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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.

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.

Refereed/Peer-reviewed Objectives: To evaluate feasibility of the Alfred Step Test Exercise Protocol (A-STEP) for the assessment of exercise capacity in adults and children with cystic fibrosis (CF); in adults to test whether demographics and/or lung function correlated with exercise capacity Methods: Adults and children with stable CF from two centres completed the A-STEP (a recently developed incremental maximal-effort step test). Feasibility was evaluated by: usefulness for exercise capacity assessment (measures of exercise capacity were: level reached, exercise-induced desaturation, and achievement of at least one maximal effort criteria); safety; operational factors; time to complete; floor and/or ceiling effects. We used multiple linear regression to test whether demographics and/or lung function correlated with exercise capacity Results: A total of 49 participants: 38 adults (18 male), percent predicted (pp) forced expiration in one second (FEV1) 29–109, aged 22–48 years and 11 children (6 male), ppFEV1 68–107, aged 10–15 years were included. Levels reached (mean (SD) [range]) were 10.2 (2.4) [6–15] (adults), 10.1 (2.5) [7–14] (children); desaturation (change between baseline and peak-exercise SpO2): was 8.4 (3.8 [0–15]% (adults), 2.0 (2.0) [0–7]% (children). A total of 8 (21%) adults and no children desaturated

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.

Gonorrhea is caused by Neisseria gonorrhoeae. For men, classic manifestations of gonorrhea include urethritis and oropharyngeal exudates with lymphadenopathy. In women, classic manifestations are cervicitis, infertility, ectopic pregnancy, chronic pelvic pain, and pelvic inflammatory disease, but women commonly may be asymptomatic. Nucleic acid amplification test is preferred for diagnosing genital and extragenital gonococcal infections. Ceftriaxone cures about 98%-99% of uncomplicated gonorrhea infections, but dual treatment with ceftriaxone and azithromycin is recommended. Retesting is recommended 3 months after treatment because patients with gonorrhea constitute a high-risk group with potential for reinfection.

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.

Fungal infections within the central nervous system (CNS) occur more commonly in patients with immunosuppressive conditions but occasionally are diagnosed in immunocompetent patients as well. This may reflect the route of infection and the specific pathogen. Fungal infections resulting from hematogenous seeding are typically encountered in patients with profound and prolonged immunosuppression (including neutropenia); however, pathogens such as Cryptococcus gattii and some dimorphic fungi can also produce CNS disease in otherwise healthy persons. A common avenue of infection in immunocompetent patients is traumatic or nosocomial inoculation, including neurosurgical procedures, foreign body implants, and contaminated spinal fluid injections.

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

Accurately quantifying species’ area requirements is a prerequisite for effective area‐based conservation. This typically involves collecting tracking data on species of interest and then conducting home‐range analyses. Problematically, autocorrelation in tracking data can result in space needs being severely underestimated. Based on the previous work, we hypothesized the magnitude of underestimation varies with body mass, a relationship that could have serious conservation implications. To evaluate this hypothesis for terrestrial mammals, we estimated home‐range areas with global positioning system (GPS) locations from 757 individuals across 61 globally distributed mammalian species with body masses ranging from 0.4 to 4000 kg. We then applied block cross‐validation to quantify bias in empirical home‐range estimates. Area requirements of mammals 1, meaning the scaling of the relationship changed substantially at the upper end of the mass spectrum., Article impact statement: Due to autocorrelation‐induced bias, conventional methods severely underestimate the area requirements of GPS‐tracked large mammals.

Grade 91 steels have been used in power generation for more than 20 years in high temperature, high pressure applications such as steam piping, headers and tubing because it provides superior creep and oxidation resistance at elevated temperatures. The mechanical properties of the material are dependent on the creation of a martensitic microstructure, however incorrect heat treatment during manufacture, installation or repair can result in a weak ferritic or semi-ferritic microstructure which can cause premature component failure. Currently, components with incorrect, weak microstructures are identified using hardness testing; a manual technique which is prone to error. This work details a series of tests carried out at the University of Manchester to assess the suitability of multi-parameter magnetic testing for the identification of incorrect microstructures. The tests stem from a workshop organized by the Electric Power Research Institute (EPRI) where three sets of samples (eight pipe sections, eight tube sections and eight unidentified tube sections) with different microstructures were circulated world-wide. The results of the work show that the magnetic measurement techniques employed in these tests have the potential to provide a basis for the development of a portable NDE system for the identification of incorrect microstructures in Grade 91 plant components. The developed system would enable fast scanning of components with very little surface preparation along with digital data storage, improving on current manual hardness testing.

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....

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.

BACKGROUND: The objective of the study was to provide estimates of and risk factors for engagement in LTBI care in the overall U.S. population and among specific risk groups. METHODS: We used nationally representative data from 7,080 participants in the 2011-2012 National Health and Nutrition Examination Survey. Engagement in LTBI care was assessed by estimating the proportion with a history of testing, diagnosis, treatment initiation and treatment completion. Weighted methods were used to account for the complex survey design and to derive national estimates. RESULTS: Only 1.4 million (10%) of an estimated 14.0 million individuals with LTBI had previously completed treatment. Of the 12.6 million who did not complete LTBI treatment, 3.7 million (29%) had never been tested and 7.2 million (57%) received testing but had no history of diagnosis. High-risk groups showed low levels of engagement, including TB contacts and persons born outside the United States. CONCLUSIONS AND RELEVANCE: There is a reservoir of more than 12 million individuals in the U.S. who may be at risk for progression to TB disease and potential transmission. TB control programs and community providers should consider focused efforts to increase testing, diagnosis, and treatment for LTBI.

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

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.

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.

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.

International audience; The overlap in the mass symmetric region of the reaction products from fusion-fission and quasifission complicates the assignment of symmetric events to complete fusion on the basis of the mass distribution alone. Additional observables, besides mass distribution, should be used. The approach proposed here relies on the fact that fusion-fission and quasifission are characterized by different timescales. Within this framework, we performed a detailed study to find out how timescales can be probed via angular momentum transfer as measured via γ-ray multiplicities. The proof of principle was carried out by measuring the γ rays in coincidence with fusion-fission and quasielastic binary fragments in the reaction S32 + Au197 at beam energy near the Coulomb barrier. The experiment was performed at the Accélérateur Linéaire Tandem à Orsay (ALTO) facility at the Institut De Physique Nucléaire (IPN) in Orsay (France) using a detection setup consisting of ORGAM (ORsay GAMma) and PARIS (Photon Array Radioactive Ion Stable beams) γ-detectors arrays coupled with the CORSET (CORrelation SETup) time-of-flight spectrometer. Results of the sensitivity of this method to distinguish reaction channels with different dynamics are discussed.

NASA's deterministic transport code HZETRN, and its three-dimensional (3D) counterpart, 3DHZETRN, are being used to characterize the space radiation environment over a wide range of scenarios, including future planned missions to the moon or Mars. Combined with available spaceflight measurements, these tools provide the fundamental input for risk models used to quantify possible astronaut health decrements and satisfy agency limits in support of exploration initiatives. Further research is therefore needed to improve radiation transport and nuclear physics models while at the same time continuing to expand the available measurement database (ground-based and spaceflight) to validate such efforts. In this work, significant updates to the deterministic radiation transport models are presented. Charged muons and pions are fully coupled with the existing solutions developed for neutron and light ion (Z ≤ 2) transport. This update includes the 3D nature of pion production as well as the pion interactions, resulting in further production of energetic nucleons within shielding. Additional updates related to low energy proton recoils in hydrogenous materials and capture/decay processes associated with charged pions at rest are also described. Included in this work is the coupling of single and double-differential cross sections from Geant4 into HZETRN and 3DHZETRN. This enables a direct comparison of deterministic and Monte Carlo transport methodologies using the same nuclear databases for specific interactions. Comparisons between Geant4 and 3DHZETRN are shown and establish that the transport methodologies are in excellent agreement when the same cross sections are used. The deterministic codes are also compared to ISS data, and it is found that the updated 3D procedures are within measurement uncertainty (±5%) at cutoff rigidities below 1 GV, which approaches free space conditions.

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.

3DHZETRN-v2 includes a detailed three dimensional (3D) treatment of neutron/light-ion transport based on a quasi-elastic/multiple production assumption allowing improved agreement of the neutron/light-ion fluence compared with results of three Monte Carlo (MC) codes in the sense that the variance with respect to the individual MC results is less than the variance among the MC code results. The current numerical methods are no longer the main limitation to HZETRN code development and further changes in the nuclear model are required. In a prior study, an improved quasi-elastic spectrum based on a solution of the transport approximation to nuclear media effects showed promise, but the remaining multiple-production spectrum was based on a database derived from the Ranft model that used Bertini multiplicities. In the present paper, we will implement a more complete Serber first step into the 3DHZETRN-v2 code, but we retain the Bertini-Ranft branching ratios and evaporation multiplicities. It is shown that the new Serber model in the 3HZETRN-v2 code reduces the variance with individual MC codes, which are largely due to nuclear cross section model differences. The code will be available through the software system, OLTARIS, for shield design and validation and provides a basis for personal computer software capable of space shield analysis and optimization.

Introduction: A clean and functional microscope is necessary for accurate diagnosis of infectious diseases. In tropical climates, high humidity levels and improper storage conditions allow for the accumulation of debris and fungus on the optical components of diagnostic equipment, such as microscopes. Objective: Our objective was to develop and implement a low-cost, sustainable, easy to manage, low-maintenance, passive humidity control chamber to both reduce debris accumulation and microbial growth onto the optical components of microscopes. Methods: Constructed from easily-sourced and locally available materials, the cost of each humidity control chamber is approximately $2.35 USD. Relative humidity levels were recorded every 30 minutes over a period of 10 weeks from two chambers deployed at the Belize Vector and Ecology Center and the University of Belize. Results: The humidity control chamber deployed at the University of Belize maintained internal relative humidity at an average of 35.3% (SD = 4.2%) over 10 weeks, while the average external relative humidity was 86.4% (SD = 12.4%). The humidity control chamber deployed at the Belize Vector and Ecology Center effectively maintained internal relative humidity to an average of 54.5% (SD = 9.4%) over 10 weeks, while the average external relative humidity was 86.9% (SD = 12.9%). Conclusions: Control of relative humidity is paramount for the sustainability of medical equipment in tropical climates. The humidity control chambers reduced relative humidity to levels that were not conducive for fungal growth while reducing microscope contamination from external sources. This will likely extend the service life of the microscopes while taking advantage of low-cost, locally sourced components.

Engineering technology plays a pivotal role in the delivery of health care in under-resourced countries by providing an infrastructure to improve patient outcomes. However, sustainability of these technologies is difficult in these settings oftentimes due to limited resources or training. The framework presented in this editorial focuses on establishing medical and laboratory equipment sustainability in developing countries and is comprised of four steps: 1) establishing reliable in-country relationships with stakeholders, 2) identifying needs for sustainable solutions locally, 3) exploring potential solutions and assessing their effort-to-impact ratios, and 4) working with strategic partners to implement solutions with clear performance metrics. By focusing on the sustainability of donated equipment instead of the equipment itself, this method presented distinguishes itself from other philanthropic endeavors in the field by seeking to establish preventive maintenance habits that can impact clinical outcomes of a community long term. Application of this methodology is reported in the Original Research Article “A Low-Cost Humidity Control System to Protect Microscopes in a Tropical Climate” by Asp et. al.

Cardiovascular device infection due to rapidly growing mycobacteria (RGM) is rarely encountered in clinical practice. Due to the increasing number of indications and use of cardiovascular devices in an aging population, optimized management of these infections is of great importance. We report seven cases of RGM cardiovascular device infection. Three patients had left-ventricular assist device (LVAD) infections; two patients had cardiovascular implantable device (CIED) infections; and one had an aortic vascular stent infection. Specific cardiac valvular infection was not detected among any of the patients. All patients had a high number of comorbidities which limited some patients from receiving optimal combination antimicrobial therapy. The prognosis of cardiovascular device infections with RGM is guarded with only four patients still alive; however, the treatment approach for each patient varied considerably and often based on concurrent medical conditions, overall adjustments to goals of care, and specific patient preferences. Further analysis of cardiovascular device infections with RGM is warranted to establish a more systematic approach in successful management.

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.