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The evidence linking chronic kidney disease (CKD) to spontaneous intracerebral hemorrhage (ICH) is inconclusive owing to possible confounding by comorbidities that frequently coexist in patients with these 2 diseases.To determine whether there is an association between CKD and ICH risk.A 3-stage study that combined observational and genetic analyses was conducted. First, the association between CKD and ICH risk was tested in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, a multicenter case-control study in the US. All participants with available data on CKD from ERICH were included. Second, this analysis was replicated in the UK Biobank (UKB), an ongoing population study in the UK. All participants in the UKB were included in this study. Third, mendelian randomization analyses were implemented in the UKB using 27 CKD-related genetic variants to test for genetic associations. ERICH was conducted from August 1, 2010, to August 1, 2017, and observed participants for 1 year. The UKB enrolled participants between 2006 and 2010 and will continue to observe them for 30 years. Data analysis was performed from November 11, 2019, to May 10, 2022.CKD stages 1 to 5.The outcome of interest was ICH, ascertained in ERICH via expert review of neuroimages and in the UKB via a combination of self-reported data and International Statistical Classification of Diseases, Tenth Revision, codes.In the ERICH study, a total of 2914 participants with ICH and 2954 controls who had available data on CKD were evaluated (mean [SD] age, 61.6 [14.0] years; 2433 female participants [41.5%]; 3435 male participants [58.5%]); CKD was found to be independently associated with higher risk of ICH (odds ratio [OR], 1.95; 95% CI, 1.35-2.89; P .001). This association was not modified by race and ethnicity. Replication in the UKB with 1341 participants with ICH and 501 195 controls (mean [SD] age, 56.5 [8.1] years; 273 402 female participants [54.4%]; 229 134 male participants [45.6%]) confirmed this association (OR, 1.28; 95% CI, 1.01-1.62; P = .04). Mendelian randomization analyses indicated that genetically determined CKD was associated with ICH risk (OR, 1.56; 95% CI, 1.13-2.16; P = .007).In this 3-stage study that combined observational and genetic analyses among study participants enrolled in 2 large observational studies with different characteristics and study designs, CKD was consistently associated with higher risk of ICH. Mendelian randomization analyses suggest that this association was causal. Further studies are needed to identify the specific biological pathways that mediate this association.

The SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) trial showed the safety but not efficacy of the Symplicity system (Medtronic, Santa Rosa, CA, USA) at 6 months follow-up in patients with treatment-resistant hypertension. This final report presents the 36-month follow-up results.SYMPLICITY HTN-3 was a single-blind, multicentre, sham-controlled, randomised clinical trial, done in 88 centres in the USA. Adults aged 18-80 years, with treatment-resistant hypertension on stable, maximally tolerated doses of three or more drugs including a diuretic, who had a seated office systolic blood pressure of 160 mm Hg or more and 24 h ambulatory systolic blood pressure of 135 mm Hg or more were randomly assigned (2:1) to receive renal artery denervation using the single electrode (Flex) catheter or a sham control. The original primary endpoint was the change in office systolic blood pressure from baseline to 6 months for the renal artery denervation group compared with the sham control group. Patients were unmasked after the primary endpoint assessment at 6 months, at which point eligible patients in the sham control group who met the inclusion criteria (office blood pressure ≥160 mm Hg, 24 h ambulatory systolic blood pressure ≥135 mm Hg, and still prescribed three or more antihypertensive medications) could cross over to receive renal artery denervation. Changes in blood pressure up to 36 months were analysed in patients in the original renal artery denervation group and sham control group, including those who underwent renal artery denervation after 6 months (crossover group) and those who did not (non-crossover group). For comparisons between the renal artery denervation and sham control groups, follow-up blood pressure values were imputed for patients in the crossover group using their most recent pre-crossover masked blood pressure value. We report long-term blood pressure changes in renal artery denervation and sham control groups, and investigate blood pressure control in both groups using time in therapeutic blood pressure range analysis. The primary safety endpoint was the incidence of all-cause mortality, end stage renal disease, significant embolic event, renal artery perforation or dissection requiring intervention, vascular complications, hospitalisation for hypertensive crisis unrelated to non-adherence to medications, or new renal artery stenosis of more than 70% within 6 months. The trial is registered with ClinicalTrials.gov, NCT01418261.From Sep 29, 2011, to May 6, 2013, 1442 patients were screened, of whom 535 (37%; 210 [39%] women and 325 [61%] men; mean age 57·9 years [SD 10·7]) were randomly assigned: 364 (68%) patients received renal artery denervation (mean age 57·9 years [10·4]) and 171 (32%) received the sham control (mean age 56·2 years [11·2]). 36-month follow-up data were available for 219 patients (original renal artery denervation group), 63 patients (crossover group), and 33 patients (non-crossover group). At 36 months, the change in office systolic blood pressure was -26·4 mm Hg (SD 25·9) in the renal artery denervation group and -5·7 mm Hg (24·4) in the sham control group (adjusted treatment difference -22·1 mm Hg [95% CI -27·2 to -17·0]; p≤0·0001). The change in 24 h ambulatory systolic blood pressure at 36 months was -15·6 mm Hg (SD 20·8) in the renal artery denervation group and -0·3 mm Hg (15·1) in the sham control group (adjusted treatment difference -16·5 mm Hg [95% CI -20·5 to -12·5]; p≤0·0001). Without imputation, the renal artery denervation group spent a significantly longer time in therapeutic blood pressure range (ie, better blood pressure control) than patients in the sham control group (18% [SD 25·0] for the renal artery denervation group vs 9% [SD 18·8] for the sham control group; p≤0·0001) despite a similar medication burden, with consistent and significant results with imputation. Rates of adverse events were similar across treatment groups, with no evidence of late-emerging complications from renal artery denervation. The rate of the composite safety endpoint to 48 months, including all-cause death, new-onset end-stage renal disease, significant embolic event resulting in end-organ damage, vascular complication, renal artery re-intervention, and hypertensive emergency was 15% (54 of 352 patients) for the renal artery denervation group, 14% (13 of 96 patients) for the crossover group, and 14% (10 of 69 patients) for the non-crossover group.This final report of the SYMPLICITY HTN-3 trial adds to the totality of evidence supporting the safety of renal artery denervation to 36 months after the procedure. From 12 months to 36 months after the procedure, patients who were originally randomly assigned to receive renal artery denervation had larger reductions in blood pressure and better blood pressure control compared with patients who received sham control.Medtronic.

Context Urinary bladder paraganglioma (UBPGL) is rare. Objective We aimed to characterize the presentation and outcomes of patients diagnosed with UBPGL. Methods We conducted a multicenter study of consecutive patients with pathologically confirmed UBPGL evaluated between 1971 and 2021. Outcomes included repeat bladder surgery, metastases, and disease-specific mortality. Results Patients (n=110 total; n=56 [51%] women) were diagnosed with UBPGL at a median age of 50 years (interquartile range [IQR], 36-61 years). Median tumor size was 2 cm (IQR, 1-4 cm). UBPGL was diagnosed prior to biopsy in only 37 (34%), and only 69 (63%) patients had evaluation for catecholamine excess. In addition to the initial bladder surgery, 26 (25%) required multiple therapies, including repeat surgery in 10 (9%). Synchronous metastases were present in 9 (8%) patients, and 24 (22%) other patients with UBPGL developed metachronous metastases at a median of 4 years (IQR, 2-10 years) after the initial diagnosis. Development of metachronous metastases was associated with younger age (hazard ratio [HR] 0.97; 95% CI, 0.94-0.99), UBPGL size (HR 1.69; 95% CI, 1.31-2.17), and a higher degree of catecholamine excess (HR 5.48; 95% CI, 1.40-21.39). Disease-specific mortality was higher in patients with synchronous metastases (HR 20.80; 95% CI, 1.30-332.91). Choice of initial surgery, genetic association, sex, or presence of muscular involvement on pathology were not associated with development of metastases or mortality. Conclusions Only a minority of patients were diagnosed before biopsy/surgery, reflecting need for better diagnostic strategies. All patients with UBPGL should have lifelong monitoring for development of recurrence and metastases.

Rosacea is a chronic inflammatory skin condition of varying severity that can significantly impact patient quality of life. Intense pulsed light (IPL) is an established treatment for rosacea-associated telangiectasia, inflammation, and erythema. This study assessed whether application of a phyto-corrective mask, gel, and resveratrol antioxidant serum after IPL treatment can improve outcomes and reduce procedure-related adverse effects.In a prospective, open-label, split-face, 3-month study, 10 subjects with moderate-to-severe facial rosacea underwent IPL treatment on both sides of the face. The following were applied to the right side of the face only: phyto-corrective mask once weekly starting immediately after IPL; phyto-corrective gel twice daily; and resveratrol antioxidant treatment at night. Both sides of the face were treated with sunscreen. Subjects were assessed on Day 1, 1 and 3 months after IPL by three, independent evaluators using the 5-point Global Aesthetic Improvement Scale (GAIS). All subjects rated skin redness, hydration, and overall improvement on Day 1 and completed a patient satisfaction questionnaire at the 1- and 3-month visits.Ten women were enrolled, aged 44-72 years old, with moderate (n = 6) to severe (n = 4) rosacea. IPL was effective at reducing symptoms with rosacea classified as absent in five women and mild in five at the final 3-month visit. GAIS scores also revealed improvements on both sides of the face, but the skincare treated side showed continuous improvement over 3 months with all patients remaining at least "Improved", whereas there appeared to be a waning effect after 1 month with IPL alone. On Day 1 after IPL, all women reported less redness, improved hydration, and improved skin appearance on the right side of the face. Patient satisfaction was consistently rated higher on the right side of the face.Application of a phyto-corrective mask, gel, and resveratrol antioxidant serum may complement IPL treatment for rosacea by enhancing treatment outcomes and reducing procedure-related symptoms.

Background The World Trade Center (WTC) general responder cohort (GRC) was exposed to environmental toxins possibly associated with increased risk of developing autoimmune conditions. Objectives Two study designs were used to assess incidence and risks of autoimmune conditions in the GRC. Methods Three clinically trained professionals established the status of possible GRC cases of autoimmune disorders adhering to diagnostic criteria, supplemented, as needed, by specialists' review of consenting responders' medical records. Nested case-control analyses using conditional logistic regression estimated the risk associated with high WTC exposure (being in the 9/11/2001 dust cloud or ≥median days' response worked) compared with low WTC exposure (all other GRC members'). Four controls were matched to each case on age at case diagnosis (±2 years), sex, race/ethnicity, and year of program enrollment. Sex-specific and sensitivity analyses were performed. GRC age- and sex-adjusted standardized incidence ratios (SIRs) were compared with the Rochester Epidemiology Project (REP). Complete REP inpatient and outpatient medical records were reviewed by specialists. Conditions meeting standardized criteria on ≥2 visits were classified as REP confirmed cases. Results Six hundred and twenty-eight responders were diagnosed with autoimmune conditions between 2002 and 2017. In the nested case-control analyses, high WTC exposure was not associated with autoimmune domains and conditions (rheumatologic domain odds ratio [OR] = 1.03, 95% confidence interval [CI] = 0.77, 1.37; rheumatoid arthritis OR = 1.12, 95% CI = 0.70, 1.77). GRC members had lower SIR than REP. Women's risks were generally greater than men's. Conclusions The study found no statistically significant increased risk of autoimmune conditions with WTC exposures.

Background Postpartum hemorrhage (PPH) remains the leading cause of maternal death worldwide despite its often-preventable nature. Understanding health care providers’ knowledge of clinical protocols is imperative for improving quality of care and reducing mortality. This is especially pertinent in referral and teaching hospitals that train nursing and medical students and interns in addition to managing emergency and referral cases. Methods This study aimed to (1) measure health care providers’ knowledge of clinical protocols for risk assessment, prevention, and management of PPH in 3 referral hospitals in Kenya and (2) examine factors associated with providers’ knowledge. We developed a knowledge assessment tool based on past studies and clinical guidelines from the World Health Organization and the Kenyan Ministry of Health. We conducted in-person surveys with health care providers in three high-volume maternity facilities in Nairobi and western Kenya from October 2018-February 2019. We measured gaps in knowledge using a summative index and examined factors associated with knowledge (such as age, gender, qualification, experience, in-service training attendance, and a self-reported measure of peer-closeness) using linear regression. Results We interviewed 172 providers including consultants, medical officers, clinical officers, nurse-midwives, and students. Overall, knowledge was lowest for prevention-related protocols (an average of 0.71 out of 1.00; 95% CI 0.69–0.73) and highest for assessment-related protocols (0.81; 95% CI 0.79–0.83). Average knowledge scores did not differ significantly between qualified providers and students. Finally, we found that being a qualified nurse, having a specialization, being female, having a bachelor's degree and self-reported closer relationships with colleagues were statistically significantly associated with higher knowledge scores. Conclusion We found gaps in knowledge of PPH care clinical protocols in Kenya. There is a clear need for innovations in clinical training to ensure that providers in teaching referral hospitals are prepared to prevent, assess, and manage PPH. It is possible that training interventions focused on learning by doing and teamwork may be beneficial.

OnabotulinumtoxinA safety and efficacy are well established for upper facial lines (UFL), including forehead lines (FHL), glabellar lines (GL), and crow's feet lines (CFL).To investigate the association of onabotulinumtoxinA efficacy with patient-reported psychological impacts and satisfaction in UFL.A pooled analysis of data from 4 pivotal Phase 3 trials (onabotulinumtoxinA vs placebo in FHL ± GL, FHL + GL ± CFL, CFL, and CFL + GL for ≤180 days) evaluated investigator-assessed ≥1-grade severity improvement on the Allergan Facial Wrinkle Scale at Day 30 (responders). Facial Line Outcomes (FLO-11) Questionnaire, Facial Line Satisfaction Questionnaire (FLSQ), and Subject Assessment of Satisfaction of Appearance (SASA) were used to evaluate responder appearance-related psychological impacts and satisfaction.OnabotulinumtoxinA patients, by primary study focus (FHL, GL, or CFL), totaled 921, 921, and 833, respectively; 786 patients received placebo. Most patients were female, White, and aged 45 to 50 years (median). Through 150 days,42% FHL,43% GL, and ≥32% CFL patients were onabotulinumtoxinA responders. Responders reported improvements in appearance-related psychological impacts (FLO-11) and high satisfaction (FLSQ and SASA), sustained through ≥150 days.A ≥1-grade improvement with onabotulinumtoxinA is a clinically meaningful outcome in UFL, associated with long-lasting improved patient-reported psychological impacts and high satisfaction.

Background Metastatic breast cancer is a deadly disease with a low 5-year survival rate. Tracking metastatic spread in living patients is difficult and thus poorly understood. Methods Via rapid autopsy, we have collected 30 tumor samples over 3 timepoints and across 8 organs from a triple-negative metastatic breast cancer patient. The large number of sites sampled, together with deep whole-genome sequencing and advanced computational analysis, allowed us to comprehensively reconstruct the tumor’s evolution at subclonal resolution. Results The most unique, previously unreported aspect of the tumor’s evolution that we observed in this patient was the presence of “subclone incubators,” defined as metastatic sites where substantial tumor evolution occurs before colonization of additional sites and organs by subclones that initially evolved at the incubator site. Overall, we identified four discrete waves of metastatic expansions, each of which resulted in a number of new, genetically similar metastasis sites that also enriched for particular organs (e.g., abdominal vs bone and brain). The lung played a critical role in facilitating metastatic spread in this patient: the lung was the first site of metastatic escape from the primary breast lesion, subclones at this site were likely the source of all four subsequent metastatic waves, and multiple sites in the lung acted as subclone incubators. Finally, functional annotation revealed that many known drivers or metastasis-promoting tumor mutations in this patient were shared by some, but not all metastatic sites, highlighting the need for more comprehensive surveys of a patient’s metastases for effective clinical intervention. Conclusions Our analysis revealed the presence of substantial tumor evolution at metastatic incubator sites in a patient, with potentially important clinical implications. Our study demonstrated that sampling of a large number of metastatic sites affords unprecedented detail for studying metastatic evolution.

Background As part of the global Invasive Bacterial Vaccine-Preventable Diseases Surveillance Network, 12 African countries referred cerebrospinal fluid (CSF) samples to South Africa’s regional reference laboratory. We evaluated the utility of real-time polymerase chain reaction (PCR) in detecting and serotyping/grouping Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae (HNS). Methods From 2008 to 2017, CSF samples collected from children Results The overall HNS PCR positivity rate for all countries was 10% (1195 of 11 626 samples). In samples with both PCR and culture results, HNS PCR positivity was 11% (744 of 6747 samples), and HNS culture positivity was 3% (207 of 6747). Molecular serotype/serogroup was assigned in 75% of PCR-positive specimens (762 of 1016). Compared with PCR-negative CSF samples, PCR-positive samples were more often turbid (adjusted odds ratio, 6.80; 95% confidence interval, 5.67–8.17) and xanthochromic (1.72; 1.29–2.28), had elevated white blood cell counts (6.13; 4.71–7.99) and high protein concentrations (5.80; 4.34–7.75), and were more often HNS culture positive (32.70; 23.18–46.12). Conclusion PCR increased detection of vaccine-preventable bacterial meningitis in countries where confirmation of suspected meningitis cases is impeded by limited culture capacity.

ImportanceFacilitating access to the full range of contraceptive options is a health policy goal; however, inpatient provision of postpartum long-acting reversible contraceptive (LARC) methods has been limited due to lack of hospital reimbursement. Between March 2014 and January 2015, the Medicaid programs in 5 states began to reimburse hospitals for immediate postpartum LARC separately from the global maternity payment.ObjectiveTo examine the association between Medicaid policies and provision of immediate postpartum LARC, and to examine hospital characteristics associated with policy adoption.Design, Setting, and ParticipantsThis cross-sectional study used interrupted time series analysis. The setting was population-based in Georgia, Iowa, Maryland, New York, and Rhode Island. Participants included individuals who gave birth in these states between 2011 and 2017 (n = 3 097 188). Statistical analysis was performed from June 2021 to August 2022.ExposuresChildbirth after the start of Medicaid’s reimbursement policy.Main Outcomes and MeasuresImmediate postpartum LARC (outcome), teaching hospital, Catholic-owned or operated, obstetrical care level, and urban or rural location (hospital characteristics).ResultsThe study included a total of 1 521 491 births paid for by Medicaid and 1 575 697 paid for by a commercial payer between 2011 and 2017. Prior to Medicaid reimbursement changes, 489 389 of 726 805 births (67%) were to individuals between 18 and 29 years of age, 219 363 of 715 905 births (31%) were to non-Hispanic Black individuals, 227 639 of 715 905 births (32%) were to non-Hispanic White individuals, 155 298 of 715 905 births (22%) were to Hispanic individuals, and 113 605 of 715 905 births (16%) were to individuals from other non-Hispanic racial groups. Among Medicaid-paid births, the policies were associated with an increase in the rate of immediate postpartum LARC provision in all states, although results for Maryland were not consistent across sensitivity analyses. The change in trend ranged from a quarterly increase of 0.05 percentage points in Maryland (95% CI, 0.01-0.08 percentage points) and 0.05 percentage points in Iowa (95% CI, 0.00-0.11 percentage points) to 0.82 percentage points (95% CI, 0.73-0.91 percentage points) in Rhode Island. The policy was also associated with an increase in immediate postpartum LARC provision among commercially paid births in 4 of 5 states. After the policy, only 38 of 366 hospitals (10%) provided more than 1% of birthing people with immediate postpartum LARC. These adopting hospitals were less likely to be Catholic (0% [0 of 31] vs 17% [41 of 245]), less likely to be rural (10% [3 of 31] vs 33% [81 of 247]), more likely to have the highest level of obstetric care (71% [22 of 31] vs 29% [65 of 223]) and be teaching hospitals (87% [27 of 31] vs 43% [106 of 246]) compared with nonadopting hospitals.Conclusions and RelevanceThis cross-sectional study’s findings suggest that Medicaid policies that reimburse immediate postpartum LARC may increase access to this service; however, policy implementation has been uneven, resulting in unequal access.

To assess the impact of COVID-19 on trends in postpartum mental health diagnoses and utilization of psychotherapy and prescription drug treatment.Data were obtained from a large, national health insurance claims database that tracks individuals longitudinally.We used interrupted time series models to examine changes in trends of postpartum mental health diagnoses before and during the COVID-19 pandemic and t-tests to examine differences in treatment.We used billing codes to identify individuals who received mental health-related diagnoses and treatment in the first 90 days after a birth hospitalization. We excluded individuals diagnosed with schizophrenia or bipolar disorder and those with an unknown payer at delivery.Compared to the pre-pandemic period, the trend in new postpartum mental health diagnoses increased significantly in the post-COVID-19 period (0.06 percentage points [95%CI 0.01, 0.11]). Over 12 months, the percentage of new diagnoses was 5.0% greater relative to what would be expected in absence of COVID-19. The percentage of diagnosed individuals who did not receive treatment increased from 50.4% to 52.7% (p = 0.003).Findings point to an urgent need to improve screening and treatment pathways for perinatal individuals in the wake of COVID-19.

Background and objectives Atrial fibrillation (AF) is common in CKD and associated with poor kidney and cardiovascular outcomes. Prediction models developed using novel methods may be useful to identify patients with CKD at highest risk of incident AF. We compared a previously published prediction model with models developed using machine learning methods in a CKD population. Design, setting, participants, & measurements We studied 2766 participants in the Chronic Renal Insufficiency Cohort study without prior AF with complete cardiac biomarker (N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T) and clinical data. We evaluated the utility of machine learning methods as well as a previously validated clinical prediction model (Cohorts for Heart and Aging Research in Genomic Epidemiology [CHARGE]-AF, which included 11 predictors, using original and re-estimated coefficients) to predict incident AF. Discriminatory ability of each model was assessed using the ten-fold cross-validated C-index; calibration was evaluated graphically and with the Gronnesby and Borgan test. Results Mean (SD) age of participants was 57 (11) years, 55% were men, 38% were Black, and mean (SD) eGFR was 45 (15) ml/min per 1.73 m2; 259 incident AF events occurred during a median of 8 years of follow-up. The CHARGE-AF prediction equation using original and re-estimated coefficients had C-indices of 0.67 (95% confidence interval, 0.64 to 0.71) and 0.67 (95% confidence interval, 0.64 to 0.70), respectively. A likelihood-based boosting model using clinical variables only had a C-index of 0.67 (95% confidence interval, 0.64 to 0.70); adding N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin T, or both biomarkers improved the C-index by 0.04, 0.01, and 0.04, respectively. In addition to N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T, the final model included age, non-Hispanic Black race/ethnicity, Hispanic race/ethnicity, cardiovascular disease, chronic obstructive pulmonary disease, myocardial infarction, peripheral vascular disease, use of angiotensin-converting enzyme inhibitor/angiotensin receptor blockers, calcium channel blockers, diuretics, height, and weight. Conclusions Using machine learning algorithms, a model that included 12 standard clinical variables and cardiac-specific biomarkers N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T had moderate discrimination for incident AF in a CKD population.

RATIONALE AND OBJECTIVE. While low estimated glomerular filtration rate (eGFR) is associated with cardiovascular disease (CVD) events and mortality, the clinical significance of variability in eGFR over time is uncertain. We aimed to evaluate the association between variability in eGFR and the risk of CVD events and all-cause mortality. STUDY DESIGN. Longitudinal analysis of clinical trial participants. SETTINGS AND PARTICIPANTS. 7,520 Systolic Blood Pressure Intervention Trial (SPRINT) participants aged ≥ 50 year with 1 or more CVD risk factors. PREDICTORS. eGFR variability, estimated by the coefficients of variation of eGFR measurements at the 6, 12, and 18-month study visits. OUTCOMES. SPRINT primary CVD composite outcome (myocardial infarction, acute coronary syndrome, stroke, heart failure, or CVD death) and all-cause mortality from month 18 to end of follow-up. ANALYTICAL APPROACH. Cox models evaluated associations between eGFR variability and CVD outcomes and all-cause mortality. Models were adjusted for demographics, randomization arm, CVD risk factors, albuminuria and month 18 eGFR. RESULTS. Mean age was 68±9 years, 65% were men, and 58% were white. The mean eGFR was 73±21 ml/min/1.73m(2) at 6 months. There were 370 CVD events and 154 deaths during a median follow-up of 2.4 years. Greater eGFR variability was associated with higher risk for all-cause mortality (hazard ratio (HR) per standard deviation (SD) greater variability, 1.29; 95% confidence interval (CI) 1.14 to 1.45) but not CVD events (HR 1.05; 95% CI 0.95 to 1.16) after adjusting for albuminuria at baseline, eGFR at month 18, and other CVD risk factors. Associations were similar when stratified by treatment arm and baseline CKD status, when accounting for concurrent systolic BP changes, use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), and diuretic medications during follow-up. LIMITATIONS. Persons with diabetes and proteinuria > 1 g/day were excluded. CONCLUSIONS. In trial participants at high risk for CVD with hypertension, greater eGFR variability was independently associated with all-cause mortality but not CVD events.

Retinoic acid exposures as well as defects in the retinoic acid-degrading enzyme CYP26B1 have teratogenic effects on both limb and craniofacial skeleton. An initial report of four individuals described a syndrome of fetal and infantile lethality with craniosynostosis and skeletal anomalies caused by homozygous pathogenic missense variants in CYP26B1. In contrast, a 22-year-old female was reported with a homozygous missense pathogenic variant in CYP26B1 with complex multisuture craniosynostosis and intellectual disability, suggesting that in some cases, biallelic pathogenic variants of CYP26B1 may be compatible with life. Here we describe four additional living individuals from two families with compound heterozygous pathogenic missense variants in CYP26B1. Structural assessment of these additional missense variants places them further from the catalytic site and supports a model consistent with milder nonlethal disease. In addition to previously reported findings of multisuture craniosynostosis, conductive hearing loss, joint contractures, long slender fingers, camptodactly, broad fingertips, and developmental delay/intellectual disability, skeletal imaging in our cases also revealed gracile long bones, gracile ribs, radioulnar synostosis, and carpal and/or tarsal fusions. These individuals broaden the phenotypic range of biallelic pathogenic variants in CYPB26B1 and most significantly clarify that mortality can range from perinatal lethality to survival into adulthood.

Despite the increasing use of Coronary Artery Calcium (CAC) scoring for cardiovascular risk stratification in asymptomatic patients, the gender differences in CAC among symptomatic patients have not been well evaluated. We analyzed patients presenting to the emergency department (ED) with chest pain suggesting possible coronary artery disease (CAD) who received coronary computed tomography angiography (CCTA). Ordinal logistic regression was used to determine the odds ratio for the association of traditional cardiovascular risk factors and CAC. Patients with a CAC score ≥ 100 were followed for cardiovascular events or changes in medical management. Our cohort included 542 individuals (263 male, 279 female). Ordinal logistic regression model showed that among traditional cardiovascular risk factors, male sex had the highest odds ratio (OR) of 3.04 (p0.001, 95% CI [2.01, 4.59]) for the presence of CAC. Also, males had more diffuse distribution of coronary atherosclerosis (p=0.01). Subgroup analysis revealed that obesity was a bigger risk factor in male patients (OR 2.16), while smoking showed the greatest effect (OR 4.27) on CAC in women. Of patients who had CAC100 with an average follow-up of 346 days, there was an increase in both aspirin and statin use, yet significant sex differences were observed especially in patients with non-obstructive lesions on CCTA. Among male patients with non-obstructive lesions, 68.2% were on aspirin and 86.4% were on statin therapy after the CCTA compared to 27.3% and 45.5% respectively in their female counterparts. In conclusion, sex not only is the most powerful predictor for higher CAC among traditional cardiovascular risk factors in symptomatic patients but also influences the contribution of various traditional risk factors to elevated CAC. Furthermore, the discovery of CAD led to the initiation of medical therapy in male patients more frequently than in female patients, even after adjusting for the degree of luminal stenosis detected on coronary CT angiography.

BACKGROUND Pediatric orthopaedic fellowship directors (FDs) have a valuable impact on the education of trainees and future leaders in the field. There is currently no research on the characteristics of pediatric orthopaedic FDs. METHODS Programs were identified using the Pediatric Orthopaedic Society of North America fellowship directory. Operative, nonoperative, and specialty programs were included. Data was collected through Qualtrics survey, e-mail, telephone, and online searches. Variables included demographics (age, sex, race/ethnicity), Hirsch index (h-index) as a measure of research productivity, graduate education, residency and fellowship training, years of hire at current institution and as FD, and leadership roles. RESULTS Fifty-five FDs were identified. The majority (49/55, 89%) were male and 77% (27/35) were Caucasian. The mean age at survey was 51.1±8.2 years. The mean h-index was 17.2. Older age correlated with higher h-index (r=0.48, P=0.0002). The average duration from fellowship graduation to FD appointment was 9.6±6.7 and 6.9±6.1 years from institutional hire. Sixteen FDs (29%) had additional graduate level degrees. Almost all (52/55, 95%) FDs completed orthopaedic surgery residencies and all graduated fellowship training. Twenty-nine percent (16/55) completed more than 1 fellowship. Most FDs (51/55, 93%) completed a fellowship in pediatric orthopaedic surgery. Ten FDs (18%) completed pediatric orthopaedic surgery fellowships that included spine-specific training. One-third of all current FDs were fellowship-trained at either Boston Children's Hospital (9/55, 16%) or Texas Scottish Rite Hospital for Children (9/55, 16%). CONCLUSIONS Pediatric orthopaedic FDs are typically early-career to mid-career when appointed, with a strong research background. Nearly a third completed additional graduate degrees or multiple fellowships. Although male dominated, there are more female FDs leading pediatric orthopaedic programs compared with adult reconstruction, trauma, and spine fellowships. As fellowships continue to grow and diversify, this research will provide a baseline to determine changes in FD leadership.

Purpose To report the long-term outcomes of patients with small, pigmented, posteriorly located choroidal melanoma undergoing primary treatment using photodynamic therapy (PDT) with verteporfin at the London Ocular Oncology Service. Design Retrospective, interventional, consecutive case series. Participants All patients undergoing primary treatment using PDT with verteporfin from April 2014 to December 2015 and followed until December 2019. Methods This is a long-term follow-up study of the same cohort of patients previously reported by our group in 2017 and 2018. Main Outcome Measures Local tumor control, visual outcomes, and metastasis-free survival. Results Twenty-six patients were included with a mean (± standard deviation) age and tumor thickness of 62 ± 14 years and 1.3 ± 0.5 mm, respectively. Tumors were posteriorly located (mean distance to optic nerve and fovea = 2.0 ± 2.2 mm and 1.6 ± 1.5 mm, respectively), and the majority were fully pigmented (73%). Overall, patients were followed for a median (interquartile range [IQR], range) of 49.5 (15.3, 7.0–66.0) months from first PDT to last follow-up. Over the course of this study, 14 of 26 (54%) have developed a local recurrence at a median of 20.0 months (20.5, 4.7–60.9 months). The most common pattern of recurrence was an isolated increase in basal dimensions (9/14; 64%). Median (IQR) final logarithm of the minimum angle of resolution visual acuity of the whole cohort was 0.2 (0.5). The only statistically significant difference in baseline and outcome characteristics between treatment failures and nonfailures was the distance to the fovea (median [IQR], 0.5 [1.3] vs. 2.5 [2.8]; P = 0.002) and final logarithm of the minimum angle of resolution visual acuity (median [IQR], 0.50 [0.80] vs. 0.00 [0.14]; P = 0.002), respectively. Conclusions Although treatment of small pigmented posterior choroidal melanoma with PDT effectively preserves visual acuity, 5-year treatment-success calculated by Kaplan–Meier analysis was only 38.4%. Recurrences after PDT tend to occur along the tumor edges, often with minimal increase in thickness. Given the substantial risk of treatment failure, primary PDT with vertepofrin is recommended in exceptional cases of choroidal melanoma, for which other treatments with greater tumor control are not a feasible option.

Although screenings for breast and colorectal cancer are widely recommended, patient screening rates vary greatly and remain below public health targets, and primary care physicians' (PCPs') counseling and referrals play critical roles in patients' use of cancer screenings. Recent adverse events may influence PCPs' decision-making, but it remains unknown whether cancer screening rates of PCPs' patients change after PCPs are exposed to new cancer diagnoses.To investigate whether PCPs' exposures to patients with new diagnoses of breast or colorectal cancer were associated with changes in screening rates for other patients subsequently visiting the affected PCPs.This cohort study used stacked difference-in-differences analyses of all-payer claims data for New Hampshire and Maine in 2009 to 2015. Participants were PCPs caring for patients. Data analysis was performed from June 2020 to May 2022.New diagnosis of a PCP's patient with breast cancer or colorectal cancer.Patients' breast and colorectal cancer screening rates within 1 year of a PCP visit.The sample included 3158 PCPs (1819 male PCPs [57.6%]) caring for 1 920 189 patients (1 073 408 female patients [55.9%]; mean [SD] age, 41.0 [21.9] years) aged 18 to 64 years. During the study period, 898 PCPs had a patient with a new diagnosis of breast cancer and 370 PCPs had a patient with a new diagnosis of colorectal cancer. In the preexposure period, 68 837 female patients (37.3% of those visiting a PCP) underwent breast cancer screening within 1 year of the visit, and 13 137 patients (10.1% of those visiting a PCP) underwent colorectal cancer screening within 1 year of the visit. For both cancer types, after exposure to a new cancer diagnosis, PCPs' cancer screening rates displayed a rapid, sustained increase. Breast cancer screening rates increased by 4.5 percentage points (95% CI, 3.0-6.1 percentage points; P .001). Colorectal cancer screening rates increased by 1.3 percentage points (95% CI, 0.3-2.2 percentage points; P = .01). Observed breast cancer screening increases were higher for male PCPs than for female PCPs (3.1 percentage points; 95% CI, 0.4-5.8 percentage points; P = .03).This study found significant, sustained increases in cancer screening rates for patients visiting PCPs recently exposed to new breast and colorectal cancer diagnoses. These findings suggest that PCPs may update practice patterns on the basis of recent patient diagnoses. Future work should assess whether salient cues to PCPs about patient diagnoses when clinically appropriate can improve screening practices.

The purpose of this study was (1) to determine how much emphasis is placed on the Personal Statement (PS) by program directors (PDs) and (2) to gain a better understanding of what factors within the PS are considered most important to PDs. An anonymous survey was distributed to PDs at allopathic orthopaedic residency programs in the United States using Survey Monkey (San Mateo, CA). Survey responses were received from 51 of 152 (34%) PDs. Forty-five (88.2%) identified as male, five (9.8%) identified as female, and one (1.9%) chose not to disclose. PDs reported the PS was of average importance, with an average score of 2.82 (range,1-4). Although the PS is still given consideration as part of the overall orthopaedic surgery residency application process, it does not play a major role in determining which applicants will be invited for an interview or how they will be ranked. (Journal of Surgical Orthopaedic Advances 31(2):090-095, 2022).

Background Direct-acting antiviral (DAA) regimens and telemedicine services are both options for treating hepatitis C virus (HCV) within the prison setting. We aimed to compare factors associated with HCV treatment success over the past decade in Israeli prisons, specifically the influence of DAAs and telemedicine. Methods We retrospectively reviewed the medical records of inmates with HCV infection in Israeli prisons from 2010 through 2020. Demographic, clinical, and laboratory data were recorded, including treatment regimens and success rates. Results A total of 273 inmates were treated; mean age 45 ± 9.36 years; 98.2% males; 63.9% with a history of drug abuse. Advanced fibrosis was documented in 42.9%. The most common genotypes were 1 (46%) followed by 3 (40.7%). Interferon-based regimens were given to 68 inmates between 2010 and 2017. DAA agents were introduced in 2016, with pan-genotype regimens being exclusively used since 2019. Telemedicine services were used in 140 patients (51.3%), starting in February 2019. The sustained viral response (SVR) rate with interferon-based therapy was 78.8% and 98.8% with DAA treatment, giving an overall SVR of 93.2%. This difference between regimens proved to be the only statistically significant predictor of treatment success. The number of prisoners being treated with DAAs increased exponentially after telemedicine was introduced. Comparable SVR rates were achieved with either in-person or telemedicine consultation. Conclusion Screening of this high-risk population and using telemedicine for treatment may be an effective strategy for the elimination of HCV from the prison population.

Risk factors for intervention in terminal ileal (TI) stricturing Crohn's disease (CD) are poorly defined. Novel and rigorous definitions for TI strictures recently became available.We aimed to describe the rates of symptoms or need for endoscopic balloon dilation (EBD) or surgery as well as risk factors of progression in a well-defined stricturing CD cohort.Consecutive adult patients with non-penetrating stricturing TI CD, as defined by centrally-read magnetic resonance enterography CONSTRICT criteria, were separated into a derivation and validation cohort. Clinical and imaging characteristics were collected following prespecified scoring conventions. Primary outcome was a composite endpoint of EBD or surgery ("intervention"). Multivariable analysis was performed.Eighty-six patients (48.8% female, median age 36 years) met selection criteria, 17.4% had prior EBD, 59.3% previously received biologics and 58.1% of strictures were anastomotic. Median follow-up was 63.4 [95% CI: 57, 68.9] months. In the derivation cohort, at 12 and 48 months, 26% and 45% of patients had intervention, respectively. Multivariable analysis showed obstructive symptoms (Hazard ratio [HR] 1.444; 95% CI 1.126-1.852), stricture duration (HR 0.974; 95% CI, 0.954-0.995) and length (HR 1.039; 95% CI, 1.011-1.069) predicted intervention. The concordance index for split-sample validation was 0.74 and 0.67, respectively. Biologics were not associated with intervention. An online risk calculator was constructed.In patients with TI stricturing CD, 26% and 45% required intervention at 1 and 4 years. Obstructive symptoms, stricture duration and length were independent and validated predictors of the need for intervention. These findings are important for clinical practice and aid in the design of future trials for CD strictures.

Advanced and metastatic estrogen receptor-positive (ER

Neoadjuvant endocrine therapy is often utilized to downstage Estrogen Receptor-positive (ER+) breast cancer prior to surgery. However, this approach is sometimes met with endocrine resistance mechanisms within the tumor. This trial examines the safety and efficacy of tamoxifen in combination with an mTORC1/2 inhibitor, TAK-228, in the neoadjuvant treatment of ER+ breast cancer. In this single-arm, open-label trial, pre- and post-menopausal women were enrolled to receive neoadjuvant tamoxifen (20 mg daily) with TAK-228 (30 mg weekly) for 16 weeks prior to surgery. Patient had tissue sampling at baseline, week 6, and week 16. The primary endpoint was change in Ki-67 from baseline to 6 weeks. The toxicity, change in tumor size, pathologic complete response rate, PEPI score, and baseline Oncotype Dx score were also assessed. Twenty-eight women were enrolled on the trial, and 25 completed the entire study course. The combination of tamoxifen and TAK-228 resulted in a significant reduction in Ki-67 from 18.3 to 15.2% (p = 0.0023). The drug was also found to be safe and tolerable. While nausea and hyperglycemia were common side effects, these were manageable. The tumor size also significantly decreased with the treatment, with a median decrease of 0.75 cm (p

Background There is significant variability in poststroke locomotor learning that is poorly understood and affects individual responses to rehabilitation interventions. Cognitive abilities relate to upper extremity motor learning in neurologically intact adults, but have not been studied in poststroke locomotor learning. Objective To understand the relationship between locomotor learning and retention and cognition after stroke. Methods Participants with chronic (>6 months) stroke participated in 3 testing sessions. During the first session, participants walked on a treadmill and learned a new walking pattern through visual feedback about their step length. During the second session, participants walked on a treadmill and 24-hour retention was assessed. Physical and cognitive tests, including the Fugl-Meyer-Lower Extremity (FM-LE), Fluid Cognition Composite Score (FCCS) from the NIH Toolbox -Cognition Battery, and Spatial Addition from the Wechsler Memory Scale-IV, were completed in the third session. Two sequential regression models were completed: one with learning and one with retention as the dependent variables. Age, physical impairment (ie, FM-LE), and cognitive measures (ie, FCCS and Spatial Addition) were the independent variables. Results Forty-nine and 34 participants were included in the learning and retention models, respectively. After accounting for age and FM-LE, cognitive measures explained a significant portion of variability in learning ( R2 = 0.17, P = .008; overall model R2 = 0.31, P = .002) and retention (Δ R2 = 0.17, P = .023; overall model R2 = 0.44, P = .002). Conclusions Cognitive abilities appear to be an important factor for understanding locomotor learning and retention after stroke. This has significant implications for incorporating locomotor learning principles into the development of personalized rehabilitation interventions after stroke.

Venous thromboembolism (VTE) has emerged as an important issue in patients with COVID-19. The purpose of this study is to identify the incidence of VTE and mortality in COVID-19 patients initially presenting to a large health system. Our retrospective study included adult patients (excluding patients presenting with obstetric/gynecologic conditions) across a multihospital health system in the New York Metropolitan Region from March 1-April 27, 2020. VTE and mortality rates within 8 h of assessment were described. In 10,871 adults with COVID-19, 118 patients (1.09%) were diagnosed with symptomatic VTE (101 pulmonary embolism, 17 deep vein thrombosis events) and 28 patients (0.26%) died during initial assessment. Among these 146 patients, 64.4% were males, 56.8% were 60 years or older, 15.1% had a BMI > 35, and 11.6% were admitted to the intensive care unit. Comorbidities included hypertension (46.6%), diabetes (24.7%), hyperlipidemia (14.4%), chronic lung disease (12.3%), coronary artery disease (11.0%), and prior VTE (7.5%). Key medications included corticosteroids (22.6%), statins (21.2%), antiplatelets (20.6%), and anticoagulants (20.6%). Highest D-Dimer was greater than six times the upper limit of normal in 51.4%. Statin and antiplatelet use were associated with decreased VTE or mortality (each p

Background Pivotal studies of approved botulinum toxin type A (BoNTA) formulations for treatment of glabellar lines have mostly included treatment-naive participants, and the impact of prior BoNTA treatment on efficacy and safety is not well documented. Objective To evaluate whether prior BoNTA treatment affects efficacy, duration of response, and tolerability for treatment of glabellar lines. Methods Adults with moderate or severe glabellar lines treated with DaxibotulinumtoxinA for Injection (DAXI) or placebo from the randomized, double-blind SAKURA 1/2 trials and the open-label SAKURA 3 safety study were analyzed by prior BoNTA treatment status. Efficacy was evaluated using investigator and participant assessments. Results In this analysis, 609 participants (52.2% BoNTA-experienced) from the SAKURA 1/2 trials and 2,380 (38.0% BoNTA-experienced) from the SAKURA 3 study were evaluated. Proportion of participants with none or mild glabellar lines and duration of response were similar between the BoNTA-naive and BoNTA-experienced cohorts in both the DAXI and placebo groups. The incidence of adverse events was also comparable regardless of prior BoNTA treatment status. Conclusion Efficacy and tolerability were similar with DAXI and placebo regardless of prior BoNTA treatment. Assuming an appropriate washout is observed, future BoNTA trials should enroll both treatment-experienced and treatment-naive participants to reflect clinical practice.

Background Pediatric sickle cell disease (SCD) management can result in considerable caregiver distress. Parents of youth with chronic SCD pain may face the additional challenge of managing children’s chronic pain and chronic illness. This study examined associations between parent psychological distress and child functioning and the moderating role of chronic pain among youth with SCD. Methods Youth presenting to pediatric outpatient comprehensive SCD clinics and their primary caregivers completed a battery of questionnaires. Parents reported on parenting stress, parent mental and physical health, and family functioning. Children completed measures of pain characteristics, depressive symptoms, catastrophic thinking, functional disability, and quality of life. Results Patients (N = 73, Mage = 14.2 years, 57% female) and their caregivers (Mage = 41.1 years, 88% mothers, 88% Black) participated. Worse parent functioning was associated with worse child pain, functioning, quality of life, and depressive symptoms. Beyond the effects of SCD, chronic SCD pain magnified the negative associations between parenting stress frequency and child quality of life, parent physical health and child quality of life, and parent depressive symptoms and child depressive symptoms. Conclusions Chronic pain may exacerbate the relations between parent and child functioning beyond the effects of SCD alone. The management of both SCD and chronic pain may present additional challenges for parents that limit their psychosocial functioning. Family-focused interventions to support parents and youth with chronic SCD pain are warranted to optimize health outcomes.

Contains fulltext : 245825.pdf (Publisher’s version ) (Closed access) BACKGROUND: Phaeochromocytoma or paraganglioma (collectively known as PPGL) in pregnant women can lead to severe complications and death due to associated catecholamine excess. We aimed to identify factors associated with maternal and fetal outcomes in women with PPGL during pregnancy. METHODS: We did a multicentre, retrospective study of patients with PPGL and pregnancy between Jan 1, 1980, and Dec 31, 2019, in the International Pheochromocytoma and Pregnancy Registry and a systematic review of studies published between Jan 1, 2005, and Dec 27, 2019 reporting on at least five cases. The inclusion criteria were pregnancy after 1980 and PPGL before or during pregnancy or within 12 months post partum. Eligible patients from the retrospective study and systematic review were included in the analysis. Outcomes of interest were maternal or fetal death and maternal severe cardiovascular complications of catecholamine excess. Potential variables associated with these outcomes were evaluated by logistic regression. FINDINGS: The systematic review identified seven studies (reporting on 63 pregnancies in 55 patients) that met the eligibility criteria and were of adequate quality. A further 197 pregnancies in 186 patients were identified in the International Pheochromocytoma and Pregnancy Registry. After excluding 11 pregnancies due to potential overlap, the final cohort included 249 pregnancies in 232 patients with PPGL. The diagnosis of PPGL was made before pregnancy in 37 (15%) pregnancies, during pregnancy in 134 (54%), and after delivery in 78 (31%). Of 144 patients evaluated for genetic predisposition for phaeochromocytoma, 95 (66%) were positive. Unrecognised PPGL during pregnancy (odds ratio 27·0; 95% CI 3·5-3473·1), abdominal or pelvic tumour location (11·3; 1·5-1440·5), and catecholamine excess at least ten-times the upper limit of the normal range (4·7; 1·8-13·8) were associated with adverse outcomes. For patients diagnosed during pregnancy, α-adrenergic blockade therapy was associated with fewer adverse outcomes (3·6; 1·1-13·2 for no α-adrenergic blockade vs α-adrenergic blockade), whereas surgery during pregnancy was not associated with better outcomes (0·9; 0·3-3·9 for no surgery vs surgery). INTERPRETATION: Unrecognised and untreated PPGL was associated with a substantially higher risk of either maternal or fetal complications. Appropriate case detection and counselling for premenopausal women at risk for PPGL could prevent adverse pregnancy-related outcomes. FUNDING: US National Institutes of Health.

Lay theory interventions instill situation-general ways of thinking, often using short reading and writing exercises, and they have led to lasting changes in behavior and performance in a wide variety of policy domains. Do they work in all contexts? We suggest that lay theory intervention effects depend on psychological affordances, which are defined as cues that allow individuals to view a lay theory as legitimate and adaptive in that context. The present research directly and experimentally tested this hypothesis using the example of a "purpose for learning" lay theory intervention, which taught the lay theory that school is a place to develop skills that allow one to make progress toward self-transcendent aims. A double-blind 2 (student purpose intervention) × 2 (purpose-affording note) field experiment was conducted in a relatively low-performing public middle school in the United States. Students first received a web-based purpose for learning lay theory intervention (or a control activity), and 2 weeks later attended a class in which an assignment was accompanied by a purpose-affording note that was hand-written by a teacher (or a control note). Results showed that the purpose lay theory intervention increased performance on an English class writing assignment, but only when it was accompanied by a purpose-affording note. Exploratory analyses revealed that the effects of the manipulations were apparent among students who were at greater risk for poor performance in the class: nonnative English-speaking students. Thus short, online lay theory interventions may reduce performance gaps, provided that the contexts afford the opportunity for the proffered lay theory to seem legitimate and adaptive. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Objective: Sporadic Creutzfeldt–Jakob disease (sCJD) comprises several subtypes as defined by genetic and prion protein characteristics, which are associated with distinct clinical and pathological phenotypes. To date, no clinical test can reliably diagnose the subtype. We established two procedures for the antemortem diagnosis of sCJD subtype using diffusion magnetic resonance imaging (MRI). Methods: MRI of 1,458 patients referred to the National Prion Disease Pathology Surveillance Center were collected through its consultation service. One neuroradiologist blind to the diagnosis scored 12 brain regions and generated a lesion profile for each MRI scan. We selected 487 patients with autopsy-confirmed diagnosis of “pure” sCJD subtype and at least one positive diffusion MRI examination. We designed and tested two data-driven procedures for subtype diagnosis: the first procedure—prion subtype classification algorithm with MRI (PriSCA_MRI)—uses only MRI examinations; the second—PriSCA_MRI + Gen—includes knowledge of the prion protein codon 129 genotype, a major determinant of sCJD subtypes. Both procedures were tested on the first MRI and the last MRI follow-up. Results: PriSCA_MRI classified the 3 most prevalent subtypes with 82% accuracy. PriSCA_MRI + Gen raised the accuracy to 89% and identified all subtypes. Individually, the 2 most prevalent sCJD subtypes, MM1 and VV2, were diagnosed with sensitivities up to 95 and 97%, respectively. The performances of both procedures did not change in 168 patients with longitudinal MRI studies when the last examination was used. Interpretation: This study provides the first practical algorithms for antemortem diagnosis of sCJD subtypes. MRI diagnosis of subtype is likely to be attainable at early disease stages to prognosticate clinical course and design future therapeutic trials. ANN NEUROL 2021;89:560–572.

Background Patients with chronic kidney disease (CKD) face risks of not only end-stage kidney disease (ESKD), cardiovascular disease (CVD) and death, but also decline in kidney function, quality of life (QOL) and mental and physical well-being. This study describes the multidimensional trajectories of CKD using clinical events, kidney function and patient-reported outcome measures (PROMs). We hypothesized that more advanced CKD stages would associate with more rapid decline in each outcome. Methods Among 3939 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study, we evaluated multidimensional disease trajectories by G- and A-stages of enrollment estimated glomerular filtration rate (eGFR) and albuminuria, respectively. These trajectories included clinical events (ESKD, CVD, heart failure and death), eGFR decline and PROMs [kidney disease QOL (KDQOL) burden, effects and symptoms questionnaires, as well as the 12-item short form mental and physical component summaries]. We also evaluated a group-based multitrajectory model to group participants on the basis of longitudinal PROMs and compared group assignments by enrollment G- and A-stage. Results The mean participant age was 58 years, 45% were women, mean baseline eGFR was 44 mL/min/1.73 m2 and median urine albumin:creatinine ratio was 52 mg/g. The incidence of all clinical events was greater and eGFR decline was faster with more advanced G- and A-stages. While baseline KDQOL and physical component measures were lower with more advanced G- and A-stage of CKD, changes in PROMs were inconsistently related to the baseline CKD stage. Groups formed on PROM trajectories were fairly distinct from existing CKD staging (observed agreement 60.6%) and were associated with the risk of ESKD, CVD, heart failure and death. Conclusions More advanced baseline CKD stage was associated with a higher risk of clinical events and faster eGFR decline, and was only weakly related to changes in patient-reported metrics over time.

Objectives Although glioblastoma (GBM) is rare in the pediatric population, it is the most common cause of death among children with central nervous system neoplasms. Recent molecular profiling of these neoplasms has demonstrated distinct differences in comparison to their adult counterparts. Moreover, many pediatric GBMs occur within the context of cancer predisposition syndromes, such as constitutional mismatch repair deficiency syndrome (CMMRD). Children with CMMRD who develop GBM exhibit a high tumor mutational burden and may benefit from treatment with immune checkpoint inhibitors. Methods We performed next-generation sequencing and immunohistochemistry for mismatch repair proteins in our cohort of pediatric and adult GBMs to further characterize the molecular profiles of these groups. Results We examined a total of 11 pediatric and 11 adult GBMs. Pediatric patients had a higher number of alterations compared to their adult counterparts. They also had a higher frequency of alterations in the mismatch repair genes, which can be detected by immunohistochemistry (IHC). We also identified one pediatric patient with CMMRD syndrome. Conclusions Our study highlighted the distinct molecular differences between pediatric and adult GBM. We also demonstrated that pediatric patients have a higher frequency of alterations in the mismatch repair genes, which may render them susceptible to treatment with immune checkpoint inhibitors. These alterations can be detected using routine IHC and should be performed on all pediatric GBM.

Supplemental Digital Content is Available in the Text., BACKGROUND Real-world re-treatment intervals for botulinum toxins vary, but most subjects receive treatment less frequently than the manufacturer-recommended minimum intervals. In subjects receiving treatment with AbobotulinumtoxinA (ABO) less frequently, high levels of satisfaction and psychosocial improvements in well-being, self-confidence, and quality of life are observed. OBJECTIVE To evaluate subject satisfaction with a twice yearly re-treatment schedule. METHODS AND MATERIALS This open-label, multicenter, interventional study evaluated subject satisfaction following injections of ABO 50 U in the glabellar lines at baseline and 6 months. The primary end point was subject satisfaction at 12 months. Secondary endpoints included subject satisfaction, FACE-Q scales, and glabellar line severity scale (GLSS). RESULTS Ninety-five percent of the 120 subjects were “highly satisfied” or “satisfied” with their treatment outcomes at 12 months. FACE-Q total scores suggested that subjects were less bothered by glabellar lines and felt better about their facial appearance with each treatment versus baseline. Approximately half of subjects had ≥1-grade improvement from baseline in GLSS at 12 months. Median onset of effect was 2 days. CONCLUSION The majority of subjects (95%) were satisfied with ABO treatment every 6 months; results were supported by high subject satisfaction, long duration, rapid onset, natural-looking results, and overall psychological wellness and safety.

The Women in Gerontology Legacy (WIGL) Project involved interviewing 46 older women gerontologists between 2014 and 2015. The current study focuses on the WIGL interview questions regarding the interactions between participants’ experiences as gerontologists and their own aging. Emergent themes focus on the direction of influence: professional lives influencing personal lives, personal lives informing professional lives and mutuality between personal and professional lives. Thematic findings expand our current understanding of how professional knowledge and experiences contribute to personal aging experiences and the role personal aging experiences can have on the professional lives of women gerontologists. There is a potential for disconnect to occur between our personal experiences and the experiences of others. The current study contributes to our understanding of when and how this occurs, so we can then ensure our messages fall on receptive ears by overcoming the natural tendency to distort or ignore messages that may create anxiety.

Orthopaedic surgery is one of the most competitive specialties in the residency match. The personal statement (PS) is one component of the application. The significance of the PS to orthopaedic surgery residency applicants is unknown. This study evaluates applicant perceptions of the PS. Applicants to two separate United States orthopaedic residency programs for the 2019-2020 cycle were invited to participate. Survey was distributed via email. Twenty-one percent (204/978) of applicants completed the survey. Most were men (157/204, 77%), and most (125/204, 61%) spent up to 15 hours writing their PS. Many [79.4% (162/204)] believed the PS should continue to be included in the application. Women always edited their PS, while 7.0% (11/ 157) of men did not use any editors. Applicants believe the PS is valuable. The PS is time consuming but allows applicants to communicate details that otherwise may not be included in their application. (Journal of Surgical Orthopaedic Advances 31(1):034-041, 2022).

BackgroundLoss of arm function is common after stroke. Robot-assisted training may improve arm outcomes.ObjectiveThe objectives were to determine the clinical effectiveness and cost-effectiveness of robot-assisted training, compared with an enhanced upper limb therapy programme and with usual care.DesignThis was a pragmatic, observer-blind, multicentre randomised controlled trial with embedded health economic and process evaluations.SettingThe trial was set in four NHS trial centres.ParticipantsPatients with moderate or severe upper limb functional limitation, between 1 week and 5 years following first stroke, were recruited.InterventionsRobot-assisted training using the Massachusetts Institute of Technology-Manus robotic gym system (InMotion commercial version, Interactive Motion Technologies, Inc., Watertown, MA, USA), an enhanced upper limb therapy programme comprising repetitive functional task practice, and usual care.Main outcome measuresThe primary outcome was upper limb functional recovery ‘success’ (assessed using the Action Research Arm Test) at 3 months. Secondary outcomes at 3 and 6 months were the Action Research Arm Test results, upper limb impairment (measured using the Fugl-Meyer Assessment), activities of daily living (measured using the Barthel Activities of Daily Living Index), quality of life (measured using the Stroke Impact Scale), resource use costs and quality-adjusted life-years.ResultsA total of 770 participants were randomised (robot-assisted training,n = 257; enhanced upper limb therapy,n = 259; usual care,n = 254). Upper limb functional recovery ‘success’ was achieved in the robot-assisted training [103/232 (44%)], enhanced upper limb therapy [118/234 (50%)] and usual care groups [85/203 (42%)]. These differences were not statistically significant; the adjusted odds ratios were as follows: robot-assisted training versus usual care, 1.2 (98.33% confidence interval 0.7 to 2.0); enhanced upper limb therapy versus usual care, 1.5 (98.33% confidence interval 0.9 to 2.5); and robot-assisted training versus enhanced upper limb therapy, 0.8 (98.33% confidence interval 0.5 to 1.3). The robot-assisted training group had less upper limb impairment (as measured by the Fugl-Meyer Assessment motor subscale) than the usual care group at 3 and 6 months. The enhanced upper limb therapy group had less upper limb impairment (as measured by the Fugl-Meyer Assessment motor subscale), better mobility (as measured by the Stroke Impact Scale mobility domain) and better performance in activities of daily living (as measured by the Stroke Impact Scale activities of daily living domain) than the usual care group, at 3 months. The robot-assisted training group performed less well in activities of daily living (as measured by the Stroke Impact Scale activities of daily living domain) than the enhanced upper limb therapy group at 3 months. No other differences were clinically important and statistically significant. Participants found the robot-assisted training and the enhanced upper limb therapy group programmes acceptable. Neither intervention, as provided in this trial, was cost-effective at current National Institute for Health and Care Excellence willingness-to-pay thresholds for a quality-adjusted life-year.ConclusionsRobot-assisted training did not improve upper limb function compared with usual care. Although robot-assisted training improved upper limb impairment, this did not translate into improvements in other outcomes. Enhanced upper limb therapy resulted in potentially important improvements on upper limb impairment, in performance of activities of daily living, and in mobility. Neither intervention was cost-effective.Future workFurther research is needed to find ways to translate the improvements in upper limb impairment seen with robot-assisted training into improvements in upper limb function and activities of daily living. Innovations to make rehabilitation programmes more cost-effective are required.LimitationsPragmatic inclusion criteria led to the recruitment of some participants with little prospect of recovery. The attrition rate was higher in the usual care group than in the robot-assisted training or enhanced upper limb therapy groups, and differential attrition is a potential source of bias. Obtaining accurate information about the usual care that participants were receiving was a challenge.Trial registrationCurrent Controlled Trials ISRCTN69371850.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 24, No. 54. See the NIHR Journals Library website for further project information.

Purpose The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and the Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP) are scoring systems to predict metastatic potential in pheochromocytomas (PCC) and paragangliomas (PGLs). The goal of this study is to assess PASS and GAPP as metastatic predictors and to correlate with survival outcomes. Methods The cohort included PCC/PGL with ≥5 years of follow-up or known metastases. Surgical pathology slides were rereviewed. PASS and GAPP scores were assigned. Univariable and multivariable logistic regression, Kaplan–Meier survival analysis, and Cox proportional hazards were performed to assess recurrence-free survival (RFS) and disease-specific survival (DSS). Results From 143 subjects, 106 tumors were PCC and 37 were PGL. Metastases developed in 24%. The median PASS score was 6.5 (interquartile range [IQR]: 4.0-8.0) and median GAPP score was 3.0 (IQR: 2.0-4.0). Interrater reliability was low–moderate for PASS (intraclass correlation coefficient [ICC]: 0.6082) and good for GAPP (ICC 0.7921). Older age (OR: 0.969, P = .0170) was associated with longer RFS. SDHB germline pathogenic variant (OR: 8.205, P = .0049), extra-adrenal tumor (OR: 6.357, P Conclusion Higher GAPP scores were associated with aggressive PCC/PGL. PASS score was not associated with metastases and demonstrated significant interobserver variability. Scoring systems for predicting metastatic PCC/PGL may be improved by incorporation of histopathology, clinical data, and germline and somatic tumor markers.

Significance Political polarization increasingly threatens democratic institutions. The belief that “my side” sees the world objectively while the “other side” sees it through the lens of its biases contributes to this political polarization and accompanying animus and distrust. This conviction, known as the “objectivity illusion,” was strong and persistent among Trump and Clinton supporters in the weeks before the 2016 presidential election. We show that the objectivity illusion predicts subsequent bias and polarization, including heightened partisanship over the presidential debates. A follow-up study showed that both groups impugned the objectivity of a putative blog author supporting the opposition candidate and saw supporters of that opposing candidate as evil., Two studies conducted during the 2016 presidential campaign examined the dynamics of the objectivity illusion, the belief that the views of “my side” are objective while the views of the opposing side are the product of bias. In the first, a three-stage longitudinal study spanning the presidential debates, supporters of the two candidates exhibited a large and generally symmetrical tendency to rate supporters of the candidate they personally favored as more influenced by appropriate (i.e., “normative”) considerations, and less influenced by various sources of bias than supporters of the opposing candidate. This study broke new ground by demonstrating that the degree to which partisans displayed the objectivity illusion predicted subsequent bias in their perception of debate performance and polarization in their political attitudes over time, as well as closed-mindedness and antipathy toward political adversaries. These associations, furthermore, remained significant even after controlling for baseline levels of partisanship. A second study conducted 2 d before the election showed similar perceptions of objectivity versus bias in ratings of blog authors favoring the candidate participants personally supported or opposed. These ratings were again associated with polarization and, additionally, with the willingness to characterize supporters of the opposing candidate as evil and likely to commit acts of terrorism. At a time of particular political division and distrust in America, these findings point to the exacerbating role played by the illusion of objectivity.

Supplemental Digital Content is Available in the Text., BACKGROUND DaxibotulinumtoxinA for Injection (DAXI) is botulinum toxin Type A formulated with a novel peptide excipient. Two pivotal, single-treatment, placebo-controlled trials demonstrated efficacy and safety for moderate or severe glabellar lines. OBJECTIVE To further evaluate DAXI in a large, open-label, repeat-treatment study. METHODS Subjects (n = 2,691) were enrolled from the preceding pivotal trials or de novo and received 40U DAXI. Those who received repeat treatments could be retreated when they returned to baseline on the Investigator Global Assessment–Frown Wrinkle Severity (IGA-FWS) and Patient FWS (PFWS) scales at/after 12 weeks and up to 36 weeks after treatment. RESULTS High (>96%) response rates (none or mild severity) on the IGA-FWS scale were seen after each of the 3 treatments, with peak response between Weeks 2 to 4. At Week 24, ≥32% had a response of none or mild severity. Peak response rates of ≥92% were observed at Weeks 2 to 4 on the PFWS scale. The median duration for return to moderate or severe severity was 24 weeks. The safety profile was favorable and consistent with previous trials. CONCLUSION DaxibotulinumtoxinA for Injection efficacy was highly consistent across treatment cycles. These results confirm the previously observed efficacy rates and duration of response.

There is minimal information on coronavirus disease 2019 (COVID‐19) in immunocompromised individuals. We have studied 10 patients treated at 12 adult care hospitals. Ten kidney transplant recipients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) by polymerase chain reaction, and 9 were admitted. The median age was 57 (interquartile range [IQR] 47‐67), 60% were male, 40% Caucasian, and 30% Black/African American. Median time from transplant to COVID‐19 testing was 2822 days (IQR 1272‐4592). The most common symptom was fever, followed by cough, myalgia, chills, and fatigue. The most common chest X‐ray and computed tomography abnormality was multifocal patchy opacities. Three patients had no abnormal findings. Leukopenia was seen in 20% of patients, and allograft function was stable in 50% of patients. Nine patients were on tacrolimus and a mycophenolic antimetabolite, and 70% were on prednisone. Hospitalized patients had their antimetabolite agent stopped. All hospitalized patients received hydroxychloroquine and azithromycin. Three patients died (30%), and 5 (50%) developed acute kidney injury. Kidney transplant recipients infected with COVID‐19 should be monitored closely in the setting of lowered immunosuppression. Most individuals required hospitalization and presenting symptoms were similar to those of nontransplant individuals.

Sporadic Creutzfeldt–Jakob disease (sCJD) is a transmissible brain proteinopathy. Five main clinicopathological subtypes (sCJD-MM(V)1, -MM(V)2C, -MV2K, -VV1, and -VV2) are currently distinguished. Histopathological evidence suggests that the localisation of prion aggregates and spongiform lesions varies among subtypes. Establishing whether there is an initial site with detectable imaging abnormalities (epicentre) and an order of lesion propagation would be informative for disease early diagnosis, patient staging, management and recruitment in clinical trials. Diffusion magnetic resonance imaging (MRI) is the most-used and most-sensitive test to detect spongiform degeneration. This study was designed to identify, in vivo and for the first time, subtype-dependent epicentre and lesion propagation in the brain using diffusion-weighted images (DWI), in the largest known cross-sectional dataset of autopsy-proven subjects with sCJD. We estimate lesion propagation by cross-sectional DWI using event-based modelling, a well-established data-driven technique. DWI abnormalities of 594 autopsy-diagnosed subjects (448 patients with sCJD) were scored in 12 brain regions by 1 neuroradiologist blind to the diagnosis. We used the event-based model to reconstruct sequential orderings of lesion propagation in each of five pure subtypes. Follow-up data from 151 patients validated the estimated sequences. Results showed that epicentre and ordering of lesion propagation are subtype specific. The two most common subtypes (-MM1 and -VV2) showed opposite ordering of DWI abnormality appearance: from the neocortex to subcortical regions, and vice versa, respectively. The precuneus was the most likely epicentre also in -MM2 and -VV1 although at variance with -MM1, abnormal signal was also detected early in cingulate and insular cortices. The caudal-rostral sequence of lesion propagation that characterises -VV2 was replicated in -MV2K. Combined, these data-driven models provide unprecedented dynamic insights into subtype-specific epicentre at onset and propagation of the pathologic process, which may also enhance early diagnosis and enable disease staging in sCJD.

Introduction There are no effective treatments for gliomas after progression on radiation, temozolomide, and bevacizumab. Microglia activation may be involved in radiation resistance and can be inhibited by the brain penetrating antibiotic minocycline. In this phase 1 trial, we examined the safety and effect on survival, symptom burden, and neurocognitive function of reirradiation, minocycline, and bevacizumab. Methods The trial used a 3 + 3 design for dose escalation followed by a ten person dose expansion. Patients received reirradiation with dosing based on radiation oncologist judgment, bevacizumab 10 mg/kg IV every two weeks, and oral minocycline twice a day. Symptom burden was measured using MDASI-BT. Neurocognitive function was measured using the COGSTATE battery. Results The maximum tolerated dose of minocycline was 400 mg twice a day with no unexpected toxicities. The PFS3 was 64.6%, and median overall survival was 6.4 months. Symptom burden and neurocognitive function did not decline in the interval between treatment completion and tumor progression. Conclusions Minocycline 400 mg orally twice a day with bevacizumab and reirradiation is well tolerated by physician and patient reported outcomes in people with gliomas that progress on bevacizumab.

Background Data on influenza burden in risk groups for severe influenza are important to guide targeted influenza immunization, especially in resource limited settings. However, this information is limited overall and in particular in low- and middle-income countries. We sought to assess the mean annual national burden of medically and non-medically attended influenza-associated mild, severe-non-fatal and fatal illness among potential target groups for influenza immunization in South Africa during 2013–2015. Methods We used published mean national annual estimates of mild, severe-non-fatal, and fatal influenza-associated illness in South Africa during 2013–2015 and estimated the number of such illnesses occurring among the following risk groups: (i) children aged 6–59 months; (ii) individuals aged 5–64 years with HIV, and/or pulmonary tuberculosis (PTB), and/or selected underlying medical conditions (UMC); (iii) pregnant women; and (iv) individuals aged ≥65 years. We also estimated the number of individuals among the same risk groups in the population. Results During 2013–2015, individuals in the selected risk groups accounted for 45.3% (24,569,328/54,086,144) of the population and 43.5% (4,614,763/10,598,138), 86.8% (111,245/128,173) and 94.5% (10,903/11,536) of the mean annual estimated number of influenza-associated mild, severe-non-fatal and fatal illness episodes, respectively. The rates of influenza-associated illness were highest in children aged 6–59 months (23,983 per 100,000 population) for mild illness, in pregnant women (930 per 100,000 population) for severe-non-fatal illness and in individuals aged ≥65 years (138 per 100,000 population) for fatal illness. Conclusion Influenza immunization of the selected risk groups has the potential to prevent a substantial number of influenza-associated severe illness. Nonetheless, because of the high number of individuals at risk, South Africa, due to financial resources constrains, may need to further prioritize interventions among risk populations. Cost-burden and cost-effectiveness estimates may assist with further prioritization.

Primary axillary hyperhidrosis has limited noninvasive, effective, and well-tolerated treatment options.To evaluate the topical treatment of axillary hyperhidrosis with the novel anticholinergic sofpironium bromide.A phase II, multicenter, randomized, controlled, double-blinded study. Participants were randomized to 1 of 3 dosages or vehicle, with daily treatment for 42 days. Coprimary end points were the percentage of participants exhibiting ≥1-point improvement in the Hyperhidrosis Disease Severity Measure-Axillary (HDSM-Ax) score by logistic regression, and change in HDSM-Ax as a continuous measure by analysis of covariance. Pair-wise comparisons were 1-sided with α = 0.10.At the end of therapy, 70%, 79%, 76%, and 54% of participants in the 5%, 10%, 15%, and vehicle groups exhibited ≥1-point improvement in HDSM-Ax (P .05). Least-square mean (SE) changes in HDSM-Ax were -2.02 (0.14), -2.09 (0.14), 2.10 (0.14), and -1.30 (0.14) (all P ≤ .0001). Most treatment-related adverse events were mild or moderate.Not powered to detect changes in gravimetric sweat production.Sofpironium bromide gel produced meaningful reductions in hyperhidrosis severity and had an acceptable safety profile.

Significance Modern life and work involve grappling with many novel challenging tasks. What makes some people more strategic, and hence more effective, as they approach these tasks? This research introduces and tests a psychological construct—a “strategic mindset”—which involves asking oneself strategy-eliciting questions, such as “What can I do to help myself?” or “Is there a way to do this even better?” in the face of challenges or insufficient progress. A strategic mindset uniquely predicts how much people report actively using strategies and, in turn, how effective they are at pursuing goals across life domains. The findings suggest that being strategic entails more than just having specific strategic skills—it appears to also entail an orientation toward accessing and employing them., Many attractive jobs in today’s world require people to take on new challenges and figure out how to master them. As with any challenging goal, this involves systematic strategy use. Here we ask: Why are some people more likely to take a strategic stance toward their goals, and can this tendency be cultivated? To address these questions, we introduce the idea of a domain-general “strategic mindset.” This mindset involves asking oneself strategy-eliciting questions, such as “What can I do to help myself?”, “How else can I do this?”, or “Is there a way to do this even better?”, in the face of challenges or insufficient progress. In three studies (n = 864), people who scored higher on (or were primed with) a strategic mindset reported using more metacognitive strategies; in turn, they obtained higher college grade point averages (GPAs) (Study 1); reported greater progress toward their professional, educational, health, and fitness goals (Study 2); and responded to a challenging timed laboratory task by practicing it more and performing it faster (Study 3). We differentiated a strategic mindset from general self-efficacy, self-control, grit, and growth mindsets and showed that it explained unique variance in people’s use of metacognitive strategies. These findings suggest that being strategic entails more than just having specific metacognitive skills—it appears to also entail an orientation toward seeking and employing them.

Retrospective case series. To describe how pediatric patients with spinal and pelvic osteomyelitis are diagnosed and treated and assess the diagnostic value of magnetic resonance imaging (MRI), needle aspiration biopsy (NAB), and blood cultures in this population. Spinal and pelvic osteomyelitis de novo are uncommon in children and minimal literature exists on the subject. Research has shown that NAB and blood cultures have variable diagnostic yield in adult native osteomyelitis. At our institution, there is no standard protocol for diagnosing and treating pediatric spinal and pelvic osteomyelitis de novo. All diagnoses of spinal and pelvic osteomyelitis at a pediatric tertiary care center from 2003 to 2017 were reviewed. Patients aged 0–21 at diagnosis were included. Patients with osteomyelitis resulting from prior spinal operations, wounds, or infections and those with chronic recurrent multifocal osteomyelitis were eliminated. All eligible patients’ diagnoses were confirmed by MRI. 29 patients (18 men, 11 women) met the inclusion criteria. The median age at diagnosis was 11 years old (range 1–18). More than half of all cases (17/29, 59%) affected the lumbar spine. The most common symptoms were back pain (20/29, 69%), fever (18/29, 62%), hip pain (11/29, 38%), and leg pain (8/29, 28%). The majority of NABs and blood cultures performed were negative, but of the positive tests Staphylococcus aureus was the most prevalent bacteria. 86% (25/29) had an MRI before a diagnosis was made and 72% (13/18) had an NAB performed post-diagnosis. MRI is a popular and helpful tool in diagnosing spinal osteomyelitis de novo. NAB cultures are often negative but can be useful in determining antibiotic treatment. Level IV.

BACKGROUND: Macroglossia, a cardinal feature of the (epi)genetic disorder Beckwith-Wiedemann syndrome, is associated with obstructive sleep apnea, speech and/or feeding difficulties, and dental or jaw malalignment. These sequelae may be treated and/or prevented with tongue reduction surgery; the authors sought to determine whether certain Beckwith-Wiedemann syndrome patients may benefit from early surgical intervention before age 12 months. METHODS: The authors conducted a retrospective review of patients with Beckwith-Wiedemann syndrome who underwent tongue reduction from 2014 to 2019. The authors assessed primary outcomes of change in obstructive sleep apnea by polysomnography, respiratory support required, and feeding route before and after tongue reduction, and reviewed postoperative complications and the need for repeated tongue reduction. RESULTS: Of the 36 patients included, the median age at tongue reduction was 9.5 months (interquartile range, 3.8 to 22.8 months). For those with severe obstructive sleep apnea, there was a significant reduction in the obstructive apnea hypopnea index from 30.9 ± 21.8 per hour to 10.0 ± 18.3 per hour (p = 0.019) and improvement in nadir oxyhemoglobin saturation from 72 ± 10 percent to 83 ± 6 percent (p = 0.008). Although there was no significant change in overall supplemental feeding tube or respiratory support, there were specific patients who experienced clinically meaningful improvement. Of note, these positive outcomes applied equally to those who underwent surgery at a younger age (

Pregnancy-associated pulmonary embolism is one of the leading causes of maternal mortality. Diagnosis of pulmonary embolism in pregnancy is challenging, with symptoms of pulmonary embolism mimicking those of pregnancy. Several key components such as clinical prediction tools, risk stratification, laboratory tests, and imaging widely used for diagnosis of pulmonary embolism in the non-pregnant population show limitations for diagnosis in pregnancy. Further, because of the difficulty of studying pregnant patients, high-quality research evaluating the performance of these diagnostic components in pregnancy is scarce. Seven international medical society guidelines present clinical diagnostic pathways for evaluation of pulmonary embolism in pregnancy that show conflicting recommendations on the use of these diagnostic components. This Review assesses all key components of diagnostic clinical pathways recommended by guidelines for evaluation of pulmonary embolism in pregnancy, reviews current evidence, compares the guideline recommendations with respect to each key component, and provides our preferred diagnostic pathway. It provides the guidelines and available data needed for informed decision making to diagnose pulmonary embolism in pregnancy.

Background As treatments, management strategies, and the role of advanced practice providers (APPs) have evolved in recent years, the Crohn’s & Colitis Foundation sought to understand the educational and resource needs of clinicians caring for patients with inflammatory bowel diseases (IBDs). The aim of this study was to describe the self-identified IBD knowledge and resource gaps of clinicians to inform the development of future programming. Methods A survey containing 19 questions created by the foundation’s Professional Education Committee, a subset of its National Scientific Advisory Committee, was conducted from September 7, 2018 to October 15, 2018. Responses were included from providers if they were currently seeing any IBD patients in a clinical setting. The foundation distributed the survey by email and various social media channels to encourage a diverse response. The survey included questions on comfort levels around diagnosis, treatment, and management of patients with IBD, in addition to preferences and utilization of educational resources. The × 2 test was used to evaluate significant differences among respondents in the various domains surveyed. Results There were 197 eligible responses, of which 75% were from MD/Dos, followed by 25% APN/PA/RN/MSN/PhD/other; and 70% of respondents provide care for adult patients. The amount of time in practice was divided evenly among respondents. Fifty-seven percent of respondents practice in an academic/university setting, and approximately 75% indicated that ≥21% of their practice consisted of patients with IBD. Forty-four percent and 46% of respondents reported access to IBD based mental health providers and social workers in their practice, respectively. Seventy-two percent reported access to radiologists, 69% had access to dietitians, and 62% had access to advance practice providers. The areas of greatest educational need were prescribing medical cannabis (if approved locally) for pain management (62%); caring for patients with prior malignancy (35%); caring for pregnant patients and family planning (33%); caring for elderly patients (30%); and therapy decisions, including use of JAK inhibitors (29%), drug holidays (25%), and use of biosimilars (24%). More than 50% of respondents stated they do not participate in shared decision-making, citing time as the most common limiting factor. The majority of providers cited live education as their preferred learning format, and they wish to earn continuing medical education (CME) hours. Conclusion This survey helped identify current IBD educational needs in our professional community. With a rapidly changing treatment landscape and an increase in the diversity of providers delivering care, additional opportunities to keep abreast of practice changes are critical to providing comprehensive, quality care in IBD. Our survey demonstrated that shared decision-making is underutilized in practice due to a need for resources that aid in its efficient integration into practice. Based on our results, a focus on creating live learning opportunities that offer CME are needed in the areas of therapeutic decision-making and treating IBD in special subsets (eg, prior malignancy, pregnancy, elderly).