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Introduction Tuberculosis (TB) continues to be one of the deadliest infectious diseases over the centuries, killing more people worldwide than any other single infectious disease. There is an urgent need for additional strategies which can expedite efforts to combat TB including a preventive vaccine. In this endeavour, we have developed a protocol for a multisite, double-blind, placebo-controlled clinical trial in India that aims to evaluate the efficacy and safety of two TB vaccines; namely, VPM1002 and Immuvac (M.w) (Mycobacterium Indicus Pranii) (MIP) among healthy household contacts (HHCs) of sputum smear-positive pulmonary TB (PTB) patients.Methods and analysis In the three-arm randomised double-blind placebo-controlled trial study protocol, a total of 12 000 HHCs (aged 6−99 years) of sputum smear-positive PTB patients will be randomised to receive either of the two vaccine candidates VPM1002 and MIP or placebo. The primary efficacy endpoint is the prevention of microbiologically confirmed TB. Secondary endpoints will include (1) prevention against Latent TB infection, (2) incidence of adverse events and serious adverse events in study participants, (3) efficacy of vaccine in prevention of PTB/extra PTB in different age groups (6–18 years, 19–35 years, 36–60 years and above 60 years) and (4) immunogenicity of VPM1002 and MIP at month 2 and month 6 after first vaccination in terms of flow cytometric analysis of M.Tb specific CD4+ and CD8+ T cells secreting cytokines and Luminex assays for the presence of different cytokines in the sera and supernatants of peripheral blood mononuclear cells cultures stimulated with whole cell lysates of M.Tb and subsequently similar analysis for the cases who develop TB postvaccination during the follow-up period.Ethics and dissemination Ethics committees’ approvals have been granted by the Institutional Human Ethics Committees of all participating centres in this study and the names of the ethics committees and approvals are as follows: (1) National Institute for Research in Tuberculosis (NIRT)-Chennai (including subsites): ECR/135/Inst/TN/2013/RR-19, Approval No. 390/NIRT-Institutional Ethics Committee (IEC)/2018 dated 5 December 2018 (NIRT-Madurai-ECR/1365/Inst/TN/2020; approval dated 8 June 2020; NIRT, Vellore: ECR/1215/Inst/TN/2019; approval dated 26 September 2020); (2) All India Institute of Medical Sciences (AIIMS), Delhi (including subsites)-Institute Ethics Committee, ECR/547/Inst/DL/2014/RR-17 ECR/538/Inst/DL/2014/RR-20; approval No.IEC-385/06-07-2018, approval OP-28/05.04.2019 and SFH- ECR/593/Inst/DL/2014/RR-20 IEC/VMMC/SJH/project/2019-05/25 ; 23 May 2019; (3) National Institute of Tuberculosis and Respiratory Diseases (NITRD), Delhi: ECR/315/Inst/DL/2013/RR-19; approval IEC-No-NITRD/EC/2019/9004; 8 January 2019; (4) Pune-National AIDS Research Institute (NARI) and subsite-ECR/23/Inst/MH/2013/RR-19; IEC-NARI/EC/approval/2018/196; 29 May 2018; (5) Regional Medical Research Centre-Bhubaneshwar-ECR/911/Inst/OR-2017/RR-21; approval, dated 25 April 2018; Subsites- AIIMS, Bhubaneshwar ECR/534/Inst/OD/2014/RR-17 and 20 approval No. T/EMF/Pulm. Med/19/01 dated 13 May 2019; SCB, Cuttack No. No.ECR/84/Inst/OR/2013/RR-20; approval no.186 dated 7 February 2020; (6) NTI-Bengaluru: Ethics Committee-No-ECR/1819/Inst/KA/2019; approval No NTI-IEC/1.2019/principal investigator, dated 31 January 2019; (7) BMMRC, Hyderabad- ECR/450/Inst/AP/2013/RR-16 approval No. 779/BMMRC/2018/IEC, dated 11 June 2018 (Subsite Share India- Mediciti Ethics Committee-ECR/283/Inst/AP/2013/RR-20; Approval no. EC/11/VII/2K20(1) dated 11 July 2020) and (8) SJMC-Bengaluru: ECR/238/Inst/KA/2013/RR-19; approval IEC/1/491/2020; 7 August 2020.The trial findings will be published in accordance with the Consolidated Standards of Reporting Trials guidance. The results of this clinical trial will be presented at scientific conferences and disseminated through publications in peer-reviewed journals, conference presentations and shared with Ministry of Health and Family Welfare, policy-makers and other stakeholders.Trial registration number CTRI/2019/01/017026.

Abstract Detailed characterisation of immune responses induced by COVID-19 vaccines rolled out in India: COVISHIELDTM (CS) and COVAXIN® (CO) in a pre-exposed population is only recently being discovered. We addressed this issue in subjects who received their primary series of vaccination between November 2021 and January 2022. Both vaccines are capable of strongly boosting Wuhan Spike-specific neutralising antibody, polyfunctional Th1 cytokine producing CD4+ T-cells and single IFN-γ + CD8+ T-cells. Consistent with inherent differences in vaccine platform, the vector-based CS vaccine-induced immunity was of greater magnitude, breadth, targeting Delta and Omicron variants compared to the whole-virion inactivated vaccine CO, with CS vaccinees showing persistent CD8+ T-cells responses until 3 months post primary vaccination. This study provides detailed evidence on the magnitude and quality of CS and CO vaccine induced responses in subjects with pre-existing SARS-CoV-2 immunity in India, thereby mitigating vaccine hesitancy arguments in such a population, which remains a global health challenge.

Summary: Background: There are limited global data on head-to-head comparisons of vaccine platforms assessing both humoral and cellular immune responses, stratified by pre-vaccination serostatus. The COVID-19 vaccination drive for the Indian population in the age group 18–45 years began in April 2021 when seropositivity rates in the general population were rising due to the delta wave of COVID-19 pandemic during April–May 2021. Methods: Between June 30, 2021, and Jan 28, 2022, we enrolled 691 participants in the age group 18–45 years across four clinical sites in India. In this non-randomised and laboratory blinded study, participants received either two doses of Covaxin® (4 weeks apart) or two doses of Covishield™ (12 weeks apart) as per the national vaccination policy. The primary outcome was the seroconversion rate and the geometric mean titre (GMT) of antibodies against the SARS-CoV-2 spike and nucleocapsid proteins post two doses. The secondary outcome was the frequency of cellular immune responses pre- and post-vaccination. Findings: When compared to pre-vaccination baseline, both vaccines elicited statistically significant seroconversion and binding antibody levels in both seronegative and seropositive individuals. In the per-protocol cohort, Covishield™ elicited higher antibody responses than Covaxin® as measured by seroconversion rate (98.3% vs 74.4%, p

Summary: This study characterized mechanisms of Bacille Calmette-Guérin (BCG) revaccination-induced trained immunity (TI) in India. Adults, BCG vaccinated at birth, were sampled longitudinally before and after a second BCG dose. BCG revaccination significantly elevated tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6 in HLA-DR+CD16−CD14hi monocytes, demonstrating induction of TI. Mycobacteria-specific CD4+ T cell interferon (IFN) γ, IL-2, and TNF-α were significantly higher in re-vaccinees and correlated positively with HLA-DR+CD16−CD14hi TI responses. This, however, did not translate into increased mycobacterial growth control, measured by mycobacterial growth inhibition assay (MGIA). Post revaccination, elevated secreted TNF-α, IL-1β, and IL-6 to “heterologous” fungal, bacterial, and enhanced CXCL-10 and IFNα to viral stimuli were also observed concomitant with increased anti-inflammatory cytokine, IL-1RA. RNA sequencing after revaccination highlighted a BCG and LPS induced signature which included upregulated IL17 and TNF pathway genes and downregulated key inflammatory genes: CXCL11, CCL24, HLADRA, CTSS, CTSC. Our data highlight a balanced immune response comprising pro- and anti-inflammatory mediators to be a feature of BCG revaccination-induced immunity.

Objectives The objective of this study was to assess the feasibility and acceptability of video-based anti-tuberculosis (TB) treatment adherence support in patients with TB (PwTB) in South India.Design An exploratory cohort.Setting Participants were recruited at the TB treatment centre (direct observed treatment short centre) of a tertiary-level teaching facility in Bangalore, Karnataka, South India.Participants The study enrolled 25 PwTB, with replacement. Adult PwTB who were on drug-sensitive treatment regimens were included, while those who had drug resistant TB were excluded from the study.Intervention Participants received scheduled adherence reminders and were trained to videorecord themselves swallowing their medication via a mobile application. The application was automated to submit these videos for evaluation. Participants were followed up monthly till treatment completion or withdrawal.Outcome measures Adherence rate and acceptability of video-based directly observed treatment (vDOT).Results The mean±SD age of the participants was 33±14 years, majority were females (16, 64%), residing in urban areas (24,96%), married (17, 68%) and had access to smart phones (23,92%). A total of 3193 person days of follow-up was completed; of the videos submitted within the first 6 months of enrollment (2501), 94% (2354/2501) were considered ‘acceptable’ and 16 (64%) participants were optimally adherent (ie, ≥80%). Participant videos improved in quality and a higher proportion met acceptability criteria over time. Twenty-one (84%) participants stated that they found the application easy to learn; 13 (52%) preferred vDOT over DOT. Mixed model logistic regression showed that those who are married are more likely have daily adherence to anti-TB treatment.Conclusion Video-based mobile phone interventions are acceptable to PwTB and the ease of using the application increases with time. To provide patient-centred care, vDOT is a promising option that can be offered to patients for treatment support and adherence monitoring.

This proof-of-concept study tested if prior BCG revaccination can qualitatively and quantitively enhance antibody and T-cell responses induced by Oxford/AstraZeneca ChAdOx1nCoV-19 or COVISHIELD™, an efficacious and the most widely distributed vaccine in India. We compared COVISHIELD™ induced longitudinal immune responses in 21 BCG re-vaccinees (BCG-RV) and 13 BCG-non-revaccinees (BCG-NRV), all of whom were BCG vaccinated at birth; latent tuberculosis negative and SARS-CoV-2 seronegative prior to COVISHIELD™ vaccination. Compared to BCG-NRV, BCG-RV displayed significantly higher and persistent spike-specific neutralizing (n) Ab titers and polyfunctional CD4+ and CD8+ T-cells for eight months post COVISHIELD™ booster, including distinct CD4+IFN-γ+ and CD4+IFN-γ- effector memory (EM) subsets co-expressing IL-2, TNF-α and activation induced markers (AIM) CD154/CD137 as well as CD8+IFN-γ+ EM,TEMRA (T cell EM expressing RA) subset combinations co-expressing TNF-α and AIM CD137/CD69. Additionally, elevated nAb and T-cell responses to the Delta mutant in BCG-RV highlighted greater immune response breadth. Mechanistically, these BCG adjuvant effects were associated with elevated markers of trained immunity, including higher IL-1β and TNF-α expression in CD14+HLA-DR+monocytes and changes in chromatin accessibility highlighting BCG-induced epigenetic changes. This study provides first in-depth analysis of both antibody and memory T-cell responses induced by COVISHIELD™ in SARS-CoV-2 seronegative young adults in India with strong evidence of a BCG-induced booster effect and therefore a rational basis to validate BCG, a low-cost and globally available vaccine, as an adjuvant to enhance heterologous adaptive immune responses to current and emerging COVID-19 vaccines.

Background: Administration of local airway anesthesia is the principal determinant of procedural comfort during flexible bronchoscopy. However, the ideal method of administration is still unknown. In this study, we compared lignocaine administration using a spray catheter (SC) with “spray-as-you-go” technique. Methods: Patients undergoing bronchoscopy were randomized to receive airway anesthesia with 2% lignocaine through the SC (SC group) or “spray-as-you-go” technique through the working channel (WC group). The primary outcome parameter was cough count, and the secondary outcome parameters compared were need for sedation, operator-rated procedural satisfaction and cough, and patient-rated comfort on a Visual Analog Scale (VAS). Results: One hundred and thirty patients were randomized with comparable baseline parameters. The median (interquartile range [IQR]) cough count was 28 (19, 37) in the WC group and 15 (9, 23) in the SC group (P < 0.001). Requirement for sedation was lower in the SC group (5 vs. 18; P = 0.003). The mean (standard deviation [SD]) VAS score for operator-rated satisfaction was 66.5 (16.8) in the WC group and 80.6 (14.2) in the SC group; P < 0.001. The median (IQR) VAS score for operator-rated cough was 35 (23, 44) in the WC group and 18 (11, 28) in the SC group; P < 0.001. However, there was no difference in the patient-rated comfort VAS (mean [SD] of 66.4 [14.5] in the WC group and 69.9 [13.0] in the SC group; P = 0.07). Conclusion: Lignocaine instillation using the SC during bronchoscopy reduced cough, need for sedation, and improved operator satisfaction.

Abstract Background Pneumothorax can present as a respiratory emergency and has varied etiology. However, literature available on assessment and management of primary spontaneous pneumothorax (PSP) based on radiological quantitation is scarce. This study was undertaken to compare two different methods of quantitating pneumothorax size with that recommended in American Thoracic Society (ATS) guideline on chest radiogram with respect to possible change in management practices. Patients and methods A prospective cohort of adults presenting with spontaneous pneumothorax (SP) over 3 years to Emergency and Pulmonology Department, St John’s Medical College Hospital, Bangalore, was included. Demographic characteristics and clinical presentation were compiled. Management of SP was based on ATS guidelines. PSP size on chest radiogram was requantitated in the included patients using Light’s index and Collin’s method and was compared with that proposed by the ATS guideline. Results Seventy-six participants with SP were studied; their mean age was 43.7 years, with a preponderance of male patients (84.2%). Twenty-four (31.6%) patients had PSP and 52 (68.4%) patients had secondary spontaneous pneumothorax. In PSP, there was poor agreement between various methods of estimating size of pneumothorax on chest radiogram (Kappa statistic=0.23; ICC of 0.263). Three (12.5%) of the 24 incidences of PSP, which were treated conservatively as per ATS guidelines, would have required invasive intervention if Light’s index or the Collin’s formula were taken into consideration. Conclusion There was poor agreement of radiological pneumothorax size estimation by Collin’s, Light’s, and that proposed in the ATS guidelines. Thus, a unified, standardized method of radiological assessment of PSP is required.

Summary: HIV infection predisposes latent tuberculosis-infected (LTBI) subjects to active TB. This study is designed to determine whether HIV infection of LTBI subjects compromises the balanced Mycobacterium tuberculosis (Mtb)-specific T helper 17 (Th17) response of recognized importance in anti-TB immunity. Comparative analysis of Mtb- and cytomegalovirus (CMV)-specific CD4+ T cell responses demonstrates a marked dampening of the Mtb-specific CD4+ T cell effectors and polyfunctional cells while preserving CMV-specific response. Additionally, HIV skews the Mtb-specific Th17 response in chronic HIV-infected LTBI progressors, but not long-term non-progressors (LTNPs), with preservation of pro-inflammatory interferon (IFN)-γ+/interleukin-17+ (IL-17+) and significant loss of anti-inflammatory IL-10+/IL-17+ effectors that is restored by anti-retroviral therapy (ART). HIV-driven impairment of Mtb-specific response cannot be attributed to preferential infection as cell-associated HIV DNA and HIV RNA reveal equivalent viral burden in CD4+ T cells from different antigen specificities. We therefore propose that beyond HIV-induced loss of Mtb-specific CD4+ T cells, the associated dysregulation of Mtb-specific T cell homeostasis can potentially enhance the onset of TB in LTBI subjects.

Flexible bronchoscopy (FB) is commonly performed by respiratory physicians for diagnostic as well as therapeutic purposes. However, bronchoscopy practices vary widely across India and worldwide. The three major respiratory organizations of the country supported a national-level expert group that formulated a comprehensive guideline document for FB based on a detailed appraisal of available evidence. These guidelines are an attempt to provide the bronchoscopist with the most scientifically sound as well as practical approach of bronchoscopy. It involved framing appropriate questions, review and critical appraisal of the relevant literature and reaching a recommendation by the expert groups. The guidelines cover major areas in basic bronchoscopy including (but not limited to), indications for procedure, patient preparation, various sampling procedures, bronchoscopy in the ICU setting, equipment care, and training issues. The target audience is respiratory physicians working in India and well as other parts of the world. It is hoped that this document would serve as a complete reference guide for all pulmonary physicians performing or desiring to learn the technique of flexible bronchoscopy.

INTRODUCTION: Asthma is a significant public health problem. The severity of asthma varies from patient to patient and the reasons for this are not fully understood. Atopy is known to play an important part in the pathogenesis of asthma. Sensitization to aeroallergens like house dust mite, animal dander from pets and environmental fungi are evaluated in asthmatics. Severe asthma seems to be associated to environmental fungi with sensitization especially to Aspergillus species. AIMS AND OBJECTIVE: The study aimed at determining the prevalence of Cutaneous Sensitization to Aspergillus species by Skin Prick Test (SPT) in moderate- severe asthmatics. MATERIAL AND METHODS: This study was done on 205 clinically diagnosed asthmatic patients, between September 2012 and August 2013. SPT and spirometry was done in all subjects along with a detailed history. RESULTS: The prevalence rate of Aspergillus sensitized patients is 59.5%. Observations of this study also suggest that the severity of asthma is more in Aspergillus sensitized patients when compared to non-sensitized patients and the duration of asthma was more in Non sensitized. There was no significant association between AEC, total IgE levels and Aspergillus species culture positivity in Aspergillus sensitized patients. Aspergillus terreus was the predominant fungal isolate from both SPT positive and negative patient. There was no significant correlation of fungal culture with SPT. CONCLUSIONS: High levels of Aspergillus sensitization is seen in south Indian subjects and is associated with greater severity and shorter duration of asthma.

Lung ultrasound (LUS) has been proven to yield valuable information for lung and pleural pathology. It is well validated for assessing extravascular lung water. It can also be used to monitor stages of controlled lung de-aeration in whole lung lavage (WLL) which is the treatment for Pulmonary Alveolar Protienosis (PAP),characterized by abnormal surfactant in the alveoli affecting gas exchange .LUS can help decide the point of termination of lung flooding. A 55 year old lady with biopsy proven pulmonary alveolar proteinosis presented with respiratory failure. WLL was planned. LUS was used to study the stages of lung flooding as previously described for ARDS model.6 areas screened based on six areas that are normally examined like upper zone, mid zone and lower zone showed alveolar interstitial pattern. One lung ventilation (OLV) was done and isolation of lavage lung was confirmed which was seen as lung collapse (lung pulse) on LUS. Saline infusion resulted in increase in B lines followed by tissue like pattern with fluid bronchogram on LUS(alveolar flooding) in all the areas. During the lavage of the second lung, appearance of alveolar flooding pattern resulted in termination of saline infusion. The use of LUS in monitoring WLL reduced amount of saline used for lavage, pick up complications like pleural effusion and spillage.

Efficient diagnosis of tuberculosis (TB) is met with multiple challenges, calling for a shift of focus from pathogen-centric diagnostics towards identification of host-based multi-marker signatures. Transcriptomics offer a list of differentially expressed genes, but cannot by itself identify the most influential contributors to the disease phenotype. Here, we describe a computational pipeline that adopts an unbiased approach to identify a biomarker signature. Data from RNA sequencing from whole blood samples of TB patients were integrated with a curated genome-wide molecular interaction network, from which we obtain a comprehensive perspective of variations that occur in the host due to TB. We then implement a sensitive network mining method to shortlist gene candidates that are most central to the disease alterations. We then apply a series of filters that include applicability to multiple publicly available datasets as well as additional validation on independent patient samples, and identify a signature comprising 10 genes — FCGR1A, HK3, RAB13, RBBP8, IFI44L, TIMM10, BCL6, SMARCD3, CYP4F3 and SLPI, that can discriminate between TB and healthy controls as well as distinguish TB from latent tuberculosis and HIV in most cases. The signature has the potential to serve as a diagnostic marker of TB.

Summary: Background: Bronchiectasis is a common but neglected chronic lung disease. Most epidemiological data are limited to cohorts from Europe and the USA, with few data from low-income and middle-income countries. We therefore aimed to describe the characteristics, severity of disease, microbiology, and treatment of patients with bronchiectasis in India. Methods: The Indian bronchiectasis registry is a multicentre, prospective, observational cohort study. Adult patients (≥18 years) with CT-confirmed bronchiectasis were enrolled from 31 centres across India. Patients with bronchiectasis due to cystic fibrosis or traction bronchiectasis associated with another respiratory disorder were excluded. Data were collected at baseline (recruitment) with follow-up visits taking place once per year. Comprehensive clinical data were collected through the European Multicentre Bronchiectasis Audit and Research Collaboration registry platform. Underlying aetiology of bronchiectasis, as well as treatment and risk factors for bronchiectasis were analysed in the Indian bronchiectasis registry. Comparisons of demographics were made with published European and US registries, and quality of care was benchmarked against the 2017 European Respiratory Society guidelines. Findings: From June 1, 2015, to Sept 1, 2017, 2195 patients were enrolled. Marked differences were observed between India, Europe, and the USA. Patients in India were younger (median age 56 years [IQR 41–66] vs the European and US registries; p

Vaccines that confer protection through induction of adaptive T-cell immunity rely on understanding T-cell epitope (TCE) evolution induced by immune escape. This is poorly understood in tuberculosis (TB), an ancient, chronic disease, where CD4 T-cell immunity is of recognized importance. We probed 905 functionally validated, curated human CD4 T cell epitopes in 79 Mycobacterium tuberculosis (Mtb) whole genomes from India. This screen resulted in identifying 64 mutated epitopes in these strains initially using a computational pipeline and subsequently verified by single nucleotide polymorphism (SNP) analysis. SNP based phylogeny revealed the 79 Mtb strains to cluster to East African Indian (EAI), Central Asian Strain (CAS), and Beijing (BEI) lineages. Eighty-nine percent of the mutated T-cell epitopes (mTCEs) identified in the 79 Mtb strains from India has not previously been reported. These mTCEs were encoded by genes with high nucleotide diversity scores including seven mTCEs encoded by six antigens in the top 10% of rapidly divergent Mtb genes encoded by these strains. Using a T cell functional assay readout, we demonstrate 62% of mTCEs tested to significantly alter CD4 T-cell IFNγ and/or IL2 secretion with associated changes in predicted HLA-DR binding affinity: the gain of function mutations displayed higher predicted HLA-DR binding affinity and conversely mutations resulting in loss of function displayed lower predicted HLA-DR binding affinity. Most mutated antigens belonged to the cell wall/cell processes, and, intermediary metabolism and respiration families though all known Mtb proteins encoded mutations. Analysis of the mTCEs in an SNP database of 5,310 global Mtb strains identified 82% mTCEs to be significantly more prevalent in Mtb strains isolated from India, including 36 mTCEs identified exclusively in strains from India. These epitopes had a significantly higher predicted binding affinity to HLA-DR alleles that were highly prevalent in India compared to HLA-DR alleles rare in India, highlighting HLA-DR maybe an important driver of these mutations. This first evidence of region-specific TCE mutations potentially employed by Mtb to escape host immunity has important implications for TB vaccine design.

Background: About half of the population in developing countries are exposed to indoor pollution such as combustion fuels at present. Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality globally and the primary cause of COPD in women is indoor air pollution exposure, while tobacco smoking is the leading cause in men. The aim of this systematic review and meta-analysis is to evaluate the correlation between the indoor air pollution and deaths related to COPD and COPD prevalence in South Asia. Methods: A systematic search on studies with sufficient statistical power has been conducted from 1985 until 30 June 2020, in English electronic databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in MEDLINE and PubMed databases with the terms Chronic Obstructive Pulmonary disease COPD or Chronic Bronchitis or Emphysema or COPD Deaths or Chronic Obstructive Lung Disease or Airflow Obstruction or Chronic Airflow Obstruction or Airflow Obstruction, Chronic or Bronchitis, Chronic and Mortality or Death or Deceased was conducted. Studies were eligible if they were Prospective controlled or non-controlled trials conducted in Southern Asia/ Asia and Retrospective studies conducted in Southern Asia/ Asia. Results: The results have concluded that long term exposure to indoor pollution had a significant effect on COPD deaths as well as its symptoms. Odd’s ratio was in a range of 1.05 (Randomized controlled trials) to 7.87 (Cross sectional studies) for all the studies mentioned. Meta-analysis observed a significantly higher Odds Ratio of 2.13 for COPD mortality and 2.08 for COPD prevalence on exposure to indoor air pollution. Conclusion: Exposure to solid fuel smoke is consistently and significantly correlated with COPD mortality and COPD prevalence in South Asian countries, in spite of heterogeneity observed in the studies included. For performing domestic tasks, initiatives are to be taken to reduce dependency on solid fuel by using cleaner alternatives or comparatively cleaner technology.

This study aimed to describe real-life microbiological testing of adults hospitalised with community-acquired pneumonia (CAP) and to assess concordance with the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) and 2011 European Respiratory Society (ERS) CAP guidelines. This was a cohort study based on the Global Initiative for Methicillin-resistant Staphylococcus aureus Pneumonia (GLIMP) database, which contains point-prevalence data on adults hospitalised with CAP across 54 countries during 2015. In total, 3702 patients were included. Testing was performed in 3217 patients, and included blood culture (71.1%), sputum culture (61.8%), Legionella urinary antigen test (30.1%), pneumococcal urinary antigen test (30.0%), viral testing (14.9%), acute-phase serology (8.8%), bronchoalveolar lavage culture (8.4%) and pleural fluid culture (3.2%). A pathogen was detected in 1173 (36.5%) patients. Testing attitudes varied significantly according to geography and disease severity. Testing was concordant with IDSA/ATS and ERS guidelines in 16.7% and 23.9% of patients, respectively. IDSA/ATS concordance was higher in Europe than in North America (21.5% versus 9.8%; p

Summary: Introduction: India accounts for about a fifth of cardiovascular deaths globally, but nationally representative data on mortality trends are not yet available. In this nationwide mortality study, we aimed to assess the trends in ischaemic heart disease and stroke mortality over 15 years using the Million Death Study. Methods: We determined national and subnational cardiovascular mortality rates and trends by sex and birth cohort using cause of death ascertained by verbal autopsy from 2001 to 2013 among 2·4 million households. We derived mortality rates for ischaemic heart disease and stroke by applying mortality proportions to UN mortality estimates for India and projected the rates from 2000 to 2015. Findings: Cardiovascular disease caused more than 2·1 million deaths in India in 2015 at all ages, or more than a quarter of all deaths. At ages 30–69 years, of 1·3 million cardiovascular deaths, 0·9 million (68·4%) were caused by ischaemic heart disease and 0·4 million (28·0%) by stroke. At these ages, the probability of dying from ischaemic heart disease increased during 2000–15, from 10·4% to 13·1% in men and 4·8% to 6·6% in women. Ischaemic heart disease mortality rates in rural areas increased rapidly and surpassed those in urban areas. By contrast, the probability of dying from stroke decreased from 5·7% to 5·0% in men and 5·0% to 3·9% in women. A third of premature stroke deaths occurred in the northeastern states, inhabited by a sixth of India's population, where rates increased significantly and were three times higher than the national average. The increased mortality rates of ischaemic heart disease nationally and stroke in the northeastern states were higher in the cohorts of adults born in the 1970s onwards, than in earlier decades. A large and growing proportion of the ischaemic heart disease nationally and stroke deaths in high-burden states reported earlier diagnosis of cardiovascular disease, but low medication use. Interpretation: The unexpectedly diverse patterns of cardiovascular mortality require investigation to identify the role of established and new cardiovascular risk factors. Secondary prevention with effective and inexpensive long-term treatment and adult smoking cessation could prevent substantial numbers of premature deaths. Without progress against the control of cardiovascular disease in India, global goals to reduce non-communicable diseases by 2030 will be difficult to achieve. Funding: Fogarty International Center of the US National Institutes of Health, Dalla Lana School of Public Health, University of Toronto, Indian Council of Medical Research, and the Disease Control Priorities.

Background: Systemic sclerosis is a generalized disorder of connective tissue affecting skin and internal organs. Lung involvement accounts for significant morbidity and is a leading cause of mortality in patients. Objectives: This study intends to study the frequency of occurrence of pulmonary involvement in progressive systemic sclerosis (PSS) and to describe the clinical and radiological picture of pulmonary involvement in PSS. Materials and Methods: This was a descriptive cross-sectional study. A detailed history, modified Rodnan score, clinical examination, routine investigation, antinuclear antibody, immuno biot, chest X-ray (CXR), pulmonary function test (PFT), and 6 min walk test (6MWT) were performed on all patients. High resolution computed tomography was done on those who consented. Results: Hundred subjects with PSS were included in the study; 90 were females and 10 were males. Common presenting complaints were skin thickening in 98% and Raynaud's phenomenon in 98%. Skin thickening of digits beyond metacarpo phalangeal was seen in 98%, face and neck in 92%, and hands in 92%. Chest wall thickening was seen in 40 subjects (40%). 90 (90%) of the studied subjects had pulmonary involvement, longer duration of disease was significantly associated with pulmonary involvement (P < 0.05). Dyspnea, cough, bilateral crepitations, CXR, Borg score, and Rodnan score was found to be significantly associated with severe pulmonary involvement (P < 0.05). Conclusion: The prevalence of pulmonary involvement in this cohort study was 90%. Almost 1/3rd of patients, that is 29 (29%) were detected to have pulmonary involvement despite being asymptomatic for respiratory complaints, hence early screening and evaluation is recommended. PFT and 6MWT are noninvasive, cost-effective, and easily available screening tests which can be used in resource-limited settings.

Background: Tobacco-attributable mortality in India is estimated to be at least 10%. Tobacco cessation is more likely to avert millions of deaths before 2050 than prevention of tobacco use initiation. Objective: To describe the clinico-epidemiological profile of attendees of a tobacco cessation clinic in a teaching hospital in Bangalore city. Materials and Methods: A descriptive study of 189 attendees seen over 2 years in the Tobacco Cessation Clinic of a tertiary-care teaching hospital in Bangalore, with information on socio demographic characteristics, tobacco-use details, nicotine dependence, family/medical history, past quit attempts, baseline stage-of-change, and treatment initiated. Results: Only 5% were ′walk-in′ patients; 98% of attendees were smokers; 97% were males. The mean (±SD) age of attendees was 48.0 (±14.0) years. Most participants were married (88%), and predominantly urban (69%). About 62% had completed at least 8 years of schooling. Two-thirds of smokers reported high levels of nicotine dependence (Fagerström score >5/10). About 43% of patients had attempted quitting earlier. Four-fifths (79%) of tobacco-users reported a family member using tobacco. Commonly documented comorbidities included: Chronic respiratory disease (44%), hypertension (23%), diabetes (12%), tuberculosis (9%), myocardial infarction (2%), stroke (1%), sexual dysfunction (1%) and cancer (0.5%). About 52% reported concomitant alcohol use. At baseline, patients′ motivational stage was: Precontemplation (14%), contemplation (48%), preparation/action (37%) and maintenance (1%). Treatment modalities started were: Counseling alone (41%), nicotine replacement therapy alone (NRT) (34%), medication alone (13%), and NRT+medication (12%). Conclusions: This is the first study of the baseline profile of patients attending a tobacco cessation clinic located within a chest medicine department in India. Important determinants of outcome have been captured for follow-up and prospective documentation of outcomes.

BACKGROUND: Adherence is central to the success of antiretroviral therapy. Supporting adherence has gained importance in HIV care in many national treatment programs. The ubiquity of mobile phones, even in resource-constrained settings, has provided an opportunity to utilize an inexpensive, contextually feasible technology for adherence support in HIV in these settings. We aimed to assess the influence of mobile phone reminders on adherence to antiretroviral therapy in South India. Participant experiences with the intervention were also studied. This is the first report of such an intervention for antiretroviral adherence from India, a country with over 800 million mobile connections. METHODS: STUDY DESIGN: Quasi-experimental cohort study involving 150 HIV-infected individuals from Bangalore, India, who were on antiretroviral therapy between April and July 2010. The intervention: All participants received two types of adherence reminders on their mobile phones, (i) an automated interactive voice response (IVR) call and (ii) A non-interactive neutral picture short messaging service (SMS), once a week for 6 months. Adherence measured by pill count, was assessed at study recruitment and at months one, three, six, nine and twelve. Participant experiences were assessed at the end of the intervention period. RESULTS: The mean age of the participants was 38 years, 27% were female and 90% urban. Overall, 3,895 IVRs and 3,073 SMSs were sent to the participants over 6 months. Complete case analysis revealed that the proportion of participants with optimal adherence increased from 85% to 91% patients during the intervention period, an effect that was maintained 6 months after the intervention was discontinued (p = 0.016). Both, IVR calls and SMS reminders were considered non-intrusive and not a threat to privacy. A significantly higher proportion agreed that the IVR was helpful compared to the SMS (p