Nearly 1.2 million children with disabilities received federally administered Supplemental Security Income (SSI) payments in 2017. Based on a robust review of research and evaluation evidence and ...microsimulations, The National Academies of Sciences, Engineering, and Medicine committee identified modifications to SSI (ie, increasing the federal SSI benefit maximum by one-third or two-thirds) as 1 of 10 strategies that could reduce the US child poverty rate, improving child health and well-being on a population level.
Describing the availability and amount of SSI and State Supplementary Payment (SSP) program benefits to support families of children with disabilities may be a first step toward evaluating The National Academies of Sciences, Engineering, and Medicine-proposed modification to SSI as a potential poverty alleviation and health improvement tool for children with disabilities and their families.
We used public health law research methods to characterize the laws (statutes and state agency regulations) governing the federal SSI program and SSP programs in the 50 states and District of Columbia from January 1, 1996, through November 1, 2018.
The number of jurisdictions offering supplementary payments (SSP) was relatively stable between 1996 and 2018. In 2018, 23 US jurisdictions legally mandated that SSP programs were available for children. Among the states with SSP payment amounts in their codified laws, SSP monthly benefit amounts ranged from $8 to $64.35 in 1996 and $3.13 to $60.43 in 2018.
Our initial exploration of SSI-related policies as a tool for improving the economic stability of children with disabilities and their families suggests that current SSPs, in combination with SSI, would not rise to the level of SSI increases proposed by The National Academies of Sciences, Engineering, and Medicine. Understanding more about how SSI and SSP reach children and work in combination with other federal and state income security programs may help identify policies and strategies that better support children with disabilities in low-income households.
Documentation is important for quality improvement, education, and research. There is currently a lack of recommendations regarding key aspects of documentation in regional anesthesia. The aim of ...this study was to establish recommendations for documentation in regional anesthesia.
Following the formation of the executive committee and a directed literature review, a long list of potential documentation components was created. A modified Delphi process was then employed to achieve consensus amongst a group of international experts in regional anesthesia. This consisted of 2 rounds of anonymous electronic voting and a final virtual round table discussion with live polling on items not yet excluded or accepted from previous rounds. Progression or exclusion of potential components through the rounds was based on the achievement of strong consensus. Strong consensus was defined as ≥75% agreement and weak consensus as 50%-74% agreement.
Seventy-seven collaborators participated in both rounds 1 and 2, while 50 collaborators took part in round 3. In total, experts voted on 83 items and achieved a strong consensus on 51 items, weak consensus on 3 and rejected 29.
By means of a modified Delphi process, we have established expert consensus on documentation in regional anesthesia.
Myocardin-related transcription factor B (MRTFB) is an important transcriptional regulator, which promotes the activity of an estimated 300 genes but is not known to underlie a Mendelian disorder.
...Probands were identified through the efforts of the Undiagnosed Disease Network. Because the MRTFB protein is highly conserved between vertebrate and invertebrate model organisms, we generated a humanized Drosophila model expressing the human MRTFB protein in the same spatial and temporal pattern as the fly gene. Actin binding assays were used to validate the effect of the variants on MRTFB.
Here, we report 2 pediatric probands with de novo variants in MRTFB (p.R104G and p.A91P) and mild dysmorphic features, intellectual disability, global developmental delays, speech apraxia, and impulse control issues. Expression of the variants within wing tissues of a fruit fly model resulted in changes in wing morphology. The MRTFBR104G and MRTFBA91P variants also display a decreased level of actin binding within critical RPEL domains, resulting in increased transcriptional activity and changes in the organization of the actin cytoskeleton.
The MRTFBR104G and MRTFBA91P variants affect the regulation of the protein and underlie a novel neurodevelopmental disorder. Overall, our data suggest that these variants act as a gain of function.
Hypertensive disorders of pregnancy are associated with future cardiovascular disease, perhaps because of subclinical cardiac dysfunction before pregnancy leading to impaired adaptation to pregnancy. ...Natriuretic peptides are promising biomarkers for detecting subclinical cardiac dysfunction outside of pregnancy.
To investigate whether higher concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) in early pregnancy would be associated with hypertensive disorders of pregnancy and hypertension 2 to 7 years post partum.
This cohort study used data from the The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be Heart Health Study, a prospective multicenter observational study. A total of 4103 nulliparous women with complete data and no prepregnancy hypertension or diabetes who were treated at 8 clinical sites were included. Women were followed up with for 2 to 7 years after pregnancy. Data were collected from October 2010 to October 2017, and data were analyzed from August 2020 to November 2021.
NT-proBNP concentration, measured using an electrochemiluminescence immunoassay from a first-trimester blood sample.
Hypertensive disorders of pregnancy and incident hypertension (systolic blood pressure of 130 mm Hg or diastolic blood pressure of 80 mm Hg or use of antihypertensive agents) at follow-up visit.
A total of 4103 women met inclusion criteria; the mean (SD) age was 27.0 (5.6) years. Among these women, 909 (22.2%) had an adverse pregnancy outcome, and 817 (19.9%) had hypertension at the follow-up visit. Higher NT-proBNP concentrations were associated with a lower risk of hypertensive disorders of pregnancy (adjusted odds ratio per doubling, 0.81; 95% CI, 0.73-0.91), which persisted after adjustment for age, self-reported race and ethnicity, early-pregnancy body mass index, smoking, and aspirin use. Similarly, higher NT-proBNP concentration in early pregnancy was also associated with a lower risk of incident hypertension 2 to 7 years after delivery (adjusted odds ratio per doubling, 0.84; 95% CI, 0.77-0.93), an association that persisted after controlling for confounders, including hypertensive disorders of pregnancy.
In this cohort study, higher NT-proBNP concentrations in early pregnancy were associated with a lower risk of hypertensive disorders of pregnancy and hypertension 2 to 7 years post partum. These findings suggest that normal early-pregnancy cardiovascular physiology, as assessed by NT-proBNP concentration, may provide biologic insights into both pregnancy outcome and cardiovascular disease risk.
To describe the drug therapy problems (DTPs) identified for patients enrolled in an Appointment Based Model (ABM) for medication synchronization, describe the pharmacist-delivered clinical ...interventions, and assess what patient characteristics are associated with the number of DTPs identified.
A cross-sectional chart review of 1 month of pharmacist notes for telephone ABM encounters at one independent community pharmacy in the Midwest U.S. was performed for a systematic random sample of patients active in the program during September 2017. Included patients were 18 years and older and took one or more synchronized medications. Data included months in the program, gender, age, insurance type, refill interval, medications (synchronized and total), DTP category, and intervention category. Descriptive statistics were calculated, and a multiple linear regression tested the association between patient characteristics and the number of DTPs identified.
The study involved 209 subjects, 54% women, with a mean age of 69.5 years and. The average number of medications synchronized was 4.7, the mean total number of medications was 6.3, and mean length of time in the program was 20 months. The DTPs (n=334) identified included needs additional drug therapy (43.1%), inappropriate adherence (31.4%), unnecessary drug therapy (15.0%), and adverse drug reaction (9.6%). The regression showed age and number of medications was positively associated with number of DTPs identified, but months enrolled was not.
This ABM approach identified several hundred DTPs with corresponding interventions within a one-month period, suggesting that ABMs have a significant potential to improve patient care. The data also suggest that pharmacist interventions within an ABM program are valuable beyond the first few fills as patients move into maintenance use of their medications, especially for patients of advancing age and polypharmacy.
Although many large mammals currently face significant threats that could lead to their extinction, resources for conservation are often scarce, resulting in the need to develop efficient plans to ...prioritize conservation actions. We combined several methods in spatial ecology to identify the distribution of the endangered Baird's tapir across its range from southern Mexico to northern Colombia. Twenty-eight habitat patches covering 23% of the study area were identified, harboring potentially 62% or more of the total population for this flagship species. Roughly half of the total area is under some form of protection, while most of the remaining habitat (~70%) occurs in indigenous/local communities. The network with maximum connectivity created from these patches contains at least one complete break (in Mexico between Selva El Ocote and Selva Lacandona) even when considering the most generous dispersal scenario. The connectivity analysis also highlighted a probable break at the Panama Canal and high habitat fragmentation in Honduras. In light of these findings, we recommend the following actions to facilitate the conservation of Baird's tapir: 1) protect existing habitat by strengthening enforcement in areas already under protection, 2) work with indigenous territories to preserve and enforce their land rights, and help local communities maintain traditional practices; 3) re-establish connections between habitat patches that will allow for connectivity across the species' distribution; 4) conduct additional noninvasive surveys in patches with little or no species data; and 5) collect more telemetry and genetic data on the species to estimate home range size, dispersal capabilities, and meta-population structure.
The Undiagnosed Disease Network (UDN) is comprised of clinical and research experts collaborating to diagnose rare disease. The UDN is funded by the National Institutes of Health and includes 12 ...different clinical sites (About Us, 2022). Here we highlight the success of collaborative efforts within the UDN Clinical Site at Vanderbilt University Medical Center (VUMC) in utilizing a cohort of experts in bioinformatics, structural biology, and genetics specialists in diagnosing rare disease. Our UDN team identified a de novo mosaic CACNA1D variant c.2299T>C in a 5‐year‐old female with a history of global developmental delay, dystonia, dyskinesis, and seizures. Using a collaborative multidisciplinary approach, our VUMC UDN team diagnosed the participant with Primary Aldosteronism, Seizures, and Neurologic abnormalities (PASNA) OMIM: 615474 due to a rare mosaic CACNA1D variant (O'Neill, 2013). Interestingly, this patient was mosaic, a phenotypic trait previously unreported in PASNA cases. This report highlights the importance of a multidisciplinary approach in diagnosing rare disease.
Introduction
Among men who have sex with men (MSM) and transgender women (TW), stimulant use is high and has been associated with an increased risk of HIV infection, suicide and cardiovascular ...disease (CVD) mortality. We used epidemic modelling to investigate these intersecting health harms among MSM/TW in Lima, Peru and assess whether they could be mitigated by prioritizing HIV pre‐exposure prophylaxis (PrEP) and harm reduction interventions among MSM/TW who use stimulants.
Methods
We adapted a dynamic model of HIV transmission among MSM/TW in Lima to incorporate stimulant use and increased HIV risk, suicide and CVD mortality. Among 6% to 24% of MSM/TW using stimulants (mostly cocaine), we modelled an increased risk of unprotected anal sex (RR = 1.35 95%CI: 1.17 to 1.57) obtained from local data, and increased risk of suicide (SMR = 6.26 95%CI: 2.84 to 13.80) and CVD (SMR = 1.83 95%CI: 0.39 to 8.57) mortality associated with cocaine use based on a global systematic review. We estimated the proportion of health harms occurring among MSM/TW who use stimulants in the next year (01‐2020/01‐2021). We also investigated the 10‐year impact (01‐2020/01‐2030) of: (1) PrEP prioritization for stimulant‐using MSM/TW compared to random allocation, and (2) integrating PrEP with a theoretical intervention halving stimulant‐associated risk.
Results
MSM/TW in Lima will experience high HIV incidence, suicide mortality and CVD mortality (1.6/100 py, and 0.018/100 py, 0.13/100 py respectively) in 2020. Despite stimulant using MSM/TW comprising an estimated 9.5% (95%CI: 7.8 to 11.5) of all MSM/TW, in the next year, 11% 95%CI (i.e. 2.5% to 97.5% percentile) 10% to 13%) of new HIV infections, 39% (95%CI: 18% to 60%) of suicides and 15% (95%CI: 3% to 44%) of CVD deaths could occur among this group. Scaling up PrEP among all stimulant using MSM/TW could prevent 19% (95%CI: 11% to 31%) more HIV infections over 10 years compared to random allocation. Integrating PrEP and an intervention to halve stimulant‐associated risks could reduce new HIV infections by 20% (95%CI: 10% to 37%), suicide deaths by 14% (95%CI: 5% to 27%) and CVD deaths by 3% (95%CI: 0% to 16%) over a decade.
Conclusions
MSM/TW who use stimulants experience a disproportionate burden of health harms. Prioritizing PrEP based on stimulant use, in addition to sexual behaviour/gender identity criteria, could increase its impact. Integrated substance use, harm reduction, mental health and HIV care among MSM/TW is needed.
To assess systemic vascular endothelial growth factor (VEGF)-A levels after treatment with intravitreous aflibercept, bevacizumab, or ranibizumab.
Comparative-effectiveness trial with participants ...randomly assigned to 2 mg aflibercept, 1.25 mg bevacizumab, or 0.3 mg ranibizumab after a re-treatment algorithm.
Participants with available plasma samples (N = 436).
Plasma samples were collected before injections at baseline and 4-week, 52-week, and 104-week visits. In a preplanned secondary analysis, systemic-free VEGF levels from an enzyme-linked immunosorbent assay were compared across anti-VEGF agents and correlated with systemic side effects.
Changes in the natural log (ln) of plasma VEGF levels.
Baseline free VEGF levels were similar across all 3 groups. At 4 weeks, mean ln(VEGF) changes were -0.30±0.61 pg/ml, -0.31±0.54 pg/ml, and -0.02±0.44 pg/ml for the aflibercept, bevacizumab, and ranibizumab groups, respectively. The adjusted differences between treatment groups (adjusted confidence interval CI; P value) were -0.01 (-0.12 to +0.10; P = 0.89), -0.31 (-0.44 to -0.18; P < 0.001), and -0.30 (-0.43 to -0.18; P < 0.001) for aflibercept-bevacizumab, aflibercept-ranibizumab, and bevacizumab-ranibizumab, respectively. At 52 weeks, a difference in mean VEGF changes between bevacizumab and ranibizumab persisted (-0.23 -0.38 to -0.09; P < 0.001); the difference between aflibercept and ranibizumab was -0.12 (P = 0.07) and between aflibercept and bevacizumab was +0.11 (P = 0.07). Treatment group differences at 2 years were similar to 1 year. No apparent treatment differences were detected at 52 or 104 weeks in the cohort of participants not receiving injections within 1 or 2 months before plasma collection. Participants with (N = 9) and without (N = 251) a heart attack or stroke had VEGF levels that appeared similar.
These data suggest that decreases in plasma free-VEGF levels are greater after treatment with aflibercept or bevacizumab compared with ranibizumab at 4 weeks. At 52 and 104 weeks, a greater decrease was observed in bevacizumab versus ranibizumab. Results from 2 subgroups of participants who did not receive injections within at least 1 month and 2 months before collection suggest similar changes in VEGF levels after stopping injections. It is unknown whether VEGF levels return to normal as the drug is cleared from the system or whether the presence of the drug affects the assay's ability to accurately measure free VEGF. No significant associations between VEGF concentration and systemic factors were noted.
Mendelian etiologies for acute encephalopathies in previously healthy children are poorly understood, with the exception of RAN binding protein 2 (RANBP2)–associated acute necrotizing encephalopathy ...subtype 1 (ANE1). We provide clinical, genetic, and neuroradiological evidence that biallelic variants in ribonuclease inhibitor (RNH1) confer susceptibility to a distinctive ANE subtype.
This study aimed to evaluate clinical data, neuroradiological studies, genomic sequencing, and protein immunoblotting results in 8 children from 4 families who experienced acute febrile encephalopathy.
All 8 healthy children became acutely encephalopathic during a viral/febrile illness and received a variety of immune modulation treatments. Long-term outcomes varied from death to severe neurologic deficits to normal outcomes. The neuroradiological findings overlapped with ANE but had distinguishing features. All affected children had biallelic predicted damaging variants in RNH1: a subset that was studied had undetectable RNH1 protein. Incomplete penetrance of the RNH1 variants was evident in 1 family.
Biallelic variants in RNH1 confer susceptibility to a subtype of ANE (ANE2) in previously healthy children. Intensive immunological treatments may alter outcomes. Genomic sequencing in children with unexplained acute febrile encephalopathy can detect underlying genetic etiologies, such as RNH1, and improve outcomes in the probands and at-risk siblings.
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