Prospective assessment of canine thyroid cancer-part I: nodal metastatic rate and impact of nodal immunohistochemistry in 70 dogs.

OBJECTIVE: To determine the rate of nodal metastasis in dogs with thyroid cancer and evaluate whether immunohistochemistry (IHC) identifies additional metastases beyond evaluation with H&E. ANIMALS: 70 prospectively enrolled client-owned dogs with thyroid cancer managed with thyroidectomy. METHODS: Dogs underwent thyroidectomy with concurrent elective bilateral medial retropharyngeal (MRP) ± deep cervical lymphadenectomy. Thyroid tumors and associated lymph nodes were reviewed by a single board-certified pathologist. Immunohistochemistry was used for all primary tumors (thyroid transcription factor-1 and calcitonin) to support a diagnosis of follicular or medullary carcinoma. Lymph nodes without evidence of metastasis after H&E review were labeled with the antibody associated with the wider uptake in the primary tumor. RESULTS: 77 thyroid cancers were resected from the 70 dogs enrolled, including 61 (79.2%) follicular, 8 (10.7%) medullary, and 7 (9.3%) mixed follicular/medullary carcinomas, with 1 (1.3%) carcinosarcoma. Twelve dogs had evidence of nodal metastasis following H&E review. Occult micrometastasis was identified in 1 dog following nodal IHC, resulting in documented metastasis in 13 of 70 (18.6%) dogs. Metastasis was more common with medullary (5/8) and follicular/medullary carcinoma (3/7) than follicular carcinoma (5/61). All MRP metastases were ipsilateral (7/77 [9.1%]), without contralateral MRP metastases (0/62). Fourteen of 41 (34.1%) deep cervical lymph nodes were metastatic. CLINICAL RELEVANCE: Nodal metastasis was uncommon for follicular carcinoma but was seen in > 50% of dogs with thyroid cancer involving a medullary component. Routine nodal IHC appears to be low yield for thyroid carcinoma. Extirpation of ipsilateral MRP and identifiable deep cervical lymph nodes is recommended with thyroidectomy until detailed preoperative risk stratification becomes available.

TAVR in Older Adults: Moving Toward a Comprehensive Geriatric Assessment and Away From Chronological Age: JACC Family Series.

Calcific aortic stenosis can be considered a model for geriatric cardiovascular conditions due to a confluence of factors. The remarkable technological development of transcatheter aortic valve replacement was studied initially on older adult populations with prohibitive or high-risk for surgical valve replacement. Through these trials, the cardiovascular community has recognized that stratification of these chronologically older adults can be improved incrementally by invoking the concept of frailty and other geriatric risks. Given the complexity of the aging process, stratification by chronological age should only be the initial step but is no longer sufficient to optimally quantify cardiovascular and noncardiovascular risk. In this review, we employ a geriatric cardiology lens to focus on the diagnosis and the comprehensive management of aortic stenosis in older adults to enhance shared decision-making with patients and their families and optimize patient-centered outcomes. Finally, we highlight knowledge gaps that are critical for future areas of study.

Hip Fracture Treatment and Outcomes Among Community-Dwelling People Living With Dementia.

Importance: The decision for surgical vs nonsurgical treatment for hip fracture can be complicated among community-dwelling people living with dementia. Objective: To compare outcomes of community-dwelling people living with dementia treated surgically and nonsurgically for hip fracture. Design, Setting, and Participants: This retrospective cross-sectional study undertook a population-based analysis of national Medicare fee-for-service data. Participants included community-dwelling Medicare beneficiaries with dementia and an inpatient claim for hip fracture from January 1, 2017, to June 30, 2018. Analyses were conducted from November 10, 2022, to October 17, 2023. Exposure: Surgical vs nonsurgical treatment for hip fracture. Main Outcomes and Measures: The primary outcome was mortality within 30, 90, and 180 days. Secondary outcomes consisted of selected post-acute care services. Results: Of 56 209 patients identified with hip fracture (73.0% women; mean [SD] age, 86.4 [7.0] years), 33 142 (59.0%) were treated surgically and 23 067 (41.0%) were treated nonsurgically. Among patients treated surgically, 73.3% had a fracture of the femoral head and neck and 40.2% had moderate to severe dementia (MSD). Among patients with MSD and femoral head and neck fracture, 180-day mortality was 31.8% (surgical treatment) vs 45.7% (nonsurgical treatment). For patients with MSD treated surgically vs nonsurgically, the unadjusted odds ratio (OR) of 180-day mortality was 0.56 (95% CI, 0.49-0.62; P < .001) and the adjusted OR was 0.59 (95% CI, 0.53-0.66; P < .001). Among patients with mild dementia and femoral head and neck fracture, 180-day mortality was 26.5% (surgical treatment) vs 34.9% (nonsurgical treatment). For patients with mild dementia who were treated surgically vs nonsurgically for femoral head and neck fracture, the unadjusted OR of 180-day mortality was 0.67 (95% CI, 0.60-0.76; P < .001) and the adjusted OR was 0.71 (95% CI, 0.63-0.79; P < .001). For patients with femoral head and neck fracture, there was no difference in admission to a nursing home within 180 days when treated surgically vs nonsurgically. Conclusions and Relevance: In this cohort study of community-dwelling patients with dementia and fracture of the femoral head and neck, patients with MSD and mild dementia treated surgically experienced lower odds of death compared with patients treated nonsurgically. Although avoiding nursing home admission is important to persons living with dementia, being treated surgically for hip fracture did not necessarily confer a benefit in that regard. These data can help inform discussions around values and goals with patients and caregivers when determining the optimal treatment approach.

Shifts in Clinical Characteristics, Treatment, and Outcome for Rheumatic Mitral Stenosis: Insights From a 20-Year Multicentre Registry Study in Korea.

BACKGROUND: The rapid economic development of South Korea provides a unique model to study changes in the clinical characteristics, treatment approaches, and clinical outcomes of patients with rheumatic mitral stenosis (MS) relative to socioeconomic growth. METHODS: From the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, 2,337 patients diagnosed with moderate or severe rheumatic MS between January 2001 and December 2020 were analyzed. Patients were grouped into consecutive 5-year intervals based on their year of diagnosis. Clinical characteristics, echocardiographic data, and clinical outcomes were assessed. RESULTS: Over 20 years, the severity of mitral stenosis increased from 79.1% to 90.2%; similarly, the average age at diagnosis increased from 54.3 to 63.0 years (all P < 0.001). Comorbidities such as hypertension and atrial fibrillation increased (6.3% to 29.5% and 41.4% to 46.9%, respectively; all P for trend < 0.05). The rate of mitral intervention within five years after diagnosis increased from 31.2% to 47.4% (P for trend < 0.001). However, clinical outcomes of rheumatic mitral stenosis deteriorated over time in the composite outcomes (log-rank test, P < 0.001). Conversely, the incidence of stroke remained stable (60.6-73.7%; P < 0.001), which might be attributed to the increased use of anticoagulation therapy. CONCLUSION: This study observed an increase in patient age, comorbidities, and valve disease severity as the country transitioned from a developing to developed status. Despite a rise in mitral valve interventions, clinical outcomes deteriorated over 20 years, highlighting the need for modified treatment approaches to improve patient outcomes.

Claims-Based Frailty Index and Its Relationship With Commonly Used Clinical Frailty Measures.

BACKGROUND: The relationship of claims-based frailty index (CFI), a validated measure to identify frail individuals using Medicare data, and frailty measures used in clinical practice has not yet been fully explored. METHODS: We identified community-dwelling participants of the 2015 National Health and Aging Trends Study (NHATS) whose CFI scores could be calculated using linked Medicare claims. We calculated 9 commonly used clinical frailty measures from their NHATS in-person examination: Study of Osteoporotic Fracture Index (SOF), FRAIL Scale, Frailty Phenotype, Clinical Frailty Scale (CFS), Vulnerable Elder Survey-13 (VES-13), Tilburg Frailty Indicator (TFI), Groningen Frailty Indicator (GFI), Edmonton Frail Scale (EFS), and 40-item Frailty Index (FI). Using equipercentile method, CFI scores were linked to clinical frailty measures. C-statistics and test characteristics of CFI to identify frailty as defined by each clinical frailty measure were calculated. RESULTS: Of the 3 963 older adults, 44.5% were ≥75 years, 59.4% were female, and 82.3% were non-Hispanic White. A CFI of 0.25 was equipercentile to the following clinical frailty measure scores: SOF 1.4, FRAIL 1.8, Phenotype 1.8, CFS 5.4, VES-13 5.7, TFI 4.6, GFI 5.0, EFS 6.0, and FI 0.26. The C-statistics of using CFI to identify frailty as defined by each clinical measure were ≥0.70, except for CFS and VES-13. The optimal CFI cutpoints to identify frailty per clinical frailty measure ranged from 0.212 to 0.242, with sensitivity and specificity of 0.37-0.83 and 0.66-0.84, respectively. CONCLUSIONS: Understanding the relationship of CFI and commonly used clinical frailty measures can enhance the interpretability and potential utility of CFI.

Performance of a Claims-Based Frailty Proxy Using Varying Frailty Ascertainment Lookback Windows.

BACKGROUND: Frailty is an aging-related syndrome of reduced physiological reserve to maintain homeostasis. The Faurot frailty index has been validated as a Medicare claims-based proxy for predicting frailty using billing information from a user-specified ascertainment window. OBJECTIVES: We assessed the validity of the Faurot frailty index as a predictor of the frailty phenotype and 1-year mortality using varying frailty ascertainment windows. RESEARCH DESIGN: We identified older adults (66+ y) in Round 5 (2015) of the National Health and Aging Trends Study with Medicare claims linkage. Gold standard frailty was assessed using the frailty phenotype. We calculated the Faurot frailty index using 3, 6, 8, and 12 months of claims prior to the survey or all-available lookback. Model performance for each window in predicting the frailty phenotype was assessed by quantifying calibration and discrimination. Predictive performance for 1-year mortality was assessed by estimating risk differences across claims-based frailty strata. RESULTS: Among 4253 older adults, the 6 and 8-month windows had the best frailty phenotype calibration (calibration slopes: 0.88 and 0.87). All-available lookback had the best discrimination (C-statistic=0.780), but poor calibration. Mortality associations were strongest using a 3-month window and monotonically decreased with longer windows. Subgroup analyses revealed worse performance in Black and Hispanic individuals than counterparts. CONCLUSIONS: The optimal ascertainment window for the Faurot frailty index may depend on the clinical context, and researchers should consider tradeoffs between discrimination, calibration, and mortality. Sensitivity analyses using different durations can enhance the robustness of inferences. Research is needed to improve prediction across racial and ethnic groups.

Assessment of Bone Marrow Involvement in B-Cell non-Hodgkin Lymphoma Using Immunoglobulin Gene Rearrangement Analysis with Next-Generation Sequencing.

BACKGROUND: Assessment of bone marrow involvement (BMI) in non-Hodgkin lymphoma (NHL) is crucial for determining patient prognosis and treatment strategy. We assessed the prognostic value of next-generation sequencing (NGS)-based immunoglobulin (Ig) gene clonality analysis as an ancillary test for BMI evaluation in NHL. METHODS: A retrospective cohort of 124 patients newly diagnosed with B-cell NHL between 2019 and 2022 was included. NGS-based Ig clonality analysis was conducted using LymphoTrak IGH FR1 Assay and IGK Assay (Invivoscribe Technologies, San Diego, CA, USA) on BM aspirate samples, and the results were compared with those of histopathological BMI (hBMI). RESULTS: Among the 124 patients, hBMI was detected in 16.9% (n = 21). The overall agreement of BMI between Ig clonality analyses and histopathological analysis for IGH, IGK, and either IGH or IGK was 86.3%, 92.7%, and 90.3%. The highest positive percent agreement was observed with clonal rearrangements of either IGH or IGK gene (90.5%), while the highest negative percent agreement was observed with clonal rearrangement of IGK gene (96.1%). For the prediction of hBMI, positive prediction value ranged between 59.1% and 80.0% and the negative prediction value ranged between 91.3% and 97.9%. CONCLUSION: NGS-based clonality analysis is an analytic platform with a substantial overall agreement with histopathological analysis. Assessment of both IGH and IGK genes for the clonal rearrangement analysis could be considered for the optimal diagnostic performance of BMI detection in B-cell NHL.

Identifying Functional Status Impairment in People Living With Dementia Through Natural Language Processing of Clinical Documents: Cross-Sectional Study.

BACKGROUND: Assessment of activities of daily living (ADLs) and instrumental ADLs (iADLs) is key to determining the severity of dementia and care needs among older adults. However, such information is often only documented in free-text clinical notes within the electronic health record and can be challenging to find. OBJECTIVE: This study aims to develop and validate machine learning models to determine the status of ADL and iADL impairments based on clinical notes. METHODS: This cross-sectional study leveraged electronic health record clinical notes from Mass General Brigham's Research Patient Data Repository linked with Medicare fee-for-service claims data from 2007 to 2017 to identify individuals aged 65 years or older with at least 1 diagnosis of dementia. Notes for encounters both 180 days before and after the first date of dementia diagnosis were randomly sampled. Models were trained and validated using note sentences filtered by expert-curated keywords (filtered cohort) and further evaluated using unfiltered sentences (unfiltered cohort). The model's performance was compared using area under the receiver operating characteristic curve and area under the precision-recall curve (AUPRC). RESULTS: The study included 10,000 key-term-filtered sentences representing 441 people (n=283, 64.2% women; mean age 82.7, SD 7.9 years) and 1000 unfiltered sentences representing 80 people (n=56, 70% women; mean age 82.8, SD 7.5 years). Area under the receiver operating characteristic curve was high for the best-performing ADL and iADL models on both cohorts (>0.97). For ADL impairment identification, the random forest model achieved the best AUPRC (0.89, 95% CI 0.86-0.91) on the filtered cohort; the support vector machine model achieved the highest AUPRC (0.82, 95% CI 0.75-0.89) for the unfiltered cohort. For iADL impairment, the Bio+Clinical bidirectional encoder representations from transformers (BERT) model had the highest AUPRC (filtered: 0.76, 95% CI 0.68-0.82; unfiltered: 0.58, 95% CI 0.001-1.0). Compared with a keyword-search approach on the unfiltered cohort, machine learning reduced false-positive rates from 4.5% to 0.2% for ADL and 1.8% to 0.1% for iADL. CONCLUSIONS: In this study, we demonstrated the ability of machine learning models to accurately identify ADL and iADL impairment based on free-text clinical notes, which could be useful in determining the severity of dementia.

Long-term Effectiveness and Outcome-Determining Factors of Arthroscopic Bankart Repair for Recreational Sports Population: An Assessment of 100 Patients With a Mean Follow-up of 12.7 Years.

BACKGROUND: A limited number of studies have reported the long-term effectiveness of and associated factors for recurrence of anterior shoulder instability after arthroscopic Bankart repair (ABR). PURPOSE: To report the long-term clinical outcomes after ABR in a recreational sports population and identify the associated factors that influence the final instability status. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A retrospective study was performed in patients treated with ABR between 2007 and 2013 by a single surgeon. Patient data, magnetic resonance imaging measurements of bone loss and glenoid track, and intra- and perioperative factors were analyzed. After a minimum follow-up of 10 years, patient-reported outcomes including the Western Ontario Shoulder Instability Index score, the Rowe score, the visual analog scale for pain and function, the American Shoulder and Elbow Surgeons score, and sports activity were assessed. The current instability status was classified into 3 groups: stable, apprehensive, and redislocated. These groups were statistically compared with respect to outcomes and associated factors. RESULTS: A total of 100 patients with a mean age of 22.4 ± 5.5 years and a mean follow-up of 12.7 ± 2.1 years were included. At the final follow-up, 38 patients (38%) showed recurrent symptoms: 19 patients (19%) with subjective apprehension and 19 patients (19%) with redislocation, including 10 patients (10%) with revision surgery. At the final follow-up, the redislocated group showed the lowest patient-reported outcomes and return to sports (both P < .001). The apprehensive group also showed a lower Western Ontario Shoulder Instability Index score (P = .011), Rowe score (P = .003), American Shoulder and Elbow Surgeons score (P = .027), and return to sports (P = .005) than the stable group. Participation in contact sports (P = .026), glenoid bone loss (P = .005), size of Hill-Sachs lesion (P = .009), and off-track lesions (P = .016) were all associated with recurrent symptoms, whereas age <20 years (P = .012), participation in contact sports (P = .003), and off-track lesions (P = .042) were associated with redislocation. CONCLUSION: After long-term follow-up in a recreational sports population, ABR demonstrated a 19% rate of subjective apprehension and 19% rate of redislocation, with a gradual decline in clinical outcomes and sports activity over time. Therefore, candidates for ABR should be selected based on consideration of risk factors such as off-track lesions, age <20 years, and participation in contact sports.

Use of Diabetes Medications before and after a Heart Failure-Related Hospitalization among Nursing Home Residents.

OBJECTIVES: Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) offer cardiovascular benefits, whereas thiazolidinediones (TZDs) and sulfonylureas (SUs) increase cardiovascular risk. The objective of this study was to describe the use of SGLT-2is, GLP-1RAs, TZDs, and SUs before and after a heart failure (HF)-related hospitalization in nursing home (NH) residents with type 2 diabetes (T2D). DESIGN: This was a cohort study using a 20% sample of Medicare claims linked with Minimum Data Set resident assessments. SETTING AND PARTICIPANTS: The study population was long-stay NH residents with T2D and an HF-related hospitalization between January 1, 2013, and August 31, 2018. For individuals with multiple HF hospitalizations, 1 hospitalization was randomly selected. METHODS: We ascertained diabetes medications using Medicare Part D claims during the 120 days before and after hospital discharge (or skilled nursing facility discharge, where applicable). We calculated (1) the proportion of study participants who received a medication class of interest during pre- and posthospitalization periods; (2) the proportion of continuous users; and (3) the proportion of posthospitalization users who were new users. RESULTS: A total of 12,990 NH residents with T2D and an HF-related hospitalization were included (mean age 78 years, 66% female, 19% Black). Before hospitalization, 1.5% received TZDs, 14.1% received SUs, 1.2% received GLP-1RAs, and 0.3% received SGLT-2is. Among prehospitalization users of TZDs, SUs, GLP-1RAs, and SGLT-2is, 49%, 62%, 60%, and 40% continued the medications, respectively. Among posthospitalization users of TZDs, SUs, GLP-1RAs, and SGLT-2is, 37%, 10%, 28%, and 11%, respectively, were new users. CONCLUSIONS: Among NH residents with hospitalized HF, GLP-1RAs and SGLT-2is were seldom used. TZDs and SUs were still used by many residents with T2D after HF hospitalizations. IMPLEMENTATIONS: Barriers may exist in the use of newer diabetes medications to prevent heart failure in NH residents with T2D, which warrants further studies in older adults with multimorbidity.

Comparative Safety and Effectiveness of Warfarin or Rivaroxaban Versus Apixaban in Patients With Advanced CKD and Atrial Fibrillation: Nationwide US Cohort Study.

RATIONALE & OBJECTIVE: Head-to-head data comparing the effectiveness and safety of oral anticoagulants in patients with atrial fibrillation (AF) and advanced chronic kidney disease (CKD) are lacking. We compared the safety and effectiveness of warfarin or rivaroxaban versus apixaban in patients with AF and non-dialysis-dependent CKD stage 4/5. STUDY DESIGN: Propensity score-matched cohort study. SETTING & PARTICIPANTS: 2 nationwide US claims databases, Medicare and Optum's deidentified Clinformatics Data Mart Database, were searched for the interval from January 1, 2013, through March 31, 2022, for patients with nonvalvular AF and CKD stage 4/5 who initiated warfarin versus apixaban (matched cohort, n=12,488) and rivaroxaban versus apixaban (matched cohort, n = 5,720). EXPOSURES: Warfarin, rivaroxaban, or apixaban. OUTCOMES: Primary outcomes included major bleeding and ischemic stroke. Secondary outcomes included all-cause mortality, major gastrointestinal bleeding, and intracranial bleeding. ANALYTICAL APPROACH: Cox regression was used to estimate HRs, and 1:1 propensity-score matching was used to adjust for 80 potential confounders. RESULTS: Compared with apixaban, warfarin initiation was associated with a higher rate of major bleeding (HR, 1.85; 95% CI, 1.59-2.15), including major gastrointestinal bleeding (1.86; 1.53-2.25) and intracranial bleeding (2.15; 1.42-3.25). Compared with apixaban, rivaroxaban was also associated with a higher rate of major bleeding (1.69; 1.33-2.15). All-cause mortality was similar for warfarin (1.08; 0.98-1.18) and rivaroxaban (0.94; 0.81-1.10) versus apixaban. Furthermore, no statistically significant differences for ischemic stroke were observed for warfarin (1.14; 0.83-1.57) or rivaroxaban (0.71; 0.40-1.24) versus apixaban, but the CIs were wide. Similar results were observed for warfarin versus apixaban in the positive control cohort of patients with CKD stage 3, consistent with randomized trial findings. LIMITATIONS: Few ischemic stroke events, potential residual confounding. CONCLUSIONS: In patients with AF and advanced CKD, rivaroxaban and warfarin were associated with higher rates of major bleeding compared with apixaban, suggesting a superior safety profile for apixaban in this high-risk population. PLAIN-LANGUAGE SUMMARY: Different anticoagulants have been shown to reduce the risk of stroke in patients with atrial fibrillation, such as warfarin and direct oral anticoagulants like apixaban and rivaroxaban. Unfortunately, the large-scale randomized trials that compared direct anticoagulants versus warfarin excluded patients with advanced chronic kidney disease. Therefore, the comparative safety and effectiveness of warfarin, apixaban, and rivaroxaban are uncertain in this population. In this study, we used administrative claims data from the United States to answer this question. We found that warfarin and rivaroxaban were associated with increased risks of major bleeding compared with apixaban. There were few stroke events, with no major differences among the 3 drugs in the risk of stroke. In conclusion, this study suggests that apixaban has a better safety profile than warfarin and rivaroxaban.

Preclinical and dose-ranging assessment of hESC-derived dopaminergic progenitors for a clinical trial on Parkinson's disease.

Human embryonic stem cell (hESC)-derived midbrain dopaminergic (mDA) cell transplantation is a promising therapeutic strategy for Parkinson's disease (PD). Here, we present the derivation of high-purity mDA progenitors from clinical-grade hESCs on a large scale under rigorous good manufacturing practice (GMP) conditions. We also assessed the toxicity, biodistribution, and tumorigenicity of these cells in immunodeficient rats in good laboratory practice (GLP)-compliant facilities. Various doses of mDA progenitors were transplanted into hemi-parkinsonian rats, and a significant dose-dependent behavioral improvement was observed with a minimal effective dose range of 5,000-10,000 mDA progenitor cells. These results provided insights into determining a low cell dosage (3.15 million cells) for human clinical trials. Based on these results, approval for a phase 1/2a clinical trial for PD cell therapy was obtained from the Ministry of Food and Drug Safety in Korea, and a clinical trial for treating patients with PD has commenced.

Fall risk and cardiovascular outcomes of first-line antihypertensive medications in nursing home residents.

BACKGROUND: Little evidence exists about the comparative effects of first-line antihypertensive medications (i.e., renin-angiotensin-aldosterone converting enzyme inhibitors (RAASi), amlodipine, or thiazide diuretics) in older adults with limited life expectancy. We compared the rates of injurious falls and short-term cardiovascular events between different first-line antihypertensive medication classes in adults receiving care in nursing homes (NH). METHODS: This was a retrospective cohort of Medicare fee-for-service beneficiaries receiving care in NHs. Patients newly dispensed first-line antihypertensive medications were identified using Part D claims (2015-2018) and linked with clinical assessments (i.e., Minimum Data Set). Fall-related injuries (FRI), hip fractures, and major adverse cardiac events (MACE) outcomes were identified using hospitalization claims. Patients were followed from the date of antihypertensive dispensing until the occurrence of outcomes, death, disenrollment, or 6-month follow-up. Inverse-probability-of-treatment-weighted (IPTW) cause-specific hazards regression models were used to compare outcomes between patients who were new users of RAASi, amlodipine, or thiazides. RESULTS: Our cohort included 16,504 antihypertensive users (RAASi, n = 9574; amlodipine, n = 5049; thiazide, n = 1881). Mean age was 83.5 years (± 8.2), 70.6% were female, and 17.2% were non-white race. During a mean follow-up of 5.3 months, 326 patients (2.0%) experienced an injurious fall, 1590 (9.6%) experienced MACE, and 2123 patients (12.9%) died. The intention-to-treat IPTW hazard ratio (HR) for injurious falls for amlodipine (vs RAASi) use was 0.85 (95% confidence interval (CI) 0.66-1.08) and for thiazides (vs RAASi) was 1.22 (95% CI 0.88-1.66). The rates of MACE were similar between those taking anti-hypertensive medications. Thiazides were discontinued more often than other classes; however, inferences were largely unchanged in as-treated analyses. Subgroup analyses were generally consistent. CONCLUSIONS: Older adults with limited life expectancy experience similar rates of injurious falls and short-term cardiovascular events after initiating any of the first-line antihypertensive medications.

Low-Cost Angle Sensor for Robotics Applications Using Plastic Optical Fiber Based on Optical Loss Mechanism.

Robotic systems and the human body consist of numerous joint structures, all of which require precise angle adjustments. At present, encoder, strain gauge, and electrical resistance-based sensors are commonly used for angle measurement. However, these sensors have limitations when used in underwater or in environments with strong electromagnetic waves. Therefore, we have developed an angle sensor based on step-index profile plastic optical fiber (SI-POF), which is cost-effective and highly durable, in this study in order to overcome the limitations of existing angle measurement sensors. To this end, the amount of light loss according to the gab and angle changes that occur when the POF angle sensor is applied to the robot arm was experimentally measured, and based on the results, a simulation of the amount of light loss when the two losses occurred at the same time was conducted. In addition, the performance of the POF angle sensor was evaluated by measuring sensitivity and resolution, and comparative verification with a commonly used encoder was conducted to verify the reliability of sensors in extreme environments, such as those with electromagnetic fields and those that are underwater. Through this, the reliability and practicality of the POF angle sensor were confirmed. The results obtained in this study suggest that POF-based angle sensors can contribute to the development of the biomimetic robot industry as well as ordinary robots, especially in environments where existing sensors are difficult to apply, such as areas with underwater or electromagnetic interference (EMI).

Immune checkpoint inhibitors with chemotherapy for primary advanced mismatch repair-deficient endometrial cancer: A cost-effectiveness analysis.

OBJECTIVE: The addition of immune checkpoint inhibitors (ICIs), pembrolizumab or dostarlimab, to paclitaxel and carboplatin (TC) has shown better response rates and survival outcomes for patients with primary advanced mismatch repair-deficient (MMRd) endometrial cancer (EC) in NRG-GY018 and RUBY, respectively. Nonetheless, the high cost of ICIs remains a major concern when implementing this strategy in the real world. This study aimed to determine the cost-effectiveness of pembrolizumab and dostarlimab with chemotherapy compared to TC for primary advanced MMRd EC. METHODS: We developed a Markov model including 6600 patients with primary advanced MMRd EC to simulate treatment outcomes. The initial decision points in the model were treatment with pembrolizumab with TC (PEM-TC), dostarlimab with TC (DOS-TC), and TC. Model probabilities, costs, and health utility values were derived with assumptions from published literature. Effectiveness was determined as average quality-adjusted life years (QALYs) gained. The primary outcome was the incremental cost-effectiveness ratio (ICER). RESULTS: TC was the least costly strategy, whereas PEM-TC was the most effective strategy for primary advanced MMRd EC. TC was cost-effective based on a willingness-to-pay (WTP) threshold of $100,000/QALY compared with PEM-TC (ICER, $377,718/QALY), and DOS-TC exhibited absolute dominance (ICER, $401,859/QALY). PEM-TC was cost-effective when the cost of pembrolizumab 200 mg was reduced to $4361 (61% reduction). PEM-TC was selected in 16.5% with a WTP threshold of $300,000/QALY, but in <1% with a WTP threshold range of $100,000-200,000/QALY. CONCLUSION: PEM-TC can become cost-effective for primary advanced MMRd EC when the cost of pembrolizumab substantially decreases.

Assessing the Seafood Trade Diversion Arising from Economic Sanctions: Evidence from Russia and Western Countries.

Since 2014, economic sanctions between Russia and Western nations have significantly altered the global seafood trade. The consequent decline in bilateral trade also had spillover effects on the rest of the world (ROW). According to earlier studies, economic sanctions appear to negatively impact bilateral trade and income. However, few studies examine how Russian sanctions affect the world as a whole and estimate their effects on the fisheries industry. This study seeks to close this gap by quantifying the extent to which Russian sanctions have impacted trade in terms of trade deflection, trade destruction, trade depression, and trade creation. To this end, panel data from 185 countries were created for the years from 2005 to 2020. With trade policy variables that account for changes in trade channels, a structural gravity trade model was specified. Based on calculations using the Poisson pseudo-maximum likelihood (PPML) fixed effect model, economic sanctions led to a 119.28% surge in Russia's seafood imports from the rest of the world (ROW), alongside a 39% decline in imports from Western countries. The extent of trade deflection, which includes the exports of Western nations diverted from Russia to the ROW markets, increased by 5.49%. The results demonstrate that trade between sanctioned states, as well as global trade, is significantly impacted by economic sanctions.

Benefits and Harms of Standard Versus Reduced-Dose Direct Oral Anticoagulant Therapy for Older Adults With Multiple Morbidities and Atrial Fibrillation.

Background Dose reduction of direct oral anticoagulant (DOAC) medications is inconsistently applied to older adults with multiple morbidities, potentially due to perceived harms and unknown benefits of standard dosing. Methods and Results Using 2013 to 2017 US Medicare claims linked to Minimum Data Set records, we conducted a retrospective cohort study. We identified DOAC initiators (apixaban, dabigatran, rivaroxaban) aged ≥65 years with nonvalvular atrial fibrillation residing in a nursing home. We estimated inverse-probability of treatment weights for DOAC dose using propensity scores. We examined safety (hospitalization for major bleeding) and effectiveness outcomes (all-cause mortality, thrombosis [myocardial infarction, stroke, systemic embolism, venous thromboembolism]). We estimated hazard ratios (HRs) and 95% CIs using cause-specific hazard-regression models. Of 21 878 DOAC initiators, 48% received reduced dosing. The mean age of residents was 82.0 years, 66% were female, and 31% had moderate/severe cognitive impairment. After estimating inverse-probability of treatment weights, standard dosing was associated with a higher rate of bleeding (HR, 1.18 [95% CI, 1.03-1.37]; 9.4 versus 8.0 events per 100 person-years). Standard-dose therapy was associated with the highest rates of bleeding among those aged >80 years (9.1 versus 6.7 events per 100 person-years) and with a body mass index <30 kg/m2 (9.4 versus 7.4 events per 100 person-years). There was no association of dosing with mortality (HR, 0.99 [95% CI, 0.96-1.06]) or thrombotic events (HR, 1.16 [95% CI, 0.96-1.41]). Conclusions In this nationwide study of nursing home residents with nonvalvular atrial fibrillation, we found a higher rate of bleeding and little difference in effectiveness of standard versus reduced-dose DOAC treatment. Our results support the use of reduced-dose DOACs for many older adults with multiple morbidities.

Frailty, Home Time, and Health Care Costs in Older Adults With Atrial Fibrillation Receiving Oral Anticoagulants.

Importance: There are no data on patient-centered outcomes and health care costs by frailty in patients with atrial fibrillation (AF) taking oral anticoagulants (OACs). Objective: To compare home time, clinical events, and health care costs associated with OACs by frailty levels in older adults with AF. Design, Setting, and Participants: This community-based cohort study assessed Medicare fee-for-service beneficiaries 65 years or older with AF from January 1, 2013, to December 31, 2019. Data analysis was performed from January to December 2022. Exposures: Apixaban, rivaroxaban, and warfarin use were measured from prescription claims. Frailty was measured using a validated claims-based frailty index. Main outcomes and measures: Outcome measures were (1) home time (days alive out of the hospital and skilled nursing facility) loss greater than 14 days; (2) a composite end point of ischemic stroke, systemic embolism, major bleeding, or death; and (3) total cost per member per year after propensity score overlap weighting. Results: The weighted population comprised 136 551 beneficiaries, including 45 950 taking apixaban (mean [SD] age, 77.6 [7.3] years; 51.3% female), 45 320 taking rivaroxaban (mean [SD] age, 77.6 [7.3] years; 51.9% female), and 45 281 taking warfarin (mean [SD] age, 77.6 [7.3] years; 52.0% female). Compared with apixaban, rivaroxaban was associated with increased risk of home time lost greater than 14 days (risk difference per 100 persons, 1.8 [95% CI, 1.5-2.1]), composite end point (rate difference per 1000 person-years, 21.3 [95% CI, 16.4-26.2]), and total cost (mean difference, $890 [95% CI, $652-$1127]), with greater differences among the beneficiaries with frailty. Use of warfarin relative to apixaban was associated with increased home time lost (risk difference per 100 persons, 3.2 [95% CI, 2.9-3.5]) and composite end point (rate difference per 1000 person-years, 29.4 [95% CI, 24.5-34.3]), with greater differences among the beneficiaries with frailty. Compared with apixaban, warfarin was associated with lower total cost (mean difference, -$1166 [95% CI, -$1396 to -$937]) but higher cost when excluding OAC cost (mean difference, $1409 [95% CI, $1177 to $1642]) regardless of frailty levels. Conclusions and Relevance: In older adults with AF, apixaban was associated with increased home time and lower rates of clinical events than rivaroxaban and warfarin, especially for those with frailty. Apixaban was associated with lower total cost compared with rivaroxaban but higher cost compared with warfarin due to higher OAC cost. These findings suggest that apixaban may be preferred for older adults with AF, particularly those with frailty.

Ultrathin Self-Powered Heavy-Metal-Free Cu-In-Se Quantum Dot Photodetectors for Wearable Health Monitoring.

Mechanically deformable photodetectors (PDs) are key device components for wearable health monitoring systems based on photoplethysmography (PPG). Achieving high detectivity, fast response time, and an ultrathin form factor in the PD is highly needed for next-generation wearable PPG systems. Self-powered operation without a bulky power-supply unit is also beneficial for point-of-care application. Here, we propose ultrathin self-powered PDs using heavy-metal-free Cu-In-Se quantum dots (QDs), which enable high-performance wearable PPG systems. Although the light-absorbing QD layer is extremely thin (∼40 nm), the developed PD exhibits excellent performance (specific detectivity: 2.10 × 1012 Jones, linear dynamic range: 102 dB, and spectral range: 250-1050 nm at zero bias), which is comparable to that of conventional rigid QD-PDs employing thick Pb-chalcogenide QD layers. This is attributed to material and device strategies─materials that include Cu-In-Se QDs, a MoS2-nanosheet-blended poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) hole transport layer, a ZnO nanoparticle electron transport layer, Ag and ITO electrodes, and an ultrathin form factor (∼120 nm except the electrodes) that enable excellent mechanical deformability. These allow the successful application of QD-PDs to a wearable system for real-time PPG monitoring, expanding their potential in the field of mobile bioelectronics.