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INTRODUCTION Identifying pediatric patients who may benefit from gastrostomy tube (GT) placement can be challenging. We hypothesized that many GTs would no longer be in use after 6 months. METHODS Inpatient GT placements in patients < 18 years old at a tertiary children's hospital from 9/2014 to 2/2020 were included. The primary outcome was GT use

Objective Amyotrophic lateral sclerosis (ALS) is often associated with a range of difficult neuropsychiatric symptoms and conditions, including depression, apathy, pseudobulbar affect, and frontotemporal dementia (FTD). Despite the potential role for psychiatrists in the treatment of ALS, they are not typically involved in the ALS clinical team. The investigators describe a quality improvement intervention providing embedded psychiatric services within a multidisciplinary clinic (MDC). Methods A psychiatrist working within an ALS MDC evaluated patients (N=116) over a 1-year period. The clinic assessed the prevalence of neuropsychiatric symptoms and conditions in patients with ALS (depression, anxiety, pseudobulbar affect, and cognitive impairment, including FTD) using standardized screening methods. Fifty-five patients and 47 family members completed surveys about perceptions of their need for psychiatric care, their experience of meeting with a psychiatrist, and their desire for future access to psychiatric care. Results Prevalence rates for neuropsychiatric symptoms were 14.9% for depression, 11.3% for anxiety, 19% for cognitive impairment (including FTD, 8.6%), and 36.2% for pseudobulbar affect; 62.0% of patients were being prescribed at least one psychotropic medication. Both patients and family members reported that meeting with a psychiatrist was helpful, that the treatment provided was helpful, and that they would prefer continued availability of psychiatric services in the future. The presence of cognitive impairment and use of antidepressants increased the likelihood of patients reporting a benefit from psychiatric care. Conclusions Patients with ALS report a benefit from increased access to psychiatric services. The inclusion of a psychiatrist within the ALS MDC model should be considered to improve quality of care for this patient population.

Background Trauma patients undergo a standardized history and physical, however identification of mental health risk factors is not typically included. We aimed to assess the feasibility of using a modified version of Psychological Simple Triage and Rapid Treatment (PsySTART) to identify post-traumatic stress disorder (PTSD) risk factors in pediatric trauma patients. We hypothesized that PsySTART could identify risk factors and be integrated into the electronic medical record (EMR). Methods Trauma patients 10–17 years old at a level II pediatric trauma center from 2014 to 2015 were screened. PsySTART was used on a pilot cohort to determine if risk factors were present. PsySTART was then integrated into an automated EMR workflow and completion rates were evaluated. Results PsySTART was completed in a pilot cohort of 63 patients with the following findings: 33.3% (n = 21) with 1 risk factor, 22.2% (n = 14) with 2 risk factors, and 19.1% (n = 12) with ≥3 risk factors. The most commonly identified risk factor was, “felt or expressed extreme fear or panic” (n = 27, 43.0%). After EMR integration, PsySTART was successfully completed with automatic consults in 156 of 198 patients (78.8%). Conclusions PsySTART identified risk factors in pediatric trauma patients. EMR integration was feasible and led to proactive psychological management and intervention. Level of Evidence IV

BACKGROUND Traumatic diaphragmatic hernia (TDH) is rare in children, most often occurring following blunt thoracoabdominal trauma from high energy mechanisms, such as motor vehicle collisions (MVC). We performed a systematic review to describe injury details and management. METHODS Following PRISMA guidelines, a systematic literature search was performed to identify publications of blunt TDH in patients < 18 y old. Conflicts were resolved by consensus. Data were collected on demographics, TDH location, mechanism of injury, associated intraabdominal injuries (IAI), management, and outcomes. Denominators vary depending on number of patients with such information reported. RESULTS Fifty-eight articles were reviewed with 142 patients with TDH. The median age was seven y (range 0.25-16). Most were left-sided (85 of 126, 67.5%). MVC was the most common mechanism (66 of 142, 46.5%). IAI was present in 50.0% (57 of 114), most commonly liver injuries (25 of 57, 43.9%). Delayed diagnoses occurred in 49.6% (57 of 115, range 8 h-10 y), and were more common with right-sided TDH (76.0% versus 48.5%, P = 0.02). Chest radiography was 59.0% sensitive for TDH, while computed tomography sensitivity was 65.8%. Operative repair was performed on all surviving patients, and all underwent primary diaphragm repair. The overall mortality was 11.3% (n = 16), with four attributable to the TDH. There were no reported recurrences over a median follow-up of 12 mo. CONCLUSIONS Pediatric TDH is a rare diagnosis with a high rate of associated IAI and delayed diagnosis. Primary diaphragm repair was performed in all cases. Surgeons should maintain a high suspicion for diaphragm injury in blunt thoracoabdominal trauma.

Abstract:: COVID-19 (Virus named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) is a pandemic disease characterized with respiratory infection caused by coronavirus. It has worldwide after an outbreak began in Wuhan, China, in December 2019. SARS-CoV-2 has infected more than 15 million people globally. The disease severity and mortality increased in patients with heart-related comorbidities. Cardiovascular disease patients are more susceptible and infected with SARS-CoV-2. Early screening and managements these patients prevent or ameliorate adverse outcomes. Several treatments have been used to combat these effects as previously seen in MERS and SARS. This review will cover the association of cardiovascular diseases with COVID 19. It showed that cardiovascular diseases are common in patients with COVID- 19. Increased attention to highlight the gaps should be paid to the care of this unique group of patients.

Ezeldine K Abdalhabib,1 Denise E Jackson,2 Badr Alzahrani,1 Elyasa Elfaki,1 Alneil Hamza,1 Abdelbaset Mohamed Elasbali,1 Fehaid Alanazi,1 Abdulrahman Algarni,3 Ibrahim Khider Ibrahim,4 Muhammad Saboor5,6 1Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, AlQurayyat, Jouf University, Sakaka, Saudi Arabia; 2Thrombosis and Vascular Diseases Laboratory, School of Health and Biomedical Sciences, RMIT University, Victoria, Australia; 3Department of Medical Laboratory Technology, College of Applied Medical Sciences, Northern Borders University, Arar, Saudi Arabia; 4Department of Hematology, Faculty of Medical Laboratory Sciences, Al Neelain University, Khartoum, Sudan; 5Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 6Medical Research Center (MRC), Jazan University, Jazan, Saudi ArabiaCorrespondence: Muhammad SaboorDepartment of Medical Laboratory Technology, Faculty of Applied Medical Science, Jazan University, Jazan, Saudi ArabiaTel +966 54 495 9029Email msaboor@jazanu.edu.saEzeldine K AbdalhabibDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences-AlQurayyat, Jouf University, Saudi ArabiaTel +966 538949566Email ezeldine@ju.edu.saPurpose: DNA damage to hematopoietic progenitor cells is an essential factor for leukemia development as a failure of the host DNA repair system to fix errors in DNA. This study aimed to assess the association of XRCC1 gene polymorphisms including Arg194Trp, Arg399Gln, and Arg280His with the risk of development of CML in Sudanese population.Patients and Methods: The present study was conducted on 186 newly diagnosed patients with CML, aged 19– 70 years (118 males and 68 females; mean age of 46.15± 13.91 years) and 186 normal healthy controls (123 males and 63 females; mean age of 44.94± 8.97 years). Polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) assay was utilized to analyze the XRCC1 (Arg194Trp, Arg399Gln, and Arg280His) gene polymorphisms.Results: The genotypic frequencies of Arg399Gln polymorphism in cases were 131 (70.4%) homozygous Arg/Arg, 46 (24.7%) homozygous Gln/Gln, and 9 (4.8%) heterozygous Arg/Gln as compared to the controls ie, 153 (82.3%), 73 (14.5%), and 6 (3.2%), respectively. The Arg399Gln variant genotypic frequencies significantly differed between the cases and controls (χ2 = 7.249, P = 0.027). By comparison, no statistically significant difference was observed in the variant genotype frequencies between the cases and controls in terms of Arg194Trp and Arg280His polymorphisms.Conclusion: XRCC1 Arg399Gln gene polymorphism might have an important role in increasing the risk of chronic myeloid leukemia among Sudanese patients. Furthermore, all tested three polymorphisms showed no association of risk of the development of CML with age and gender.Keywords: XCCR1, chronic myeloid leukemia, polymorphism

Limited English proficiency (LEP) is associated with decreased access to healthcare. We hypothesized that LEP children with appendicitis would experience more delays in care than EP children.Retrospective review of patients18 y presenting to a tertiary pediatric hospital July 2014-July 2019 with appendicitis. LEP patients were compared to EP patients. The primary outcome was appendiceal perforation. Secondary outcomes included prior pediatrician or emergency department (ED) visits without definitive management, duration of symptoms, length of stay (LOS), initial operative or non-operative management, time from presentation to operation and return to the ED within 30 d. Multivariable regression was performed to evaluate LEP as a predictor of study outcomes.A total of 893 patients with appendicitis were identified, 15.6% (n = 140) had LEP. On multivariate regression LEP was not a significant predictor of appendiceal perforation (AOR 1.20, 95% CI 0.79, 1.80, P = 0.390). LEP was a significant predictor of a prior ED or pediatrician visit without definitive management (AOR 2.05, 95 % CI 1.05, 3.98, P= 0.034) and longer LOS (Coefficient 1.01, 95% CI 0.41, 1.61, P= 0.001). LEP was associated with a minimal increase in duration of pain prior to presentation that was not clinically significant and was not associated with initial operative or non-operative management or a significantly longer time between presentation and operation.LEP children did not experience higher rates of appendiceal perforation at our institution, but were more frequently initially evaluated by a pediatrician or at an ED and discharged without definitive management and had longer LOS.

Racial health disparities persist among black and white women for colorectal cancer. Understanding racial differences in the gut microbiota and related covariates (e.g., stress) may yield new insight into unexplained colorectal cancer disparities.Healthy non-Hispanic black or white women (age ≥19 years) provided survey data, anthropometrics, and stool samples. Fecal DNA was collected and isolated from a wipe. Polymerase chain reaction was used to amplify the V4 region of the 16SrRNA gene and 250 bases were sequenced using the MiSeq platform. Microbiome data were analyzed using QIIME. Operational taxonomic unit data were log transformed and normalized. Analyses were conducted using linear models in R Package "limma."Fecal samples were analyzed for 80 women (M (SD) age = 39.9 (14.0) years, 47 black, 33 white). Blacks had greater average body mass index (33.3 versus 27.5 kg/m, p.01) and waist circumference (98.3 versus 86.6 cm, p = .003) than whites. Whites reported more stressful life events (p = .026) and greater distress (p = .052) than blacks. Final models accounted for these differences. There were no significant differences in dietary variables. Unadjusted comparisons revealed no racial differences in alpha diversity. Racial differences were observed in beta diversity and abundance of top 10 operational taxonomic units. Blacks had higher abundances than whites of Faecalibacterium (p = .034) and Bacteroides (p = .038). Stress was associated with abundances of Bifidobacterium. The association between race and Bacteroides (logFC = 1.72, 0 = 0.020) persisted in fully adjusted models.Racial differences in the gut microbiota were observed including higher Bacteroides among blacks. Efforts to cultivate an "ideal" gut microbiota may help reduce colorectal cancer risk.

Objective: To develop an ALS respiratory symptom scale (ARES) and evaluate how ARES compares to Medical Research Council Modified Dyspnea Scale (MRC), Borg dyspnea scale, and respiratory subscores ...

Background Recent trials have suggested use of balanced crystalloids may decrease the incidence of major adverse kidney events compared to saline in critically ill adults. The effect of crystalloid composition on biomarkers of early acute kidney injury remains unknown. Methods From February 15 to July 15, 2016, we conducted an ancillary study to the Isotonic Solutions and Major Adverse Renal Events Trial (SMART) comparing the effect of balanced crystalloids versus saline on urinary levels of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) among 261 consecutively-enrolled critically ill adults admitted from the emergency department to the medical ICU. After informed consent, we collected urine 36 ± 12 h after hospital admission and measured NGAL and KIM-1 levels using commercially available ELISAs. Levels of NGAL and KIM-1 at 36 ± 12 h were compared between patients assigned to balanced crystalloids versus saline using a Mann-Whitney U test. Results The 131 patients (50.2%) assigned to the balanced crystalloid group and the 130 patients (49.8%) assigned to the saline group were similar at baseline. Urinary NGAL levels were significantly lower in the balanced crystalloid group (median, 39.4 ng/mg [IQR 9.9 to 133.2]) compared with the saline group (median, 64.4 ng/mg [IQR 27.6 to 339.9]) (P P = 0.36). Conclusions In this ancillary analysis of a clinical trial comparing balanced crystalloids to saline among critically ill adults, balanced crystalloids were associated with lower urinary concentrations of NGAL and similar urinary concentrations of KIM-1, compared with saline. These results suggest only a modest reduction in early biomarkers of acute kidney injury with use of balanced crystalloids compared with saline. Trial registration ClinicalTrials.gov number: NCT02444988. Date registered: May 15, 2015.

Reproductive health outcomes are indicators of larger social processes and researchers have long documented inequalities in these outcomes among Blacks and Whites in the United States. However, we do not fully understand the underlying mechanisms responsible for these inequalities. We believe that this is partially due to the treatment of the Black population as a monolith, which masks underlying variation in health risks and outcomes. By examining the variation that exists beneath the average, we can begin to develop a better understanding of the potential sources of health inequalities between Blacks and other racialized populations. We provide an application of this perspective through a geographic examination of reproductive health outcomes within the Black population. Using national birth records data from 2013 to 2016, we examine differences in low birth weight, preterm birth, gestational hypertension, and gestational diabetes by nativity (i.e., US- or foreign-born), region of origin (e.g., Sub-Saharan Africa, the Caribbean), and current US division of residence (e.g., Middle Atlantic, South Atlantic) within the Black population. While foreign-born Blacks are at a lower risk for low birth weight, preterm birth, and gestational hypertension, they are at an elevated risk for gestational diabetes compared to US-born Blacks. Moreover, we find substantial variation in this general pattern across region of origin and division of residence in the US. These findings demonstrate the potential role of migration, context, and selectivity in the health of foreign-born Blacks and demonstrate that national averages mask geographic variation, limiting our understanding of the contributions of these and other social processes to the health of racialized groups in the US.

Objectives There are no approved pharmacologic therapies for chronic sensorineural hearing loss (SNHL). The combination of CHIR99021+valproic acid (CV, FX-322) has been shown to regenerate mammalian cochlear hair cells ex vivo. The objectives were to characterize the cochlear pharmacokinetic profile of CV in guinea pigs, then measure FX-322 in human perilymph samples, and finally assess safety and audiometric effects of FX-322 in humans with chronic SNHL. Study designs Middle ear residence, cochlear distribution, and elimination profiles of FX-322 were assessed in guinea pigs. Human perilymph sampling following intratympanic FX-322 dosing was performed in an open-label study in cochlear implant subjects. Unilateral intratympanic FX-322 was assessed in a Phase 1b prospective, randomized, double-blinded, placebo-controlled clinical trial. Setting Three private otolaryngology practices in the US. Patients Individuals diagnosed with mild to moderately severe chronic SNHL (≤70 dB standard pure-tone average) in one or both ears that was stable for ≥6 months, medical histories consistent with noise-induced or idiopathic sudden SNHL, and no significant vestibular symptoms. Interventions Intratympanic FX-322. Main outcome measures Pharmacokinetics of FX-322 in perilymph and safety and audiometric effects. Results After intratympanic delivery in guinea pigs and humans, FX-322 levels in the cochlear extended high-frequency region were observed and projected to be pharmacologically active in humans. A single dose of FX-322 in SNHL subjects was well tolerated with mild, transient treatment-related adverse events (n = 15 FX-322 vs 8 placebo). Of the six patients treated with FX-322 who had baseline word recognition in quiet scores below 90%, four showed clinically meaningful improvements (absolute word recognition improved 18-42%, exceeding the 95% confidence interval determined by previously published criteria). No significant changes in placebo-injected ears were observed. At the group level, FX-322 subjects outperformed placebo group in word recognition in quiet when averaged across all time points, with a mean improvement from baseline of 18.9% (p = 0.029). For words in noise, the treated group showed a mean 1.3 dB signal-to-noise ratio improvement (p = 0.012) relative to their baseline scores while placebo-treated subjects did not (-0.21 dB, p = 0.71). Conclusions Delivery of FX-322 to the extended high-frequency region of the cochlea is well tolerated and enhances speech recognition performance in multiple subjects with stable chronic hearing loss.

Background: The inherent morbidity associated with fetal ovine models of myelomeningocele (MMC) has created challenges for long-term survival of lambs. We aimed to develop a fetal ovine surgical spinal exposure model which could be used to evaluate long-term safety after direct spinal cord application of novel therapeutics for augmentation of in utero MMC repair. Methods: At gestational age (GA) 100–106, fetal lambs underwent surgical intervention. Laminectomy of L5–L6 was performed, dura was removed, and an experimental product was directly applied to the spinal cord. Paraspinal muscles and skin were closed and the fetus was returned to the uterus. Lambs were delivered via cesarean section at GA 140–142. Lambs were survived for 3 months with regular evaluation of motor function by the sheep locomotor rating scale. Spinal angulation was evaluated by magnetic resonance imaging at 2 weeks and 3 months. Results: Five fetal surgical intervention lambs and 6 control lambs who did not undergo surgical intervention were included. All lambs survived to the study endpoint of 3 months. No lambs had motor function abnormalities or increased spinal angulation. Conclusion: This model allows for long-term survival after fetal spinal cord exposure with product application directly onto the spinal cord.

Background: Care for infants with Trisomy 13 and 18 is evolving with more children being offered medical and surgical interventions. Parents and clinicians of children diagnosed with trisomy 13 and 18 would benefit from understanding how parental goals of care correlate with the subsequent clinical course of children with these conditions. Objective: To describe and compare parental goals of care (GOC) and clinical course in infants with trisomy 13 and 18. Design: Single center, retrospective (2013-19) analysis of electronic health record repository at a birthing center and a tertiary care hospital. Measurements: ICD-9/10 codes were used to identify patients with trisomy 13 or 18 born between 2013-2019. Their records were abstracted for their diagnosis, hospitalization days, interventions, GOC, death location and length of life. Result: Twenty-eight total patients were identified; trisomy 13, mosaic trisomy 13 and trisomy 18 were diagnosed in 9, 2 and 17 patients respectively. Among the 26 patients with complete trisomy 13 or 18, 8 had life-prolonging and 18 had comfort care goals at birth/diagnosis. Life-prolonging goals were not associated with longer life (p = 0.36) but were associated with more mean hospital days (70 vs. 12, p = 0.01), ICU days (66 vs. 9, p = 0.009), intubation (7/8 vs 7/18, p = 0.04), and death in ICU (7/7 vs. 10/17, p = 0.02). Zero patients underwent cardiac surgery. Conclusion: Parental GOC did not affect length of life in children with complete trisomy, but did alter treatment intensity. This may inform decision making for patients with trisomy 13 or 18.

This chapter discusses the ‘classical causes’ of heart failure. Heart failure is the common endpoint of a diverse range of cardiovascular and non-cardiovascular conditions. The list of potential causes of this syndrome continues to expand as the knowledge of the pathophysiology of heart failure increases. In western societies, coronary heart disease and hypertension are the commonest causes of heart failure. However, valvular heart disease, arrhythmias, and alcohol are also frequently implicated. The prevalence of heart failure secondary to coronary heart disease has increased in recent years, due in part to improved survival following acute myocardial infarction. The chapter then highlights the importance of establishing an aetiology of heart failure. Establishing the aetiology of heart failure is important, but it is often challenging for the clinician. Several causes of heart failure frequently coexist and determining the primary aetiology can be difficult: one cause may obviously dominate, but frequently patients may have multiple contributing aetiologies.

BackgroundWhile fetal repair of myelomeningocele (MMC) revolutionized management, many children are still unable to walk independently. Preclinical studies demonstrated that research-grade placental mesenchymal stromal cells (PMSCs) prevent paralysis in fetal ovine MMC, however this had not been replicated with clinical-grade cells that could be used in an upcoming human clinical trial. We tested clinical-grade PMSCs seeded on an extracellular matrix (PMSC-ECM) in the gold standard fetal ovine model of MMC.MethodsThirty-five ovine fetuses underwent MMC defect creation at a median of 76 days gestational age, and defect repair at 101 days gestational age with application of clinical-grade PMSC-ECM (3×105 cells/cm2, n=12 fetuses), research-grade PMSC-ECM (3×105 cells/cm2, three cell lines with n=6 (Group 1), n=6 (Group 2), and n=3 (Group 3) fetuses, respectively) or ECM without PMSCs (n=8 fetuses). Three normal lambs underwent no surgical interventions. The primary outcome was motor function measured by the Sheep Locomotor Rating scale (SLR, range 0: complete paralysis to 15: normal ambulation) at 24h of life. Correlation of lumbar spine large neuron density with SLR was evaluated.ResultsClinical-grade PMSC-ECM lambs had significantly better motor function than ECM-only lambs (SLR 14.5vs. 6.5, p=0.04) and were similar to normal lambs (14.5vs. 15, p=0.2) and research-grade PMSC-ECM lambs (Group 1: 14.5vs. 15, p=0.63; Group 2: 14.5vs. 14.5, p=0.86; Group 3: 14.5vs. 15, p=0.50). Lumbar spine large neuron density was strongly correlated with motor function (r=0.753, p

Despite the known association between autoimmune and psychiatric conditions, pertinent evaluations are often overlooked in clinical practice.

An orally administered, fixed‐dose coformulation of sodium phenylbutyrate‐taurursodiol (PB‐TURSO) significantly slowed functional decline in a randomized, placebo‐controlled, phase 2 trial in ALS (CENTAUR). Herein we report results of a long‐term survival analysis of participants in CENTAUR. In CENTAUR, adults with ALS were randomized 2:1 to PB‐TURSO or placebo. Participants completing the 6‐month (24‐week) randomized phase were eligible to receive PB‐TURSO in the open‐label extension. An all‐cause mortality analysis (35‐month maximum follow‐up post‐randomization) incorporated all randomized participants. Participants and site investigators were blinded to treatment assignments through the duration of follow‐up of this analysis. Vital status was obtained for 135 of 137 participants originally randomized in CENTAUR. Median overall survival was 25.0 months among participants originally randomized to PB‐TURSO and 18.5 months among those originally randomized to placebo (hazard ratio, 0.56; 95% confidence interval, 0.34‐0.92; P = .023). Initiation of PB‐TURSO treatment at baseline resulted in a 6.5‐month longer median survival as compared with placebo. Combined with results from CENTAUR, these results suggest that PB‐TURSO has both functional and survival benefits in ALS.

Surgical excision is important for melanoma treatment. Delays in surgical excision after diagnosis of melanoma have been linked to decreased survival in hospital-based cohorts. This study was aimed at quantifying the association between the timeliness of surgical excision and overall survival in patients diagnosed with melanoma in hospital- and non-hospital-based settings, using a retrospective cohort study of patients with stage 0–III melanoma and using data linked between the North Carolina Central Cancer Registry to Medicare, Medicaid, and private health insurance plan claims across the state. We identified 6,496 patients diagnosed between 2004 and 2012 with follow-up through 2017. We categorized the time from diagnostic biopsy to surgical excision as 90 days after melanoma diagnosis. Multivariable Cox regression was used to estimate differences in survival probabilities. Five-year overall survival was lower for those with time to surgery over 90 days (78.6%) compared with those with less than 6 weeks (86%). This difference appeared greater for patients with Stage 1 melanoma. This study was retrospective, included one state, and could not assess melanoma specific mortality. Surgical timeliness may have an effect on overall survival in patients with melanoma. Timely surgery should be encouraged. Electronic supplementary material The online version of this article (10.1007/s00403-020-02146-2) contains supplementary material, which is available to authorized users.

To evaluate safety, dose response, and preliminary efficacy of reldesemtiv over 12 weeks in patients with amyotrophic lateral sclerosis (ALS). Methods: Patients (≤2 years since diagnosis) with slow...

Osteoporosis is a major concern in patients with Duchenne muscular dystrophy. In this novel study of teriparatide treatment in 6 patients with severe osteoporosis, bone health (fractures, vertebral morphometry, and DXA) remained stable, with no adverse events. These findings will help inform future osteoporosis research in this challenging population. Despite standard therapy with vitamin D and bisphosphonates (BP), many patients with Duchenne muscular dystrophy (DMD) continue to sustain fragility fractures due to long-term glucocorticoid treatment and limited mobility. We aimed to evaluate the safety and efficacy of teriparatide for the treatment of severe osteoporosis in adolescent and young adult patients with DMD. We prospectively treated 6 patients with DMD who had severe osteoporosis with teriparatide 20 mcg subcutaneously daily for 1–2 years. Inclusion criteria were long-term glucocorticoid therapy, and severe osteoporosis despite treatment with BP, or intolerance to BP. We examined long bone and vertebral fracture outcomes, including vertebral morphometry measures, bone mineral density and content, bone formation markers, safety indices, and adverse events. The mean age at teriparatide start was 17.9 years (range 13.9–22.1 years). All 6 patients were on daily glucocorticoids (mean ± SD; duration 10.9 ± 2.5 years) and 5 were non-ambulatory. Five patients had been treated with BP for 7.9 ± 4.2 years. All had vertebral and a history of long bone fragility fractures at baseline. Vertebral heights and Genant fracture grading remained stable. Long bone fracture rate appeared to decrease (from 0.84/year to 0.09/year); one patient sustained a long bone fracture at 6 months of treatment. Trajectories for change in bone mineral density and content were not different post- vs. pre-teriparatide. Procollagen type 1 amino-terminal propeptide (P1NP) increased, while laboratory safety indices remained stable and non-concerning. No adverse events were observed. In six patients with DMD treated with teriparatide for severe osteoporosis, we observed stable bone health and modest increases in P1NP, without safety concerns. Further studies are needed to better understand teriparatide efficacy for treatment of osteoporosis in patients with DMD.

Objectives: Primary aldosteronism is one of the most common causes of secondary hypertension. Distinguishing unilateral from bilateral disease is essential as those with unilateral adrenal disease will benefit from adrenalectomy. This is best achieved by adrenal vein sampling (AVS) which may be a difficult procedure with significant radiation to both patient and operator. This study aims to measure the radiation dose during AVS before and after the installation of a new angiography platform. Materials and Methods: The dose area product (DAP), air kerma, and fluoroscopy time were collected retrospectively together with demographic data for the first ten patients who underwent AVS between April and September 2018 following the installation of the Philips Azurion 7 M20 interventional platform. These results were compared with those from ten patients who underwent AVS before the installation of the new machine using the Philips Allura Xper FD20 platform. Mann–Whitney test was used to compare DAP, air kerma, and fluoroscopy time. P < 0.05 was considered statistically significant. Results: Successful bilateral adrenal vein catheterization was achieved in all cases in both groups. There was no significant difference in fluoroscopy time: 5.5 (3.3–10.8) min (new) versus 5.3 (4.5–8.4) min (old) (P = 0.9502). The DAP and air kerma were both significantly lower on the new machine: 11.3 (5.2–26.7) Gy.cm2 versus 45.5 (17.2–56.5) Gy.cm2 (P = 0.0089) and 201.5 (88.1–464.0) mGy versus 682.5 (300.5–998.5) mGy (P = 0.0115), respectively. Conclusion: The installation of the Philips Azurion 7 M20 interventional platform has allowed a significant reduction in radiation dose during AVS.

Aims None of the existing studies on adherence have directly measured levels of all medications (or their metabolites) in patients with heart failure (HF). Methods and results We used liquid chromatography–tandem mass spectrometry to measure the presence of prescribed drugs (diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists) in the urine of patients reviewed 4–6 weeks after hospitalization with HF. Patients were unaware that adherence was being assessed. Of the 341 patients studied, 281 (82.4%) were adherent, i.e. had all prescribed drugs of interest detectable in their urine. Conversely, 60 patients (17.6%) were partially or completely non-adherent. Notably, 24 of the 60 were non-adherent to only diuretic therapy and only seven out of all 341 patients studied (2.1%) were completely non-adherent to all prescribed HF drugs. There were no major differences in baseline characteristics between adherent and non-adherent patients. Conclusion Non-adherence, assessed using a single spot urine measurement of drug levels, was confirmed in one of five patients evaluated 4–6 weeks after hospitalization with HF.

Highlights • Understanding feeding tube risk is critical to optimal weight maintenance during radiotherapy. • T-stage, Level II lymphadenopathy risk stratify feeding tube use into 4 groups. • The addition of cervical oesophagus dose can further refine these risk stratified groups., Introduction To identify organs to which dose limitation using intensity modulated radiotherapy (IMRT) can potentially modify the incidence and duration of feeding tube use, during and immediately following therapy for head and neck cancer. Materials and methods One hundred and fourteen patients treated with definitive IMRT (± concurrent chemotherapy) head and neck mucosal cancers were included. Patients received a prophylactic feeding tube and followed up by a dietician for at least eight weeks post-radiotherapy. Salivary and swallowing organs were delineated for each patient. Tumour and dosimetric variables were recorded for all patients and analysed for incidence and duration of feeding tube use for at least 25% of dietary requirements. Results Multivariate analysis showed T-classification ≥3 and level II lymphadenopathy as independent significant predictors of incidence and duration of feeding tube use in oral cavity, pharyngeal and supraglottic primaries. Mean dose deposited in the cervical oesophagus over 36Gy further increased the incidence and duration of feeding tube use. Mean dose deposited in the base of tongue and superior pharyngeal constrictor muscles affected incidence and duration of feeding tube use, respectively. Discussion In patients treated with definitive IMRT, T-classification and Level II lymphadenopathy, combined with a mean cervical oesophagus dose over 36Gy can a stratify patients into eight distinct risk groups for using feeding tubes for at least 25% of their dietary requirements.

Introduction Our aim in this study was to identify the prevalence and clinical characteristics of LRP4/agrin‐antibody–positive double‐seronegative myasthenia gravis (DNMG). Methods DNMG patients at 16 sites in the United States were tested for LRP4 and agrin antibodies, and the clinical data were collected. Results Of 181 DNMG patients, 27 (14.9%) were positive for either low‐density lipoprotein receptor–related protein 4 (LRP4) or agrin antibodies. Twenty‐three DNMG patients (12.7%) were positive for both antibodies. More antibody‐positive patients presented with generalized symptoms (69%) compared with antibody‐negative patients (43%) (P ≤ .02). Antibody‐positive patients’ maximum classification on the Myasthenia Gravis Foundation of America (MGFA) scale was significantly higher than that for antibody‐negative patients (P ≤ .005). Seventy percent of antibody‐positive patients were classified as MGFA class III, IV, or V compared with 39% of antibody‐negative patients. Most LRP4‐ and agrin‐antibody–positive patients (24 of 27, 89%) developed generalized myathenia gravis (MG), but with standard MG treatment 81.5% (22 of 27) improved to MGFA class I or II during a mean follow‐up of 11 years. Discussion Antibody‐positive patients had more severe clinical disease than antibody‐negative patients. Most DNMG patients responded to standard therapy regardless of antibody status.

MLKL is the essential effector of necroptosis, a form of programmed lytic cell death. We have isolated a mouse strain with a single missense mutation, MlklD139V, that alters the two-helix ‘brace’ that connects the killer four-helix bundle and regulatory pseudokinase domains. This confers constitutive, RIPK3 independent killing activity to MLKL. Homozygous mutant mice develop lethal postnatal inflammation of the salivary glands and mediastinum. The normal embryonic development of MlklD139V homozygotes until birth, and the absence of any overt phenotype in heterozygotes provides important in vivo precedent for the capacity of cells to clear activated MLKL. These observations offer an important insight into the potential disease-modulating roles of three common human MLKL polymorphisms that encode amino acid substitutions within or adjacent to the brace region. Compound heterozygosity of these variants is found at up to 12-fold the expected frequency in patients that suffer from a pediatric autoinflammatory disease, chronic recurrent multifocal osteomyelitis (CRMO)., Necroptosis is a regulated form of inflammatory cell death driven by activated MLKL. Here, the authors identify a mutation in the brace region that confers constitutive activation, leading to lethal inflammation in homozygous mutant mice and providing insight into human mutations in this region.

Physical activity contributes to body weight regulation. At least 150 minutes per week of moderate-to-vigorous intensity physical activity may be needed. When not coupled with dietary restriction, physical activity contributes to an average weight loss of approximately 2 to 3 kg in interventions up to 6 months in duration; when added to modest dietary restriction it adds 20% additional weight loss compared with modest dietary restriction alone. Physical activity is associated with enhanced long-term weight loss and attenuation of weight regain and should be included within clinical and public health approaches to prevent weight regain and to treat obesity.

A symptomatic patient with atrial fibrillation and Cheyne-Stokes respiration (CSR) was implanted with a transvenous phrenic nerve stimulation (TPNS) device—the remedē System—that is indicated for adult patients with moderate to severe central sleep apnea. Sleep recordings demonstrated that TPNS eliminated periodic breathing by activating the diaphragm and stabilizing respiratory patterns. These recordings of preprogrammed periods on versus off TPNS illustrate prompt (1) stabilization of tidal airflow, respiratory effort, and oxygenation as stimulation amplitude increased stepwise and (2) recurrence of CSR immediately after TPNS deactivated. Despite differences in respiratory patterns, minute ventilation was comparable during periods on and off TPNS. These findings suggest that diaphragmatic pacing entrains ventilation without disrupting sleep, accounting for observed improvements in periodic breathing, gas exchange, sleep architecture, and quality of life. Effective means to relieve CSR could potentially mitigate nocturnal cardiovascular stress and disease progression. CITATION: Schwartz AR, Sgambati FP, James KJ, et al. Novel phrenic nerve stimulator treats Cheyne-Stokes respiration: polysomnographic insights. J Clin Sleep Med. 2020;16(5):817–820.

ObjectiveDetermining the genetic basis of speech disorders provides insight into the neurobiology of human communication. Despite intensive investigation over the past 2 decades, the etiology of most speech disorders in children remains unexplained. To test the hypothesis that speech disorders have a genetic etiology, we performed genetic analysis of children with severe speech disorder, specifically childhood apraxia of speech (CAS).MethodsPrecise phenotyping together with research genome or exome analysis were performed on children referred with a primary diagnosis of CAS. Gene coexpression and gene set enrichment analyses were conducted on high-confidence gene candidates.ResultsThirty-four probands ascertained for CAS were studied. In 11/34 (32%) probands, we identified highly plausible pathogenic single nucleotide (n = 10; CDK13, EBF3, GNAO1, GNB1, DDX3X, MEIS2, POGZ, SETBP1, UPF2, ZNF142) or copy number (n = 1; 5q14.3q21.1 locus) variants in novel genes or loci for CAS. Testing of parental DNA was available for 9 probands and confirmed that the variants had arisen de novo. Eight genes encode proteins critical for regulation of gene transcription, and analyses of transcriptomic data found CAS-implicated genes were highly coexpressed in the developing human brain.ConclusionWe identify the likely genetic etiology in 11 patients with CAS and implicate 9 genes for the first time. We find that CAS is often a sporadic monogenic disorder, and highly genetically heterogeneous. Highly penetrant variants implicate shared pathways in broad transcriptional regulation, highlighting the key role of transcriptional regulation in normal speech development. CAS is a distinctive, socially debilitating clinical disorder, and understanding its molecular basis is the first step towards identifying precision medicine approaches.

The objective of the present study was to investigate the association between angiotensin-converting enzyme (ACE) inhibitor use and cancer incidence (overall, and breast, prostate, and colorectal cancers specifically) in a large representative sample of US adults. Cross-sectional data on cancer diagnosis, timing of cancer diagnosis, ACE inhibitor use, and other characteristics were extracted from 49 512 adults aged ≥ 20years participating in the National Health and Nutrition Examination Survey (1999–2016). Multivariable-logistic and propensity score matching (PSM) regressions examined the relationship between pre-diagnosis use of ACE inhibitors and diagnosis of all cancers, and breast, prostate, and colorectal cancers specifically. Overall, we observed an increased likelihood of cancer diagnosis [odds ratio (OR) 1.269, 95% confidence interval (CI) 1.088–1.480] among those who used ACE inhibitors compared to non-ACE inhibitor use, and for prostate cancer diagnosis (OR 1.438, 95% CI 1.090–1.897), after adjusting for age, sex, body mass index, race/ethnicity, educational attainment, physical activity, alcohol drinking status, smoking status, and high blood pressure. PSM regression retrieved more conservative estimates such that the increased likelihood of cancer diagnosis was only observed when comparing ACE inhibitor users with non-drug users (OR 1.022, 95% CI 1.016–1.027). Compared with non-ACE inhibitor use, ACE inhibitor use was associated with an increased risk of prostate cancer. In conclusion, in this large representative sample of US adults, it was found that ACE inhibitor use may have a marginal influence on some cancers. © 2020, Springer Nature Switzerland AG.

Multiple myeloma (MM), a plasma cell malignancy, is characterised by lesions in multiple bones involving transformed, matured post-follicular B cells. The course of the disease involves an initial development of monoclonal gammopathy of undetermined significance (MGUS), followed by smouldering MM, before the full MM disease emerges. Despite novel therapies, MM remains incurable, managed by combination therapies, including proteasome inhibitors (PIs), immunomodulators (IMiDs) and anti-human CD38 (daratumumab). MM patients have an increased risk of thromboembolic events due to combination treatments with IMiDs, PIs and anti-human CD38 antibody, and steroids. This review will examine the efficacy and pro-thrombotic effects of MM therapies.

Background: Genetic factors influence chronic obstructive pulmonary disease (COPD) risk, but the individual variants that have been identified have small effects. We hypothesised that a polygenic risk score using additional variants would predict COPD and associated phenotypes. Methods: We constructed a polygenic risk score using a genome-wide association study of lung function (FEV1 and FEV1/forced vital capacity [FVC]) from the UK Biobank and SpiroMeta. We tested this polygenic risk score in nine cohorts of multiple ethnicities for an association with moderate-to-severe COPD (defined as FEV1/FVC 1

Disturbances in acid-base balance leading to the development of hypertension are currently gaining increased attention among researchers. Perturb acid-base balance characterized by metabolic acidosis has been demonstrated in hypertensive animals and humans. Research suggests that acid-base changes are not only the consequences of elevated blood pressure but can precede the development of hypertension. However, no exact mechanism has been identified to link acid-base imbalance with alterations in blood pressure. The kidney proximal tubule is the major site for maintaining normal bicarbonate concentrations which is an important component of acid-base balance. Acid-base transporter proteins in the renal proximal tubule such as Na+/HCO-3 cotransporters, Na+/H+ exchangers, and anion-exchangers play important roles in controlling acid secretion, ammonia production and bicarbonate reabsorption for maintaining acid-base balance. It is well known that sodium retention in the renal tubules leads to increase in blood volume and consequently increases in blood pressure. Therefore, it is the purpose of this review to discuss the role of sodium-coupled acid-base transporters in regulating proximal tubular sodium retention and controlling blood pressure homeostasis. We will also focus on the capacity of local mediators; angiotensin II, cortisol, prosta-glandin and aldosterone, to regulate acid-base and blood pressure homeostasis.

International audience; Background: Exercise addiction is associated with multiple adverse outcomes and can be classified as co-occurring with an eating disorder, or a primary condition with no indication of eating disorders. We conducted a meta-analysis exploring the prevalence of exercise addiction in adults with and without indicated eating disorders. Methods: A systematic review of major databases and grey literature was undertaken from inception to 30/04/2019. Studies reporting prevalence of exercise addiction with and without indicated eating disorders in adults were identified. A random effect meta-analysis was undertaken, calculating odds ratios for exercise addiction with versus without indicated eating disorders. Results: Nine studies with a total sample of 2140 participants (mean age = 25.06; 70.6% female) were included. Within these, 1732 participants did not show indicated eating disorders (mean age = 26.4; 63.0% female) and 408 had indicated eating disorders (mean age = 23.46; 79.2% female). The odds ratio for exercise addiction in populations with versus without indicated eating disorders was 3.71 (95% CI 2.00–6.89; I2 = 81; p ≤ 0.001). Exercise addiction prevalence in both populations differed according to the measurement instrument used. Discussion: Exercise addiction occurs more than three and a half times as often as a comorbidity to an eating disorder than in people without an indicated eating disorder. The creation of a measurement tool able to identify exercise addiction risk in both populations would benefit researchers and practitioners by easily classifying samples.

Introduction We evaluated how effective an advertising campaign that was piloted by Cancer Research UK in January/February 2018 was at promoting quit attempts by increasing awareness of the relative harms of e-cigarettes compared with smoking. Methods Adults (≥16 years, n = 2217) living in Greater Manchester (campaign region), Yorkshire & Humber and the North East of England (control regions) completed cross-sectional surveys immediately before and after the campaign period. Surveys measured socio-demographics, perceptions and use of e-cigarettes, and motivation and attempts to quit smoking. We tested interactions between time (pre, post) and region (campaign, control). Results 36.7% (95% CI 33.0%–40.6%) of those in the intervention region recognized the campaign. In the general population, interactions were nonsignificant for all outcomes except for perception of e-cigarettes as effective cessation aids, with smaller increases from pre- to post-campaign in the campaign (49.9% to 54.0%) compared with the control region (40.5% to 55.0%; odds ratio [OR] = 0.66, 95% CI .45–0.98). Among smokers, motivation to quit increased in the intervention region (44.0% to 48.0%) but decreased in the control region (40.5% to 21.5%; OR = 2.97, 95% confidence interval [CI] 1.25–7.16), with no other significant differences between regions over time. Bayes factors confirmed that nonsignificant results were inconclusive. Conclusions Compared with the control region, the campaign was associated with an increase in smokers’ motivation to quit but a smaller increase in adults’ perception of e-cigarettes as an effective cessation aid. There was insufficient evidence to determine whether the campaign affected other outcomes. Implications Past extended mass media tobacco control campaigns have been shown to change public attitudes towards smoking, improve motivation to quit smoking, and reduce smoking prevalence. Much less is known about shorter, targeted campaigns. Here we show that using mass media to communicate accurate information about the relative harms of e-cigarettes compared with smoking may be an effective strategy in increasing smokers’ motivation to quit. Moreover, even when only run for a month, such campaigns can reach a large proportion of the targeted population. Further research is needed to evaluate effects on quit attempts and success.

Observational epidemiological studies provide valuable information regarding naturally occurring protective factors observed in populations with very low prevalences of vascular disease. Between 1935 and 1965, the Italian-American inhabitants of Roseto (Pennsylvania, USA) observed a traditional Italian diet and maintained half the mortality rates from myocardial infarction compared with neighboring cities. In the Seven Countries Study, during 40years (1960-2000) Crete maintained the lowest overall mortality rates and coronary heart disease fatalities, which was attributed to strict adherence to the Mediterranean diet. In the French Three-City Study, a ten-year follow-up (2000-2010) showed that higher consumption of olive oil was associated with lower risk of death, as well as protection from cognitive decline and stroke. A large number of population-based studies and intervention trials have demonstrated that the Mediterranean diet is associated with lower prevalence of vascular disease, obesity, arthritis, cancer, and age-associated cognitive decline. Many of these effects are the result of consumption of fruits, seeds, legumes and vegetables but olive oil is the chief dietary fat in Mediterranean countries and the main source of monounsaturated fatty acids, as well as an important source of beneficial polyphenols and other antioxidants. Considering the critical role of vascular factors in the pathogenesis of late-onset Alzheimer disease it seems appropriate to focus on disease modification through proven dietary therapy. The authors base their hypothesis on meta-analyses of epidemiological data, numerous experimental studies, and a comprehensive review of the mechanisms of action of extra-virgin olive oil and its components in the prevention of vascular disease. In addition, extra-virgin olive oil has had positive effects on experimental animal models of Alzheimer disease. We therefore propose that extra-virgin olive oil is a promising tool for mitigating the effects of adverse vascular factors and may be utilized for potential prevention of late-onset Alzheimer disease.

Acute megakaryoblastic leukemia (AMKL) is a subtype of acute myeloid leukemia (AML) accounting for 3%–10% of primary AML in childhood. Clinical manifestations of AML patients can include low grade of fever, diarrhea, easy bruising, failure to growth, and life-threatening clinical manifestations. Laboratory tests are very crucial to make a definitive diagnosis and treatment. We report here an uncommon case of AMKL in a 12-month-old boy who presented with general paleness and fatigue. Based on blood film investigation, bone marrow examination report, and immunophenotyping, he was diagnosed as a case of AMKL without Down syndrome.

Introduction Inflammation may play a role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Interleukin-6 (IL-6) is an important inflammatory mediator but information about its prognostic relevance in HFpEF is lacking. Purpose To examine the association between IL-6 and outcomes in patients with HFpEF. Methods We assessed the relationship between IL-6 tertile (T1–3) and all cause death, cardiovascular (CV) death and first HF hospitalisation (HFH) in 340 patients admitted to hospital with HFpEF. The association between log IL-6 and outcomes was examined in a Cox regression model adjusted for MAGGIC risk score and log B-type natriuretic peptide (BNP). Results Range of IL-6 (pg/ml) was: T1 (0.71–4.27), T2 (4.28–7.91) and T3 (7.94–236.32). Patients with higher IL-6 were older (73.9 versus 70.3 years), more commonly male (58.4% versus 39.5%) and had higher serum creatinine (117.6 versus 106.5 μmol/l), C-reactive protein ([CRP] 17.4 versus 4.4mg/l), troponin I (6.2 versus 5.0μg/l) and BNP (331.0 versus 254.5pg/ml). Rates of CV death and all-cause mortality, but not HFH, remained significantly higher in T3 versus T1 after adjustment. When modelled as a continuous variable, one log unit increase in IL-6 was associated with higher risk of CV death (HR 1.34 [1.05–1.70]), p=0.02) and all cause death (HR 1.41 [1.13–1.75], p=0.002). Conclusion In patients recently hospitalised with decompensated HFpEF, IL-6 is an independent predictor of CV death and all-cause mortality after adjusting for the MAGGIC risk score and BNP. The potential utility of IL-6 as a therapeutic target in HFpEF warrants investigation. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Scottish Executive Chief Scientist Office [project grant entitled, “Microvolt T-Wave Alternans in Chronic Heart Failure: A Study of Prevalence and Incremental Prognostic Value” (Ref CZH/4/439)]

PurposeSouthSeq, a translational research study to perform genome sequencing (GS) for infants with symptoms suggestive of a genetic disorder, was conducted in NICUs in the Southeastern US. Recruitment targeted racial/ethnic minorities and rural, medically underserved areas that are historically under-represented in genomic medicine research.MethodsGS and analysis were performed for 367 newborns to detect disease-causal genetic variation concurrent with standard of care evaluation and testing.ResultsDefinitive diagnostic (DD) or likely diagnostic (LD) genetic findings were identified in 30% of newborns and 14% harbored an uncertain result. Only 39% of DD/LD findings were identified via concurrent standard of care suggesting that GS testing is better for obtaining early genetic diagnosis. We also identified phenotypes that correlate with the likelihood of receiving a DD/LD finding, such as craniofacial, ophthalmologic, auditory, skin, and hair abnormalities. We did not observe any differences in diagnostic rates between racial/ethnic groups.ConclusionWe describe one of the largest to-date GS cohorts of ill newborns, enriched for African American and rural patients. Our results demonstrate the utility of GS as it provides early in life detection of clinically relevant genetic variation not identified via current standard clinical testing, particularly for newborns exhibiting certain phenotypic features.

Background: There has been no comprehensive longitudinal study of pulmonary functions (PFTS) in ALS determining which measure is most sensitive to declines in respiratory muscle strength. Objective: To determine the longitudinal decline of PFTS in ALS and which measure supports Medicare criteria for NIV initiation first. Methods: Serial PFTs (maximum voluntary ventilation (MVV), maximum inspiratory pressure measured by mouth (MIP) or nasal sniff pressure (SNIP), maximum expiratory pressure (MEP), and Forced Vital Capacity (FVC)) were performed over 12 months on 73 ALS subjects to determine which measure showed the sentinel decline in pulmonary function. The rate of decline for each measure was determined as the median slope of the decrease over time. Medicare-based NIV initiation criteria were met if %FVC was ≤ 50% predicted or MIP was ≤ 60 cMH2O. Results: 65 subjects with at least 3 visits were included for analyses. All median slopes were significantly different than zero. MEP and sitting FVC demonstrated the largest rate of decline. Seventy subjects were analyzed for NIV initiation criteria, 69 met MIP criteria first; 11 FVC and MIP criteria simultaneously and none FVC criteria first. Conclusions: MEP demonstrated a steeper decline compared to other measures suggesting expiratory muscle strength declines earliest and faster and the use of airway clearance interventions should be initiated early. When Medicare criteria for NIV initiation are considered, MIP criteria are met earliest. These results suggest that pressure-based measurements are important in assessing the timing of NIV and the use of pulmonary clearance interventions.

Alzheimer’s disease (AD) is a chronic neurodegenerative disease and the most common form of dementia in older adults. Treatment of AD symptoms is very challenging and expensive. Appropriate diet as well as mental and physical activity may delay or reduce the occurrence of AD. It is unknown whether environmental factors offer potentially protective effects against the development of AD. We explored the possible beneficial effects of greenspace (trees and herbaceous cover) on the rate of AD in the mid-Atlantic US. Data for initial AD medical claims during 2011–2013 were obtained from Medicare records for 2999 ZIP codes. The percentages of land cover classes in each ZIP code were calculated based on high-resolution land cover imagery. Associations between AD and greenspace, blue space (water), and other variables were examined using zero-inflated Poisson models. The rate of AD was negatively associated with greenspace (for a greenspace increase of 10%, risk ratio (RR) = 0.91, 95% confidence interval (CI): 0.89–0.94), and blue space (for a water area increase of 10%, RR = 0.85, 95% CI: 0.81–0.89). The inverse relationships between greenspace and the risk of AD held across season, gender, and race. The rate of AD was positively associated with the concentration of fine particulate matter (PM2.5) (RR = 1.03, 95% CI: 1.02–1.05 for an increase in PM2.5 of 1 µg/m3). Our results suggest that greenspace may have protective effects for AD, although potential mechanisms are unclear and require further investigation.

Obesity is associated with an increased risk for type 2 diabetes, and weight loss in adults with obesity and type 2 diabetes may be indicated to reduce health risk and improve diabetes control. It is important to understand the effectiveness of weight loss interventions for the prevention and treatment of type 2 diabetes. Lifestyle interventions for weight loss show effectiveness for prevention of type 2 diabetes. Weight loss in patients with type 2 diabetes can decrease cardiometabolic risk and improve diabetes control. However, diabetes remission with lifestyle approaches is limited and to achieve this medical approaches such as bariatric surgery that result in greater magnitudes of weight loss may be necessary. Dissemination of lifestyle interventions for weight loss, along with other medical approaches such as bariatric surgery when indicated, are needed to reduce the health burden of type 2 diabetes in patients with obesity.

PURPOSE: Availability of targeted oral anticancer agents (OAAs) has transformed care for patients with metastatic renal cell carcinoma (mRCC). Our objective was to identify patterns and predictors of OAA use within 12 months after mRCC was detected to understand real-world adoption of OAAs. METHODS: We used a novel, North Carolina cancer registry–linked multipayer claims data resource to examine patterns of use of five oral therapies among patients with mRCC diagnosed in 2006-2015, with claims through 2016. Patients were required to have 12 months of continuous enrollment before metastatic index date. Log-Poisson models estimated unadjusted and adjusted risk ratios (RRs) for associations between patient characteristics and OAA use. In sensitivity analyses, we used a competing risk framework to estimate adjusted risk differences in OAA use. RESULTS: Our population-based study of 713 patients demonstrated low (37%) OAA use during the first year after metastatic index date among both publicly and privately insured patients, with shifting patterns of use consistent with regulatory approvals over time. Compared with patients age 18-49 years, patients age 70-74 years were half likely to use OAAs (95% confidence limit [CL], 0.34 to 0.78) and patients age 80+ years were 71% less likely to use OAAs (95% CL, 0.17 to 0.50). Patients with two comorbidities (RR, 0.73; 95% CL, 0.55 to 0.98) and those with 3+ comorbidities (RR, 0.68; 95% CL, 0.50 to 0.91) were less likely to receive OAA than those without comorbidities. Patients with higher frailty also had lower OAA utilization (RR, 0.67; 95% CL, 0.52 to 0.85). CONCLUSION: These findings suggest a need to better understand the system-level and provider-level drivers of OAA underuse, as well as OAA adherence and associated survival.

Introduction Insufficient attention has been directed towards urosepsis. Notably, no protocols or clinical decision rules currently exist outlining the appropriate use of imaging in uroseptic patients. The primary objective of our study was to retrospectively evaluate uroseptic emergency department (ED) patients who underwent abdominal imaging, to report the proportion of patients with imaging findings necessitating emergent surgical consultation. Methods We retrospectively identified 1142 patients ≥ 18 years of age that presented to the ED from January 2009 to December 2012 with ICD9 code indicative of urosepsis. All included patients underwent ED-ordered abdominal computerized tomography (CT) or retroperitoneal ultrasound (US). Imaging and urinalysis (UA) results were categorized. We report proportions with odds ratios and 95% confidence intervals. Results Of 1142 patients, we excluded 80 for neg UA, 167 for < 2 SIRS (systemic inflammatory response syndrome), 320 for positive blood cultures, and 37 for incomplete data. This yielded 538 patients which the authors reviewed the results of the CT or US to determine the proportion who required emergent surgical consultation and who underwent surgical or interventional procedure. There were 243 (45%) that had CT or US results that necessitated emergency surgical consultation, of those 180 (33%) underwent surgical or interventional procedure. Similar rates of emergency surgical consultation occurred when sub-divided by positive versus equivocal UA, with 43% and 47%, respectively. Conclusions Forty-five percent of our abdominally imaged urosepsis cohort had imaging findings that necessitated emergent surgical consultation, with a similar proportion in the subset with positive versus equivocal UA. The utility of abdominal imaging in this population should be studied prospectively.

BackgroundCoronary artery bypass graft (CABG) patients are under-represented in acute coronary syndrome (ACS) trials. We compared characteristics and outcomes for patients who did and did not participate in a randomised trial of invasive versus non-invasive management (CABG-ACS).MethodsACS patients with prior CABG in four hospitals were randomised to invasive or non-invasive management. Non-randomised patients entered a registry. Primary efficacy (composite of all-cause mortality, rehospitalisation for refractory ischaemia/angina, myocardial infarction (MI), heart failure) and safety outcomes (composite of bleeding, stroke, procedure-related MI, worsening renal function) were independently adjudicated.ResultsOf 217 patients screened, 84 (39%) screenfailed, of whom 24 (29%) did not consent and 60 (71%) were ineligible. Of 133 (61%) eligible, 60 (mean±SD age, 71±9 years, 72% male) entered the trial and 73 (age, 72±10 years, 73% male) entered a registry (preferences: physician (79%), patient (38%), both (21%)).Compared with trial participants, registry patients had more valve disease, lower haemoglobin, worse New York Heart Association class and higher frailty.At baseline, invasive management was performed in 52% and 49% trial and registry patients, respectively, of whom 32% and 36% had percutaneous coronary intervention at baseline, respectively (p=0.800). After 2 years follow-up (694 (median, IQR 558–841) days), primary efficacy (43% trial vs 49% registry (HR 1.14, 95% CI 0.69 to 1.89)) and safety outcomes (28% trial vs 22% registry (HR 0.74, 95% CI 0.37 to 1.46)) were similar. EuroQol was lower in registry patients at 1 year.ConclusionsCompared with trial participants, registry participants had excess morbidity, but longer-term outcomes were similar.Trial registration numberNCT01895751.

Background: Literature regarding cardiovascular disease (CVD) and incident physical performance limitations and disability in older people is equivocal. Aims: This study aimed to investigate whether CVD is longitudinally associated with incident physical performance limitations and disability in alarge population-based sample. Methods: This was an 8‑year prospective study using data collected as part of the Osteoarthritis Initiative. Participants were community-dwelling adults with knee osteoarthritis or at high risk for this condition. Diagnosed CVD was self-reported. Physical performance was assessed with measures of chair stand time and gait speed, whereas disability was assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Longitudinal associations between CVD and changes in physical performance tests (chair stand time and gait speed) and disability score were analyzed using generalized linear models with repeated measurements. Results: The analyzed sample comprised 4796 adults (mean age 61.2 years, 58.5% female), of whom 313 people (6.5%) reported CVD at baseline. During 8years of follow-up, after adjustment for 11 potential confounders measured at baseline, those with CVD experienced aworse profile in chair stand time over the 8‑year follow-up period than those without CVD (p = 0.006). Conclusion: In acohort of middle-aged and older adults with knee osteoarthritis or at high risk for this condition those with CVD experienced aworse profile in chair stand time over the 8‑year follow-up period than those without CVD; however, CVD was not significantly associated with an increased incidence of poor gait speed and disability over 8years of follow-up. Importantly, no associations were observed when utilizing propensity score matching. © 2019, Springer-Verlag GmbH Austria, part of Springer Nature.

This article reviews the important role of radiotherapy in the management of early non-melanoma skin cancer, in the definitive and adjuvant settings. Therapeutic considerations and appropriate patient selection will be discussed, as well as evidence for efficacy and potential side-effects. Additionally, we present some recent advances which may improve accessibility and quality of radiotherapy, such as more convenient dose-fractionation, wide-field treatments, electronic brachytherapy and 3D printed bolus.

Pathogenic variants in DDX3X have recently been identified to be a relatively common cause of intellectual disability in females. In this study, we describe six female probands, from five unrelated families, with five novel heterozygous variants in DDX3X, and the identification of potential germline mosaicism. Consistent features between this cohort and previously described cases include developmental delay or intellectual disability, growth disturbance and movement disorder. Common facial dysmorphism within the cohort include short palpebral fissures, micrognathia, bulbous nasal tip, protruding ears, high arched palate, thin upper vermillion and smooth philtrum. Novel clinical features identified from this cohort include facial dysmorphisms, perinatal complications, valgus feet deformity, lipoatrophy, dystonic episodes, and cutaneous mastocytosis. This case series attempts to expand the phenotype of the DDX3X syndrome; however, it remains heterogeneous. Description of further cases is required to more accurately identify the significance of novel phenotypes within this cohort.

The objective of this study was to investigate cross-sectional and longitudinal associations between declines in sexual activity and function and health outcomes in a large population-based sample of older adults. Data were from 2577 men and 3195 women aged ≥ 50 years participating in the English Longitudinal Study of Ageing. Past-year changes in sexual desire, frequency of sexual activity, and ability to have an erection (men)/become sexually aroused (women) were assessed at baseline by self-completion questionnaire. Health outcomes (self-rated health, limiting long-standing illness, doctor-diagnosed diseases of the vascular system, and cancer) were self-reported at baseline (2012/2013) and 4-year follow-up (2016/2017). Data were analyzed using logistic regression, adjusted for sociodemographics, health behaviors, and depressive symptoms. Prospectively, men who reported a decline in sexual desire had higher odds of incident limiting long-standing illness (OR 1.41, 95% CI 1.04–1.91) and incident cancer (OR 1.63, 95% CI 1.06–2.50) than those who maintained their sexual desire. Men who reported a decline in the frequency of sexual activities had higher odds of deterioration in self-rated health (OR 1.47, 95% CI 1.04–2.08) and incident limiting long-standing illness (OR 1.69, 95% CI 1.20–2.37). In women, a decline in frequency of sexual activities was associated with deterioration of self-rated health (OR 1.64, 95% CI 1.07–2.51). Erectile dysfunction was longitudinally associated with poorer health outcomes including incident cancer (OR 1.73, 95% CI 1.11–2.70), coronary heart disease (OR 2.29, 95% CI 1.29–4.07), and fair/poor self-rated health (OR 1.66, 95% CI 1.19–2.32). Practitioners should be mindful that a decline in sexual activity, desire, or function in older age may be an important indicator of future adverse health outcomes. Electronic supplementary material The online version of this article (10.1007/s10508-019-1443-4) contains supplementary material, which is available to authorized users.