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Introduction: Cavernous malformations in the pediatric population are exceedingly rare, especially in infants. Giant cavernous malformations (GCM) are even more rare and have a diameter >4 cm. The onset of symptoms predominantly occurs in adulthood, but the rate of hemorrhage is significantly higher in the pediatric population. Similar to non-GCM, GCM can be misidentified as tumors on imaging due to their tumefactive pattern with edema. Here, we present a rare case of a right frontotemporal GCM in a 2-month-old girl, the youngest recorded case in the existing literature. Case Presentation: A previously healthy 2-month-old girl presented to the emergency department following an increasing frequency of seizure-like activity that began 3 days prior to presentation. Magnetic resonance imaging of the brain with and without contrast characterized a large (5.8 × 4.3 × 4.2 cm) heterogeneous lesion of the right temporal lobe with diffuse scattered blood products of various ages seen throughout the lesion. She underwent a right-sided craniotomy where a gross total excision was achieved. Pathology confirmed the diagnoses of a GCM. The patient’s seizures subsequently resolved, and she continues to do well postoperatively. Discussion/Conclusion: GCM can be mistaken for tumors due to their large size, cystic nature, and surrounding edema, but a vascular lesion should always remain in the differential diagnosis before operating, even in infants. Surgery is generally recommended in patients that present with a symptomatic hemorrhage, recurrent hemorrhages, persistent seizures despite medical management, or progressively worsening neurological deficits if the GCM is in a safe location. It has been shown that 70–99% of patients undergoing surgery with successful removal of the GCM can achieve seizure freedom 2 years postoperatively. Complete surgical excision of this infant’s GCM was successful in treating her neurologic symptoms; therefore, pathological confirmation of this lesion is critical and should prompt a complete surgical excision.

Objective Few obstetric-specific guidelines detail the indications for screening echocardiography in pregnancy. The objective of the study is to examine the association of common indications for maternal echocardiography with the likelihood of abnormality identification, pregnancy management alteration, and conformity with current American College of Cardiology Foundation (ACCF) guidelines. Study Design This retrospective cohort analysis categorized all echocardiograms performed within pregnancy and the first month postpartum within a tertiary health system to correlate indications with abnormal findings. Results Data from 226 echocardiograms were analyzed from 205 women. The most common indication for initial echocardiography was cardiac symptoms (34.6%). History of cardiac disease was the only indication demonstrating a significant association with an abnormal finding on initial echocardiography (odds ratio [OR]: 2.6; p = 0.006). Postpartum status (OR: 4.9; p Conclusion Although the presence of cardiac symptoms or history of diabetes failed to demonstrate association with abnormal echocardiographic findings, a history of prior cardiac disease, tobacco use, multiparity, and postpartum status were factors associated with identification of abnormal findings on initial maternal echocardiography. The ACCF appropriateness criteria for obtaining echocardiography can be applied to pregnant women with consideration for these additional risk factors. Key Points

Background The impact of lumacaftor/ivacaftor on exercise tolerance in people with cystic fibrosis (CF) has not been thoroughly studied. Methods We conducted a multisite Phase 4 trial comparing the impact of lumacaftor/ivacaftor on exercise tolerance with that of placebo in participants ≥ 12 years of age with CF homozygous for F508del-CFTR. The primary endpoint was relative change from baseline in maximum oxygen consumption (VO2max) during cardiopulmonary exercise testing (CPET) at Week 24. The key secondary endpoint was relative change from baseline in exercise duration during CPET at Week 24. Other secondary endpoints included changes in other indices of exercise tolerance and changes in CF assessments; safety and tolerability were assessed as an endpoint. Results Seventy participants were randomized to receive lumacaftor/ivacaftor (n = 34) or placebo (n = 36). The least-squares mean difference for lumacaftor/ivacaftor versus placebo in relative change in VO2max from baseline at Week 24 was −3.2% (95% CI: −9.2, 2.9; P=0.3021); the least-squares mean difference in relative change from baseline in exercise duration at Week 24 was −3.2% (95% CI: −8.0, 1.6). Safety results were consistent with the known lumacaftor/ivacaftor safety profile. Conclusions Definitive conclusions regarding the impact of lumacaftor/ivacaftor on exercise tolerance cannot be drawn from these results; however, multicenter studies using CPETs can be reliably performed with multiple time points and conventional methods, provided that calibration can be achieved. Future studies of exercise tolerance may benefit from lessons learned from this study. NCT02875366.

Objective Sport-related concussion (SRC) is a known risk of contact sports and strategies to minimize risk have been used. We aimed to determine if an independent medical spotter (IMS) identified more SRCs than would otherwise be detected by trained sideline medical staff (SMS). Design Prospective review of SRCs during competition in the 2019 season and retrospective review of SRCs in the 2015 to 2018 seasons, which also used an IMS. Setting Division I football games (home and away) of a Big 10 Conference institution. Participants All football team members who participated in competition. Independent variables Occurrence of SRC during competition and whether the IMS or SMS directly visualized the injury. Main outcome measures The total number of SRCs that occurred during competition in the 2015 to 2019 football seasons and whom observed the SRC-SMS or IMS-or if a student athlete reported symptoms after competition. Results Over the 5-year study period, 24 SRCs occurred during competition. Of those, 19 (79.2%) were observed by SMS, 2 (8.3%) by the IMS, and 3 (12.5%) were reported to SMS after competition ended. Conclusions Most SRCs are accurately identified by SMS, but a small number were apparent only to the IMS who seemed to add sensitivity in detecting a SRC. Instances remain in which SRC recognition and diagnosis were delayed despite trained SMS and IMS. Clinical relevance An IMS allows for a small-added player protection benefit using different vantage points to identify potential SRCs during competition.

Liver disease is a major global health- care problem, affecting an estimated 844 million people worldwide. Despite this substantial burden, therapeutic options for liver disease remain limited, in part owing to a paucity of detailed analyses defining the cellular and molecular mechanisms that drive these conditions in humans. Single- cell transcriptomic technologies are transforming our understanding of cellular diversity and function in health and disease. In this Review, we discuss how these technologies have been applied in hepatology, advancing our understanding of cellular heterogeneity and providing novel insights into fundamental liver biology such as the metabolic zonation of hepatocytes, endothelial cells and hepatic stellate cells, and the cellular mechanisms underpinning liver regeneration. Application of these methodologies is also uncovering critical pathophysiological changes driving disease states such as hepatic fibrosis, where distinct populations of macrophages, endothelial cells and mesenchymal cells reside within a spatially distinct fibrotic niche and interact to promote scar formation. In addition, single- cell approaches are starting to dissect key cellular and molecular functions in liver cancer. In the near future, new techniques such as spatial transcriptomics and multiomic approaches will further deepen our understanding of disease pathogenesis, enabling the identification of novel therapeutic targets for patients across the spectrum of liver diseases

The management of multidrug-resistant tuberculosis (MDR TB) is notably complex among patients with human immunodeficiency virus (HIV). TB treatment recommendations typically include very little information specific to HIV and MDR TB, which often is derived from clinical trials conducted in low-resource settings. Mortality rates among patients with HIV and MDR TB remain high. We reviewed the published literature and recommendations to synthesize possible patient management approaches demonstrated to improve treatment outcomes in high-resourced countries for patients with MDR TB and HIV. Approaches to diagnostic testing, impact and timing of antiretroviral therapy on mortality, anti-MDR TB and antiretroviral drug interactions, and the potential role for short-course MDR TB therapy are examined. The combination of antiretroviral therapy with expanded TB drug therapy, along with the management of immune reconstitution inflammatory syndrome, other potential HIV-associated opportunistic diseases, and drug toxicities, necessitate an integrated multidisciplinary patient care approach using public health case management and provider expertise in drug-resistant TB and HIV management.

Drug pharmacokinetics may be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). Ensuring the optimized effective dosing of antimicrobials on ECMO remains a challenge. To date, limited data are available regarding the optimal use of amphotericin and triazoles during ECMO. We report a case of altered pharmacokinetics, insufficient liposomal amphotericin B and isavuconazole levels, and the need for escalated doses during ECMO in a patient with severe acute respiratory distress syndrome secondary to pulmonary blastomycosis. A 2-fold increase in the standard total daily dose of both drugs was necessary to overcome low serum concentrations thought to be secondary to drug loss from ECMO circuit sequestration. These findings have important implications for optimizing antimicrobial therapy in patients receiving ECMO to maximize therapeutic efficacy. The use of therapeutic drug monitoring for patients receiving antimicrobial therapy with concurrent ECMO may facilitate appropriate drug dosing to achieve adequate serum concentrations and optimize favorable patient outcomes. Further studies exploring antimicrobial pharmacokinetics during ECMO are needed to inform dosing recommendations in critically ill patients.

Background Immunocompromised individuals are at risk for Nocardia infection, with a recurrence rate of approximately 5%. Solid organ transplant (SOT) recipients often receive secondary prophylaxis due to their requirement of lifelong immunosuppression. However, data supporting this practice is sparse. We sought to evaluate Nocardia recurrence in SOT recipients, specifically evaluating secondary prophylaxis. Methods We conducted a retrospective cohort study of SOT recipients diagnosed with nocardiosis from 2000 through 2020. We included adult SOT recipients who completed their course of Nocardia therapy and had at least 6 months of post-therapy follow-up. The primary outcome was Nocardia recurrence, which included relapse and reinfection. Results 102 patients met inclusion criteria. Sixty-six (64.7%) were male and mean age was 58.6±11.7 years. Most common SOT types were kidney (46.1%), heart (18.6%), kidney-pancreas (11.8%), and lung (10.8%). Most common sites of infection were lung (85.3%), skin (17.6%), and brain (14.7%). Secondary prophylaxis was utilized in 53 (52.0%) patients. TMP-SMX single-strength daily was the most common prophylaxis agent and dose. Five patients (4.9%) experienced Nocardia recurrence, 3 of which were receiving secondary prophylaxis at time of recurrence. Two recurrences were with the same Nocardia species. Factors associated with recurrence were lung transplantation (p = 0.011), chronic lung disease (p = 0.032), and treatment ≤ 120 days (p = 0.006). Time from treatment completion to recurrence ranged from 107 to 875 days. Conclusions Nocardia recurrence in SOT recipients is an uncommon event. TMP-SMX secondary prophylaxis is incompletely protective and recurrence may be dependent upon other factors. Further study of secondary prophylaxis is warranted. This article is protected by copyright. All rights reserved.

BACKGROUND Exercise testing is important in people with cystic fibrosis (pwCF). The aim was to develop an incremental maximal step test to assess exercise capacity across the range of pwCF, without floor or ceiling effects, within restrictions of space, and infection prevention. METHODS The step test was developed in adults with stable CF. Subjects assisted in selecting: step height, start rate, increments, stage and test duration parameters. Equipment to externally pace and time the test and measure exercise parameters were selected. Reasons for stopping, criteria for achieving a maximal test, and key outcome measures were determined. Documentation to record and standardize the test and instructions to set up the metronome and timer App were developed. Infection control practices were considered. RESULTS Eight subjects were recruited to develop the Alfred Step Test Exercise Protocol (A-STEP) on a 20 cm portable step. The A-STEP package included a pretest information sheet, clinical assessment and instructions, recording worksheet, and the metronome/timer instructions. The test started at 18 steps/min. Each level increased by two steps/min to a maximum of 48 steps (Level 16). Results were presented as mean (SD) [range] for: age 30.63 (5.89) [21-39] years; FEV1 58.13 (18.33) [32-89]%; levels: 10.31 (3.29) [6-15.5]. The A-STEP required space of 2 m2 and complied with current infection control guidelines. CONCLUSIONS The A-STEP is a new incremental maximal step test to assess exercise capacity in pwCF, without floor or ceiling effects. It addresses the issues of space restrictions and the need for strict infection prevention in the clinical setting.

Background Quality of life has improved dramatically over the past two decades in people with cystic fibrosis (CF). Quantification has been enabled by patient-reported outcome measures (PROMs); however, many are lengthy and can be challenging to use in routine clinical practice. We propose a short-form PROM that correlates well with established quality-of-life measures. Methods We evaluated the utility of a 10-item score (AWESCORE) by measuring reliability, validity and responsiveness in adults with CF. The questions were developed by thematic analysis of survey questions to patients in a single adult CF centre. Each question was scored using a numerical rating scale 0 to 10. Total scores ranged from 0 to 100. Test–retest reliability was assessed over 24 h. To determine validity, comparisons were sought between stable subjects and those in pulmonary exacerbation, and between AWESCORE and Cystic Fibrosis Questionnaire – Revised (CFQ-R). Responsiveness to pulmonary exacerbation in individual subjects was evaluated. Results Five domains, each with two questions, were identified for respiratory, physical, nutritional, psychological and general health. A total of 246 consecutive adults attending the outpatient clinic completed the AWESCORE. Scores were higher during clinical stability compared to pulmonary exacerbation (mean± sd): 73±11 versus 48±11 (p, The AWESCORE: a new, short patient-reported outcome measure for adults with cystic fibrosis in clinical settings. It is feasible, valid, reliable and responsive to change, and developed to enhance communication and decision-making in clinical practice. https://bit.ly/2TWDaj3

The purpose of this study is to compare masks (non-medical/fabric, surgical, and N95 respirators) on filtration efficiency, differential pressure, and leakage with the goal of providing evidence to improve public health messaging. Masks were tested on an anthropometric face filtration mount comparing both sealed and unsealed. Overall, surgical and N95 respirators provided significantly higher for filtration efficiency and differential pressure. Leakage comparisons are one of the most significant factors in mask efficiency. Higher weight and thicker fabric masks had significantly higher filtration efficiency. The findings of this study have important implications for communication and education regarding the use of masks to prevent the spread of COVID-19 and other respiratory illnesses specifically the differences between sealed and unsealed masks. One-Sentence Summary: The type and fabric of facial masks and whether a mask is sealed or unsealed has a significant impact on the effectiveness of a mask.

Summary Background Tezacaftor–ivacaftor is an approved cystic fibrosis transmembrane conductance regulator (CFTR) modulator shown to be efficacious and generally safe and well tolerated over 8–24 weeks in phase 3 clinical studies in participants aged 12 years or older with cystic fibrosis homozygous for the Phe508del CFTR mutation (F/F; study 661-106 [EVOLVE]) or heterozygous for the Phe508del CFTR mutation and a residual function mutation (F/RF; study 661-108 [EXPAND]). Longer-term (>24 weeks) safety and efficacy of tezacaftor–ivacaftor has not been assessed in clinical studies. Here, we present results of study 661-110 (EXTEND), a 96-week open-label extension study that assessed long-term safety, tolerability, and efficacy of tezacaftor–ivacaftor in participants aged 12 years or older with cystic fibrosis who were homozygous or heterozygous for the Phe508del CFTR mutation. Methods Study 661-110 was a 96-week, phase 3, multicentre, open-label study at 170 clinical research sites in Australia, Europe, Israel, and North America. Participants were aged 12 years or older, had cystic fibrosis, were homozygous or heterozygous for Phe508del CFTR, and completed one of six parent studies of tezacaftor–ivacaftor: studies 661-103, 661-106, 661-107, 661-108, 661-109, and 661-111. Participants received oral tezacaftor 100 mg once daily and oral ivacaftor 150 mg once every 12 h for up to 96 weeks. The primary endpoint was safety and tolerability. Secondary endpoints were changes in lung function, nutritional parameters, and respiratory symptom scores; pulmonary exacerbations; and pharmacokinetic parameters. A post-hoc analysis assessed the rate of lung function decline in F/F participants who received up to 120 weeks of tezacaftor–ivacaftor in studies 661-106 (F/F) and/or 661-110 compared with a matched cohort of CFTR modulator-untreated historical F/F controls from the Cystic Fibrosis Foundation Patient Registry. Primary safety analyses were done in all participants from all six parent studies who received at least one dose of study drug during this study. This study was registered at ClinicalTrials.gov ( NCT02565914 ). Findings Between Aug 31, 2015, to May 31, 2019, 1044 participants were enrolled in study 661-110 from the six parent studies of whom 1042 participants received at least one dose of study drug and were included in the safety set. 995 (95%) participants had at least one TEAE; 22 (2%) had TEAEs leading to discontinuation; and 351 (34%) had serious TEAEs. No deaths occurred during the treatment-emergent period; after the treatment-emergent period, two deaths occurred, which were both deemed unrelated to study drug. F/F (106/110; n=459) and F/RF (108/110; n=226) participants beginning tezacaftor–ivacaftor in study 661-110 had improvements in efficacy endpoints consistent with parent studies; improvements in lung function and nutritional parameters and reductions in pulmonary exacerbations observed in the tezacaftor–ivacaftor groups in the parent studies were generally maintained in study 661-110 for an additional 96 weeks. Pharmacokinetic parameters were also similar to those in the parent studies. The annualised rate of lung function decline was 61·5% (95% CI 35·8 to 86·1) lower in tezacaftor–ivacaftor-treated F/F participants versus untreated matched historical controls. Interpretation Tezacaftor–ivacaftor was generally safe, well tolerated, and efficacious for up to 120 weeks, and the safety profile of tezacaftor–ivacaftor in study 661-110 was consistent with cystic fibrosis manifestations and with the safety profiles of the parent studies. The rate of lung function decline was significantly reduced in F/F participants, consistent with cystic fibrosis disease modification. Our results support the clinical benefit of long-term tezacaftor–ivacaftor treatment for people aged 12 years or older with cystic fibrosis with F/F or F/RF genotypes. Funding Vertex Pharmaceuticals Incorporated.

The occurrence of telomere attrition in brain may cause senescence and death of neurons, leading to cognitive decline. Folic acid (FA) has been reported to improve cognitive performance in mild cognitive impairment; however, its association with telomere remains unclear. The study aimed to investigate if alleviation of telomere attrition by FA supplementation could act as a potential mechanism to delay age-related cognitive decline in senescence-accelerated mouse prone 8 (SAMP8). Aged SAMP8 mice were assigned to four treatment groups: FAdeficient diet (FA-D) group, FA-normal diet (FA-N) group, low FA-supplemented diet (FA-L) group and high FAsupplemented diet (FA-H) group. There was also an age-matched senescence-accelerated mouse resistant 1 (SAMR1) control group (Con-R), and a young SAMP8 control group (Con-Y). The results demonstrated that FA supplementation delayed age-related cognitive decline and neurodegeneration in SAMP8 mice. Importantly, this effect could be attributed to the alleviated telomere attrition, which might be interpreted by the decreased levels of reactive oxygen species. Additionally, improved telomere integrity stimulated mitochondrial function via telomere-p53-mithondria pathway, consequently delayed neuronal degeneration. In conclusion, we demonstrate that FA supplementation delays age-related neurodegeneration and cognitive decline in SAMP8 mice, in which alleviated telomere attrition could serve as one influential factor in the process.

Background: The American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America jointly sponsored this new practice guideline on the treatment of drug-resistant tuberculosis (DR-TB). The document includes recommendations on the treatment of multidrug-resistant TB (MDR-TB) as well as isoniazid-resistant but rifampin-susceptible TB. Methods: Published systematic reviews, meta-analyses, and a new individual patient data meta-analysis from 12,030 patients, in 50 studies, across 25 countries with confirmed pulmonary rifampin-resistant TB were used for this guideline. Meta-analytic approaches included propensity score matching to reduce confounding. Each recommendation was discussed by an expert committee, screened for conflicts of interest, according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: Twenty-one Population, Intervention, Comparator, and Outcomes questions were addressed, generating 25 GRADE-based recommendations. Certainty in the evidence was judged to be very low, because the data came from observational studies with significant loss to follow-up and imbalance in background regimens between comparator groups. Good practices in the management of MDR-TB are described. On the basis of the evidence review, a clinical strategy tool for building a treatment regimen for MDR-TB is also provided. Conclusions: New recommendations are made for the choice and number of drugs in a regimen, the duration of intensive and continuation phases, and the role of injectable drugs for MDR-TB. On the basis of these recommendations, an effective all-oral regimen for MDR-TB can be assembled. Recommendations are also provided on the role of surgery in treatment of MDR-TB and for treatment of contacts exposed to MDR-TB and treatment of isoniazid-resistant TB.

Nontuberculous mycobacteria (NTM) comprise a heterogeneous group of organisms, with only a small subset known to cause disease in humans. Although NTM infection is not a reportable disease, both the increasing clinical recognition and recent advancements in laboratory diagnostic capabilities of NTM infections in immunocompromised and immunocompetent patients are rapidly evolving. We reviewed antimicrobial agents used to treat the most frequently encountered NTM infections and examined optimized drug dosing strategies, toxicity profiles, drug-drug interactions, and the role of therapeutic drug monitoring. Antimicrobial susceptibility testing and patient monitoring on therapy were also examined. We used PubMed to review the published literature on the management of select NTM pathogens, the common syndromes encountered since 2000, and select pharmacokinetic principles of select antimicrobial agents used since 1990. We included select clinical trials, systematic reviews, published guidelines, and observational studies when applicable. The prolonged duration and the necessity for combination therapy for most forms of NTM disease can be problematic for many patients. A multidisciplinary care team that includes pharmacy engagement may help increase rates of optimal patient tolerability and successful treatment completion.

Introduction: Mycobacterium scrofulaceum infection has been identified in cases of paediatric cervical lymphadenitis but is less well defined in adults. To further characterize manifestations of M....

Background Radiation therapy for malignant head and neck cancers includes a risk for off-target effects to bony structures, posing a risk for osteoradionecrosis (ORN). Patients in whom ORN develops can also harbor concomitant osteomyelitis and reduced healing capacity, making for a particularly challenging entity to treat. Hyperbaric oxygen therapy (HBO) has been shown to be effective in the treatment of mandibular ORN in the otolaryngology literature; yet, few reports exist detailing its utility when treating ORN of the craniocervical junction. Herein, we report 2 cases of ORN of the craniocervical junction who received both neoadjuvant and adjuvant HBO in combination with posterior spinal fusion. Case Description Two patients with craniocervical junction ORN were treated with HBO delivered over 20 sessions before and after surgery in 90-minute treatments to 2.5 atmospheres of pressure. The patients underwent posterior occipital–cervical fusions with an average operative time of 301 (±21.5) minutes with 250 (±150) mL of blood loss. Both patients stayed in the hospital for 5 days, with no periprocedural complications. Outcomes included a 30% improvement of global assessment of function on follow-up EuroQol 5-Dimension Questionnaire. Postoperative imaging demonstrated solid bony fusion, and both patients returned to full work duty. Conclusions ORN is a difficult-to-treat radiation complication in head and neck cancers. Few reports exist detailing treatment options for ORN of the craniocervical junction in conjunction with surgical stabilization. We report 2 successful cases of HBO-assisted treatment of ORN and highlight the important role HBO can play in promoting bony fusion in these at-risk patients.

Objectives To determine in women with clinically stable chronic lung disease (CLD) and healthy women; (1) prevalence of urinary incontinence; (2) risk factors for urinary incontinence; (3) effects of a standard course of specialised physiotherapy treatment (PT) in women with CLD. Design Prospective prevalence study; PT study in CLD subgroup. Setting Tertiary metropolitan public hospital. Participants Women with cystic fibrosis (CF, n = 38), chronic obstructive pulmonary disease (COPD, n = 27) and 69 healthy women without CLD. PT study — 10 women with CLD. Interventions Five continence PT sessions over 3 months. Main outcome measures Prevalence and impact of incontinence (questionnaire), number of leakage episodes (7-day accident diary), pelvic floor muscle function (ultrasound imaging) and quality of life (King’s Health Questionnaire). Results The majority of women in all three groups reported episodes of incontinence (CF 71%; COPD 70%; healthy women 55%). Compared to age-matched healthy controls, women with CF reported more episodes of incontinence (P = 0.006) and more commonly reported stress incontinence (P = 0.001). A logistic regression model revealed that women with CLD were twice as likely to develop incontinence than healthy women (P = 0.05). Women with COPD reported significantly more ‘bother’ with incontinence than age-matched women with incontinence. There was a significant reduction in incontinence episodes following treatment, which was maintained after three months. Conclusions The presence of CLD is an independent predictor of incontinence in women. In older women this is associated with more distress than in age-matched peers without CLD. Larger treatment studies are indicated for women with CLD and incontinence.

This mixed methods retrospective case series and qualitative descriptive study describes pregnancy outcomes during the postincarceration period. A retrospective case series via electronic medical record chart review from a subset of women attending a postincarceration primary care clinic with a condition of interest (pregnancy) described demographics, substance use, diagnoses, and pregnancy outcomes. We compared 27 pregnant to 79 nonpregnant women and contextualized quantitative data with qualitative descriptive vignettes. Twenty-seven women completed 29 pregnancies (2 women with 2 deliveries each), all of which were unplanned; there were 11 live births, 8 pregnant at study closure, 7 miscarriages, and 3 terminations. Although substance use history was high, rates were higher among nonpregnant women (92% vs 74%). Among the 5 births, 4 tested positive for substance use during pregnancy. All 11 infants had pregnancy or delivery complications. Although 7 of the 10 pregnant women with live births had prior pregnancy complications, only 4 were placed in a special care obstetrics clinic. Although unplanned pregnancies were common, most births did not demonstrate maternal substance use. All live births had pregnancy or delivery complications, but few were accepted to specialist prenatal care, suggesting potential considerations for recently incarcerated women.

Psychiatric and justice-involved populations are known to be stigmatized and particularly vulnerable to adverse outcomes during COVID-19. The increased attention toward vulnerable populations from healthcare authorities, the media, and the general public has made it critical to uncover any developing stigmatization toward these groups and the possible consequences. The prioritization of public safety and shift in the prioritization of resource allocation and service delivery could lead to a rise in negative perceptions toward these already stigmatized groups. Thus, it is imperative to consider how the unique characteristics of vulnerable groups may impact their physical and mental health as well as their care during this pandemic. In this paper, we describe the challenges that psychiatric, correctional, and forensic psychiatry populations have faced during COVID-19 and how a rise in stigmatization could lead to adverse outcomes. Specifically, we outline the influence of the media on public perceptions and how stigmatization may be reflected in the allocation of resources, policies, and related decision-making during COVID-19., Highlights • Psychiatric and justice-involved populations are vulnerable during COVID-19. • Understanding perceptions toward vulnerable populations during COVID-19 is critical. • Stigma toward vulnerable groups may increase during COVID-19. • Stigma may be exacerbated by the media among vulnerable groups. • Stigma may affect the allocation of resources and healthcare access during COVID-19.

PURPOSE Sport-related concussion (SRC) is a known risk of contact sports and strategies have been employed to help minimize risk. Multiple NCAA conferences and professional sports leagues have instituted independent medical spotters (IMS) to serve as "eyes in the sky" during events to help identify SRCs. We aimed to determine if the IMS identified more SRCs than would otherwise be detected by the trained sideline medical staff …

Folic acid (FA) has been reported to inhibit astrocyte apoptosis and improve aging-induced disorders; however, its role in telomere attrition remains unclear. In present study, 4-month-old senescence-accelerated mouse prone 8 (SAMP8) mice were assigned to four treatment groups for the in vivo experiment: FA-deficient diet (FA-D) group, FA-normal diet (FA-N) group, low FA-supplemented diet (FA-L) group, and high FA-supplemented diet (FA-H) group. These mice were euthanized when 10 months old. There was also a young SAMP8 (4 months old) control group (Con-Y) fed with FA-normal diet. In in vitro study, primary cultures of astrocytes from hippocampus and cerebral cortex were incubated for five generations with various concentrations of FA (0–40 μM) and were assigned to five groups: FA 0 μM (generation 5), FA 10 μM (generation 5), FA 20 μM (generation 5), FA 40 μM (generation 5), and FA 10 μM (generation 1). The results showed that FA supplementation inhibited aging-induced astrocytosis, astrocyte apoptosis, neurodegeneration, and prevented telomere attrition in hippocampus and cortex of SAMP8 mice. FA supplementation also decreased apoptosis and telomere attrition, and increased telomerase activity, in primary cultures of astrocytes. These results showed that it may be one of the mechanisms that FA inhibiting aging-induced apoptosis of astrocyte by alleviating telomere attrition.

Introduction Intimate partner violence (IPV) and suicide are pressing public health issues, yet their intersection in mental health care settings is understudied. We conducted a qualitative study to characterize mental health therapists' personal and system barriers in preparation for an upcoming training curriculum seeking to help patients address these interconnected issues. Method We partnered with an urban community mental health center in New York to facilitate focus groups grounded in community-based participatory research principles. Twenty-three therapists formed 3 focus groups. Participant responses were audio-recorded, transcribed, and coded using Bronfenbrenner's socioecological model. We performed a primary qualitative framework analysis, coding for therapist barriers in addressing the intersection of IPV-suicide at individual, relational, community, and societal levels. Results Therapists perceived numerous barriers in all 4 domains. Individually, some struggled with feelings of helplessness and a lack of appropriate training. At the relational level, therapists expressed apprehension about harming the therapeutic relationship by discussing IPV and suicide at length. From a community perspective, therapists voiced concerns for clients' limited local access to support systems and financial resources. Societal barriers included policy-related limitations such as length of appointment times. Discussion Community mental health center therapists face considerable barriers working with patients affected by IPV and suicide. The socioecological model is a fitting framework for understanding multisystem barriers at individual, relational, community, and societal levels. A better understanding of these challenges is critical for advancing therapist education, enhancing patient outcomes, and improving health systems. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background In 2019, the World Health Organization released guidelines reflecting major changes in multidrug-resistant tuberculosis (MDR-TB) management—prioritizing fluoroquinolones, bedaquiline, and linezolid (LZD) while de-emphasizing previously favored injectable agents. In some cases, linezolid use is associated with gastrointestinal intolerance, mitochondrial toxicity, and significant drug interactions. CDC’s Division of Tuberculosis Elimination supports a network of regional TB Centers of Excellence, which provide medical consultation to healthcare providers. Consultations are documented in a medical consultation database (MCD) enabling evaluation of management questions and recommendations. We describe the scope of clinical inquiries and responses specific to linezolid use for MDR-TB in the US. Research Question What are the major themes of provider and patient challenges regarding the use of linezolid for the treatment of MDR-TB in the US? Methods We queried MCD consults categorized as “MDR/XDR-TB” from 1/1/2013 to 12/31/2018. Only linezolid-specific consultations were included; incomplete and duplicate entries were excluded as were those citing linezolid historically or theoretically. Subgroup characteristics were assessed (e.g., Center, year, provider type). A descriptive coding scheme was developed through inductive thematic analysis. Results In 2013–2018 of the 1889 consults regarding MDR/XDR-TB, 934 MDR-TB consults referenced linezolid; 137 met inclusion criteria, representing between 4 and 10% of MDR-TB consults annually. Four main themes emerged: adverse effects (71.5%); concerns about linezolid use due to co-morbidities or concurrent medication use (15.3%); dosing adjustments (8.8%); and monitoring and maintenance logistics (4.4%). Interpretations Linezolid consults consistently exceeded 4% of all consults annually over the 6-year period, suggesting a need for access to expert opinion for providers using linezolid to manage MDR-TB. While only a snapshot of MDR-TB in the US, this evaluation summarizes major provider concerns regarding particular adverse effects, and highlights a need for evidence-based guidance regarding linezolid dosing and toxicity management.

Introduction Lumacaftor/ivacaftor (LUM/IVA) has been shown to improve clinical outcomes in cystic fibrosis (CF) patients homozygous for Phe508del with forced expiratory volume in 1 s (FEV1) % pred >40%. We assessed the clinical utility of LUM/IVA in all eligible adult CF patients with FEV1 % pred, In adults with severe cystic fibrosis lung disease, 1 year of treatment with lumacaftor/ivacaftor was associated with reduced infective exacerbations, days of intravenous antibiotics and rate of pulmonary function decline, and improved nutritional status https://bit.ly/2I07suR

Historically, the surgical management of gunshot wounds to the spine has been controversial. Repair of a persistent cerebrospinal fluid (CSF) leak is a generally agreed upon indication. The management of such CSF leaks typically involves lumbar drainage or direct surgical repair. Here, the authors report two cases of CSF diversion with an external ventricular drain (EVD) in patients with cervical gunshot wounds. Both patients had spinal canal obliteration or physiologic myelographic block at or below the level of injury. To the best of the author’s knowledge, these are the first two reports of successful EVD treatment of persistent CSF leaks related cervical gunshot wounds. The authors also propose a CSF treatment algorithm for cervical gunshot wounds that includes EVD.

Objective To study the impact of a 60-day pilot of an innovative virtual-care model using general internal medicine physicians and nurses to respond rapidly to more than 1200 coronavirus disease-2019 (COVID-19)-positive nasopharyngeal polymerase chain reaction tests. Patients and Methods The current study was approved by the Mayo Clinic COVID-19 Research Committee and the Mayo Clinic Institutional Review Board. The data for all SARS-CoV-2–positive patients treated by our team were entered into a prospectively maintained internal research electronic data capture database. We searched this database retrospectively for the first 60 days of our program (March 23, 2020 to May 22, 2020). The data included basic deidentified demographics; symptoms at intake into the program; date of symptom onset; risk factors; location; and outcomes including hospitalization, admission to intensive care unit, and death. Results Patients were contacted, on average, 6.3 hours after their results became available. There was a total of 138 ED visits. Of these, 40% were admitted to the hospital, with 36% of those admitted requiring intensive care unit level of care. Of the 849 patients in this sample, there were only 2 deaths (0.23%) at 60 days. Conclusion Our innovative multidisciplinary COVID team provided excellent clinical care for patients with COVID, with a very low mortality rate compared with the national average. Although data are not available on a national scale for time to contact patient, our team was able to contact patients within the established recommendation for contact within 48 hours of testing, which is optimal.

Rationale: Current diagnostic tests fail to identify individuals at higher risk of progression to tuberculosis disease, such as those with recent Mycobacterium tuberculosis infection, who should be prioritized for targeted preventive treatment. Objectives: To define a blood-based biomarker, measured with a simple flow cytometry assay, that can stratify different stages of tuberculosis infection to infer risk of disease. Methods: South African adolescents were serially tested with QuantiFERON-TB Gold to define recent (QuantiFERON-TB conversion 1 yr) infection. We defined the ΔHLA-DR median fluorescence intensity biomarker as the difference in HLA-DR expression between IFN-γ+ TNF+ Mycobacterium tuberculosis–specific T cells and total CD3+ T cells. Biomarker performance was assessed by blinded prediction in untouched test cohorts with recent versus persistent infection or tuberculosis disease and by unblinded analysis of asymptomatic adolescents with tuberculosis infection who remained healthy (nonprogressors) or who progressed to microbiologically confirmed disease (progressors). Measurements and Main Results: In the test cohorts, frequencies of Mycobacterium tuberculosis–specific T cells differentiated between QuantiFERON-TB− (n = 25) and QuantiFERON-TB+ (n = 47) individuals (area under the receiver operating characteristic curve, 0.94; 95% confidence interval, 0.87–1.00). ΔHLA-DR significantly discriminated between recent (n = 20) and persistent (n = 22) QuantiFERON-TB+ (0.91; 0.83–1.00); persistent QuantiFERON-TB+ and newly diagnosed tuberculosis (n = 19; 0.99; 0.96–1.00); and tuberculosis progressors (n = 22) and nonprogressors (n = 34; 0.75; 0.63–0.87). However, ΔHLA-DR median fluorescent intensity could not discriminate between recent QuantiFERON-TB+ and tuberculosis (0.67; 0.50–0.84). Conclusions: The ΔHLA-DR biomarker can identify individuals with recent QuantiFERON-TB conversion and those with disease progression, allowing targeted provision of preventive treatment to those at highest risk of tuberculosis. Further validation studies of this novel immune biomarker in various settings and populations at risk are warranted.

Mycobacterium septicum is a rarely identified nontuberculous mycobacterium capable of causing infections in both healthy and immunocompromised individuals. Only a few cases of M. septicum infections have been reported, which makes recognizing corresponding clinical disease more challenging for clinicians. Antimicrobial susceptibility profiles for this organism are not well described, and corresponding optimal therapeutic regimens have not been established. We report a tertiary care center’s experience with M. septicum from 2014 to 2020. Twelve adult patients with positive cultures for M. septicum were identified. Most cases were identified from sputum samples of individuals with underlying lung disease. Most cases involving M. septicum isolation in culture were not felt to be clinically significant. Two cases were considered possible infections, while only one case was considered a definite infection that required antimicrobial treatment. All M. septicum isolates were susceptible in vitro to amikacin, ciprofloxacin, imipenem, linezolid, moxifloxacin, and trimethoprim-sulfamethoxazole. Isolates were universally resistant to clarithromycin and doxycycline. The isolation of M. septicum in culture is uncommon and requires clinical correlation to determine its clinical relevance and need for treatment. Susceptibility testing should be performed to guide therapy.

Many collegiate athletes use scooters and mopeds for transportation, and they are at greater risk for head injury without helmets. Objective: Investigate college athletes' reasons for wearing/not wearing helmets while riding a scooter or moped. Participants, Methods: 125 Division I athletes across five teams (two with helmet mandates) completed a cross sectional survey on rates and attitudes about helmet use on scooters or mopeds. Results: Helmet use on mandated vs non-mandated teams was 100% vs 3.6% (OR 1141; 95% CI 56.97, 22,850). For the question, "if you do not wear a helmet, what might make you change your mind and wear one?", players most commonly wrote in a law or coaches' rule (57%). Conclusions: A coach's rule is associated with a higher rate of helmet use in collegiate athletes, and athletes primarily report a rule or law as the reason they would wear a helmet on a scooter or moped.

Drug treatment court (DTC) is a diversion program for individuals with drug-related crimes. However, the DTC literature is conflicting with regard to substance use and recidivism outcomes. This study examines factors associated with improved client outcome trajectories among a multisite, national DTC sample. We conducted a secondary analysis of 2,295 participants using the Global Appraisal of Individual Needs assessment tool. Participants in community-based treatment comprised a nonequivalent comparison group. Zero-inflated Poisson (ZIP) regression examined client sociodemographics in relation to substance use and rearrest at 6-month follow-up. Employed DTC clients were more likely to abstain from substances, but among all study participants, higher baseline use, male gender, and employment predicted substance use. Similarly, among DTC clients, older age and employment predicted no rearrests, but among all study participants, older and employed individuals had worse arrest outcome trajectories. Future work is needed to better understand how client characteristics may inform individualized treatment approaches.

Objectives In patients with cystic fibrosis (CF) who carry the G551D mutation, treatment with ivacaftor improves lung function and weight; however, short- and long-term impacts on body composition have not been well studied. Methods Twenty adults with CF carrying the G551D mutation (mean ± standard deviation body mass index [BMI] 23.3 ± 4.3 kg/m2) were recruited for a single-center, double-blind, placebo-controlled, 28-d, crossover study of ivacaftor, followed by an open-label extension (OLE) for 5 mo. Eleven patients underwent measurements 2 y later. The study variables included weight, BMI, and body composition (including fat-free mass [FFM] and fat mass). Results After 28 d of treatment with ivacaftor, weight increased by 1.1 ± 1.3 kg, BMI by 0.4 ± 0.5 kg/m2, and FFM by 1.1 ± 1.2 kg (all P Conclusions Small gains were seen in FFM in the first month of ivacaftor treatment. Weight, BMI, and fat-mass gains in the first 6 mo on ivacaftor plateaued by 2.5 y. The metabolic and clinical consequences of weight and fat-mass gains remain to be determined.

Somatic expansion of the Huntington’s disease (HD) CAG repeat drives the rate of a pathogenic process ultimately resulting in neuronal cell death. Although mechanisms of toxicity are poorly delineated, transcriptional dysregulation is a likely contributor. To identify modifiers that act at the level of CAG expansion and/or downstream pathogenic processes, we tested the impact of genetic knockout, in HttQ111 mice, of Hdac2 or Hdac3 in medium-spiny striatal neurons that exhibit extensive CAG expansion and exquisite disease vulnerability. Both knockouts moderately attenuated CAG expansion, with Hdac2 knockout decreasing nuclear huntingtin pathology. Hdac2 knockout resulted in a substantial transcriptional response that included modification of transcriptional dysregulation elicited by the HttQ111 allele, likely via mechanisms unrelated to instability suppression. Our results identify novel modifiers of different aspects of HD pathogenesis in medium-spiny neurons and highlight a complex relationship between the expanded Htt allele and Hdac2 with implications for targeting transcriptional dysregulation in HD.

BackgroundPersons living with human immunodeficiency virus (HIV) are at a greater risk of developing tuberculosis (TB) compared to people without HIV and of developing complications due to the complexity of TB/HIV coinfection management.MethodsDuring 2013-2017, the Centers for Disease Control and Prevention (CDC) funded 5 TB Regional Training and Medical Consultation Centers (RTMCCs) (now known as TB Centers of Excellence or COEs) to provide medical consultation to providers for TB disease and latent TB infection (LTBI), with data entered into a Medical Consultation Database (MCD). Descriptive analyses of TB/HIV-related consultations were conducted using SAS® software, version [9.4] to determine the distribution of year of consultation, medical setting and provider type, frequency of consultations regarding a pediatric (ResultsOf 14,586 consultations captured by the MCD in 2013-2017, 544 (4%) were categorized as TB/HIV-related, with 100 (18%) received in 2013, 129 (24%) in 2014, 104 (19%) in 2015, 117 (22%) in 2016, and 94 (17%) in 2017. Most TB/HIV consultations came from nurses (54%) or physicians (43%) and from local (65%) or state health departments (10%). Only 17 (3%) of HIV-related consultations involved pediatric cases. Off the 544 TB/HIV consultations, 347 (64%) concerned the appropriate treatment regimen for TB/HIV or LTBI/HIV for a patient on or not on antiretroviral therapy (ART).ConclusionsThe data support a clear and ongoing gap in areas of specialized HIV knowledge by TB experts that could be supplemented with proactive educational outreach. The specific categories of TB/HIV inquiries captured by this analysis are strategically informing future targeted training and educational activities planned by the CDC TB Centers of Excellence, as well as guiding HIV educational efforts at regional and national TB meetings.

Sensorineural hearing loss is a prevalent problem that adversely impacts quality of life by compromising interpersonal communication. While hair cell damage is readily detectable with the clinical audiogram, this traditional diagnostic tool appears inadequate to detect lost afferent connections between inner hair cells and auditory nerve (AN) fibers, known as cochlear synaptopathy. The envelope-following response (EFR) is a scalp-recorded response to amplitude modulation, a critical acoustic feature of speech. Because EFRs can have greater amplitude than wave I of the auditory brainstem response (ABR; i.e., the AN-generated component) in humans, the EFR may provide a more sensitive way to detect cochlear synaptopathy. We explored the effects of kainate- (kainic acid) induced excitotoxic AN injury on EFRs and ABRs in the budgerigar (Melopsittacus undulatus), a parakeet species used in studies of complex sound discrimination. Kainate reduced ABR wave I by 65–75 % across animals while leaving otoacoustic emissions unaffected or mildly enhanced, consistent with substantial and selective AN synaptic loss. Compared to wave I loss, EFRs showed similar or greater percent reduction following kainate for amplitude-modulation frequencies from 380 to 940 Hz and slightly less reduction from 80 to 120 Hz. In contrast, forebrain-generated middle latency responses showed no consistent change post-kainate, potentially due to elevated “central gain” in the time period following AN damage. EFR reduction in all modulation frequency ranges was highly correlated with wave I reduction, though within-animal effect sizes were greater for higher modulation frequencies. These results suggest that even low-frequency EFRs generated primarily by central auditory nuclei might provide a useful noninvasive tool for detecting synaptic injury clinically.

Damage to auditory-nerve-fiber synapses (i.e. cochlear synaptopathy) degrades the neural coding of sound and is predicted to impair sound perception in noisy listening environments. However, establishing a causal relationship between synaptopathy and speech intelligibility is difficult because we have no direct access to synapse counts in humans. Hence, we rely on the quality of noninvasive auditory-evoked potential (AEP) markers developed in rodent studies of histologically-verified synaptopathy. However, there are a number of reasons which render the interpretation of these markers in humans difficult. To bridge this translational gap, we apply a multi-method approach to enable a meaningful interpretation of the relationship between the histopathology of sensorineural hearing loss (SNHL) and speech perception. We first selected a synaptopathy-sensitive AEP marker and verified its sensitivity (i) in an animal model using a Kainic-acid induced synaptopathy, and (ii), via auditory model simulations which connect the histopathology of SNHL to the source generators of AEPs. Secondly, we restricted the frequency content of the speech-material to ensure that both AEP and speech metrics targeted similar cochlear frequency regions and associated auditory coding mechanisms. Following this approach, we studied the relative contribution of AEP markers of synaptopathy and hearing sensitivity to speech recognition thresholds in 44 listeners (24 women) of different ages and SNHL profiles. Our analysis shows that synaptopathy plays an important role for speech intelligibility in noise, but that outer-hair-cell integrity predicts performance in the absence of noise. Our results corroborate conclusions from animal studies regarding the prevalence of age-related synaptopathy, and its occurrence before outer-hair-cell loss damage.Significance StatementTemporal-bone histology demonstrates that cochlear synaptopathy, i.e. damage to inner-hair-cell auditory-nerve fiber synapses, sets in before sensory cell damage and associated hearing threshold elevation. Clinical practice assesses hearing status on the basis of audiometric thresholds, and is hence overlooking a -likely prevalent-aspect of sensorineural hearing damage given that ageing, noise exposure or ototoxic drugs can cause synaptopathy. We present a multi-method approach to study the relationship between synaptopathy and speech intelligibility and address an important unresolved issue in hearing science, namely why speech-intelligibility-in-noise degrades as we age, even when hearing sensitivity remains normal. Our study outcomes have important implications for hearing diagnostics and treatment.

The American Board of Neurological Surgery (ABNS) was incorporated in 1940 in recognition of the need for detailed training in and special qualifications for the practice of neurological surgery and for self-regulation of quality and safety in the field. The ABNS believes it is the duty of neurosurgeons to place a patient’s welfare and rights above all other considerations and to provide care with compassion, respect for human dignity, honesty, and integrity. At its inception, the ABNS was the 13th member board of the American Board of Medical Specialties (ABMS), which itself was founded in 1933. Today, the ABNS is one of the 24 member boards of the ABMS.To better serve public health and safety in a rapidly changing healthcare environment, the ABNS continues to evolve in order to elevate standards for the practice of neurological surgery. In connection with its activities, including initial certification, recognition of focused practice, and continuous certification, the ABNS actively seeks and incorporates input from the public and the physicians it serves. The ABNS board certification processes are designed to evaluate both real-life subspecialty neurosurgical practice and overall neurosurgical knowledge, since most neurosurgeons provide call coverage for hospitals and thus must be competent to care for the full spectrum of neurosurgery.The purpose of this report is to describe the history, current state, and anticipated future direction of ABNS certification in the US.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which presents an unprecedented challenge to medical providers worldwide. Although most SARS-CoV-2-infected individuals manifest with a self-limited mild disease that resolves with supportive care in the outpatient setting, patients with moderate to severe COVID-19 will require a multidisciplinary collaborative management approach for optimal care in the hospital setting. Laboratory and radiologic studies provide critical information on disease severity, management options, and overall prognosis. Medical management is mostly supportive with antipyretics, hydration, oxygen supplementation, and other measures as dictated by clinical need. Among its medical complications is a characteristic proinflammatory cytokine storm often associated with end-organ dysfunction, including respiratory failure, liver and renal insufficiency, cardiac injury, and coagulopathy. Specific recommendations for the management of these medical complications are discussed. Despite the issuance of emergency use authorization for remdesivir, there are still no proven effective antiviral and immunomodulatory therapies, and their use in COVID-19 management should be guided by clinical trial protocols or treatment registries. The medical care of patients with COVID-19 extends beyond their hospitalization. Postdischarge follow-up and monitoring should be performed, preferably using telemedicine, until the patients have fully recovered from their illness and are released from home quarantine protocols.

Collagen-producing cells maintain the complex architecture of the lung and drive pathologic scarring in pulmonary fibrosis. Here we perform single-cell RNA-sequencing to identify all collagen-producing cells in normal and fibrotic lungs. We characterize multiple collagen-producing subpopulations with distinct anatomical localizations in different compartments of murine lungs. One subpopulation, characterized by expression of Cthrc1 (collagen triple helix repeat containing 1), emerges in fibrotic lungs and expresses the highest levels of collagens. Single-cell RNA-sequencing of human lungs, including those from idiopathic pulmonary fibrosis and scleroderma patients, demonstrate similar heterogeneity and CTHRC1-expressing fibroblasts present uniquely in fibrotic lungs. Immunostaining and in situ hybridization show that these cells are concentrated within fibroblastic foci. We purify collagen-producing subpopulations and find disease-relevant phenotypes of Cthrc1-expressing fibroblasts in in vitro and adoptive transfer experiments. Our atlas of collagen-producing cells provides a roadmap for studying the roles of these unique populations in homeostasis and pathologic fibrosis., Collagen production by lung cells is critical to maintain organ architecture but can also drive pathological scarring. Here the authors perform single cell RNA sequencing of collagen-producing lung cells identifying a subset of pathologic fibroblasts characterized by Cthrc1 expression which are concentrated within fibroblastic foci in fibrotic lungs and show a pro-fibrotic phenotype.

Suicidal behavior occurs at much higher rates in correctional facilities than in the community, yet little is known about factors that distinguish inmates at risk for attempting versus dying by suicide. Individuals in the current study included 925 inmates housed in 2 large U.S. jails and 8 state correctional systems who attempted (79.5%) or died by (20.5%) suicide for whom archival data were available. Mental health professionals completed a tracking sheet after suicide-related incidents, documenting inmate psychological, diagnostic, and treatment related risk factors. Differences between inmates who attempt versus those who die by suicide indicate that when mental health staff are aware of inmates' current and historical risk factors, deaths by suicide are less likely to occur. (PsycINFO Database Record

The relevance of medical colleges has been questioned and their ability to respond to members' needs and system failures is unknown. We hypothesise that members believe that medical colleges are relevant to the current health agenda. We conducted a survey by email to determine satisfaction with the current state of the Royal Australasian College of Physicians (RACP) relevance and tested agreement with suggestions for change. We found that of 21 000 survey links sent, 13.1% of addressees replied. When questioned regarding the current state, less than 50% of respondents agreed with any of eight positive statements. Over two thirds supported involvement in policy and advocacy, as well as the use of digital plebiscites to express their views. Clarity around the use of members' subscriptions and value for money had the lowest scores. Of importance was the expression of need for a medical college (71%) and the finding that 58% of respondents would give more time to the RACP if asked. Of all respondents, 22% provided written comments that closely reflected scores on categorical questions. We conclude that, despite reported disengagement and lack of support for the current state, the majority of respondents to a survey of relevance believed in the need for a medical college.

Background: The U.S. Centers for Disease Control and Prevention (CDC) funds five Regional Tuberculosis Training and Medical Consultation Centers (RTMCCs) that provide training and consultation for tuberculosis (TB) control and management. RTMCC utilization for assistance with diagnosis and management of TB in children has not been described. We analyzed pediatric TB consultations performed across all RTMCCs in terms of question type, provider type, and setting. Methods: The CDC medical consultation database was queried for consultations regarding patients ≤ 18 years provided between 1/1/13–4/22/15 by all RTMCCs (Curry International TB Center, Heartland National TB Center, Mayo Clinic Center for TB, New Jersey Medical School Global TB Institute, Southeastern National TB Center). Each query was categorized into multiple subject areas based on provider type, setting, consultation topic, and patient age. Results: The 5 RTMCCs received 1164 pediatric consultation requests, representing approximately 20% of all consultations performed by the centers during the study period. Providers requesting consults were primarily physicians (46.3%) or nurses (45.0%). The majority of pediatric consult requests were from state and local public health departments (679, 58.3%) followed by hospital providers (199, 17.1%); fewer requests came from clinicians in private practice (84, 7.2%) or academic institutions (40, 3.4%). Consults addressed 14 different topics, most commonly management of children with TB disease (19.1%), latent TB infection (LTBI) (18.2%), diagnosis or laboratory testing (18.7%), and pharmacology (9.2%). Discussion: Pediatric consultations accounted for approximately 20% of all consultations performed by RTMCCs during the study period. RTMCCs were utilized primarily by public health departments regarding management of TB disease, LTBI, and diagnosis or laboratory testing. The relative underutilization of the RTMCCs by clinicians in non-public health settings, who often manage children with TB exposure or infection, warrants further study. As US TB case rates decline and providers become less experienced with childhood TB, medical consultation support may become increasingly important. Keywords: Tuberculosis, Pediatric, Consultation

In people with cystic fibrosis (CF) reduced fitness and lower levels of physical activity have been associated with poorer prognosis [1] and greater decline in lung function [2]. Despite the health benefits of being physically active [3], in people with CF adherence to exercise programmes is often poor [4], and prescribed exercise training programmes have seldom translated into increased daily physical activity [5]., Achieving physical activity guidelines by undertaking multiple bouts of moderate-vigorous physical activity ≥10 min duration, but not shorter periods of activity, was independently associated with less decline in FEV1 over 3 years among adults with CF http://ow.ly/yk6930ivCV8

Background: Significant resource constraints and critical care training gaps are responsible for the limited development of intensive care units (ICUs) in resource limited settings. We describe the implementation of an ICU in Haiti and report the successes and difficulties encountered throughout the process. We present a consecutive case series investigating an anesthesiologist, emergency, and critical care physician implemented endotracheal intubation and mechanical ventilation protocol in an austere environment with the assistance of telemedicine. Methods: A consecutive case series of fifteen patients admitted to an ICU at St. Luc Hospital located in Portau-Prince, Haiti, between the months of February 2012 to April 2014 is reported. Causes of respiratory failure and the clinical course are presented. Patients were followed to either death or discharge. Results: Fifteen patients (eight women and seven men) were included in the study with an average age of 37.7 years. The mean duration of ventilation was three days. Of the fifteen patients intubated, five patients (33.3%) survived and were discharged from the ICU. Of the five surviving patients, two were intubated for status epilepticus, one for status asthmaticus and one for hyperosmolar coma associated with intracerebral hemorrhage. Of the patients dying on the ventilator, four patients died from pneumonia, two from renal failure, and one from tetanus. The remaining three died from strokes and cardiac arrests. Conclusions: Mortality of mechanically ventilated patients in a resource-limited country is significant. Focused training in core critical care skills aimed at increasing the endotracheal intubation and ventilatory management capacity of local medical staff should be a priority in order to continue to develop ICUs in these austere environments. Collaborative educational and training efforts directed by anesthesiologists, emergency, and critical care physicians, and aided by telemedicine can facilitate realizing this goal.

Background: Mycobacterium abscessus complex (MAbsC) is a significant management dilemma when taking care of patients with cystic fibrosis (CF). Methods: We undertook a retrospective cohort analysis of all CF patients in whom MAbsC was isolated from 2005 to 2014. The natural history of MAbsC was determined and clinical factors examined in an attempt to predict transient compared to persistent colonization. Results: No correlation was found between recurrent MAbsC isolation and clinical factors such as body mass index, respiratory function, or age. Over two-thirds of our cohort cleared MAbsC colonization with no intervention and no consistent effect on lung function was identified. Four CF patients were initiated on treatment with only one successful outcome. Conclusion: This analysis demonstrates there are no clear predictors of those CF patients who will become persistently colonized with MAbsC and that a significant proportion will spontaneously clear carriage. As treatment success rate is poor, more work is urgently required in improving patient outcomes.

Background G551D is a class III mutation of the cystic fibrosis transmembrane regulator (CFTR) that results in impaired chloride channel function in cystic fibrosis (CF). Ivacaftor, a CFTR-potentiating agent improves sweat chloride, weight, lung function, and pulmonary exacerbation rate in CF patients with G551D mutations, but its effect on the airway microbiome remains poorly characterised. Methods Twenty CF patients with at least one G551D mutation from a single centre were recruited to a 4month double-blind, placebo-controlled, crossover study of ivacaftor with 28days of active treatment. Sputum microbiota composition was assessed by 16S rRNA gene amplicon sequencing and quantitative PCR at five key time points, along with regular clinical review, respiratory function assessment, and peripheral blood testing. Results No significant difference in microbiota composition was observed in subjects following ivacaftor treatment or placebo (PERMANOVA P = 0.95, square root ECV=−4.94, 9479 permutations). Microbiota composition variance was significantly greater between subjects, than within subjects over time ( P U test), and an additional within-patient paired assessment of microbiota similarity was therefore performed. Again, change in microbiota composition was not significantly greater during treatment with ivacaftor compared to placebo (Wilcoxon test, P =0.51). A significant change in microbiota composition was however associated with any change in antibiotic exposure, regardless of whether ivacaftor or placebo was administered ( P =0.006). In a small, subgroup analysis of subjects whose antibiotic exposure did not change within the study period, a significant reduction in total bacterial load was observed during treatment with ivacaftor ( P =0.004, two-tailed paired Student's t- test). Conclusions The short-term impact of ivacaftor therapy on sputum microbiota composition in patients with G551D mutations are modest compared to those resulting from antibiotic exposure, and may be masked by changes in antibiotic treatment regimen.

Objective Large-scale studies analyzing neurosurgical published research are lacking. This pilot study was designed to assess feasibility of an ongoing annual neurosurgical literature and research analysis of published articles in English-language neurosurgery journals. Methods All scientific articles published during 2015 in the print version of 14 English-language neurosurgery journals were reviewed individually. Results During 2015, 4065 articles were published in 14 neurosurgical journals. Of these, 1116 (27.5%) were nonscientific articles and were excluded from the analysis, and 2949 scientific articles were analyzed. Of these, 2% and 8.5% of publications met criteria for levels of evidence 1 and 2, respectively. One third of published manuscripts (33.2%) were retrospective chart reviews. There were 1742 different centers (mean 1.95 centers per article; range, 1–19) represented in 2949 articles from 67 countries (mean 1.23 countries per article; range, 1–12). Multicenter collaboration was present in 47.5% of published articles, and international collaboration was present in 17.5%. The highest numbers of U.S. author international collaborations were with Canada (70 collaborations), China (33 collaborations) and Italy (25 collaborations). Data for levels of evidence, multicenter collaborations, and international collaborations are presented for each individual journal and subject within neurosurgery. Conclusions This pilot analysis provides a descriptive assessment of levels of evidence and collaboration based on journal, general subject matter, and subcategories of subject allowing for comparison. This methodology may be used on an annual basis to establish neurosurgery publication trends and to identify underrepresented areas of research within the specialty.

Patient: Female, 18-month-old Final Diagnosis: Moyamoya disease Symptoms: Seizures Medication: — Clinical Procedure: — Specialty: Neurosurgery Objective: Rare co-existance of disease or pathology Background: Cerebral hyperperfusion syndrome is a rare complication of indirect revascularization due to moyamoya disease, but has not been reported previously in the pediatric population. We present a case of an 18-month-old girl with moyamoya disease that was treated with bilateral pial synangiosis and had complications consistent with cerebral hyperperfusion syndrome. This case report discusses the pathophysiological mechanisms involved in cerebral hyperperfusion in moyamoya syndrome. Case Report: An 18-month-old female Caucasian presented with seizures and weakness of the left side. Angiography confirmed bilateral cerebral moyamoya disease that was worse on the right side. Indirect revascularization with pial synangiosis was first performed on the right side to allow for healing. Five months later, pial synangiosis was then performed on the left side. Postoperatively, the patient experienced increased intracranial pressure (ICP), suggesting cerebral hyperperfusion syndrome. She was treated with a repeat lumbar puncture, a lumbar drain, and a lumbar shunt. Conclusions: This report demonstrates a case of cerebral hyperperfusion syndrome as a complication of moyamoya disease in a pediatric patient. Although the patient progressed well after placement of a lumbar shunt, this case demonstrates the occurrence of cerebral hyperperfusion syndrome as a complication of revascularization in pediatric patients and highlights the need for further research in this area.