Sahajal Dhooria

Outcomes of antiretroviral therapy in a northern Indian urban clinic

PROBLEM Antiretroviral therapy (ART) programmes have been successful in several countries. However, whether they would succeed as part of a national programme in a resource-constrained setting such as India is not clear. The outcomes and specific problems encountered in such a setting have not been adequately studied. APPROACH We assessed the efficacy and functioning of Indias national ART programme in a tertiary care centre in northern India. All ART-naive patients started on ART between May 2005 and October 2006 were included in the study and were followed until 31 April 2008. Periodic clinical and laboratory evaluations were carried out in accordance with national guidelines. Changes in CD4+ lymphocyte count, body weight and body mass index were assessed at follow-up, and the operational problems analysed. LOCAL SETTING The setting was a tertiary care centre in northern India with a mixed population of patients, mostly of low socioeconomic status. The centre is reasonably well resourced but faces constraints in health-care delivery, such as lack of adequate human resources and a high patient load. RELEVANT CHANGES The response to ART in the cohort studied was comparable to that reported from other countries. However, the programme had a high attrition rate, possibly due to patient-related factors and operational constraints. LESSONS LEARNT A high rate of attrition can affect the overall efficacy and functioning of an ART programme. Addressing the issues causing attrition might improve patient outcomes in India and in other resource-constrained countries.

Nevirapine versus efavirenz-based antiretroviral therapy regimens in antiretroviral-naive patients with HIV and tuberculosis infections in India: a pilot study

BackgroundAdministration of rifampicin along with nevirapine reduces the plasma concentration of nevirapine in human immunodeficiency virus positive individuals with concomitant tuberculosis (HIV-TB patients). Nevirapine is a much cheaper drug than its alternative efavirenz, and might be beneficial in resource constrained settings.MethodsA randomised open label trial was conducted at All India Institute of Medical Sciences, New Delhi, India. During the regimen of an antiretroviral therapy (ART), naive HIV-TB patients were randomly assigned to receive either nevirapine or efavirenz based ART with concomitant rifampicin based anti-tubercular therapy (ATT). Participants were followed for 24 months after starting ART. The end points were virological, immunological and clinical responses, and progression of HIV disease marked by failure of ART.ResultsOf the 135 HIV-TB patients, who were receiving rifampicin based ATT, 68 were selected randomly to receive efavirenz based ART and 67 to receive nevirapine based ART. The virological failure rates in the overall population, and the nevirapine and efavirenz groups were 14.1% (19/135); 14.9% (10/67) and 13.2% (9/68), respectively (p = 0.94). No significant difference was found between the groups in the rate of clinical, immunological or virological failures. The overall mortality was 17% with no significant difference between the two groups. Except for the lead in period on day 14, the mean nevirapine concentration remained above 3 mg/L. No association was found between plasma levels of nevirapine and incidence of unfavourable outcomes in this group.ConclusionsOutcome of ART in HIV-TB patients on rifampicin based ATT showed no significant difference, irrespective of whether efavirenz or nevirapine was used. Therefore, nevirapine based ART could be an alternative in the resource limited settings in patients with HIV and tuberculosis co-infection.Trial registrationNCT No. 01805258.

Sleep after critical illness: Study of survivors of acute respiratory distress syndrome and systematic review of literature.

Background and Aims: This study aims to evaluate the sleep quality, architecture, sleep-related quality of life, and sleep-disordered breathing (SDB) in acute respiratory distress syndrome (ARDS) survivors early after discharge. Materials and Methods: In this prospective, observational study, consecutive patients with ARDS discharged from the Intensive Care Unit (ICU) underwent evaluation with Epworth sleepiness scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Functional Outcomes of Sleep Questionnaire (FOSQ), and overnight polysomnography. Patients having one or more of the following characteristics were classified as having abnormal sleep: ESS>10, PSQI>5, FOSQ <17.9, apnea–hypopnea index (AHI) ≥5, or AHI during rapid eye movement (REM) sleep ≥5. Results: Twenty patients (median interquartile range [IQR] age of 24 [22–28] years, 11 [55%] females) were included in the study. Acute febrile illness of unknown etiology with multi-organ dysfunction syndrome was the most common underlying etiology for ARDS. The median (IQR) PaO2/FiO2 ratio and APACHE II scores on admission were 176 (151–191.5) and 14 (14–16), respectively. The median (IQR) duration of stay in the ICU was 10 days (7.3–19.5). The overall sleep efficiency (median [IQR], 54% [32.3–65.4%]) was poor. None of the patients had ESS>10, seven (35%) had global PSQI>5 and one had FOSQ <17.9. Ten (50%) patients had at least one characteristic that suggested abnormal sleep (4 insomnia, 2 central sleep apnea, 1 obstructive sleep apnea, 1 REM-SDB, and 2 with a high PSQI, but no specific sleep abnormality). Conclusions: Sleep disturbances are common in ARDS survivors early after discharge from the ICU.

The antiretroviral efficacy of highly active antiretroviral therapy and plasma nevirapine concentrations in HIV-TB co-infected Indian patients receiving rifampicin based antituberculosis treatment

BackgroundRifampicin reduces the plasma concentrations of nevirapine in human immunodeficiency virus (HIV) and tuberculosis (TB) co-infected patients, who are administered these drugs concomitantly. We conducted a prospective interventional study to assess the efficacy of nevirapine-containing highly active antiretroviral treatment (HAART) when co-administered with rifampicin-containing antituberculosis treatment (ATT) and also measured plasma nevirapine concentrations in patients receiving such a nevirapine-containing HAART regimen.Methods63 cases included antiretroviral treatment naïve HIV-TB co-infected patients with CD4 counts less than 200 cells/mm3 started on rifampicin-containing ATT followed by nevirapine-containing HAART. In control group we included 51 HIV patients without tuberculosis and on nevirapine-containing HAART. They were assessed for clinical and immunological response at the end of 24 and 48 weeks. Plasma nevirapine concentrations were measured at days 14, 28, 42 and 180 of starting HAART.Results97 out of 114 (85.1%) patients were alive at the end of 48 weeks. The CD4 cell count showed a mean increase of 108 vs.113 cells/mm3 (p=0.83) at 24 weeks of HAART in cases and controls respectively. Overall, 58.73% patients in cases had viral loads of less than 400 copies/ml at the end of 48 weeks. The mean (± SD) Nevirapine concentrations of cases and control at 14, 28, 42 and 180 days were 2.19 ± 1.49 vs. 3.27 ± 4.95 (p = 0.10), 2.78 ± 1.60 vs. 3.67 ± 3.59 (p = 0.08), 3.06 ± 3.32 vs. 4.04 ± 2.55 (p = 0.10) respectively and 3.04 μg/ml (in cases).ConclusionsGood immunological and clinical response can be obtained in HIV-TB co-infected patients receiving rifampicin and nevirapine concomitantly despite somewhat lower nevirapine trough concentrations. This suggests that rifampicin-containing ATT may be co administered in resource limited setting with nevirapine-containing HAART regimen without substantial reduction in antiretroviral effectiveness. Larger sample sized studies and longer follow-up are required to identify populations of individuals where the reduction in nevirapine concentration may result in lower ART response or shorter response duration.

Impact of Rapid On-Site Cytological Evaluation (ROSE) on the Diagnostic Yield of Transbronchial Needle Aspiration During Mediastinal Lymph Node Sampling: Systematic Review and Meta-Analysis

BACKGROUND: Whether the use of rapid on‐site cytologic evaluation (ROSE) increases the diagnostic yield of transbronchial needle aspiration (TBNA) remains unclear. This article is a systematic review of studies describing the utility of ROSE in subjects undergoing TBNA. METHODS: The study included a systematic review of the PubMed, Embase, and Scopus databases for randomized controlled trials investigating the diagnostic yield of conventional transbronchial needle aspiration (c‐TBNA) or endobronchial ultrasound (EBUS)‐TBNA, with or without ROSE, in subjects with mediastinal lymphadenopathy. RESULTS: Five studies (618 subjects; two EBUS‐TBNA, two c‐TBNA, and one both) were identified. Overall, the studies were of good quality. The pooled risk difference (95% CI) of the diagnostic yield of EBUS‐TBNA and c‐TBNA was 0.04 (–0.01 to 0.09) and 0.12 (–0.08 to 0.33), respectively, suggesting no added benefit with ROSE. The use of ROSE during EBUS‐TBNA (but not c‐TBNA) resulted in significantly fewer needle passes (mean difference [95% CI], –1.1 [–2.2 to –0.005]; P < .001). There was no difference in the procedure time during EBUS‐TBNA. The complication rate was significantly lower (OR [95% CI], 0.26 [0.10 to 0.71]; P = .009) when ROSE was used during c‐TBNA due to fewer additional procedures required to make a diagnosis. There was evidence of heterogeneity in the studies involving c‐TBNA but not EBUS‐TBNA. There was no publication bias. CONCLUSIONS: The use of ROSE neither improved the diagnostic yield nor reduced the procedure time during TBNA. However, the use of ROSE was associated with fewer number of needle passes during EBUS‐TBNA and overall lower requirement for additional bronchoscopy procedures during TBNA to make a final diagnosis. TRIAL REGISTRY: PROSPERO; No.: CRD42017058937; URL: www.crd.york.ac.uk/prospero/.

A Randomized Trial of Itraconazole vs Prednisolone in Acute-Stage Allergic Bronchopulmonary Aspergillosis Complicating Asthma

OBJECTIVE Whether itraconazole monotherapy is effective in the acute stage of allergic bronchopulmonary aspergillosis (ABPA) remains unknown. The goal of this study was to compare the efficacy and safety of itraconazole and prednisolone monotherapy in ABPA. METHODS Treatment‐naive subjects with ABPA complicating asthma (January 2012 to December 2013) were randomized to receive either oral itraconazole or prednisolone for 4 months. The study was not blinded. The primary outcomes were proportion of subjects exhibiting a composite response after 6 weeks, percent decline in IgE after treatment, and numbers of subjects experiencing exacerbation. The secondary outcomes included the time to first exacerbation, change in lung function, and treatment‐related adverse effects. RESULTS A total of 131 subjects (prednisolone group, n = 63; itraconazole group, n = 68) were included in the study. The number of subjects exhibiting a composite response was significantly higher in the prednisolone group compared with the itraconazole group (100% vs 88%; P = .007). The percent decline in IgE after 6 weeks and 3 months and the number of subjects with exacerbations after 1 and 2 years of treatment were similar in the two groups. The time to first exacerbation (mean: 437 vs 442 days) and the improvement in lung function after 6 weeks was also similar in the two groups. The occurrence of side effects was significantly higher in the glucocorticoid arm (P < .001). CONCLUSIONS Prednisolone was more effective in inducing response than itraconazole in acute‐stage ABPA. However, itraconazole was also effective in a considerable number and, with fewer side effects compared with prednisolone, remains an attractive alternative in the initial treatment of ABPA. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT01321827; URL: www.clinicaltrials.gov).

Diagnostic Yield and Complications of EBUS-TBNA Performed Under Bronchoscopist-directed Conscious Sedation: Single Center Experience of 1004 Subjects.

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) can be performed under either conscious sedation or general anesthesia. Herein, we describe the diagnostic yield and complications of EBUS-TBNA performed under bronchoscopist-directed conscious sedation. Methods: This is a retrospective analysis of data collected in the bronchoscopy suite of this center on EBUS-TBNA or endoscopic ultrasound with a bronchoscope-guided fine needle aspiration (EUS-B-FNA) procedures performed between July 2011 and January 2016. All procedures were performed under bronchoscopist-directed conscious sedation with midazolam and pentazocine. The diagnostic yield, sample adequacy rate, complications, and doses of sedative agents are presented. Results: Of the total 1005 EBUS-TBNA/EUS-B-FNA procedures performed during the study period, 1004 were performed under conscious sedation in spontaneously breathing subjects [mean (SD) age, 45.9 (15.8) years; 378 (37.6%) women]. The mean (SD) doses of midazolam and pentazocine used were 2.53 (1.8) mg and 30.9 (6.9) mg, respectively. The diagnostic yield of the procedure (972 subjects) was 61.2%. Complications related to EBUS were observed in 60 (5.9%) subjects. Majority of them were minor and self-limiting; major complications occurred in 11 (1.1%) subjects and included respiratory failure requiring assisted ventilation (n=6), arrhythmia (n=3), and hypotension (n=2). Escalation of the level of care was needed in only 8 (0.8%) subjects. Conclusion: EBUS-TBNA/EUS-B-FNA performed under bronchoscopist-guided conscious sedation was found to be safe and is associated with a reasonable diagnostic yield.

A Multicenter Experience With the Placement of Self-Expanding Metallic Tracheobronchial Y Stents.

Background:Deployment of a bifurcation (Y) stent is often required in patients with airway obstruction or fistulization near the tracheal carina. Herein, we describe our experience with placement of self-expanding metallic Y stents. Methods:This was a retrospective analysis of data of consecutive subjects who underwent placement of self-expanding metallic Y stent over 2 years at 6 different centers. We describe the technique, complications, and outcomes of metallic Y stent placement at the tracheal carina. Results:Thirty-eight subjects (25 men) with a mean age of 54.8 years underwent Y stent placement. The most common underlying disease was carcinoma of the esophagus (65.8%). The most common indication for stent insertion was central airway obstruction in 30 (78.9%) subjects followed by airway-esophageal fistula. Respiratory failure was present in 17 (44.7%) subjects at admission. The Y stent was deployed using either the rigid (n=32) or the flexible (n=6) bronchoscope, and was successfully placed in 37 of the 38 (97.4%) subjects. There was rapid improvement in symptoms and subsequent resolution of respiratory failure after stent placement. There was no periprocedural mortality and few stent-related complications. On follow-up at 12 weeks, 18 patients had died due to progression of the underlying disease. Conclusion:The insertion of a metallic Y stent results in immediate palliation of malignant airway obstruction or airway fistulization near the tracheal carina with rapid improvement of symptoms.

Efficacy of endosonographic procedures in mediastinal re-staging of lung cancer after neoadjuvant therapy: A systematic review and diagnostic accuracy meta-analysis

BACKGROUND: The optimal modality for restaging the mediastinum following neoadjuvant therapy for lung cancer remains unclear. Surgical methods are currently considered the reference standard. The present study evaluates the role of endosonographic techniques for mediastinal restaging in lung cancer. METHODS: A systematic review of PubMed and Embase databases was performed to identify studies using endoscopic ultrasound, endobronchial ultrasound, or a combination of the two for mediastinal restaging following induction therapy for stage III lung cancer. The quality of the included studies was assessed by using the Quality Assessment of Diagnostic Accuracy Studies–2 tool. The accuracy of endosonography was analyzed by calculating the sensitivity, specificity, likelihood ratio, and diagnostic OR for each study and pooling the results by using a bivariate model. Heterogeneity and publication bias were assessed. Potential causes of heterogeneity were explored by using sensitivity analysis and meta‐regression. RESULTS: Ten studies (N = 574) were included. The pooled sensitivity, specificity, diagnostic OR, and positive and negative likelihood ratios were 67% (95% CI, 56–77), 99% (95% CI, 89–100), 157, 52.0, and 0.33, respectively. No complications were reported. Significant heterogeneity was observed for the outcome of sensitivity. Sensitivity analysis identified several factors accounting for heterogeneity, including study design and risk of bias. The sensitivity of the endosonographic procedure was also linked to the prevalence of N2 disease on meta‐regression. Funnel plot showed publication bias, but this finding was not evident on statistical tests. CONCLUSIONS: Endosonographic procedures are safe and highly specific in mediastinal restaging of lung cancer.

A Randomized Trial of Antimicrobial Prophylaxis in Patients Undergoing Medical Thoracoscopy (APT)

Background: There is no data on the role of prophylactic antibiotics in patients undergoing medical thoracoscopy. Objective: In this study, we evaluated the efficacy and safety of a single dose of intravenous cefazolin in subjects undergoing medical thoracoscopy. Methods: Subjects undergoing medical thoracoscopy were randomized 1:1 to receive either intravenous cefazolin 2 g (antibiotic group) or intravenous saline (control group). The primary outcome was the incidence of infections (surgical site infections and empyema) in the study groups, while the secondary outcomes were complications related to intravenous antibiotics. Results: Of the 121 subjects screened, 100 (mean age ± SD: 52.2 ± 15.2 years; 38 [38%] women) were randomized to the study groups. The incidence of postprocedural infections was not different between the antibiotic and the control group (4 [8%] vs. 6 [12%], p = 0.28). Surgical site infection occurred in 1 subject (2%) in the antibiotic group and 3 subjects (6%) in the saline group (p = 0.62); empyema occurred in 3 subjects (6%) in each group (p = 1.00). There was no association between age, comorbid illness (diabetes mellitus or chronic kidney disease), study group allocation, type of thoracoscope used, duration of procedure, histological diagnosis (benign or malignant), and the occurrence of infections in the postprocedural period. Conclusion: The use of a single dose of cefazolin prior to medical thoracoscopy was not associated with a reduction in the occurrence of postprocedural infection.