A comparison of peak cough flow and peak expiratory flow in children with neuromuscular disorders.

Spirometry and peak cough flow testing (PCF) are commonly used in the respiratory assessment of children with a neuromuscular disorder (NMD). Testing uses two different machines, increases laboratory time, costs and resource utilisation. No studies have assessed the correlation between peak expiratory flow (PEF) obtained from spirometry and PCF in children with NMD using one device. An audit of children with a NMD managed at the Children's Hospital at Westmead in 2022-2024 aged < 20 years who performed spirometry and PCF testing on the same device (Vyaire Body BoxTM, Ultrasonic flow meter-based, or Vyaire PneumotachographTM, Pneumotach flow meter-based; Germany) was conducted to assess the correlation between PCF and PEF. Fifty-one sets of testing were identified, and 40 subjects (9F) had reproducible testing and were included. Median (range) age was 14.95 (7.20-19.00) years. Median PEF (L/min) was 4.05 (1.22-10.26) and median PCF (L/min) was 4.29 (1.69-10.82). PEF and PCF had a strong Pearson's correlation coefficient, (R = 0.97, p = 0.03). The coefficient of determination was 0.93. If laboratory resources permit, spirometry should be the test of choice for children with NMD. On average, spirometry required multiple practices to achieve reproducibility to meet ATS/ERS standards. PCF testing can be utilised for children where performing technically acceptable spirometry is not possible.

Can postural changes in spirometry in children with Duchenne muscular dystrophy predict sleep hypoventilation?

AIM: To explore the relationship between postural changes in lung function and polysomnography (PSG) in children with Duchenne muscular dystrophy (DMD). METHODS: In this prospective cross-sectional study, children with DMD performed spirometry in sitting and supine positions. A control group of age and gender matched healthy children also underwent postural lung function testing. PSG was performed within six months of spirometry. RESULTS: Seventeen children with DMD, aged 12.3 ± 3 years performed sitting spirometry. 14 (84%) performed acceptable spirometry in the supine position. Mean FEV1sit and FVCsit were 77% (SD ± 22) and 74% (SD ± 20.4) respectively, with mean% ΔFVC(sit-sup) 9% (SD ± 11) (range 2% to 20%), and was significantly greater than healthy controls 4% (n = 30, SD ± 3, P < 0.001). PSG data on the 14 DMD children with acceptable supine spirometry showed total AHI 6.9 ± 5.9/hour (0.3 to 29), obstructive AHI 5.2 ± 4.0/hour (0.2 to 10), and REM AHI 14.1 ± -5.3/hour (0.1 to 34.7). ΔFVC(sit-sup) had poor correlation with hypoventilation on polysomnography. CONCLUSION: Children with DMD and mild restrictive lung disease showed greater postural changes in spirometry than healthy controls but lower supine spirometry was not predictive of sleep hypoventilation.

Respiratory and sleep outcomes in children with SMA treated with nusinersen - real world experience.

It is unclear how improvements in peripheral motor function in children with spinal muscular atrophy (SMA), treated with nusinersen, translate into clinically significant respiratory/sleep outcomes. A retrospective chart review of SMA children at the Sydney Children's Hospital Network was undertaken looking at 2 years before and after receiving their first dose of nusinersen. Polysomnography (PSG), spirometry and clinical data were collected and analysed using paired and unpaired t-tests for PSG parameters and generalised estimating equations for longitudinal lung function data. Forty-eight children (10 Type 1, 23 Type 2, 15 Type 3) at mean age 6.98 yrs (SD 5.25) for nusinersen initiation were included. There was a statistically significant improvement in oxygen nadir during sleep in individuals post nusinersen (mean of 87.9% to 92.3% (95%CI 1.24 - 7.63, p = 0.01)). Based on clinical and PSG findings, 6/21 patients (5 Type 2, 1 Type 3) ceased nocturnal NIV post nusinersen. Non-significant improvements were demonstrated in mean slope for FVC% predicted, FVC Z-score and mean FVC% predicted. Within 2 years of commencing nusinersen, stabilisation of respiratory outcomes occurred. Whilst some of the SMA type 2/3 cohort ceased NIV, there were no statistically significant improvements lung function and most PSG parameters.

Examining the impact of premature birth on parental mental health and family functioning in the years following hospital discharge: A review.

BACKGROUND: This review provides an update of the current research related to the impact of extreme and very premature birth on parental mental health and family functioning following discharge from hospital. METHODS: Full-text peer reviewed articles in English, describing parents' and families' health and wellbeing after the discharge from hospital of their baby using validated questionnaires, were evaluated. Results of included studies are presented in a summarized format. Embase, Medline and PsycINFO databases were accessed in January 2021. RESULTS: 38 studies were included. Nine manuscripts reported on parental mental health and 13 on stress, which are a concern after the birth of a premature infant, especially in the first year. Depression, anxiety, and stress are known to measure higher compared to parents of infants born at term. Over several years, these measures of mental health decrease significantly. Four reported on quality of life for parents of premature infants, which is reduced immediately after discharge, but then improves over time. The impact of premature birth on the family functioning was described in ten included studies and was described to have positive and negative consequences. CONCLUSION: The negative impact of the premature birth and hospital journey on parental mental health lessens significantly with time.

Is perinatal substance abuse falling through the cracks?

OBJECTIVES: Perinatal substance abuse (PSA) is associated with increased risk of prematurity, low birth weight, neonatal abstinence syndrome, behavioral issues and learning difficulties. It is imperative that robust care pathways are in place for these high-risk pregnancies and that staff and patient education are optimized. The present study explores the knowledge and attitudes of healthcare professionals toward PSA to identify knowledge gaps to enhance care and reduce stigma. METHODS: This is a cross-sectional study using questionnaires to survey healthcare professionals (HCPs) working in a tertiary maternity unit (n = 172). RESULTS: The majority of HCPs were not confident in the antenatal management (75.6%, n = 130) or postnatal management (67.5%, n = 116) of PSA. More than half of HCPs surveyed (53.5%, n = 92) did not know the referral pathway and 32% (n = 55) did not know when to make a TUSLA referral. The vast majority (96.5%, n = 166) felt that they would benefit from further training, and 94.8% (n = 163) agreed or strongly agreed that the unit would benefit from a drug liaison midwife. Among study participants, 54.1% (n = 93) agreed or strongly agreed that PSA should be considered a form of child abuse and 58.7% (n = 101) believe that the mother is responsible for damage done to her child. CONCLUSIONS: Our study highlights the urgent need for increased training on PSA to enhance care and reduce stigma. It is imperative that staff training, drug liaison midwives and dedicated clinics are introduced to hospitals as a matter of high priority.

Reevaluating the wave power-salt marsh retreat relationship.

Salt marshes are threatened by rising sea levels and human activities, and a major mechanism of marsh loss is edge retreat or erosion. To understand and predict loss in these valuable ecosystems, studies have related erosion to marsh hydrodynamics and wave characteristics such as wave power. Across global studies, erosion is reported to be largely linearly related to wave power, with this relationship having implications for the resilience of marshes to extreme events such as storms. However, there is significant variability in this relationship across marshes because of marsh heterogeneity and the uniqueness of each physical setting. Here, we investigate the results of individual studies throughout the world that report a linear relationship and add a new dataset from the Great Marsh in Massachusetts (USA). We find that most marsh wave power and erosion data are not normally distributed and when these datasets are properly plotted to account for their distributions, the resulting relationships vary from previously published curves. Our Great Marsh data suggest that events from specific wind directions can have an outsized impact on edge erosion due to their larger fetch and wind speeds. We also find that factors other than wave attack such as edge erosion along tidal channels, can have a measurable impact on retreat rates. We show the importance of maintaining statistical assumptions when performing regressions, as well as emphasize the site-specificity of these relationships. Without calibration of a marsh erosion-wave power relationship using robust regressions for each individual marsh, such a relationship is not fully constrained, resulting in unreliable predictions of future marsh resilience and response to climate change.

Exercise testing for young athletes.

With increasing competitiveness across the sporting landscape, there is a need for more research into monitoring and managing the young athlete, as the needs of a young athlete are vastly different to those of an older athlete who is already established in their respective sport. As the age of sports specialisation seems to decrease, exercise testing in the younger cohort of athletes is crucial for safety and long-term success. This article provides a comprehensive summary of available testing and monitoring methods that can be used to assist young athletes as they mature and attempt to excel in their chosen sport.

Applying lessons learnt from research of child pneumonia management in Vietnam.

Pneumonia is the leading cause of paediatric hospitalisation in Vietnam, placing a huge burden on the health care system. Pneumonia is also the main reason for antibiotic use in children. Unfortunately many hospital admissions for child pneumonia in Vietnam are unnecessary and inappropriate use of antibiotics is common, as in the rest of Asia, with little awareness of its adverse effects. We explored the value of an alternative approach that, instead of focusing on the identification of children with severe bacterial pneumonia, focuses on the identification of children with 'unlikely bacterial pneumonia' to improve patient care and rational antibiotic use. Implementing improved models of care require pragmatic management algorithms that are well validated, but it is ultimately dependent on financial structures, management support and evidence-based training of healthcare providers at all relevant levels. Apart from better case management, sustained reductions in the pneumonia disease burden also require increased emphasis on primary prevention.

Pro con debates in clinical medicine infection prevention and control in cystic fibrosis: One size fits all? The argument in favour.

This article advocates for a universal approach to infection control measures in cystic fibrosis. The central tenets of infection control include hand hygiene, contact precautions, regular microbiological surveillance and adopting inpatient, outpatient, domestic and social practices to minimise acquisition of common CF pathogens. Infection control measures should be proactive and prospective, assuming all patients harbour aggressive pathogens, and not relying on past culture results. The challenges of implementing these policies include cost, equipment, education, consistency, meticulousness all whilst balancing additional procedures to a busy clinical workload.

European and United Kingdom COVID-19 pandemic experience: The same but different.

The global healthcare landscape has changed dramatically and rapidly in 2020. This has had an impact upon paediatricians and in particular respiratory paediatricians. The effects in Europe, with its mature healthcare system, have been far faster and greater than most authorities anticipated. Within six weeks of COVID-19 being declared a public health emergency by the World Health Organisation [WHO] in China, Europe had become the new epicentre of disease. A pandemic was finally declared by the WHO on March 11th 2020. Continued international travel combined with the slow response of some political leaders and a variable focus on economic rather than health consequences resulted in varying containment strategies in response to the threat of the initial wave of the pandemic. It is likely that this variation has contributed to widely differing outcomes across Europe. Common to all countries was the stark lack of preparations and initial poor co-ordination of responses between levels of government to this unforeseen but not unheralded global health crisis. In this article we highlight the impact of the first wave of the COVID-19 pandemic in Italy, Austria, Germany, and the United Kingdom.

Preliminary analysis of the FAM174A gene suggests it lacks a strong association with equine metabolic syndrome in ponies.

Equine metabolic syndrome (EMS) describes a group of risk factors, including obesity and insulin dysregulation (hyperinsulinemia and/or insulin resistance), that can lead to the development of the debilitating hoof disease laminitis. Although the underlying mechanisms of EMS are not fully understood, a genetic component has been reported, and an 11 guanine polymorphism located at the FAM174A gene has been identified as a risk locus for the syndrome in Arabian horses. To examine associations between the FAM174A risk allele and the clinical signs of EMS, the allele was examined in an Australian cohort of ponies (n = 20) with known metabolic status. The 11 guanine polymorphism was identified in only 3 of 13 ponies with EMS, and no significant association could be made between the risk loci and morphometric measurements associated with obesity (BCS [P = 0.21], cresty neck score [P = 0.58], basal triglyceride concentration [P = 0.85], and adiponectin concentration [P = 0.48]), or insulin dysregulation (insulin dysregulation status [P = 0.35] and serum insulin concentration during an oral glucose test [P = 0.44]). These results suggest that the FAM174A 11 guanine homopolymer allele is unlikely to be a singular key gene polymorphism associated with EMS in ponies. However, due to the small number of ponies identified with the polymorphism, further study of the FAM174A risk allele in a larger cohort of horses and ponies of uniform breed would be useful.

Early Bactericidal Activity Trial of Nitazoxanide for Pulmonary Tuberculosis.

This study was conducted in treatment-naive adults with drug-susceptible pulmonary tuberculosis in Port-au-Prince, Haiti, to assess the safety, bactericidal activity, and pharmacokinetics of nitazoxanide (NTZ). This was a prospective phase II clinical trial in 30 adults with pulmonary tuberculosis. Twenty participants received 1 g of NTZ orally twice daily for 14 days. A control group of 10 participants received standard therapy over 14 days. The primary outcome was the change in time to culture positivity (TTP) in an automated liquid culture system. The most common adverse events seen in the NTZ group were gastrointestinal complaints and headache. The mean change in TTP in sputum over 14 days in the NTZ group was 3.2 h ± 22.6 h and was not statistically significant (P = 0.56). The mean change in TTP in the standard therapy group was significantly increased, at 134 h ± 45.2 h (P < 0.0001). The mean NTZ MIC for Mycobacterium tuberculosis isolates was 12.3 µg/ml; the mean NTZ maximum concentration (Cmax) in plasma was 10.2 µg/ml. Negligible NTZ levels were measured in sputum. At the doses used, NTZ did not show bactericidal activity against M. tuberculosis Plasma concentrations of NTZ were below the MIC, and its negligible accumulation in pulmonary sites may explain the lack of bactericidal activity. (This study has been registered at ClinicalTrials.gov under identifier NCT02684240.).

Diagnostic yield of active case finding for tuberculosis at human immunodeficiency virus testing in Haiti.

SETTING: The Groupe Haïtien d'étude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO) Centres, Port-au-Prince, Haiti, facilitate "test and treat" strategies by screening all patients for tuberculosis (TB) at human immunodeficiency virus (HIV) testing.OBJECTIVE: 1) To determine the proportion of patients with chronic cough at HIV testing diagnosed with TB, stratified by HIV test results; and 2) to evaluate the additional diagnostic yield of Xpert® MTB/RIF vs. sputum microscopy.DESIGN: We conducted a retrospective cohort analysis including all adults tested for HIV at GHESKIO from August 2014 to July 2015.RESULTS: Of 29 233 adult patients tested for HIV, 2953 (10%) were diagnosed as HIV-positive. Chronic cough lasting ≥2 weeks was reported by 1116 (38%) HIV-positive patients; 984 (88%) were tested and 265 (27%) were diagnosed with TB. Chronic cough was reported by 5985 (23%) HIV-negative patients; 5654 (94%) were tested and 1179 (21%) were diagnosed with TB. Of all bacteriologically confirmed cases, 27% were smear-negative and Xpert-positive. Among all TB patients, 81% were HIV-negative.CONCLUSIONS: Screening for TB at HIV testing was high-yield, among both HIV-infected and HIV-negative individuals. Testing for both diseases should be conducted among patients who present with chronic cough at HIV testing.

Use of non-invasive ventilation in children with congenital tracheal stenosis.

INTRODUCTION: Congenital tracheal stenosis (CTS) is a rare airway condition characterized by complete tracheal rings. Most patients undergo a slide tracheoplasty, which greatly reduces mortality but significant morbidity remains. The assessment of sleep disordered breathing (SDB) and use of non-invasive ventilation (NIV) in these children has not been described. AIM: To describe the presence of SDB and use of NIV in children diagnosed with CTS over a 10-year period (2005-2015). DESIGN: Retrospective case series at a tertiary children's hospital. RESULTS: There were 16 patients identified with CTS with a median [range] age at diagnosis of 2.5 months (0-9 months). One child died in the immediate post-operative period following a slide tracheoplasty, leaving 15 survivors. There were no later deaths during follow-up while using NIV for up to 3 years after surgery. Slide tracheoplasty was undertaken in (12/15) with long-segment tracheal stenosis. 3/15 patients had a short-segment tracheal stenosis and were managed conservatively. The use of NIV occurred in 10/15 (66.67%) patients, all of whom had long-segment CTS. Pre-operative polysomnography (PSG) showed a median (±SD) obstructive apnoea/hypopnoea index (OAHI) of 14.6/hr (±6.2) which reduced to 7.2/hour (±4.2) on NIV prior to slide tracheoplasty. The median oxygen desaturation index (ODI) before NIV use was 15.3 (±19.4) episodes/hour, which reduced to 6.3 (±11) on NIV. The median period of NIV use was 5 [1-24 months] months. CONCLUSION: Patients with CTS have obstructed sleep disordered breathing. Trials of NIV are well-tolerated and improve sleep disordered breathing.

Rabies Necropsy Techniques in Large and Small Animals.

The New York State Department of Health (NYSDOH) Rabies Laboratory receives between 6,000 to 9,000 specimens annually and performs rabies testing for the entire state, with the exception of New York City. The Rabies laboratory necropsies a variety of animals ranging in size from bats to bovids. Most of these specimens are animals exhibiting neurological signs, however, less than 10% actually test positive for rabies; implying trauma, lesions or other infectious agents as the cause of these symptoms. Due to the risk of aerosolizing undiagnosed infectious agents, the Rabies Laboratory does not use power tools or saws. Three necropsy techniques will be presented for animals whose skulls are impenetrable with scissors. The laboratory has implemented these techniques to decrease potential exposure to infectious agents, eliminate unnecessary manipulation of the specimen and reduce processing time. The advantages of a preferred technique opposed to another is subject to the trained individual processing the specimen.

Abnormal preschool Lung Clearance Index (LCI) reflects clinical status and predicts lower spirometry later in childhood in cystic fibrosis.

BACKGROUND: Clinical and prognostic value of preschool Multiple Breath Washout (MBW) remains unclear. METHODS: Initial MBW results (Exhalyzer® D, EcoMedics AG) in preschool Cystic Fibrosis (CF) subjects (age 2-6 years) at a time of clinical stability were compared to (1) concurrent clinical status measures and (2) later spirometry outcomes. Abnormal Lung Clearance Index (LCI) was defined using published reference data (ULN for LCI 8.0). RESULTS: LCI was abnormal in 56% (28/50), with mean (SD) LCI 8.61(1.85) at age 4.71(1.3) years. Abnormal LCI was associated with higher dornase alfa use, previous positive bacterial cultures and pF508.del homozygous genotype. Later spirometry (n = 44; mean (SD) 2.3(0.5) years after MBW) demonstrated that abnormal initial preschool LCI was a strong predictor of lower later spirometry outcomes. CONCLUSION: Abnormal preschool LCI was associated with concurrent measures of clinical status and later spirometry deficits, suggesting early prognostic utility of MBW testing in this age range.

The efficacy and safety of velagliflozin over 16 weeks as a treatment for insulin dysregulation in ponies.

BACKGROUND: A previous six-week (wk) study demonstrated the potential of the sodium-glucose linked transport inhibitor velagliflozin as a novel treatment for equine insulin dysregulation. The present study examined the safety and efficacy of velagliflozin over 16 wk. of treatment, and over 4 wk. of withdrawal. Twenty-four insulin dysregulated ponies were selected, based on their hyper-responsiveness to a diet challenge meal containing 3.8 g non-structural carbohydrates (NSC)/kg bodyweight (BW). Ponies with serum insulin > 90 µIU/mL either 2 or 4 h after feeding were enrolled, and randomly allocated to receive either velagliflozin (0.3 mg/kg BW orally once daily, n = 12), or a placebo (n = 10-12) for 16 wk. The subjects were fed 7.5 g NSC/kg BW/day to maintain a fat body condition. Safety was assessed through daily monitoring, veterinary examination, and the measurement of fasting blood glucose, biochemistry and haematology. Efficacy at reducing post-prandial hyperinsulinemia was assessed using a diet challenge every 8 wk. during treatment and 4 wk. after withdrawal. RESULTS: Velagliflozin was well accepted by all subjects and caused no adverse effects or hypoglycaemia. Post-prandial serum insulin (insulin Cmax) did not change significantly in the control animals over the entire study period (P = 0.101). In contrast, insulin Cmax (mean ± SE) concentrations fell over time in the velagliflozin-treated group from 205 ± 25 µIU/mL in wk. 0, to 119 ± 19 µIU/mL (P = 0.015) and 117 ± 15 µIU/ml (P = 0.029) after 8 and 16 wk. of treatment, respectively. Although the insulin Cmax in this group was not significantly lower than in controls at wk-8 (P = 0.061), it was lower at wk-16 (P = 0.003), and all 12 treated ponies were below the previously-determined risk threshold for laminitis at this time. After 4 wk. withdrawal, the insulin Cmax returned to 199 ± 36 µIU/mL in the treated group, with no rebound effect. CONCLUSIONS: Velagliflozin appears to be a promising and safe treatment for equine insulin dysregulation, bringing post-prandial insulin concentrations below the laminitis risk threshold, albeit without normalising them.

Outcomes across the tuberculosis care continuum among adolescents in Haiti.

Setting: GHESKIO (Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes) clinic, Port-au-Prince, Haiti. Objective: To evaluate tuberculosis (TB) care continuum outcomes among adolescents. Design: Among a retrospective cohort of 10-24 year olds diagnosed with active TB, we report completion of the following steps of the TB care continuum stratified by human immunodeficiency virus (HIV) status: diagnosis of microbiologically confirmed TB, initiation of anti-tuberculosis treatment, retention in care at 2 months on anti-tuberculosis treatment, and TB treatment success. Factors associated with attrition at each step were identified using multivariable regression. Results: A total of 1005 adolescents were diagnosed with active TB; 74 (7%) were HIV-positive at the time of TB diagnosis. HIV-positive patients had poorer outcomes than non-HIV-infected patients: 73% vs. 85% initiated anti-tuberculosis treatment (P < 0.01), 46% vs. 74% were retained in care at 2 months (P < 0.01), and 41% vs. 68% achieved TB treatment success (P < 0.01). Among those who initiated treatment, same-day initiation resulted in less treatment failure. Attrition before treatment initiation was associated with female sex and HIV coinfection. Attrition after treatment initiation was associated with age ⩾16 years and HIV coinfection. Conclusion: Outcomes across the TB care continuum are suboptimal among adolescents, with only two thirds of patients achieving treatment success. Interventions tailored to adolescents are needed to improve retention in care, particularly for those who are co-infected with HIV.

Contexte : Centre de santé, Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes, Port-au-Prince, Haïti.Objectif : Evaluer les résultats tout au long de la prise en charge de la tuberculose (TB) parmi les adolescents.Schéma : Parmi une cohorte rétrospective d'adolescents âgés de 10­24 ans ayant eu un diagnostic de TB active, nous rapportons le déroulement des étapes suivantes des soins de la TB stratifiés par statut virus de l'immunodéficience humaine (VIH) : diagnostic de TB confirmée par microbiologie ; mise en route du traitement de la TB ; rétention en soins à 2 mois sous traitement de TB ; et succès du traitement de TB. Les facteurs associés à l'attrition à chaque étape ont été identifiés grâce à une régression logistique multivariée.Résultats: Des 1005 adolescents qui ont eu un diagnostic de TB active, 74 (7%) ont été positifs au VIH au moment du diagnostic de TB. Les patients VIH positifs ont eu des résultats plus médiocres comparés aux patients non infectés par le VIH : 73% contre 85% ont mis en route le traitement de TB (P < 0,01), 46% contre 74% sont restés sous traitement à 2 mois (P < 0,01) et 41% contre 68% ont achevé le traitement avec succès (P < 0,01). Parmi ceux qui ont mis en route le traitement, une prise dès le premier jour a abouti à moins d'échec du traitement. L'attrition avant le début du traitement a été associée au sexe féminin et à la coinfection à VIH. L'attrition après mise en route du traitement a été associée à un âge ⩾16 ans et à la coinfection à VIH.Conclusion : Les résultats au niveau de la continuité des soins de TB sont sousoptimaux parmi les adolescents, dont seulement deux tiers achèvent le traitement avec succès. Des interventions adaptées aux adolescents sont requises pour améliorer la rétention en soins, particulièrement pour ceux qui sont coinfectés par le VIH.

Marco de Referencia: El centro du Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes de Port-au-Prince, en Haití.Objetivo: Evaluar los resultados del proceso asistencial continuo de la tuberculosis (TB) en los adolescentes.Método: En una cohorte retrospectiva de jóvenes de 10­24 años de edad con diagnóstico de TB activa, se comunican los resultados logrados en las siguientes etapas del proceso asistencial continuo de la TB, estratificados según la situación frente al virus de la inmunodeficiencia humana (VIH): diagnóstico de TB confirmada microbiológicamente; inicio del tratamiento antituberculoso; retención en la atención a los 2 meses del tratamiento; y el éxito del tratamiento antituberculoso. Se determinaron los factores asociados con el abandono en cada etapa mediante un modelo de regresión multivariante.Resultados: Se diagnosticó TB activa en 1005 adolescentes; 74 de ellos (7%) eran positivos frente al VIH en el momento del diagnóstico de TB. Los pacientes positivos frente al VIH presentaron desenlaces más desfavorables que los pacientes sin infección por el VIH (73% contra 85% inició el tratamiento antituberculoso, P < 0,01; 46% contra 74% continuaba en la atención a los 2 meses, P < 0,01; y 41% contra 68% alcanzó un tratamiento antituberculoso exitoso, P < 0,01). Los jóvenes que iniciaron tratamiento el mismo día de la consulta presentaron menos fracasos terapéuticos. El abandono antes de iniciar el tratamiento se asoció con el sexo femenino y la coinfección por el VIH. El abandono después de haber iniciado el tratamiento se asoció con la edad ⩾16 años y la coinfección por el VIH.Conclusión: Los resultados a lo largo de la continuidad asistencial de la TB son deficientes en los adolescentes, pues solo dos tercios de ellos alcanzan el éxito terapéutico. Se precisan intervenciones adaptadas a los adolescentes que mejoren la retención en los servicios de atención, sobre todo en los pacientes coinfectados por el VIH.

Blood transcriptomic markers of Mycobacterium tuberculosis load in sputum.

BACKGROUND: Peripheral blood transcriptome signatures that distinguish active pulmonary tuberculosis (TB) from control groups have been reported, but correlations of these signatures with sputum mycobacterial load are incompletely defined. METHODS: We assessed the performance of published TB transcriptomic signatures in Haiti, and identified transcriptomic biomarkers of TB bacterial load in sputum as measured by Xpert® MTB/RIF molecular testing. People in Port au Prince, Haiti, with untreated pulmonary TB (n = 51) formed the study cohort: 19 people with low and 32 with high sputum Mycobacterium tuberculosis load. Peripheral whole blood transcriptomes were generated using RNA sequencing. RESULTS: Twenty of the differentially expressed transcripts in TB vs. no TB were differentially expressed in people with low vs. high sputum mycobacterial loads. The difference between low and high bacterial load groups was independent of radiographic severity. In a published data set of transcriptomic response to anti-tuberculosis treatment, this 20-gene subset was more treatment-responsive at 6 months than the full active TB signature. CONCLUSION: We identified genes whose transcript levels in the blood distinguish active TB with high vs. low M. tuberculosis loads in the sputum. These transcripts may reveal mechanisms of mycobacterial control of M. tuberculosis during active infection, as well as identifying potential biomarkers for bacterial response to anti-tuberculosis treatment.