 to 0.82, P = 0.0001; I2 = 58%) were all reduced in the colchicine group. Rates of CV and all-cause mortality did not differ between the two groups, but there was an increase in noncardiac deaths with colchicine (OR 1.54, 95% CI 1.10 to 2.15, P = 0.01; I2 = 51%). The occurrence of all other adverse events was similar between the two groups, including GI reactions (OR 1.06, 95% CI 0.94 to 1.20, P = 0.35; I2 = 42%) and infections (OR 1.04, 95% CI 0.84 to 1.28, P = 0.74; I2 = 53%). Colchicine therapy may reduce the risk of future cardiovascular events in patients with established CAD; however, there remains a concern about non-CV mortality. Further trials are underway that will shed light on non-CV mortality and colchicine NCT03048825, and NCT02898610.

A Delirium Prevention and Management Initiative: Implementing a Best Practice Recommendation for the NICU.

Medically complex infants experiencing NICU stays can be difficult to manage, exhibiting refractory agitation, disengagement, or both-all signs of delirium, which can present in a hypoactive, hyperactive, or mixed form. Though documented in other settings, delirium is under-recognized in NICUs. Pediatric studies show that a high percentage of patients with delirium are under the age of 12 months. Delirium is associated with increased ventilation days, hospital days, and costs. It negatively affects neurodevelopment and social interaction. Studies show that pediatric nurses are unprepared to recognize delirium. Our nurse-led multidisciplinary group created a best practice recommendation (BPR) focused on detecting delirium and minimizing risk through thoughtful sedation management, promotion of sleep hygiene and mobility, and facilitation of meaningful caregiver presence. Occasionally, medications, including melatonin and risperidone, are helpful. In 2019, we introduced this BPR to reduce delirium risk in our NICU. Practice changes tied to this initiative correlate with a significant reduction in delirium scores and risk including exposure to deliriogenic medications. A multidisciplinary care bundle correlates with decreased delirium screening scores in NICU patients.

Relationship between sex differences in drinking, smoking, and exercising and the incidence of malignancies and medical procedures: a cross-sectional study of 21,916 participants in China.

Objectives: The unresolved issue of the relationship between sex differences in tea, coffee, and beverage consumption and malignancy risk prompted our study in 2022. Methods: Logistic proportional hazards models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) in our investigation of the associations between cancer risk and tea, coffee, and beverage consumption. Results: Our findings revealed that frequent consumption of white tea significantly reduced the occurrence of malignant tumours, but this effect was detected only in the fully adjusted model for males (OR: 0.736, 95% CI: 0.095-5.704). The amount of sugar added to coffee was associated with an increased risk of malignancy in a dose-dependent manner (P for trend = 0.001), with significance observed for both men (P for trend = 0.049) and women (P for trend = 0.005) in the final model. Notably, individuals who consumed more than 2100 ml of sugary beverages daily had a statistically significant reduction in malignancy risk (OR: 0.219, 95% CI: 0.052-0.917). Interestingly, the intake of sugary beverages had a protective effect on cancer incidence, with a significant effect on males (P for trend = 0.031) but not females (P for trend = 0.096) in the final model. Conclusions: Our study highlights the substantial impact of regular white tea consumption on reducing the risk of malignant tumours in males. This study first reported that the potential protective effect of consuming sugary beverages is predominantly observed in males, and a correlation between the amount of sugar added to coffee and a heightened risk of malignancy.

Omega-3 Fatty Acid Therapy: A Review of Study Design Flaws, Quality, and Composition

There is marked heterogeneity in the clinical response to omega-3 fatty acid therapy with many authors documenting futility in large-scale trials, secondary re-analysis, and meta-analysis. The question of failure in the context of omega-3 therapy is multifactorial and complicated by the observation that fish intake has been broadly linked to significant risk reductions across a range of conditions. The question that remains is how can we resolve the discrepancy between pre-clinical evidence and epidemiology, which dually emphasize the benefit of omega-3 therapy against the limited success of large-scale clinical trials and smaller scale clinical studies that do not consistently report benefit and may even report harm, especially as it pertains to atrial fibrillation. We present three primary considerations that may clarify the supposed failures of omega-3 therapy: 1) correction for omega-3:omega-6 ratio and competition, 2) variation in the fatty acid composition and quality of omega-3 products, and 3) fundamental concerns pertaining to the omega-3 vehicle and its impact on omega-3 metabolism. While the predominant source of omega-3 therapy is supplements, they are typically not regulated prior to market like drugs and have significant variability in fatty acid composition, vehicle, oxidation, and quality control. Further, the individual response to omega-3 therapy is likely variable and dependent on ambient dietary conditions and inherited differences in endogenous desaturase activity, which has infrequently been accounted for in large studies. The net effect of these concerns should engender pharmaceutical and consumer companies alike to consider 1) refining trial design and 2) consider the role of oxidation in the failure of omega-3 products.

A Meta-analysis on the Comparison of Carbetocin Versus Oxytocin on Additional Uterotonic Use, Incidence of Postpartum Hemorrhage, and Need for Blood Transfusion after Cesarean Section under Neuraxial Anesthesia

ABSTRACT Postpartum hemorrhage (PPH) remains to be the leading cause of maternal deaths worldwide. The first-line treatment in its prevention is the administration of uterotonics before the delivery of the placenta. Recently, a newer synthetic analog has been developed – carbetocin. With its introduction, new questions arise as to which is more effective in preventing PPH. Four major electronic databases were searched for randomized controlled trials comparing carbetocin and oxytocin in terms of additional uterotonic use, incidence of PPH, and need for blood transfusion. Only randomized controlled studies involving pregnant women undergoing cesarean section under regional anesthesia were included. Outcomes included are the need for additional uterotonic use, the incidence of PPH, and the need for blood transfusion. Of the three outcomes, carbetocin was found to show statistically significant protection against the need for additional uterotonic administration and the need for blood transfusion. Results showed that carbetocin provided a statistically significant risk reduction for the need for additional uterotonics (risk ratio [RR] = 0.53, 95% confidence interval [CI] 0.46–0.81, P &lt; 0.00001) and need for blood transfusion (RR = 0.34, 95% CI 0.19–0.62, P = 0.0004). Need for additional uterotonics and for blood transfusion was found to be almost twice (1/0.53 = 1.88) and almost thrice (1/0.34 = 2.94) as likely, respectively, to occur in the oxytocin group versus the carbetocin group. Reduction of PPH pointed toward carbetocin providing greater protection against it, but it was found not to be statistically significant (RR = 0.85, 95% CI 0.56–1.28, P = 0.43).

AHA Life's Essential 8 and new-onset CKD: a prospective cohort study from the UK Biobank.

The AHA has recently introduced a novel metric, Life's Essential 8, to assess cardiovascular health (CVH). Nevertheless, the association between varying levels of LE8 and the propensity for CKD is still unclear from a large prospective cohort. Our objective is to meticulously examine the relationship between LE8 and its associated susceptibilities to CKD. A total of 251,825 participants free of CKD from the UK Biobank were included. Cardiovascular health was scored using LE8 and categorized as low, moderate, and high. Cox proportional hazard models were employed to evaluate the associations of LE8 scores with new-onset CKD. The genetic risk score for CKD was calculated by a weighted method. Over a median follow-up of 12.8years, we meticulously documented 10,124 incident cases of CKD. Remarkably, an increased LE8 score correlated with a significant reduction of risk in new-onset CKD (high LE8 score vs. low LE8 score: HR = 0.300, 95% CI 0.270-0.330, p < 0.001; median LE8 score vs. low LE8 score: HR = 0.531, 95% CI 0.487-0.580, p < 0.001). This strong LE8-CKD association remained robust in extensive subgroup assessments and sensitivity analysis. Additionally, these noteworthy associations between LE8 scores and CKD remained unaffected by genetic predispositions to CKD. An elevated degree of CVH, as delineated by the discerning metric LE8, exhibited a pronounced and statistically significant correlation with a marked reduction in the likelihood of CKD occurrence.

Comparison of GLP-1 Receptor Agonists and Other Glucose-Lowering Agents on Cardiovascular Outcomes in Individuals with Type 2 Diabetes and Obesity: A Spanish Real-World Population-Based Study

AimsAssess the impact of glucagon-like peptide receptor agonists (GLP-1RA) compared to other glucose-lowering agents on cardiovascular outcomes in individuals with type 2 diabetes and obesity in a Spanish metropolitan area MethodsA retrospective population-based type 2 diabetes cohort was identified from the Valencia Clinic-Malvarrosa Department electronic databases (2014-2019). Study groups included GLP-1RA, sodium-glucose co-transporter-2 inhibitors (SGLT2i), Insulin, and Miscellany (other glucose-lowering agents). 1:1:1:1 propensity score matching was conducted. The primary outcome was a composite of major adverse cardiovascular events (4-point MACE) comprising myocardial infarction, stroke, all-cause mortality, and heart failure. Secondary outcomes included individual 4-point MACE components. Hazard ratios were estimated using Cox regression analyses against the Miscellany group. ResultsFrom 26,944 subjects, 1,848 adults were selected per group. GLP-1RA did not show a significant reduction in 4-point MACE risk (HR 1.05 [95%CI 0.82-1.34]). SGLT2i significantly reduced the risk of heart failure (HR 0.16 [95%CI 0.05-0.54]) and atrial fibrillation (HR 0.58, [95%CI 0.35-0.95]). The Insulin group exhibited a higher risk for 4-point MACE and most individual outcomes compared to GLP-1RA and SGLT2i. ConclusionsOur findings do not provide evidence of a reduced cardiovascular risk, as assessed by 4-point MACE, with GLP-1RA. In contrast, SGLT2i demonstrated protective effects against heart failure and atrial fibrillation.

Large-scale data reveal disparate associations between leisure time physical activity patterns and mental health

BackgroundLeisure time physical activity (LTPA) is known to be associated with a lower risk for mental health burden, while whether the underlying mechanisms vary across populations is unknown. We aimed to explore the disparate associations between LTPA and mental health based on large-scale data.MethodsIn this study, we analyzed data including 711,759 individuals aged 15 years or above from the latest four rounds (2003, 2008, 2013, and 2018) of the National Health Service Survey (NHSS) in China. We used multiple logistic regression models adjusted for potential confounders to investigate associations between LTPA and mental health in the total population and subgroups by measuring a diverse set of activity frequencies, intensities, and types. To examine the dose-response associations between total activity volume and mental health, we conducted restricted cubic splines to investigate possible nonlinearity.ResultsLTPA was associated with remarkably lower self-reported mental health burden (OR 0.56, 95% CI 0.54–0.58). The dose-response relationship between total activity volume and mental health was highly nonlinear (p < 0.001), presenting L-shaped with first 1200 metabolic equivalents of task (METs)-min/week for significant risk reduction (OR 0.58, 95% CI 0.56–0.60). Notably, merely exercising 3–5 times per week with moderate swimming was significantly associated with lower mental health burden among younger people, while the association was strongly large in older adults aged 60 years or above doing 55-min moderate apparatus exercise at least six times a week.ConclusionsIn a large Chinese sample, LTPA was meaningfully and disparately associated with mental health burden across different people. Policy targeted at prompting activity may be effective for reducing mental health burden, but importantly, tailored strategies are needed based on population contexts.

Protective Effects Against Dementia Undergo Different Statin Type, Intensity, and Cumulative Dose in Older Adult Type 2 Diabetes Mellitus Patients

ObjectivesThis study investigated the relationship between statin use and dementia risk in older adults with type 2 diabetes (T2DM). It also assessed the impact of various statin types, dosage intensity, and cumulative doses on dementia risk. DesignEmploying the inverse probability of treatment weighting (IPTW) Cox hazards model, this research explored the influence of statin utilization on dementia incidence. Setting and ParticipantsThe study included older adult T2DM patients aged 60 years or older who received statins (case group) and those who did not (control group) during the follow-up period. MethodsThe IPTW Cox hazards model quantified the association between statin use and dementia incidence. Subgroup analyses investigated different statin types, usage intensity, and cumulative dose–dependent relationships with dementia risk, measured by adjusted hazard ratios (aHRs) with corresponding 95% CIs. ResultsStatin users experienced a significant reduction in dementia risk (aHR: 0.47, 95% CI: 0.46-0.48). Subgroup analysis using IPTW Cox regression revealed varying dementia incidence reductions among users of different statin types, with aHRs (95% CIs) ranging from 0.09 to 0.69. Multivariate analyses unveiled a dose-dependent relationship, showing reduced dementia incidence based on cumulative defined daily doses (cDDDs) per year. The corresponding aHRs (95% CIs) were 0.20 to 0.72 across quartiles 4 to 1 of cDDD-years, with a significant trend (P < .001). The optimal daily statin use was 0.88 defined daily doses (DDDs), associated with the lowest dementia risk. Conclusions and ImplicationsStatins significantly reduced dementia risk in older adult T2DM patients. Higher cumulative defined daily doses (cDDD-years) were linked to more substantial risk reductions. This research underscores the clinical benefits of statin use in preventing dementia in this population and calls for further investigation into the underlying mechanisms. It also raises the possibility of influencing policy decisions to manage dementia risk in this vulnerable group.

Coronectomy? A case report following coronectomy of a ‘high-risk’ mandibular third molar

Background The surgical removal of mandibular third molar (M3M) is a common procedure performed by oral and maxillofacial surgeons, oral surgeons, and general dental practitioners. Apart from risks such as pain, swelling, bruising, bleeding, trismus, alveolar osteitis, post-op infection, and damage to adjacent structures which are common to all surgical extractions, M3M removal includes the risk of permanent or temporary damage to the inferior alveolar nerve (IAN) or the lingual nerve. IAN damage can significantly impact the quality of life due to altered sensation of the lip and chin area. As such, the alternative surgical option of coronectomy, which is the sectioning of the crown from the tooth and deliberate retention of the roots, can be offered to high-risk cases to avoid IAN damage. Case presentation 36-year-old female was diagnosed with recurrent pericoronitis of her left M3M. Her left M3M was partially erupted and horizontally impacted with bulbous roots that were in close proximity to the IAN. Due to a higher risk of IAN damage, she underwent a coronectomy procedure of her left M3M instead of a complete removal. She experienced typical post-operative pain and swelling but no other complications such as altered nerve sensation were reported. The surgical site was healed with full mucosal coverage after 12 weeks. Conclusion Coronectomy provides a viable alternative surgical option to removal for mandibular third molars that are at high risk of IAN damage. This is due to the significant reduction of risk of IAN damage and low incidence of failure.

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.

Predictive Value of Methicillin-Resistant Staphylococcus aureus Nasal Swab PCR Assay for MRSA Infection in Critically Ill Pediatric Patients.

Critically ill pediatric patients are frequently initiated methicillin-resistant Staphylococcus aureus (MRSA) active antibiotics during infection evaluation even though MRSA infections are rare in many patient populations. The MRSA nasal swab polymerase chain reaction assay (MRSA-NS-PCR) is a test that has been shown to have a high negative predictive value (NPV) for MRSA infection in adults. This study evaluated the diagnostic test characteristics of the MRSA-NS-PCR in predicting the presence of MRSA infection in critically ill pediatric patients. A retrospective cohort study was performed in a 44-bed pediatric intensive care unit (PICU) between 2013 and 2017. 3860 pediatric patients (54% male, median age 4 years [IQR 1-11 years]) admitted to the PICU who met pediatric systemic inflammatory response syndrome (pSIRS) criteria, were screened with a MRSA-NS-PCR, and had cultures obtained within seven days of MRSA-NS-PCR collection were included. Predictive values and post-test probabilities of the MRSA-NS-PCR for MRSA infection were calculated. MRSA-NS-PCR was positive in 8.6% of patients. MRSA infection was identified in 40 patients, equaling an incidence rate of 2 per 1000 patient days. The MRSA-NS-PCR demonstrated a positive predictive value (PPV) of 9.7%, a NPV of 99.8%, and a post-test probability for a negative test of 0.2% for MRSA infection. The MRSA-NS-PCR has a poor PPV but a high NPV for MRSA infection in PICU patients when the incidence of MRSA infection is low. Creation of protocols to guide antimicrobial selection based on MRSA-NS-PCR results may lead to improved antimicrobial stewardship and significant risk reduction.

Phytonutrients and outcomes following breast cancer: a systematic review and meta-analysis of observational studies.

Phytonutrient intakes may improve outcomes following breast cancer, but the impact of postdiagnosis introduction vs established prediagnostic exposure as well as optimum doses has not been established. Evidence from observational studies for key exposures was evaluated, including dosage and intake time frames. MEDLINE, EMBASE, CINAHL, Cochrane Library, ClinicalTrials.gov, and the ISRCTN registry were searched for prospective and retrospective observational studies investigating the impact of soybean, lignans, cruciferous (cabbage-family) vegetables, green tea, or their phytonutrients on breast cancer survival outcomes. A random-effects model was used to calculate summary hazard ratios (HRs) and 95% confidence intervals (CIs). Nonlinear dose-response analyses were conducted using restricted cubic splines. Thirty-two articles were included. Soy isoflavones were associated with a 26% reduced risk of recurrence (HR = 0.74, 95% CI = 0.60 to 0.92), particularly among postmenopausal (HR = 0.72, 95% CI = 0.55 to 0.94) and estrogen receptor-positive survivors (HR = 0.82, 95% CI = 0.70 to 0.97), with the greatest risk reduction at 60 mg/day. In mortality outcomes, the reduction was mostly at 20 to 40 mg/day. Soy protein and products were inversely associated with cancer-specific mortality for estrogen receptor-positive disease (HR = 0.75, 95% CI = 0.60 to 0.92). An inverse association was observed for serum or plasma enterolactone, measured prediagnosis and early postdiagnosis, with cancer-specific mortality (HR = 0.72, 95% CI = 0.58 to 0.90) and all-cause mortality (HR = 0.69, 95% CI = 0.57 to 0.83). No effects were observed for cruciferous vegetables. There was a 44% reduced risk of recurrence with prediagnostic green tea for stage I and II breast cancer (HR = 0.56, 95% CI = 0.38 to 0.83). Soy, enterolactone, and green tea demonstrated significant risk reductions in outcomes following breast cancer. Evidence is needed regarding the impact of postdiagnostic introduction or substantial increase of these exposures.

Are green loans less risky? Micro-evidence from a European Emerging Economy

The role played by the banking sector in supporting the green transition has been limited but is expected to increase substantially. We investigate whether the green loans granted by Romanian financial institutions during the period from 2010 to 2020 bear less credit risk compared with other loans in their portfolio. In this respect, we use a novel micro database with information on all green loans granted by a representative share of Romanian financial institutions, combined with debtors’ financial statements. We use different approaches to control for the small share of green loans and find that firms with a sounder financial profile are more likely to access green loans. Using a matched sample of non-green loans, we are able to disentangle the factors that contribute to the increase in credit risk, but we do not observe a significant risk reduction in the case of green loans.

Efficacy and safety of bempedoic acid among patients with and without diabetes: prespecified analysis of the CLEAR Outcomes randomised trial

Statins reduce LDL cholesterol and cardiovascular events among those with or without diabetes but have been reported to increase new-onset diabetes. The CLEAR Outcomes trial demonstrated that bempedoic acid reduced the risk of major adverse cardiovascular events among statin-intolerant patients at high cardiovascular risk. In this prespecified analysis, our dual aims were to evaluate the cardiovascular benefits of bempedoic acid, an ATP-citrate lyase inhibitor, in individuals with diabetes, and to evaluate the risk of new-onset diabetes and HbA1c among those without diabetes in the CLEAR Outcomes trial. CLEAR Outcomes was a randomised, double-blind, placebo-controlled trial conducted across 1250 primary care and outpatient sites in 32 countries. Patients with or without cardiovascular disease who were unwilling or unable to take guideline-recommended doses of statins and an LDL cholesterol of 2·59 mmol/L or more were randomly assigned (1:1) in a double-blinded manner to either bempedoic acid 180 mg once per day or placebo. In this prespecified analysis, the efficacy endpoint was a time-to-event analysis of four-component major adverse cardiovascular event (MACE-4), which is the composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularisation, using the intention-to-treat population stratified by baseline glycaemia status. The prespecified analysis of risk of new-onset diabetes and HbA1c increase was evaluated in patients without diabetes at baseline. The CLEAR Outcomes trial was completed on Nov 7, 2022, and is registered with ClinicalTrials.gov (NCT02993406). Between Dec 22, 2016, and Nov 7, 2022, 13 970 patients were screened and randomly assigned; 6373 (45·6%) with diabetes, 5796 (41·5%) with prediabetes, and 1801 (12·9%) with normoglycaemia. Over a median of 3·4 years follow up, patients with diabetes had significant relative and absolute cardiovascular risk reductions in MACE-4 endpoints with bempedoic acid (HR 0·83; 95% CI 0·72-0·95; absolute risk reduction of 2·4%) compared to placebo, with no statistical evidence of effect modification across glycaemic strata (interaction p=0·42). The proportion of patients who developed new-onset diabetes were similar between the bempedoic acid and placebo groups, with 429 of 3848 (11·1%) with bempedoic acid versus 433 of 3749 (11·5%) with placebo (HR 0·95; 95% CI 0·83-1·09). HbA1c concentrations at month 12 and the end of the study were similar between randomised groups in patients who had prediabetes and normoglycaemia. Placebo-corrected LDL cholesterol concentrations and high-sensitivity C-reactive protein at 6 months were reduced in each glycaemic stratum (diabetes, prediabtes, and normoglycaemia) for patients randomly assigned to bempedoic acid (all p<0·001). Among patients with diabetes, bempedoic acid reduces LDL cholesterol and high-sensitivity C-reactive protein and risk of cardiovascular events. Patients without diabetes had no increase in new-onset diabetes or worsening HbA1c with bempedoic acid. The efficacy and cardiometabolic safety profile of bempedoic acid makes it a clinical option for those with and without diabetes. Esperion Therapeutics.

The Antidepressant Therapy Selective Norepinephrine Reuptake Inhibitors (SNRIs) Reduces the Risk of Alzheimer’s Disease

AbstractBackgroundDepression has been established as a risk factor for developing Alzheimer’s Disease (AD). Further, depression is a common symptom of the prodromal phase of the disease and acts as an accelerating factor for cognitive decline before and after dementia diagnosis. Based on this association, analyses of real‐world medical data were conducted to determine the impact of anti‐depressive pharmacological therapy, Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs), on risk of AD diagnosis. This study aimed to determine the effect of SNRI therapy on AD incidence, as well as determining responder vs non‐responder phenotypes on demographic characteristics, comorbidity burden, and co‐treatment profile.MethodA retrospective analysis was conducted using the Mariner insurance claims dataset and included patients 60 years of age and older with a diagnosis of depression. To minimize bias, a propensity score matching was conducted to adjust for age, gender, cci and comorbidities. The propensity score matched population was surveyed for a diagnosis of AD after at least 1 year of SNRI drug exposure, and different durations of SNRI therapy were analyzed. Responders were detected through sensitivity analyses based on comorbidities and drug combinations.ResultThe propensity score matched group included 307,671 patients exposed to SNRIs and 307,671 patients with no exposure to any antidepressant therapy. SNRI therapy was associated with a significant decrease in risk of AD diagnosis (RR [95%CI]: 0.73 [0.70–0.76]; P&lt;.0001), with women (RR [95%CI]: 0.66 [0.63–0.70]; P&lt;.0001) exhibiting greater risk reduction compared to men (RR [95%CI]: 0.88 [0.82–0.95]; P&lt;.0001). Long‐term SNRI treatment (&gt;6 years) was associated with the greatest AD risk reduction (RR [95%CI]: 0.50 [0.47–0.53]; P&lt;.0001). Responders exhibited higher incidence of obesity and greater use of anti‐inflammatories.ConclusionSNRI therapy was associated with a significant reduction in AD risk. Furthermore, increased duration of SNRI therapy was associated with greater AD risk reduction. Responders displayed fewer comorbidities and co‐treatments although they had a higher incidence of obesity. Clinically, these findings, based on real‐world psychiatric care, provide data regarding long‐term neurological health outcomes of SNRI anti‐depressant therapy. From a mechanistic perspective, data reported herein indicate that sustaining noradrenergic function is a key pathway involved in preventing AD.

Improving the quality and sustainability of home-based acute care models using virtual care technology

Importance COVID-19 has facilitated the rise of a new service model that combines HITH service provision with technology to create ‘virtual hospitals’, but evidence on the impact of this new model in terms of cost and clinical outcomes, compared to usual Hospital in the Home (HITH) care, is currently lacking.&#x0D; Objective To assess the clinical and financial impacts of virtual care technology on Hospital in the Home models of care.&#x0D; Design Quasi-experimental study comparing outcomes of a control group receiving ‘usual’ home-based acute care and a virtual care cohort using remote monitoring technology while also receiving usual Hospital in the Home (HITH) care.&#x0D; Main Outcomes and Measures Readmissions within 28 days, unplanned emergency department (ED) presentations, transfers-in to facility-based hospital beds, and average length of stay.&#x0D; Results During the study period, 151 adult and 26 paediatric patients utilised virtual care technology for the majority, or all, of their home-based acute care. Use of such technology was associated with a statistically significant reduction in risk of hospital readmission within 28 days—from 43% to 21%. The risk of hospital readmission within 28 days for the same diagnosis-related group (DRG) dropped from 18% to 4%, and the length of stay for the top three DRGs by volume decreased from a mean of 7.2 days to 4.0 days, saving an average of $3,698 per admission. Use of technology was also associated with reduced rates of unplanned ED presentations and transfers-in to traditional hospital beds compared to usual care for adults.&#x0D; Conclusions Our findings confirm there are clinical and economic benefits associated with embedding virtual care technology in Hospital in the Home (HITH) service models that warrant consideration in health systems facing capacity constraints and rising costs.

Impact of Hypomethylating Agents on Cardiovascular Disease Risk Among Patients with Myelodysplastic Syndromes

Introduction: The association between clonal hematopoiesis (CH) and cardiovascular disease (CVD) risk has drawn attention to cardiovascular outcomes in myelodysplastic syndromes (MDS). CVD accounts for 25% of deaths in MDS, potentially via CH-mediated accelerated atherosclerosis from inflammatory vascular responses. We previously demonstrated that MDS was independently associated with increased risk of CVD in older adults from SEER-Medicare. We subsequently hypothesized that treatment with hypomethylating agents (HMA) could reduce CVD risk by ameliorating CH clones and reducing the inflammation. In this study, we aimed to define the impact of HMA on incident cardiovascular events among older adults with MDS. Methods: We identified subjects ≥66 years diagnosed with MDS from 2007 to 2017 in SEER-Medicare. Exclusion criteria including lacking continuous Medicare parts A, B, and D, enrolled in HMO, or incomplete follow-up. Demographics included age, sex, race, rurality, socioeconomic quintile, marital status, and geographic region. Baseline CVD risk factors, defined from ICD-9/10 codes, included hypertension, hyperlipidemia, diabetes, atrial fibrillation, pre-existing cardiac disease, obesity, and smoking. MDS factors, defined using HCPCS codes, ICD-O-3 codes and prescription records, included MDS subtype and histologic risk stratification, transfusion dependence and treatment with hypomethylating agents (HMA), lenalidomide, or erythropoietin-stimulating agents (ESA) as time-varying variables. Incident CVD was defined as new myocardial infarction (MI) and/or ischemic stroke occurring after MDS diagnosis, using published ICD-9/10 algorithms. We controlled for confounding using 2 complementary analytic approaches. First, we assessed the association between HMA use and CVD using propensity score adjusted cause-specific competing risk Cox hazard models with death as competing risk, Second, we used a case-crossover design with conditional logistic regression, in which subjects with CVD served as their own controls, using a 3-month HMA treatment window and a control period 6 months prior to the incident event. Results: We identified a cohort of 15,227 eligible patients with MDS. Of these, 1,125 patients had an MI and/or ischemic stroke within 1 year before MDS diagnoses and were excluded. We analyzed 14,102 MDS patients, with median age 82 years (IQR 77 - 86), who were predominantly male (53.8%), non-Hispanic white (88.6%), and from urban/suburban areas (86.2%). MDS was of low, intermediate, and high histologic risk in 14.7%, 72.8%, and 12.5%, respectively, and 28.6% were transfusion dependent. Pre-existing CVD risk factors at time of MDS diagnosis were present in 12,538 patients, with baseline cardiovascular risk defined as low, intermediate, and high in 11.1%, 32.3%, and 56.6% of the cohort. The cumulative incidences of MI, ischemic stroke and composite CVD events were 11.3%, 10.6% and 20.4%, respectively. The propensity score (PS) conditional probability for being treated with HMA included demographic variables, CVD risk factors, MDS histology and transfusion dependence. Our PS model adequately predicted HMA treatment propensity (AUC 0.76). Cause-specific regression with death as competing risk, adjusted for PS and other MDS-specific treatments (ESA and lenalidomide), showed no significant effect of HMA on the risk of composite CVD events, MI, or ischemic stroke (Table 1). Conditional logistic regression in the case-crossover analysis of 1,907 patients with composite CVD events showed no significant effect of HMA. Results were similar for analysis of patients with MI and ischemic stroke (Table 2). Conclusions: No study has previously investigated the effect of HMA therapy on cardiovascular outcomes in patients with MDS. We demonstrate that HMA therapy is not associated with a significant risk reduction in cardiovascular events among patients with MDS patients from the SEER-Medicare database. These results show that HMA therapy is unlikely to reduce cardiovascular mortality and underscore the need for alternative therapeutic strategies targeting cardiovascular health patients with MDS.