Concomitant bedaquiline and delamanid therapy in patients with drug-resistant extra-pulmonary tuberculosis in Mumbai, India.

Background: World Health Organization suggests concurrent bedaquiline-delamanid (BDQ-DLM) as part of individualised regimens for eligible patients with pulmonary drug-resistant tuberculosis (DR-TB); however, data for patients with drug-resistant extrapulmonary tuberculosis (EPTB) is extremely limited. This study documents the treatment outcomes and adverse events associated with concurrent BDQ-DLM-based regimens in patients with drug-resistant EPTB at a Médecins Sans Frontières clinic in Mumbai, India. Methods: Retrospective cohort study based on routinely collected programmatic data. Individualised regimens were based on drug-susceptibility testing and previous drug exposure. Drug-resistant EPTB patients initiated on regimens containing concurrent BDQ and DLM from April 2016 to October 2019 were included. Patients who completed treatment were followed up at 12 months. Results: Of 17 patients, median age was 23 years (IQR = 21-30 years) and 12/17 (71 %) were female. Pre-extensively drug-resistant tuberculosis and extensively drug-resistant TB was reported in 13/17 (76.4 %) and 2/17 (11.7 %) patients respectively. Microbiological reports were unavailable for two patients with central nervous system TB. Lymph node TB was the commonest form of EPTB in 9/17 (53 %) of patients. Median duration of treatment was 18.9 months. At least one grade three or four severe adverse event (SAE) was reported by 13/17 (76.4 %) patients. Thirteen (76.4 %) patients had favourable outcomes. None of the patients relapsed or died in the one-year period of post-treatment follow-up. Conclusion: Concurrent BDQ-DLM-based regimens in drug-resistant EPTB were effective and associated with manageable adverse events.

Correction: Challenging drug-resistant TB treatment journey for children, adolescents and their care-givers: A qualitative study.

[This corrects the article DOI: 10.1371/journal.pone.0248408.].

Correction: Psychiatric comorbidities among patients with complex drug-resistant tuberculosis in Mumbai, India.

[This corrects the article DOI: 10.1371/journal.pone.0263759.].

Psychiatric comorbidities among patients with complex drug-resistant tuberculosis in Mumbai, India.

BACKGROUND: People with drug-resistant tuberculosis (DR-TB) are known to suffer from many mental-health disorders. This study aims to describe the proportion of patients diagnosed with psychiatric comorbidities, the different psychiatric diagnoses made, and treatment outcomes among DR-TB patients with or without psychiatric comorbidity and initiated on DR-TB treatment between January 2012 and March 2019 at Médecins Sans Frontières independent clinic in Mumbai, India. METHODS: This is a retrospective study using routinely collected clinical data. DR-TB care included individualised treatment, psychosocial support, and integrated psychiatric care. RESULTS: During the study period, 341 DR-TB patients were enrolled, with a median age of 25 years (IQR:20.0-36.5 years), 185 (54.2%) females, 143 (41.9%) with PreXDR-TB, and 140 (41.0%) with XDR-TB. All 341 patients were screened by a counsellor, 119 (34.9%) were referred for psychiatric evaluation, and 102 (29.9% of 341) were diagnosed with a psychiatric comorbidity. Among 102 diagnosed with a psychiatric comorbidity, 48 (47.0%) were diagnosed at baseline, and 86 (84.3%), or 25.2% of all 341 patients enrolled, were treated with psychotropic drugs. Depressive disorders were diagnosed in 49 (48.0%), mixed anxiety and depression in 24 (23.5%), neurocognitive disorders and anxiety in five (4.9%), and medication induced psychosis in two (2.0%). No anti-TB drugs were significantly associated with psychiatric comorbidities developed during treatment. Of 102 DR-TB patients with a psychiatric comorbidity, 75.5% (77) had successful DR-TB treatment outcomes, compared to 61.1% (146/239) not diagnosed with a psychiatric comorbidity (p = 0.014). CONCLUSION: In our setting, among people started on DR-TB treatment, and with a complex TB resistance profile, about one in three patients experienced a psychiatric comorbidity, of which half developed this comorbidity during treatment. With comprehensive psychiatric care integrated into DR-TB care delivery, treatment outcomes were at least as good among those with psychiatric comorbidities compared to those without such comorbidities.

Inflammatory myofibroblastic tumour of the central airways: treatment and molecular analysis.

Inflammatory myofibroblastic tumours (IMT) are a rare cause of endobronchial masses in adults. Surgery has been the mainstay of treatment of endobronchial IMTs, based on the potential for recurrence. Interventional pulmonology has emerged as a minimally invasive and lung function preserving modality in management of airway obstruction due to tumours. We present a series of three adult patients with IMT treated endobronchially with a short discussion on its potential role. We also discuss how molecular analysis of IMTs for mutations in genes such as ALK and ROS1 might provide insights into clinical behaviour and potential targetable therapy in advanced, unresectable and metastatic cases.

Challenging drug-resistant TB treatment journey for children, adolescents and their care-givers: A qualitative study.

BACKGROUND: Childhood multidrug-resistant TB (MDR-TB) still affects around 25000 children every year across the globe. Though the treatment success rates for drug-resistant TB (DR-TB) in children are better than adults, children and adolescents face unique hurdles during DR-TB (MDR-TB, Pre-XDR TB and XDR-TB) treatment. This study aimed to understand the patients, guardians and healthcare providers' perspectives about DR-TB treatment journey of patients and caregivers. METHODS: This is a qualitative study involving in depth-interviews of purposively selected adolescents (n = 6), patients guardians (for children and adolescents, n = 5) and health care providers (n = 8) of Médecins Sans Frontières (MSF) clinic, Mumbai, India. In-depth face to face interviews were conducted in English or Hindi language using interview guides during September-November 2019. The interviews were audio-recorded after consent. Thematic network analysis was used to summarize textual data. ATLAS.ti (version 7) was used for analysis. RESULT: The age of adolescent patients ranged from 15-19 years and four were female. Five guardians (of three child and two adolescent patients) and eight healthcare providers (including clinicians- 2, DOT providers-2, counselors-2 and programme managers-2) were interviewed. The overarching theme of the analysis was: Challenging DR-TB treatment journey which consisted of four sub-themes: 1) physical-trauma, 2) emotional-trauma, 3) unavailable social-support and 4) non-adapted healthcare services. Difficulties in compounding of drugs were noted for children while adolescents shared experiences around disruption in social life due to disease and treatment. Most of the patients and caregivers experienced treatment fatigue and burnout during the DR-TB treatment. Participants during interviews gave recommendations to improve care. DISCUSSION: The TB programmes must consider the patient and family as one unit when designing the package of care for paediatric DR-TB. Child and adolescent friendly services (paediatric-formulations, age-specific counselling tools and regular interaction with patients and caregivers) will help minimizing burnout in patients and caregivers.

Treatment outcomes of children and adolescents receiving drug-resistant TB treatment in a routine TB programme, Mumbai, India.

BACKGROUND: Childhood and adolescent drug-resistant TB (DR-TB) is one of the neglected infectious diseases. Limited evidence exists around programmatic outcomes of children and adolescents receiving DR-TB treatment. The study aimed to determine the final treatment outcomes, culture conversion rates and factors associated with unsuccessful treatment outcome in children and adolescents with DR-TB. METHODS: This is a descriptive study including children (0-9 years) and adolescents (10-19 years) with DR-TB were who were initiated on ambulatory based treatment between January 2017-June 2018 in Shatabdi hospital, Mumbai, India where National TB elimination programme(NTEP) Mumbai collaborates with chest physicians and Médecins Sans Frontières(MSF) in providing comprehensive care to DR-TB patients. The patients with available end-of-treatment outcomes were included. The data was censored on February 2020. RESULT: A total of 268 patients were included; 16 (6%) of them were children (0-9 years). The median(min-max) age was 17(4-19) years and 192 (72%) were females. Majority (199, 74%) had pulmonary TB. Most (58%) had MDR-TB while 42% had fluoroquinolone-resistant TB. The median(IQR) duration of treatment (n = 239) was 24(10-25) months. Median(IQR) time for culture-conversion (n = 128) was 3(3-4) months. Of 268 patients, 166(62%) had successful end-of-treatment outcomes (cured-112; completed treatment-54). Children below 10 years had higher proportion of successful treatment outcomes (94% versus 60%) compared to adolescents. Patients with undernutrition [adjusted odds-ratio, aOR (95% Confidence Interval, 95%CI): 2.5 (1.3-4.8) or those with XDR-TB [aOR (95% CI): 4.3 (1.3-13.8)] had higher likelihood of having unsuccessful DR-TB treatment outcome. CONCLUSION: High proportion of successful treatment outcome was reported, better than global reports. Further, the nutritional support and routine treatment follow up should be strengthened. All oral short and long regimens including systematic use of new TB drugs (Bedaquiline and Delamanid) should be rapidly scaled up in routine TB programme, especially for the paediatric and adolescent population.

Nasal Airway Resistance and Latent Lower Airway Involvement in Allergic Rhinitis.

INTRODUCTION: Allergic rhinitis (AR) and asthma are closely linked atopic conditions, often termed as one airway one disease. Nasal airflow obstruction is a cardinal symptom of AR and objective assessment of resistance to nasal airflow in rhinitis can be measured by active anterior rhinomanometry. This study was aimed at correlating the degree of resistance to nasal airflow (NAR) with the clinical severity of allergic rhinitis. In addition, it aimed at determining the proportion of patients with latent lower airway involvement in AR and studying the impact of ARIA severity grade and NAR on this value. MATERIALS AND METHODS: A prospective prevalence study was conducted wherein 32 patients diagnosed with allergic rhinitis underwent determination of nasal airway resistance by active anterior rhinomanometry and lung function evaluation by spirometry. If spirometry was normal; histamine challenge test was performed to check for bronchial hyper-reactivity. RESULTS: 94% of patients with moderate- severe allergic rhinitis had significantly elevated nasal airway resistance compared to 56% of patients with mild rhinitis. (p=0.014). 71.9% of patients with allergic rhinitis but no symptoms of asthma had bronchial hyper-reactivity with a positive histamine challenge or airflow obstruction on lung functions. 87.5% patients with significantly elevated nasal airway resistance compared to 25% with lower values had lower airway involvement. (p=0.001). 94% of patients with moderate - severe rhinitis and 83% of patients with persistent rhinitis compared to 50% patients with mild and 44% with intermittent symptoms had lower airways involved. (p<0.05). CONCLUSION: Significantly greater proportion of patients with moderate-severe and persistent allergic rhinitis had elevated nasal airway resistance values. 72% patients with allergic rhinitis had lower airway involvement despite having no symptoms of asthma, prevalence being greater in patients with severe and persistent disease. Proportion of patients with lower airway hyper-responsiveness is significantly higher among patients with raised nasal airway resistance as determined by rhinomanometry. This study thus concludes that measurement of nasal airway resistance determined by active anterior rhinomanometry is a good objective tool to measure severity of nasal obstruction in allergic rhinitis with good correlation with the ARIA clinical severity grade .It may also be a promising tool to identify allergic rhinitis patients who are at a higher risk of having latent lower airway involvement.

Epituberculosis Revisited: Case Report and Review.

Primary pulmonary tuberculosis can involve regional lymph nodes which may resolve spontaneously or on treatment; or they may enlarge causing extrinsic bronchial compression; or cause endobronchial inflammation and ulceration; or a node may erode through the bronchial wall with extrusion of caseous materials into the bronchial tree, causing focal or lobar pneumonia. This erosion is seen radiologically as hilar lymphadenopathy, with atelectasis and consolidation and described as "epituberculosis". It is more common in infants than older children. We hereby describe the case of a 13-year-old child with right hilar lymphadenopathy and right upper lobe consolidation on chest x-ray. We demonstrated by fibreoptic bronchoscopy that this epituberculosis resulted from perforation of a lymph node and discharge of caseous material into the upper lobe bronchus with resultant endobronchial obstruction. Thus a tuberculous ruptured lymph node may lead to clinical and radiological worsening, but this does not indicate development of drug resistance in these patients and they respond well to the same treatment regimen.

Association of Environmental Factors, Prevalence of Asthma and Respiratory Morbidity in Mumbai: Need of a Public Health Policy.

OBJECTIVE: To study the association between environmental factors, prevalence of asthma and respiratory morbidity in relation to air quality levels in a mega city. To study modifiable environmental factors in people with diagnosed asthma and increased respiratory morbidity. METHODS: Cross sectional survey of population (N-3233) from 6 localities near air quality stations was done to study prevalence of asthma and respiratory morbidity (n-1006) followed by case control study of environmental factors by air sampling to study biological contamination. RESULTS: Univariate analysis was performed to study effect of various risk factors. Respiratory morbidity was significantly high in areas with high SPM levels. Odd's ratio was 10.3 for wheezing, 9.16 for cough, and 12.6 for breathlessness. Presence of biological contamination of air [bacterial spores] was associated with respiratory morbidity with odds ratio of 2.2 in areas with open drainage system. Pigeon droppings were found to be the source of fungal spores and associated with respiratory symptoms with odds ratio of 1.8. CONCLUSIONS: Respiratory morbidity significantly rises in areas with high particulate matter levels and biological contamination of air. Identification of environmental risk factors in different localities will be useful for undertaking specific mitigation measures at local level as a public health measure.

An ultrasonic atomization assisted synthesis of self-assembled manganese oxide octahedral molecular sieve nanostructures and their application in catalysis and water treatment.

Manganese oxides of octahedral molecular sieve (OMS-2) type have important applications in oxidation catalysis, adsorption, and as battery materials. The synthesis methods employed determine their morphology and textural properties which markedly affect their catalytic activity. In this work, a room temperature ultrasonic atomization assisted synthesis of OMS-2 type materials is demonstrated. This synthesis differs from previously reported methods in that it is a simple, no-heat application that leads to a striking morphological characteristic of uniformly sized OMS-2 fibers and their self-assembly into dense as well as hollow spheres. Control of various parameters in the ultrasonic atomization assisted synthesis led to OMS-2 with high surface areas (between 136-160 m2 g-1) and mesoporosity. Catalytically these materials have higher activities in the oxidation of hydroxymethylfurfural (HMF), a bio-based chemical, (65% conversion of HMF vs. 14% with conventional OMS-2 catalyst) and a higher adsorption of lead from aqueous solutions (70% vs. 12% in conventional OMS-2 materials).

Isoniazid Induced Lupus Presenting as Oral Mucosal Ulcers with Pancytopenia.

Drug Induced Lupus Erythematous (DILE) is a rare adverse reaction to a large variety of drugs including Isoniazid (INH), with features resembling idiopathic Systemic Lupus Erythematosus (SLE). Diagnosis require identification of a temporal relationship between drug administered and symptom. It is an idiosyncratic reaction, with no pre-existing lupus. Our case highlights a rare presentation of isoniazid induced lupus with profound pancytopenia and mucosal ulcers, thus posing a diagnostic challenge. The patient was on multidrug treatment for pulmonary and knee joint tuberculosis. DILE was diagnosed on basis of strongly positive Anti Nuclear Antibodies (ANA), anti ds DNA and antihistone antibodies with clinical response to cessation of INH.

Rare Case of Unilateral Hypoplasia of Lung with Associated Ventricular Mass in an Adult.

Hypoplasia of the lung is a rare congenital condition which can be: a) primary i.e. no apparent cause is found; or b) secondary i.e. associated with other congenital anomalies that are implicated in its pathogenesis. These anomalies may involve the diaphragm, cardiovascular, central nervous, urogenital and musculoskeletal system. Patients usually present in neonatal, infancy or childhood period and very rarely in adulthood. Our patient was an adult having a unilateral hypoplastic lung associated with a ventricular mass and to our knowledge this rare combination has never been reported in the English literature; though there are reports of prenatal or newborns with hypoplastic lung and rhabdomyoma of ventricle who did not survive.

Endobronchial tuberculosis mimicking malignancy.

Endobronchial tuberculosis has a very varied presentation. Diagnosis is often very challenging as typical radiological features are absent and sputum smear for acid-fast bacilli is often negative. However, detection is essential as it may lead to long-term sequelae such as bronchial stenosis. Bronchoscopy is a very useful investigation in such cases. Our case is a rare manifestation of endobronchial tuberculosis as it mimicked malignancy.

Light-assisted synthesis of metal oxide hierarchical structures and their catalytic applications.

Short reaction times and morphology control in the synthesis of inorganic materials under nonthermal conditions remain a challenge. Herein we report a rapid, self-templating, and nonthermal method based on ultraviolet light to prepare metal oxide hierarchical structures. With this method, the morphology of the metal oxides was controlled readily without using templates.

Incidence of silicosis in flourmill workers.

BACKGROUND: Silicosis is an ancient occupational illness reported in silica mill workers, agate stone workers, slate pen workers and mining industry. However its association in flour mill workers has not been established. AIMS: To study the incidence of silicosis and respiratory morbidity in flour mill workers. SETTINGS AND DESIGN: A prospective study of 56 flour mill workers working with open silica grinding stones was undertaken. MATERIALS AND METHODS: 56 flour mill workers who volunteered following information regarding the study purpose were recruited from the community. Detailed clinical and occupational history, lung functions, chest x-ray, and high resolution computed tomography (HRCT) were done. Diagnosis was made on the basis of radiological findings. STATISTICAL ANALYSIS: Data analysis was done with the help of the statistical package for social sciences software. The Chi-square test was used for determining the relationship between qualitative data and descriptive statistics was used where required. RESULTS: 93% had respiratory symptoms that included cough (66.1%), dyspnea (75%), chest pain (17.1%), and rhinorrhea (46.4%). Radiological abnormalities were noted in chest X-ray (60.7%) and HRCT (81.48%). A significant correlation was seen between duration of exposure and HRCT abnormalities. Lung functions revealed obstruction in 28.5% subjects, restriction in 19%, mixed ventilatory defects in 21.4%, while 18.9% had a reduced diffusion capacity. CONCLUSION: Incidence of silicosis in our study on flour mill workers working with silica containing grinding stones was 30.4%. They had high respiratory morbidity (93%) cough and dyspnea being predominant symptoms. Duration of exposure correlates with radiological findings and increased incidence of silicosis.