Educational attainment, severity and short-term prognosis of intracerebral haemorrhage.

Background: Educational attainment is a critical social determinant of health that impacts the risk and severity of incident ischaemic stroke, but less is known of its impact on intracerebral haemorrhage (ICH). The objective of this study is to determine whether educational attainment is associated with ICH severity and short-term prognosis. Methods: Subjects were enrolled in a prospectively ascertained cohort with primary ICH from 1994 to 2020 at Massachusetts General Hospital. Educational attainment, medical history of ICH risk factors, ICH volume and ICH score were obtained on admission. The primary outcomes were ICH volume and the ICH score. Results: Of 2539 eligible patients eligible, the median age of the sample was 74 (IQR 64-82) and 2159 (85%) had high school-only education. 1655 (65%) presented with an ICH volume less than or equal to 30 mL and 1744 (69%) presented with an ICH score less than 3. In multivariable logistic regression analyses controlling for age, income, employment history and prestroke diagnoses of hypertension and coronary artery disease, patients with high school-only education were more likely to have an ICH volume greater than 30 mL compared with college diplomates (OR 1.58, 95% CI 1.24 to 2.08) and more likely to have an ICH score of 3 or greater compared with college diplomates (OR 2.37, 95% CI 1.77 to 3.19). Discussion: Prestroke educational attainment is independently associated with ICH severity and short-term prognosis, with lower educational attainment associated with larger ICH volumes and higher ICH scores. Future studies should examine how educational attainment impacts exposure to traditional clinical risk factors.

The neighborhood food environment modifies the association between infant feeding and childhood obesity.

BACKGROUND: The Special Supplemental Nutrition Program for Women, Infants and Children (WIC) issues infant formula to infants who are not fully breastfed, and prior research found elevated obesity risk among children receiving lactose-reduced infant formula with corn syrup solids (CSSF) issued by WIC. This study was conducted to evaluate associations between a broader set of specialty infant formulas issued by WIC and child obesity risk, whether neighborhood context (e.g. neighborhood food environment) modifies associations, and whether racial/ethnic disparities in obesity are partly explained by infant formula exposure and neighborhood context. METHODS: WIC administrative data, collected from 2013-2020 on issued amount (categorical: fully formula fed, mostly formula fed, mostly breastfed, fully breastfed) and type of infant formula (standard cow's milk formula, and three specialty formulas: any CSSF, any soy-based formula, and any cow's milk-based formula with added rice starch) and obesity at ages 2-4 years (defined as a Body Mass Index z-score ≥ 95th percentile according to World Health Organization growth standard) were used to construct a cohort (n = 59,132). Associations of infant formula exposures and race/ethnicity with obesity risk were assessed in Poisson regression models, and modification of infant feeding associations with obesity by neighborhood context was assessed with interaction terms. RESULTS: Any infant formula exposure was associated with significantly higher obesity risk relative to fully breastfeeding. Receipt of a CSSF was associated with 5% higher obesity risk relative to the standard and other specialty infant formulas (risk ratio 1.05, 95% confidence interval 1.02, 1.08) independent of breastfeeding duration and receipt of other specialty infant formulas. The association between CSSF and obesity risk was stronger in neighborhoods with healthier food environments (10% higher risk) compared to less healthy food environments (null). Racial/ethnic disparities in obesity risk were robust to adjustment for infant formula exposure and neighborhood environment. CONCLUSIONS: Among specialty infant formulas issued by WIC, only CSSFs were associated with elevated obesity risk, and this association was stronger in healthier food environments. Future research is needed to isolate the mechanism underlying this association.

Induction and maintenance of sequential intravesical gemcitabine/docetaxel for intermediate and high-risk non-muscle invasive bladder cancer with different dosage protocols.

INTRODUCTION: The combination of sequential intravesical gemcitabine and docetaxel (Gem/Doce) chemotherapy has been considered a feasible option for BCG (Bacillus Calmette-Guérin) treatment in non-muscle invasive bladder cancer (NMIBC), gaining popularity during BCG shortage period. We seek to determine the efficacy of the treatment by comparing Gem/Doce induction alone vs induction with maintenance, and to evaluate the treatment outcomes of two different dosage protocols. METHODS: A bi-center retrospective analysis of consecutive patients treated with Gem/Doce for NMIBC between 2018 and 2023 was performed. Baseline characteristics, risk group stratification (AUA 2020 guidelines), pathological, and surveillance reports were collected. Kaplan-Meier survival analysis was performed to detect Recurrence-free survival (RFS). RESULTS: Overall, 83 patients (68 males, 15 females) with a median age of 73 (IQR 66-79), and a median follow-up time of 18 months (IQR 9-25), were included. Forty-one had an intermediate-risk disease (49%) and 42 had a high-risk disease (51%). Thirty-seven patients (45%) had a recurrence; 19 (23%) had a high-grade recurrence. RFS of Gem/Doce induction-only vs induction + maintenance was at 6 months 88% vs 100%, at 12 months 71% vs 97%, at 18 months 57% vs 91%, and at 24 months 31% vs 87%, respectively (log-rank, p < 0.0001). Patients who received 2 g Gemcitabine with Docetaxel had better RFS for all-grade recurrences (log-rank, p = 0.017). However, no difference was found for high-grade recurrences. CONCLUSION: Gem/Doce induction with maintenance resulted in significantly better RFS than induction-only. Combining 2 g gemcitabine with docetaxel resulted in better RFS for all-grade but not for high-grade recurrences. Further prospective trials are necessary to validate our results.

Nutrition markers and discharge outcome in deep and lobar intracerebral hemorrhage.

INTRODUCTION: Malnutrition is common in stroke patients and has been associated with poor functional outcomes and increased mortality after stroke. Previous research on nutrition status and post-intracerebral hemorrhage (ICH) outcomes, however, is limited and conflicting. PATIENTS AND METHODS: Monocenter study of patients with spontaneous deep or lobar ICH from a longitudinal cohort enrolling consecutive patients between 1994 and 2022. Nutrition status was assessed using admission body mass index (BMI), albumin, total bilirubin, cholesterol, c-reactive protein, hemoglobin a1c, high-density lipoprotein, hemoglobin, low-density lipoprotein, mean corpuscular volume, alanine transaminase, and triglycerides. Main outcome was favorable discharge outcome (mRS 0-2). Multivariable logistic regression was conducted with adjustment for baseline differences. RESULTS: Among 2170 patients, 1152 had deep and 1018 had lobar ICH. Overweight BMI was associated with higher odds of favorable discharge outcome in all (aOR = 3.01, 95% CI 1.59-5.69, p = 0.001) and lobar (aOR = 3.26, 95% CI 1.32-8.08, p = 0.011) ICH after adjustment for baseline differences. This association did not reach statistical significance in deep (aOR = 2.77, 95% CI 0.99-7.72, p = 0.052) ICH. No lab values were associated with functional outcome in all, deep, or lobar ICH after adjustment. DISCUSSION AND CONCLUSION: Overweight BMI was associated with favorable discharge status after ICH. These findings could inform future studies to determine whether overweight BMI has a protective effect in ICH patients.

Sequential administration of peripheral nerve blocks and onabotulinumtoxinA for the treatment of chronic migraine and other headache disorders-A retrospective tolerability and safety study.

OBJECTIVE: To determine the tolerability and safety of concurrent peripheral nerve blocks and onabotulinumtoxinA treatment during a single outpatient clinic procedure visit. BACKGROUND: Procedural interventions are available for the treatment of headache disorders. OnabotulinumtoxinA and peripheral nerve blocks are used as alternatives or in addition to oral therapies to reduce the frequency and intensity of migraine attacks. There is currently a lack of safety data focusing on the sequential administration of local anesthetic via peripheral nerve blocks and onabotulinumtoxinA during a single clinical encounter for the treatment of headache. The primary aim of the study was to determine the safety and tolerability of concurrent peripheral nerve blockade and onabotulinumtoxinA injections during a single outpatient clinic procedure visit. We hypothesized that the dual intervention would be safe and well tolerated by patients with chronic migraine and other headache disorders. METHODS: A retrospective chart review was performed using clinical data from patients seen by multiple providers over a 16-month timeframe at one outpatient headache clinic. Patients were identified by procedure codes and those receiving peripheral nerve block(s) and onabotulinumtoxinA injections during a single encounter within the study period were eligible for inclusion. Inclusion criteria were (1) patients 18 years and older who were (2) receiving both peripheral nerve blocks and onabotulinumtoxinA injections for the treatment of chronic migraine. Patients were excluded if they were under age 18, received their procedure outside of the clinic (emergency room, inpatient ward), or were receiving sphenopalatine ganglion blocks. Age- and sex-matched patients who received one procedure, either peripheral nerve blocks or onabotulinumtoxinA, were used for control. The primary outcome of this safety study was the number of adverse events that occurred in the dual intervention group compared to the single intervention control arms. Information regarding adverse events was gathered via retrospective chart review. If an adverse event was recorded, it was then graded by the reviewer utilizing the Common Terminology Criteria for Adverse Events ranging from Grade 1 Mild Event to Grade 5 Death. Additionally, it was noted whether the adverse event led to treatment discontinuation. RESULTS: In total, 375 patients were considered eligible for inclusion in the study. After age and sex matching of controls, 131 patients receiving dual intervention were able to be compared to 131 patients receiving onabotulinumtoxinA alone and 104 patients receiving dual intervention were able to be compared to 104 patients receiving peripheral nerve block(s) alone. The primary endpoint analysis showed no significant difference in total adverse events between dual intervention compared to nerve blocks alone or onabotulinumtoxinA alone. The number of adverse events that led to treatment discontinuation approached but did not reach statistical significance for those receiving dual intervention versus onabotulinumtoxinA alone in the number of adverse events that led to treatment termination (4.6%, 6/131 vs. 0.8%, 1/131, p = 0.065); however, the number of patients who discontinued therapy was not significantly different between those groups (2.3%, 3/131 vs. 0.8%, 1/131; p = 0.314; odds ratio 0.3 [0-3.2]; p = 0.338). CONCLUSIONS: In this retrospective chart review, there was no significant difference in adverse events or therapy discontinuation between patients receiving sequential peripheral nerve block(s) and onabotulinumtoxinA injections versus those receiving either peripheral nerve block(s) or onabotulinumtoxinA injections alone. As a result, we concluded that the combination procedure is likely safe and well tolerated in routine clinical practice.

Hypertension control after intracerebral hemorrhage among varying small vessel disease etiologies.

INTRODUCTION: Intracerebral hemorrhage (ICH) is attributable to cerebral small vessel disease (cSVD), which includes cerebral amyloid angiopathy (CAA) and hypertensive-cSVD (HTN-cSVD). HTN-cSVD includes patients with strictly deep ICH/microbleeds and mixed location ICH/microbleeds, the latter representing a more severe form of HTN-cSVD. We test the hypothesis that more severe forms of HTN-cSVD are related to worse hypertension control in long-term follow-up after ICH. METHODS: From consecutive non-traumatic ICH patients admitted to a tertiary care center, we classified the ICH as CAA, strictly deep ICH/microbleeds, and mixed-location ICH/microbleeds. CSVD burden was quantified using a validated MRI-based score (range: 0-6 points). We created a multivariable (linear mixed effects) model adjusting for age, sex, race, year of inclusion, hypertension, and antihypertensive medication usage to investigate the association of average systolic blood pressure (SBP) during follow-up with cSVD etiology/severity. RESULTS: 796 ICH survivors were followed for a median of 48.8 months (IQR 41.5-60.4). CAA-related ICH survivors (n = 373) displayed a lower median SBP (138 mmHg, IQR 133-142 mmHg) compared to those of strictly deep ICH (n = 222, 141 mmHg, IQR 136-143 mmHg, p = 0.04), and mixed location ICH/microbleeds (n = 201, 142 mmHg, IQR 135-144 mmHg, p = 0.02). In the multivariable analysis, mixed location ICH/microbleeds (effect: + 3.8 mmHg, SE: 1.3 mmHg, p = 0.01) and increasing cSVD severity (+ 1.8 mmHg per score point, SE: 0.8 mmHg, p = 0.03) were associated with higher SBP in follow-up. CONCLUSION: CSVD severity and subtype predicts long-term hypertension control in ICH patients.

De Novo Elastin Assembly Alleviates Development of Supravalvular Aortic Stenosis.

BACKGROUND: A series of incurable cardiovascular disorders arise due to improper formation of elastin during development. Supravalvular aortic stenosis (SVAS), resulting from a haploinsufficiency of ELN, is caused by improper stress sensing by medial vascular smooth muscle cells, leading to progressive luminal occlusion and heart failure. SVAS remains incurable, as current therapies do not address the root issue of defective elastin. METHODS: We use SVAS here as a model of vascular proliferative disease using both human induced pluripotent stem cell-derived vascular smooth muscle cells and developmental Eln± mouse models to establish de novo elastin assembly as a new therapeutic intervention. RESULTS: We demonstrate mitigation of vascular proliferative abnormalities following de novo extracellular elastin assembly through the addition of the polyphenol epigallocatechin gallate to SVAS human induced pluripotent stem cell-derived vascular smooth muscle cells and in utero to Eln± mice. CONCLUSIONS: We demonstrate de novo elastin deposition normalizes SVAS human induced pluripotent stem cell-derived vascular smooth muscle cell hyperproliferation and rescues hypertension and aortic mechanics in Eln± mice, providing critical preclinical findings for the future application of epigallocatechin gallate treatment in humans.

Impaired Kidney Function, Cerebral Small Vessel Disease and Cognitive Disorders: The Framingham Heart Study.

BACKGROUND AND HYPOTHESIS: It remains unclear if the relation of chronic kidney disease (CKD) with cognitive dysfunction is independent of blood pressure (BP). We evaluated kidney function in relation to premorbid BP measurements, cerebral small vessel disease (CSVD) and incident mild cognitive impairment (MCI) and dementia in Framingham Offspring Cohort participants. METHODS: We included Framingham Offspring participants free of dementia, attending an examination during midlife (exam cycle 6, baseline) for ascertainment of kidney function status, with brain MRI late in life (exam cycles 7-9), cognitive outcome data and available interim hypertension and blood pressure assessments. We related CKD (estimated glomerular filtration rate < 60 ml/min/1.73m2) and albuminuria (urine albumin-to-creatinine ratio ≥ 30 mg/g) to CSVD markers and cognitive outcomes using multivariable regression analyses. RESULTS: Among 2604 participants (mean age 67.4 ± 9.2, 64% women, 7% had CKD and 9% albuminuria), albuminuria was independently associated with covert infarcts (adjusted OR, 1.55 [1.00-2.38]; P = 0.049) and incident MCI and dementia (adjusted HR, 1.68 [1.18-2.41]; P = 0.005 and 1.71, [1.11-2.64]; P = 0.015, respectively). CKD was not associated with CSVD markers but was associated with higher risk of incident dementia (HR, 1.53 [1.02-2.29]; P = 0.041), While albuminuria was predictive of the Alzheimer's disease subtype (Adjusted HR = 1.68, [1.03-2.74]; P = 0.04), CKD was predictive of vascular dementia (Adjusted HR, 2.78, [1.16-6.68]; P = 0.023). CONCLUSIONS: Kidney disease was associated with CSVD and cognitive disorders in asymptomatic community dwelling participants. The relation was independent of premorbid BP, suggesting that the link between kidney and brain disease may involve additional mechanisms beyond blood pressure related injury.

Do one-stage indications predict success following two-stage arthroplasty for chronic periprosthetic joint infection?

Introduction: The 2018 International Consensus Meeting (ICM) proposed criteria for one-stage exchange arthroplasty in treating periprosthetic joint infection (PJI). Our study aimed to determine what proportion of PJI patients met the 2018 ICM criteria and how this affected infection-free survivorship for patients. Methods: All chronic PJI patients treated with two-stage exchange within our institution between 2017-2020 were retrospectively reviewed. Included cases met 2011 Musculoskeletal Infection Society (MSIS) criteria for PJI and had a 2-year minimum follow-up. Treatment success was defined as Tier 1A in the 2019 MSIS working group definition. ICM one-stage criteria included non-immunocompromised host, absence of sepsis, adequate soft tissue for closure, known preoperative pathogen, and susceptibility. Immunocompromised host was analyzed as two separate definitions. Kaplan-Meier survivorship, Cox regression, and univariate analyses were performed. Results: A total of 293 chronic PJI patients were included. Overall, treatment failure occurred in 64/293 (21.8 %) patients. Only 13 % (n=37) met ICM criteria definition no. 1 for one-stage exchange; 12 % (n=33) met definition no. 2. In both definitions, infection-free survivorship at 2 years did not differ between patients who met and did not meet criteria (p>0.05). Cox proportional hazard regression analyses demonstrated that the only variable predicting treatment failure was knee joint involvement (p=0.01). Conclusions: We found that a very limited number of chronic PJI patients were suitable for a one-stage exchange. Furthermore, the supposition that healthier hosts with known pathogens (the basis of the ICM criteria) yield better PJI treatment outcomes was not observed. These results justify the ongoing multicenter randomized control trial comparing one-stage versus two-stage treatment for chronic PJI.

Incidence and management of prostatic urethra recurrence in a cohort of 21 patients who received BCG induction for non-muscle invasive bladder cancer.

PURPOSE: To describe the incidence and management of patients who develop a prostatic urethral (PU) urothelial carcinoma recurrence after Bacillus Calmette-Guerin (BCG) induction for non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: We performed a retrospective cohort study of all patients who received BCG induction at our institution from 1996 to 2021 (N = 642) for NMIBC. All patients with pathologically confirmed PU involvement following BCG induction with no known PU involvement pre-BCG were included. We describe the presentation, management, and outcomes for PU recurrence. RESULTS: Among the 642 patients, 21 (3.3%) patients had a PU recurrence after BCG induction. 8 (38%) patients received >2 cycles of BCG induction prior to the recurrence. Median time from induction to PU recurrence was 21 months and 12 (57.1%) patients had concurrent bladder recurrence. At the time of their PU recurrence, 14/21 (67%) of patients were deemed BCG Unresponsive. Nearly all (18/21) were high grade, and 10 were stage Tis, 7 Ta, and 3 T1, and 1 T2. 19/21 (90%) patients received bladder sparing treatment: 6 with TURBT and BCG, 6 with TURBT and intravesical chemotherapy, 5 with TURBT only, and 2 did not receive immediate treatment of their PU recurrence due to advanced stage of disease. 2/21 (9.5%) received a radical cystectomy for initial treatment of the post-BCG PU recurrence, of which all were >pT2. Median follow-up time from BCG induction to the patient's last visit was 64.5 months. Following treatment of PU recurrence, 15/18 patients had another recurrence at a median of 5 months: about 47% of recurrences were bladder only and 14% recurred only in the PU as well. About 1 patient received a RC after the second recurrence and was pT2. CONCLUSION: Patients with PU recurrences following intravesical BCG have a high-risk disease phenotype with a significant risk of recurrence. Conservative management may be appropriate for well-selected patients who do not desire a cystoprostatectomy.

Associations of Increased WIC Benefits for Fruits and Vegetables With Food Security and Satisfaction by Race and Ethnicity.

Introduction: The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) provides nutrition support for racially and ethnically diverse populations. In 2021, the monthly cash value benefit (CVB) for the purchase of fruits and vegetables increased from $9 to $35 and was later adjusted to $24. This study investigated, by racial and ethnic groups, whether CVB increases were associated with increases in CVB redemption, household food security, child fruit and vegetable intake, satisfaction with CVB amount, and likelihood of continued participation in WIC if the CVB returned to $9 per month. Methods: We conducted a longitudinal study of WIC participants (N = 1,770) in southern California at 3 time points, from April 2021 through May 2022; the CVB amount was $9 at baseline, $35 at Survey 2, and $24 at Survey 3. Racial and ethnic groups were Hispanic English-speakers, Hispanic Spanish-speakers, non-Hispanic Asian, non-Hispanic Black, non-Hispanic Other, and non-Hispanic White. We used mixed-effect and modified Poisson regressions to evaluate outcomes by group. Results: At baseline, groups differed significantly in dollars of CVB redeemed, percentage of CVB redeemed, household food security, and satisfaction with CVB amount. After the increase in CVB, we found increases in all groups in CVB redemption, household food security, and satisfaction. Non-Hispanic Black and Hispanic English-speaking groups, who had low levels of satisfaction at baseline, had larger increases in satisfaction than other groups. Reported likelihood of continued WIC participation if the monthly CVB returned to $9 also differed significantly by group, ranging from 62.5% to 90.0%. Conclusion: The increase in CVB for children receiving WIC benefited all racial and ethnic groups. Continued investment in an augmented CVB could improve health outcomes for a racially and ethnically diverse WIC population.

Predicting post-stroke cognitive impairment using electronic health record data.

BACKGROUND: Secondary prevention interventions to reduce post-stroke cognitive impairment (PSCI) can be aided by the early identification of high-risk individuals who would benefit from risk factor modification. AIMS: To develop and evaluate a predictive model to identify patients at increased risk of PSCI over 5 years using data easily accessible from electronic health records. METHODS: Cohort study that included primary care patients from two academic medical centers. Patients were aged 45 years or older, without prior stroke or prevalent cognitive impairment, with primary care visits and an incident ischemic stroke between 2003 and 2016 (development/internal validation cohort) or 2010 and 2022 (external validation cohort). Predictors of PSCI were ascertained from the electronic health record. The outcome was incident dementia/cognitive impairment within 5 years and beginning 3 months following stroke, ascertained using International Classification of Diseases, Ninth/Tenth Revision (ICD-9/10) codes. For model variable selection, we considered potential predictors of PSCI and constructed 400 bootstrap samples with two-thirds of the model derivation sample. We ran 10-fold cross-validated Cox proportional hazards models using a least absolute shrinkage and selection operator (LASSO) penalty. Variables selected in >25% of samples were included. RESULTS: The analysis included 332 incident diagnoses of PSCI in the development cohort (n = 3741), and 161 and 128 incident diagnoses in the internal (n = 1925) and external (n = 2237) validation cohorts, respectively. The C-statistic for predicting PSCI was 0.731 (95% confidence interval (CI): 0.694-0.768) in the internal validation cohort, and 0.724 (95% CI: 0.681-0.766) in the external validation cohort. A risk score based on the beta coefficients of predictors from the development cohort stratified patients into low (0-7 points), intermediate (8-11 points), and high (12-23 points) risk groups. The hazard ratios (HRs) for incident PSCI were significantly different by risk categories in internal (high, HR: 6.2, 95% CI: 4.1-9.3; Intermediate, HR: 2.7, 95% CI: 1.8-4.1) and external (high, HR: 6.1, 95% CI: 3.9-9.6; Intermediate, HR: 2.8, 95% CI: 1.9-4.3) validation cohorts. CONCLUSION: Five-year risk of PSCI can be accurately predicted using routinely collected data. Model output can be used to risk stratify and identify individuals at increased risk for PSCI for preventive efforts. DATA ACCESS STATEMENT: Mass General Brigham data contain protected health information and cannot be shared publicly. The data processing scripts used to perform analyses will be made available to interested researchers upon reasonable request to the corresponding author.

Long-Term Outcomes in Patients With Spontaneous Cerebellar Hemorrhage: An International Cohort Study.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) in the cerebellum has a poor short-term prognosis, whereas data on the long-term case fatality and recurrent vascular events are sparse. Herewith, we aimed to assess the long-term case fatality and recurrence rate of vascular events after a first cerebellar ICH. METHODS: In this international cohort study, we included patients from 10 hospitals (the United States and Europe from 1997 to 2017) aged ≥18 years with a first spontaneous cerebellar ICH who were discharged alive. Data on long-term case fatality and recurrence of vascular events (recurrent ICH [supratentoria or infratentorial], ischemic stroke, myocardial infarction, or major vascular surgery) were collected for survival analysis and absolute event rate calculation. RESULTS: We included 405 patients with cerebellar ICH (mean age [SD], 72 [13] years, 49% female). The median survival time was 67 months (interquartile range, 23-100 months), with a cumulative survival rate of 34% at 10-year follow-up (median follow-up time per center ranged: 15-80 months). In the 347 patients with data on vascular events 92 events occurred in 78 patients, after initial cerebellar ICH: 31 (8.9%) patients had a recurrent ICH (absolute event rate, 1.8 per 100 patient-years [95% CI, 1.2-2.6]), 39 (11%) had an ischemic stroke (absolute event rate, 2.3 [95% CI, 1.6-3.2]), 13 (3.7%) had a myocardial infarction (absolute event rate, 0.8 [95% CI, 0.4-1.3]), and 5 (1.4%) underwent major vascular surgery (absolute event rate, 0.3 [95% CI, 0.1-0.7]). The median time to a first vascular event during follow-up was 27 months (interquartile range, 8.7-50 months), with a cumulative hazard of 47% at 10 years. CONCLUSIONS: The long-term prognosis of patients who survive a first spontaneous cerebellar ICH is poor and comparable to that of patients who survive a first supratentorial ICH. Further identification of patients at high risk of vascular events following the initial cerebellar ICH is needed. Including patients with cerebellar ICH in randomized controlled trials on secondary prevention of patients with ICH is warranted.

Fibrinolytic Agents in Thromboembolic Diseases: Historical Perspectives and Approved Indications.

Fibrinolytic agents catalyze the conversion of the inactive proenzyme plasminogen into the active protease plasmin, degrading fibrin within the thrombus and recanalizing occluded vessels. The history of these medications dates to the discovery of the first fibrinolytic compound, streptokinase, from bacterial cultures in 1933. Over time, researchers identified two other plasminogen activators in human samples, namely urokinase and tissue plasminogen activator (tPA). Subsequently, tPA was cloned using recombinant DNA methods to produce alteplase. Several additional derivatives of tPA, such as tenecteplase and reteplase, were developed to extend the plasma half-life of tPA. Over the past decades, fibrinolytic medications have been widely used to manage patients with venous and arterial thromboembolic events. Currently, alteplase is approved by the U.S. Food and Drug Administration (FDA) for use in patients with pulmonary embolism with hemodynamic compromise, ST-segment elevation myocardial infarction (STEMI), acute ischemic stroke, and central venous access device occlusion. Reteplase and tenecteplase have also received FDA approval for treating patients with STEMI. This review provides an overview of the historical background related to fibrinolytic agents and briefly summarizes their approved indications across various thromboembolic diseases.

Local tree cover predicts mosquito species richness and disease vector presence in a tropical countryside landscape.

Context: Land use change drives both biodiversity loss and zoonotic disease transmission in tropical countryside landscapes. Developing solutions for protecting countryside biodiversity, public health, and livelihoods requires understanding the scales at which habitat characteristics such as land cover shape biodiversity, especially for arthropods that transmit pathogens. Evidence increasingly shows that species richness for many taxa correlates with local tree cover. Objectives: We investigated whether mosquito species richness, community composition, and presence of disease vector species responded to land use and tree cover - and if so, whether at spatial scales similar to other taxa. Methods: We paired a field survey of mosquito communities in agricultural, residential, and forested lands in rural southern Costa Rica with remotely sensed tree cover data. We compared mosquito community responses to tree cover surrounding survey sites measured across scales, and analyzed community responses to land use and environmental gradients. Results: Tree cover was positively correlated with mosquito species richness, and negatively correlated with the presence of the common invasive dengue vector Aedes albopictus, particularly at small spatial scales of 80 - 200m. Land use predicted community composition and Ae. albopictus presence. Environmental gradients of tree cover, temperature, and elevation explained 7% of species turnover among survey sites. Conclusions: The results suggest that preservation and expansion of tree cover at local scales can protect biodiversity for a wide range of taxa, including arthropods, and also confer protection against disease vector occurrence. The identified spatial range of tree cover benefits can inform land management for conservation and public health protection.

Predicting post-stroke cognitive impairment using electronic health record data.

Importance: Secondary prevention interventions to reduce post-stroke cognitive impairment (PSCI) can be aided by the early identification of high-risk individuals who would benefit from risk factor modification. Objective: To develop and evaluate a predictive model to identify patients at increased risk of PSCI over 5 years using data easily accessible from electronic health records. Design: Cohort study with patients enrolled between 2003-2016 with follow-up through 2022. Setting: Primary care practices affiliated with two academic medical centers. Participants: Individuals 45 years or older, without prior stroke or prevalent cognitive impairment, with primary care visits and an incident ischemic stroke between 2003-2016 (development/internal validation cohort) or 2010-2022 (external validation cohort). Exposures: Predictors of PSCI were ascertained from the electronic health record. Main Outcome: The outcome was incident dementia/cognitive impairment within 5 years and beginning 3 months following stroke, ascertained using ICD-9/10 codes. For model variable selection, we considered potential predictors of PSCI and constructed 400 bootstrap samples with two-thirds of the model derivation sample. We ran 10-fold cross-validated Cox proportional hazards models using a least absolute shrinkage and selection operator (LASSO) penalty. Variables selected in >25% of samples were included. Results: The analysis included 332 incident diagnoses of PSCI in the development cohort (n=3,741), and 161 and 128 incident diagnoses in the internal (n=1,925) and external (n=2,237) validation cohorts. The c-statistic for predicting PSCI was 0.731 (95% CI: 0.694-0.768) in the internal validation cohort, and 0.724 (95% CI: 0.681-0.766) in the external validation cohort. A risk score based on the beta coefficients of predictors from the development cohort stratified patients into low (0-7 points), intermediate (8-11 points), and high (12-35 points) risk groups. The hazard ratios for incident PSCI were significantly different by risk categories in internal (High, HR: 6.2, 95% CI 4.1-9.3; Intermediate, HR 2.7, 95% CI: 1.8-4.1) and external (High, HR: 6.1, 95% CI: 3.9-9.6; Intermediate, HR 2.8, 95% CI: 1.9-4.3) validation cohorts. Conclusions and Relevance: Five-year risk of PSCI can be accurately predicted using routinely collected data. Model output can be used to risk stratify and identify individuals at increased risk for PSCI for preventive efforts.

Resident Remediation: A National Survey of Urology Program Directors.

OBJECTIVES: To describe formal remediation rates and processes in urology training programs nationally. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional study by surveying program directors (PDs) through the Society of Academic Urologists. Formal remediation was defined as the process initiated when resident competency deficiencies were significant enough to necessitate documentation and notification of the Graduate Medical Education (GME) office. The primary outcome was the prevalence of urology programs that initiated formal remediation over the past 5 years. Secondary outcomes included reported competency deficiencies and formal remediation processes. RESULTS: Across 148 institutions, 73 (49%) PDs responded to the survey. The majority of PDs (67%, 49/73) stated that at least 1 resident underwent formal remediation over the last 5 years (median 1). "Professionalism" and "Interpersonal and Communication Skills" were the most common competency deficiencies that prompted formal remediation, whereas "Technical Skill" was the least common. While the majority of respondents notified the GME office of residents undergoing remediation, formal remediation plans varied from faculty coaching and mentorship (80%, 39/49) to simulation training (10%, 5/49). Absence of documented faculty feedback on poor performance was the most commonly cited barrier to formal remediation. The majority of PDs reported documentation in a resident's file (81%, 59/73); however, remediation processes differed with only half of PDs reporting that GME offices were routinely involved in creating and overseeing corrective action plans (56%, 41/73). Over the study period, 15% (11/73) of PDs did not promote a resident to the next year of training, and 23% (17/73) of PDs stated "Yes" to graduating a resident who they would not trust to care for a loved one. CONCLUSIONS: Formal remediation among urology residency programs is common, and processes vary across institutions. The most common competency areas prompting remediation were "Professionalism" and "Interpersonal and Communication Skills." Future research should address developing resources to facilitate resident remediation.

Why nature matters: A systematic review of intrinsic, instrumental, and relational values.

In this article, we present results from a literature review of intrinsic, instrumental, and relational values of nature conducted for the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services, as part of the Methodological Assessment of the Diverse Values and Valuations of Nature. We identify the most frequently recurring meanings in the heterogeneous use of different value types and their association with worldviews and other key concepts. From frequent uses, we determine a core meaning for each value type, which is sufficiently inclusive to serve as an umbrella over different understandings in the literature and specific enough to help highlight its difference from the other types of values. Finally, we discuss convergences, overlapping areas, and fuzzy boundaries between different value types to facilitate dialogue, reduce misunderstandings, and improve the methods for valuation of nature's contributions to people, including ecosystem services, to inform policy and direct future research.

Any Infant Formula Amount, but Not Infant Formula Type, Is Associated with Less Healthful Subsequent Beverage Intake among Special Supplemental Nutrition Program for Women, Infants, and Children-Participating Children.

Background: The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) provides nutrition assistance to low-income households, including infant formula for infants not fully breastfeeding. Issuance of lactose-reduced infant formula made with corn syrup solids (CSSF) is associated with elevated risk of obesity in early life, but associations between formula type and dietary intake have not been examined. Objectives: To evaluate associations between infant formula (amount and type) issued by WIC with subsequent child diet at ages 12-59 mo. Methods: Dietary data from 2014, 2017, and 2020 Los Angeles County WIC Survey respondents (n = 1339 children, 12-59 mo of age) were merged with WIC administrative data on infant feeding (amount and type of infant formula at ages 0-12 mo). Intake frequencies were available for sweetened beverages, sweets, juice, fast food, water, fruit, vegetables, and milk. Infant feeding was categorized by amount of WIC-issued formula (descending: fully formula fed, mostly formula fed, mostly breastfed, fully breastfed) and issuance of a CSSF (any, none). Associations between infant feeding (infant formula amount and type) and child diet were evaluated in multivariable generalized estimating equation negative binomial regression models, stratified by child age (12 to <24 mo, 24 to <60 mo). Results: Any infant formula issuance in the first year of life was adversely associated with subsequent dietary intake. This included 21%-23% higher 100% juice intake at 24 to <60 mo and 11%-13% (at 24 to <60 mo) or 20%-22% (at 12 to <24 mo) lower water intake. CSSF receipt compared with only other infant formula was not consistently associated with subsequent child diet. Conclusions: Any infant formula amount, but not CSSF receipt compared with other formula types, was associated with less healthful beverage intake patterns among WIC-participating children. WIC nutrition education may have a stronger impact if tailored based on infant feeding practices.

Association Between Body Mass Index and Functional Outcomes in Patients With Intracerebral Hemorrhage.

BACKGROUND AND OBJECTIVES: Evidence of the so-called "obesity paradox," which refers to the protective effect and survival benefit of obesity in patients with spontaneous intracerebral hemorrhage (ICH), remains controversial. This study aims to determine the association between body mass index (BMI) and functional outcomes in patients with ICH and whether it is modified by race/ethnicity. METHODS: Included individuals were derived from the Ethnic/Racial Variations of Intracerebral Hemorrhage study, which prospectively recruited 1,000 non-Hispanic White, 1,000 non-Hispanic Black, and 1,000 Hispanic patients with spontaneous ICH. Only patients with available BMI were included. The primary outcome was 90-day mortality. Secondary outcomes were mortality at discharge, modified Rankin Scale (mRS), Barthel Index, and self-reported health status measures at 90 days. Associations between BMI and ICH outcomes were assessed using univariable and multivariable logistic, ordinal, and linear regression models, as appropriate. Sensitivity analyses after excluding frail patients and by patient race/ethnicity were performed. RESULTS: A total of 2,841 patients with ICH were included. The median age was 60 years (interquartile range 51-73). Most patients were overweight (n = 943; 33.2%) or obese (n = 1,032; 36.3%). After adjusting for covariates, 90-day mortality was significantly lower among overweight and obese patients than their normal weight counterparts (adjusted odds ratio [aOR] = 0.71 [0.52-0.98] and aOR = 0.70 [0.50-0.97], respectively). Compared with patients with BMI <25 kg/m2, those with BMI ≥25 kg/m2 had better 90-day mRS (aOR = 0.80 [CI 0.67-0.95]), EuroQoL Group 5-Dimension (EQ-5D) (aß = 0.05 [0.01-0.08]), and EQ-5D VAS (aß = 3.80 [0.80-6.98]) scores. These differences persisted after excluding withdrawal of care patients. There was an inverse relationship between BMI and 90-day mortality (aOR = 0.97 [0.96-0.99]). Although non-Hispanic White patients had significantly higher 90-day mortality than non-Hispanic Black and Hispanic (26.6% vs 19.5% vs 18.0%, respectively; p < 0.001), no significant interactions were found between BMI and race/ethnicity. No significant interactions between BMI and age or sex for 90-day mortality were found, whereas for 90-day mRS, there was a significant interaction with age (pinteraction = 0.004). CONCLUSION: We demonstrated that a higher BMI is associated with decreased mortality, improved functional outcomes, and better self-reported health status at 90 days, thus supporting the paradoxical role of obesity in patients with ICH. The beneficial effect of high BMI does not seem to be modified by race/ethnicity or sex, whereas age may play a significant role in patient functional outcomes.