Study of risk factors and clinical management of patients with clinical non-response due to low plasma levels of anti-tubercular drugs.

This study was carried out to assess the role of therapeutic drug monitoring of crucial first-line anti-tubercular drugs: rifampicin (R) and isoniazid (H) among 75 non-responding proven drug-sensitive tuberculosis patients on treatment followed by intervention in field conditions. The intervention was done in the form of either an increase in the dosage of R and H in patients with minimally low drug levels or a modification of the regimen in a certain group of patients with significantly low drug levels by augmenting it with three or four second-line drugs in addition to standard first-line drugs. This study also aimed to determine the relationship between the measured plasma concentration of anti-tubercular drugs and various demographic, microbiological, radiological, and malabsorption factors and the presence of co-morbidities affecting them. The study also focused on the clinical impact of the intervention for low plasma levels of anti-TB drugs on TB treatment outcomes. In our study overall, 85.5% of patients had low levels of any drug. In 85.3% of patients, R levels were low, and in 39.1%, H levels were low. On univariate analysis, low body mass index (BMI), hypoalbuminemia, bilateral disease on chest X-rays, and the presence of cavities were found to be significantly associated with low drug levels, while none of the factors were independently significantly associated. Low BMI, pulmonary tuberculosis and disseminated tuberculosis, far-advanced disease and bilateral disease on chest X-ray, presence of cavities, and only low R levels were associated with unfavorable outcomes, with none of the factors found to be significant on multivariate analysis. In our study, it was seen that the treatment outcome was favorable in 59.6% of patients in whom this intervention was done by augmenting the treatment regimen with three/four second-line drugs along with increasing the dose of R and H. To conclude, various factors may be associated with low plasma levels of anti-tubercular drugs. If such patients show clinical non-response after >6 months of treatment and have significantly low drug levels, with an absence of drug resistance, their treatment regimen may need augmentation with three/four second-line drugs along with an increase in the dose of R and H, which may lead to a favorable outcome.

Indian Guidelines on Nebulization Therapy.

Inhalational therapy, today, happens to be the mainstay of treatment in obstructive airway diseases (OADs), such as asthma, chronic obstructive pulmonary disease (COPD), and is also in the present, used in a variety of other pulmonary and even non-pulmonary disorders. Hand-held inhalation devices may often be difficult to use, particularly for children, elderly, debilitated or distressed patients. Nebulization therapy emerges as a good option in these cases besides being useful in the home care, emergency room and critical care settings. With so many advancements taking place in nebulizer technology; availability of a plethora of drug formulations for its use, and the widening scope of this therapy; medical practitioners, respiratory therapists, and other health care personnel face the challenge of choosing appropriate inhalation devices and drug formulations, besides their rational application and use in different clinical situations. Adequate maintenance of nebulizer equipment including their disinfection and storage are the other relevant issues requiring guidance. Injudicious and improper use of nebulizers and their poor maintenance can sometimes lead to serious health hazards, nosocomial infections, transmission of infection, and other adverse outcomes. Thus, it is imperative to have a proper national guideline on nebulization practices to bridge the knowledge gaps amongst various health care personnel involved in this practice. It will also serve as an educational and scientific resource for healthcare professionals, as well as promote future research by identifying neglected and ignored areas in this field. Such comprehensive guidelines on this subject have not been available in the country and the only available proper international guidelines were released in 1997 which have not been updated for a noticeably long period of over two decades, though many changes and advancements have taken place in this technology in the recent past. Much of nebulization practices in the present may not be evidence-based and even some of these, the way they are currently used, may be ineffective or even harmful. Recognizing the knowledge deficit and paucity of guidelines on the usage of nebulizers in various settings such as inpatient, out-patient, emergency room, critical care, and domiciliary use in India in a wide variety of indications to standardize nebulization practices and to address many other related issues; National College of Chest Physicians (India), commissioned a National task force consisting of eminent experts in the field of Pulmonary Medicine from different backgrounds and different parts of the country to review the available evidence from the medical literature on the scientific principles and clinical practices of nebulization therapy and to formulate evidence-based guidelines on it. The guideline is based on all possible literature that could be explored with the best available evidence and incorporating expert opinions. To support the guideline with high-quality evidence, a systematic search of the electronic databases was performed to identify the relevant studies, position papers, consensus reports, and recommendations published. Rating of the level of the quality of evidence and the strength of recommendation was done using the GRADE system. Six topics were identified, each given to one group of experts comprising of advisors, chairpersons, convenor and members, and such six groups (A-F) were formed and the consensus recommendations of each group was included as a section in the guidelines (Sections I to VI). The topics included were: A. Introduction, basic principles and technical aspects of nebulization, types of equipment, their choice, use, and maintenance B. Nebulization therapy in obstructive airway diseases C. Nebulization therapy in the intensive care unit D. Use of various drugs (other than bronchodilators and inhaled corticosteroids) by nebulized route and miscellaneous uses of nebulization therapy E. Domiciliary/Home/Maintenance nebulization therapy; public & health care workers education, and F. Nebulization therapy in COVID-19 pandemic and in patients of other contagious viral respiratory infections (included later considering the crisis created due to COVID-19 pandemic). Various issues in different sections have been discussed in the form of questions, followed by point-wise evidence statements based on the existing knowledge, and recommendations have been formulated.

A new role of extracorporeal membrane oxygenation in the management of tuberculosis with acute respiratory distress syndrome: A case report and review of literature.

Pulmonary tuberculosis (PTB) can lead to acute respiratory distress syndrome (ARDS), which can be at times fatal. Venovenous extracorporeal membrane oxygenation (VV-ECMO) ensures adequate oxygenation and carbon dioxide removal, avoiding ventilator-induced lung injury. We present a case where a young woman with refractory respiratory failure caused by PTB, unresponsive to conventional mechanical ventilation, but was successfully managed with prolonged VV-ECMO support. The patient diagnosed with PTB was started on antitubercular treatment but went into respiratory failure and ARDS. The patient was put on mechanical ventilation, on which she was not improving. The patient was then put on ECMO. On the 9th day, lung compliance and gas exchange were good enough to resume conventional mechanical ventilation. ECMO was weaned and removed. This is one of few cases of survival of the patient with PTB with ARDS utilizing ECMO.

Reliability and validity of an audio signal modified shuttle walk test.

BACKGROUND: The audio signal in the conventionally accepted protocol of shuttle walk test (SWT) is not well-understood by the patients and modification of the audio signal may improve the performance of the test. OBJECTIVES: The aim of this study is to study the validity and reliability of an audio signal modified SWT, called the Singla-Richa modified SWT (SWTSR), in healthy normal adults. PATIENTS AND METHODS: In SWTSR, the audio signal was modified with the addition of reverse counting to it. A total of 54 healthy normal adults underwent conventional SWT (CSWT) at one instance and two times SWTSRon the same day. The validity was assessed by comparing outcomes of the SWTSRto outcomes of CSWT using the Pearson correlation coefficient and Bland-Altman plot. Test-retest reliability of SWTSRwas assessed using the intraclass correlation coefficient (ICC). The acceptability of the modified test in comparison to the conventional test was assessed using Likert scale. RESULTS: The distance walked (mean ± standard deviation) in the CSWT and SWTSRtest was 853.33 ± 217.33 m and 857.22 ± 219.56 m, respectively (Pearson correlation coefficient - 0.98; P < 0.001) indicating SWTSRto be a valid test. The SWTSRwas found to be a reliable test with ICC of 0.98 (95% confidence interval: 0.97-0.99). The acceptability of SWTSRwas significantly higher than CSWT. CONCLUSIONS: The SWTSRwith modified audio signal with reverse counting is a reliable as well as a valid test when compared with CSWT in healthy normal adults. It better understood by subjects compared to CSWT.

Pulmonary tuberculosis - An emerging risk factor for venous thromboembolism: A case series and review of literature.

One-third of patients with symptomatic venous thromboembolism (VTE) manifest pulmonary embolism, whereas two-thirds manifest deep vein thrombosis (DVT). Overall, 25%-50% of patients with first-time VTE have an idiopathic condition, without a readily identifiable risk factor, and its association with tuberculosis (TB) is a rare occurrence. Deep venous thrombosis has been associated with 1.5%-3.4% cases of TB. Early initiation of anti-TB treatment along with anticoagulant therapy decreases the overall morbidity and mortality associated with the disease. We report three cases of DVT associated with pulmonary TB who were diagnosed due to high index of suspicion as the risk factors for the development of DVT were present in these cases.