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Background: Hydroxychloroquine (HCQ) had generated considerable interest for coronavirus disease 2019 (COVID-19) prophylaxis. We conducted a prospective observational study at a tertiary care hospital in India, with dedicated COVID-19 care facilities. Objectives: Primary objective was incidence of adverse effects, secondary objective being efficacy in preventing COVID-19. Methods: Healthcare workers were recruited and grouped based on voluntary HCQ prophylaxis as per national guidelines. Side effects in HCQ group were graded in accordance with national cancer institute-common terminology criteria for adverse events (NCI-CTCAE) version 5.0. At 3–7-week follow-up, groups were compared for COVID-19 exposure, symptoms development and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR results. Results: Among 358 participants recruited, 216 (60.3%) were males and mean age was 31.2 ± 6.6 years. Chemoprophylaxis was initiated by 258 (72%) participants. After loading dose, 7 (2.7%) reported grade 2 and 1 (0.4%) grade 3 adverse effects. Discontinuation of HCQ due to side effects was reported in 11 (4.3%) participants. Electrocardiogram was done by 50 (19.4%) participants on HCQ; no abnormalities were noted. A total of 106 (41%) among those taking and 63 (63%) among those not taking HCQ were tested for SARS-CoV-2 due to influenza-like illness or significant exposure. Among all participants, 25 (6.9%, 95% confidence interval [CI] 4.3–9.6) developed COVID-19 during the study period. In the group taking HCQ, 10 (3.9%) tested positive compared to 15 (15%) in the group not taking HCQ (P < 0.001). Odds ratio with HCQ intake was 0.34 (95% CI 0.13–0.83, P = 0.01) and the number needed to treat was 12. Conclusion: HCQ is safe at the recommended dose for pre-exposure prophylaxis of COVID-19. [ABSTRACT FROM AUTHOR]

Background The prevalence of anti-retroviral therapy (ART) failure is not uniform in India. In this study we attempted to determine the prevalence and risk factors of treatment failure among patients who were on ART for >1 y. Methods We conducted an ambispective study from 2017 to 2019 in the All India Institute of Medical Sciences, New Delhi, India. Patients and their past medical records were examined to determine clinical, immunological and virological failure. Results Among 301 enrolled patients, the majority was male (61.8%), with a mean age of 36.98±10.84 y. The prevalence of ART failure in our study was 10.63% (32/301). Clinical, immunological and virological failure rates were 1.66%, 10.63% and 5.65%, respectively. The maximum chance of failure was the tenofovir–lamivudine–nevirapine (33.3%) regimen followed by the stavudine–lamivudine–nevirapine (30.4%) regimen. Among the nucleoside reverse transcriptase inhibitors, a stavudine-based regimen had a significantly greater chance of failure (25.8%) compared with tenofovir (9.6%) and zidovudine (7.9%) regimens (p<0.005). Low baseline CD4 count and development of tuberculosis after ART initiation were significantly (p<0.05) associated with treatment failure in univariate analysis. Patients with a low peak CD4 count (adjusted odds ratio [AOR 4.26 {95% confidence interval 1.83 to 9.88}]) and who developed symptoms after ART initiation (AOR 3.77 [95% CI 1.47 to 9.69]) had significantly higher odds of treatment failure in the multivariate analysis (p<0.001). Conclusions Early identification of risk factors by regular follow-up and selection of the proper ART regimen can reduce the rate of treatment failure. [ABSTRACT FROM AUTHOR]

Background The global burden of infections due to multidrug-resistant organism (MDRO) has a significant impact on patients' morbidity and mortality along with increased healthcare expenditure. Aim This article estimates the prevalence of MDRO and the spectrum of clinical infectious syndromes caused by these organisms in medical wards of a tertiary care hospital in India. Design and Methods A cross-sectional observational study was performed among patients admitted in medicine wards diagnosed with the various infectious syndromes and one or more clinically significant positive culture at a tertiary care hospital in North India over a period of 18 months. Results Out of 323 clinically significant microbiological culture isolates from 229 patients included in the study, 86 (27%) isolates showed multidrug resistance (MDR) pattern, 197 (61%) isolates showed possible extremely drug-resistance pattern, and only 40 (12%) isolates showed nonmultidrug-resistance pattern of antibiogram. Conclusion The prevalence of MRDOs is high in clinically significant culture isolates from medicine wards in India. This emphasizes the importance of appropriate antibiotic usage and implementation of antibiotic stewardship programs in this part of the world. [ABSTRACT FROM AUTHOR]

Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease with an unknown etiology that can be life threatening. This study aimed to study the cause of mortality among admitted SLE patients over a period of 5 years at a teaching hospital in India. Methods: A 5-year retrospective analysis of mortality in SLE patients admitted under department of medicine of our institute was done. The presenting complaints, treatment history, clinical parameters, laboratory investigations, organ involvement, systemic lupus erythematosus disease activity index (SLEDAI), and cause of mortality were collected from the medical records on a predesigned proforma. A further analysis of two groups based on the cause of mortality was done. Results: In total, 53 death records were analyzed. Mortality in 28 SLE patients was due to high disease activity (Group I) and mortality in 25 patients was attributed due to both high disease activity and concomitant infection (Group II). Most of the patients were female (98%) and mean age of patient was 30.6 years. About 19 patients (35.8%) were diagnosed with SLE during hospital admission. Fever was the most common presenting complaint (69.8%) and lupus nephritis was the most common organ dysfunction seen (84.9%). Myocarditis was observed in 11 patients and 9 patients had cerebrovascular accident. The mean hemoglobin was lower in Group II (7.4 vs. 8.7 g/dL, P = 0.02). The median total leukocyte count was significantly higher in Group II (10,200 vs. 6600, P = 0.02). The mean serum urea and creatinine levels were also significantly higher in Group II (141.41 vs. 87.8 mg/dL, P = 0.006 and 4.7 vs. 1.7, P = 0.0001), respectively. The mean SLEDAI in Group I was 20.8 ± 8.9 and in Group II was17.7 ± 7.5. Bacterial pneumonia (17) was the most common infection, followed by tuberculosis (2) and fungal infection (2). Conclusion: Mortality among SLE patients could be due to disease flare or concomitant infection. Lung is the most common organ affected by infection in these patients. [ABSTRACT FROM AUTHOR]

Congenital Zika syndrome, Guillain-Barre Syndrome, dengue, flavivirus, Zika vaccine. [Extracted from the article]

With the introduction of highly active antiretroviral therapy, there has been a dramatic improvement in the clinical course of patients with human immunodeficiency virus infection and acquired immune deficiency syndrome. However, the favorable virological, immunological, and clinical profile of highly active antiretroviral therapy comes at the cost of some common and, at times, severe metabolic adverse effects such as dyslipidemia, body fat dysregulation/lipodystrophy, insulin resistance, and diabetes mellitus. We describe a case of a male patient from North India who developed similar adverse effects including gynecomastia while on the protease inhibitor lopinavir; the mention of such case is rare in the existing literature. [ABSTRACT FROM AUTHOR]

Background: Cardiopulmonary resuscitation (CPR) should be performed as per the international guidelines; however, compliance to these guidelines is difficult to assess. This study was conducted to determine the compliance to American Heart Association (2010) guideline on CPR documentation by among resident physicians before and after resident training (two arms). Methods: This pre-postinterventional quality improvement study was conducted in a referral center, North India. Data of hospitalized in-hospital CPR patients were collected in the form of quality indicators (checklists) as defined by the guideline and compared between two arms of before--after resident training. Residents were given appropriate training in CPR technique as per the guideline. The compliance of CPR documentation was assessed pre- and post-intervention. Results: The baseline arm compliance of various components of CPR documentation was low. The postintervention arm compliances of all components significantly increased (baseline, 2.5% to postintervention, 15.11%, P = 0.03). Individual components assessed were documentation of assessment of responsiveness (65% to 77.9%, P = 0.19), assessment of breathing (37.5% to 58.1%, P = 0.03), assessment of carotid pulse (62.5% to 79%, P = 0.05), rate of chest compressions (20% to 39.5%, P = 0.04), airway management (62.5% to 82.5%, P = 0.02), and compressions to breaths ratio (12.5% to 31.4%, P = 0.02). Documentation of chest compression rate compared to nondocumentation (12 of 42 vs. 11 of 84, P = 0.04) was independently associated with a higher rate of return of spontaneous circulation. The study however did not show any survival benefits. Conclusions: This study establishes that the compliance to CPR documentation is poor as assessed by CPR documentation content and quality, which improves after physician training, but not up to the mark level (100%) that may be due to busy Indian hospital settings and human behavioral factors. Due to ethical constraints of live CPR assessment, this document checklist approach may be considered as an internal quality assessment method for CPR compliance. Furthermore, correct instruction in CPR technique along with proper documentation of the procedure is required, followed up with periodic re-education during the residency period and beyond. [ABSTRACT FROM AUTHOR]

Background. There is lack of reliable predictors of disease severity and mortality in dengue. The present study was carried out to identify these predictors during the 2015 outbreak in India. Methods. This prospective observational study included confirmed adult dengue patients hospitalized between August and November 2015 in a tertiary care centre in New Delhi, India. Appropriate statistical tests were used to compare clinicolaboratory characteristics, derive predictors of severe disease and mortality, and compute a predictive score for mortality. Serotyping was done. Results. Data of 369 patients were analyzed (mean age, 30.9 years; 67% males). Of these, 198 (54%) patients had dengue fever, 125 (34%) had dengue hemorrhagic fever (grade 1 or 2), and 46 (12%) developed dengue shock syndrome (DSS). Twenty-two (6%) patients died. Late presentation to the hospital (≥5 days after onset) and dyspnea at rest were identified as independent predictors of severe disease. Age ≥24 years, dyspnea at rest and altered sensorium were identified as independent predictors of mortality. A clinical risk score was developed (12*age + 14*sensorium + 10*dyspnea), which, if ≥22, predicted mortality with a high sensitivity (81.8%) and specificity (79.2%). The predominant serotypes in Delhi (2015) were dengue virus DENV2 and DENV4. Conclusion. Age ≥24 years, dyspnea at rest, and altered sensorium were identified as independent predictors of mortality. Platelet counts did not determine outcome in dengue patients. Timely referral/access to healthcare is important. The clinical risk score for mortality prediction that was developed in this study can be used in all healthcare settings, after validation in larger cohorts. [ABSTRACT FROM AUTHOR]

Background Diagnostic importance of asymptomatic cryptococcal antigenemia is being increasingly recognized in the last few years. Recently, WHO (World Health Organization) has recommended routine screening of CrAg (cryptococcal antigen) among PLHA with CD4 ≤100/mm3, albeit this procedure is not yet adopted by many developing countries including India. Methods We conducted a prospective observational study in a large tertiary care center of North India, upon ethical clearance. Latex agglutination test was performed to assess serum CrAg levels, followed by the lumbar puncture for detection of CrAg levels in the CSF. We analyzed the prevalence and treatment outcomes of cryptococcal antigenemia among PLHA with CD4 ≤ 100 cells/mm3. Detailed clinical examination was conducted, with follow-up of upto 3 months. Multivariate analysis was performed for the estimation of risk factors. Results The mean age (years) and BMI (kg/m2) of all the participants were 41.4 ± 11.2 and 22.1 ± 2.6, respectively. Notably, the mean CD4 count (cu.mm) at the time of recruitment was 62.3 ± 20.5. Noteworthy, 62 (60.8%) of the patients were ART naïve. We found 9.8% (n = 10) of the patients were positive for serum CrAg, and only 2.9% (n = 3) had clinical features of meningitis and 6.8% (n = 7) were asymptomatic (subclinical) CrAg positive. Strikingly, 3.9% (n = 4) of the asymptomatic cryptococcal antigenemia patients were also positive for CrAg in CSF, with 1.9% (n = 2) were only serum CrAg positive, and 1 patient was lost to follow-up (Graph 1). Multivariate analysis revealed that patients with long duration of HIV (P = 0.04), headache symptoms (P = 0.004) and possessing features of meningismus (P value=0.08) are more likely to be CrAg positive. Conversely, patients on fluconazole were protective against cryptococcal antigenemia (P = 0.1) as shown in Table 1. Overall mortality observed was 11.3% among advanced HIV patients. Moreover, mortality in CrAg-positive patients was 33.3% in comparison to CrAg-negative patients who had 9% (P = 0.06) in 3-months follow-up. Conclusion Cryptococcal antigenemia is common (9.8%) among patients with CD4 count ≤100/mm3 in India. Screening for CrAg should be made routine for PLHA with CD4 count ≤100/mm3 and if required preemptive treatment to be given in this regard. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Dengue is a life-threatening mosquito borne viral disease. We are still in the era of supportive treatment where morbidity and mortality are a major concern. Dengue infection in presence of other co-infections makes this scenario rather worse. Timely recognition and raising alarm to be intensive is the need of the hour for primary care physicians practicing in the community and indoors. This review provides a comprehensive knowledge about the recent trends of coinfection in dengue as well as their management consideration which will be particularly helpful for physicians practicing in rural and remote areas of India. [ABSTRACT FROM AUTHOR]

Introduction: Infections with drug-resistant organisms (DRO) have been associated with poor patient outcomes. To tackle this global problem, it is necessary to understand the risk factors that predispose to infections with DRO. Methodology: This was a prospective observational study conducted over a three-year period at a tertiary-care hospital. Bacterial culture isolates from patients admitted in medicine wards with community or hospital-acquired infections were included. Logistic regression analysis was used to determine risk factors for drug-resistant infections. Results: Of the 295 patients with 323 isolates included, 40 (12.3%) had non-MDR (N-MDR) infections, 86 (26.6 %) had MDR infections and 197 (61%) had possible extensively drug-resistant (P-XDR) infections. History of previous admission in the preceding three months (Odds Ratio, OR = 4.53, 95% Confidence interval, CI = 1.8 - 11.42, p = -0.01), high SOFA score at admission (OR = 1.14, 95% CI = 1.0 - 1.290, p = -0.039) and prolonged duration of ventilation (OR = 1.25, 95% CI = 1.05 - 1.41, p = -0.012) were independently associated P-XDR infections when compared to patients with N-MDR. Conclusions: High rate of multidrug-resistant infections in the studied area is alarming. In this single-centre study, we elicited various risk factors for drug-resistant bacterial infections ranging from patient characteristics to iatrogenic risk factors during the hospital stay. Infections with P-XDR and MDR isolates independently increased hospital and ICU stay duration and were associated with increased mortality. [ABSTRACT FROM AUTHOR]

Traditionally attributed only to Plasmodium falciparum, Plasmodium vivax has recently been reported to cause a significant burden of complicated malaria cases. The present study aimed to delineate the clinical spectrum and identify predictors for severe disease. This was a prospective observational cohort study conducted at a tertiary care hospital in North India. Patients with acute febrile illness (AFI) aged at least 14 years were included if they were diagnosed with vivax malaria based on rapid kits or peripheral smears. Clinical data and investigations during hospital stay was recorded. 439 cases of acute febrile illness were screened, of whom 50 (11%) were diagnosed with malaria including eight P. falciparum infections. Forty-two vivax malaria cases, 22 (52%) of whom were severe, were followed till discharge or death. The median age of the cohort was 24.5 years (Q1-Q3, 19-36 years), including a total of 29 males (69%). Severe malaria was more frequently associated with historical complaints of oliguria or dyspnea, and examination findings of pallor, splenomegaly or altered sensorium. The following five factors were identified to predict severe disease: prolonged illness over 7 days, symptoms of oliguria or dyspnea, examination findings of pallor or crepitations on auscultation. Malaria accounts for 1 in 10 cases of AFI at our North Indian tertiary care center and approximately half of them present with severe disease. Prolonged duration of disease prior to presentation is a modifiable predictor for severe disease and should be targeted for reducing morbidity. [ABSTRACT FROM AUTHOR]

The clinical profile and risk factors for mortality in dengue fever have evolved over the years. The all-cause mortality in admitted dengue patients is around 6%. We aimed to evaluate the recent change in trends of the clinical characteristics and risk factors for in-hospital mortality in adults with dengue fever. This is a retrospective study on adults with confirmed dengue fever admitted in a medical unit of a tertiary care center in North India. Medical records of confirmed dengue fever patients admitted between January 2011, and December 2016 were reviewed. Chi-squared tests with Bonferroni correction for multiple testing were used to identify risk factors for mortality. 232 records were included, of which 66.8% were males. The mean age was 31.6 ± 14 years. There were 17 deaths with an all-cause mortality rate of 7.3% with 76.5% being classified as severe dengue at admission. Among the 17 mortality cases, dyspnea (47%), tachypnea (86.7%), leucocytosis (58.8%), raised urea (80%), and elevated serum creatinine (52.9%) at presentation were significantly associated with mortality (p < 0.001). Shock at any time during the hospital stay (58.8%) was also found to be significantly associated with mortality (p < 0.001). We found that dyspnea, tachypnea, acute kidney injury, and leucocytosis at presentation was significantly associated with in-hospital mortality. Based on our results, we recommend aggressive management of patients with severe dengue and those with mild/moderate disease with the above risk factors. [ABSTRACT FROM AUTHOR]

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 India's 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. [ABSTRACT FROM AUTHOR]

Post COVID-19 sequelae are a constellation of symptoms often reported after recovering from COVID-19. There is a need to better understand the clinical spectrum and long-term course of this clinical entity. The aim of this study is to describe the clinical features and risk factors of post COVID-19 sequelae in the North Indian population. This prospective observational study was conducted at a tertiary healthcare centre in Northern India between October 2020 and February 2021. Patients aged >18 years with laboratory-confirmed COVID-19 were recruited after at least two weeks of diagnosis, and details were captured. A total of 1234 patients were recruited and followed up for a median duration of 91 days (IQR: 45-181 days). Among them, 495 (40.1%) had persistent symptoms post-discharge or recovery. In 223 (18.1%) patients, the symptoms resolved within four weeks; 150 (12.1%) patients had symptoms till 12 weeks, and 122 (9.9%) patients had symptoms beyond 12 weeks of diagnosis/symptom-onset of COVID-19. Most common symptoms included myalgia (10.9%), fatigue (5.5%), shortness of breath (6.1%), cough (2.1%), insomnia (1.4%), mood disturbances (0.48%) and anxiety (0.6%). Patients who were hospitalized were more likely to report fatigue as a feature of long COVID. Hypothyroidism (OR: 4.13, 95% CI: 2.2-7.6, p-value < 0.001) and hypoxia (SpO 2 ≤ 93%) (OR: 1.7, 95% CI: 1.1-2.4, p-value 0.012) were identified as risk factors for long COVID sequelae. In conclusion, long COVID symptoms were common (22%), and 9.9% had the post COVID-19 syndrome. Myalgias, fatigue and dyspnoea were common symptoms. Patients with hypothyroidism and hypoxia during acute illness were at higher risk of long COVID.

Cryptococcosis is a life-threatening infection caused by Cryptococcus neoformans and C. gattii species complex. In the present study, to understand the molecular epidemiology of 208 clinical isolates of Cryptococcus from different parts of India, multilocus sequence typing (MLST) using ISHAM MLST consensus scheme for C. neoformans/C. gattii species complex was used. MLST analysis yielded a total of 10 Sequence Types (STs)-7 STs for C. neoformans and 3 for C. gattii species complex. The majority of isolates identified as C. neoformans belonged to molecular type VNI with predominant STs 31 and 93. Only 3 isolates of C. gattii species complex were obtained, belonging to ST58 and ST215 of VGI and ST69 of VGIV. Phylogenetic analysis revealed less diversity among the clinical Indian isolates compared to the global MLST database. No association between prevalent STs and HIV status, geographical origin or minimum inhibitory concentration (MIC) could be established.

The clinical profile and risk factors for mortality in dengue fever have evolved over the years. The all-cause mortality in admitted dengue patients is around 6%. We aimed to evaluate the recent change in trends of the clinical characteristics and risk factors for in-hospital mortality in adults with dengue fever. This is a retrospective study on adults with confirmed dengue fever admitted in a medical unit of a tertiary care center in North India. Medical records of confirmed dengue fever patients admitted between January 2011, and December 2016 were reviewed. Chi-squared tests with Bonferroni correction for multiple testing were used to identify risk factors for mortality. 232 records were included, of which 66.8% were males. The mean age was 31.6 ± 14 years. There were 17 deaths with an all-cause mortality rate of 7.3% with 76.5% being classified as severe dengue at admission. Among the 17 mortality cases, dyspnea (47%), tachypnea (86.7%), leucocytosis (58.8%), raised urea (80%), and elevated serum creatinine (52.9%) at presentation were significantly associated with mortality (p < 0.001). Shock at any time during the hospital stay (58.8%) was also found to be significantly associated with mortality (p < 0.001). We found that dyspnea, tachypnea, acute kidney injury, and leucocytosis at presentation was significantly associated with in-hospital mortality. Based on our results, we recommend aggressive management of patients with severe dengue and those with mild/moderate disease with the above risk factors.

Traditionally attributed only to Plasmodium falciparum, Plasmodium vivax has recently been reported to cause a significant burden of complicated malaria cases. The present study aimed to delineate the clinical spectrum and identify predictors for severe disease. This was a prospective observational cohort study conducted at a tertiary care hospital in North India. Patients with acute febrile illness (AFI) aged at least 14 years were included if they were diagnosed with vivax malaria based on rapid kits or peripheral smears. Clinical data and investigations during hospital stay was recorded. 439 cases of acute febrile illness were screened, of whom 50 (11%) were diagnosed with malaria including eight P. falciparum infections. Forty-two vivax malaria cases, 22 (52%) of whom were severe, were followed till discharge or death. The median age of the cohort was 24.5 years (Q1-Q3, 19-36 years), including a total of 29 males (69%). Severe malaria was more frequently associated with historical complaints of oliguria or dyspnea, and examination findings of pallor, splenomegaly or altered sensorium. The following five factors were identified to predict severe disease: prolonged illness over 7 days, symptoms of oliguria or dyspnea, examination findings of pallor or crepitations on auscultation. Malaria accounts for 1 in 10 cases of AFI at our North Indian tertiary care center and approximately half of them present with severe disease. Prolonged duration of disease prior to presentation is a modifiable predictor for severe disease and should be targeted for reducing morbidity.

Microbiological diagnosis of extra-pulmonary tuberculosis (EPTB) has been one of the most difficult aspects of tuberculosis (TB) management. Availability of better imaging and diagnostic modalities has led to an increase in the number of diagnosed cases. The current upsurge in multidrug-resistant tuberculosis warrants routine testing of EPTB samples for resistance at baseline with shorter turn-around time. A total of 369 EPTB specimens were subjected to Ziehl-Neelsen (ZN) stain, liquid culture (LC) with phenotypic drug susceptibility testing, MTBDRplus V.2 and MTBDRsl V.2. The molecular categorisation of resistant specimens was further reconfirmed with sequencing. The sensitivity and specificity of MTBDRplus V.2 to detect Mycobacterium tuberculosis (MTB) when compared to ZN stain was 97.9% and 89.2%, respectively while it was 73.4% and 83.8%, respectively when compared to LC. Similarly, for MTBDRsl V.2, the sensitivity and specificity for detection of MTB when compared with ZN was 95.6% and 91.9%, respectively and 75% and 89.2%, respectively when compared to LC. In smear-positive specimens, 94% (141/150) and 86% (129/150) valid results were observed in MTBDRplus V.2 and MTBDRsl V.2, respectively. The utilisation of both MTBDRplus V.2 and MTBDRsl V.2 for the diagnosis of smear-positive EPTB specimens would be useful in programmatic management of TB in high-burden settings., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Antimicrobial Stewardship Program (ASP) is one of the most critical interventions required to halt the growing global antimicrobial resistance. The study aimed to evaluate the effect of trainee driven ASP implementation with limited available resources on outcome variables. An ASP team comprising of infectious diseases trainees and consultants was constituted to conduct stewardship activities in the Department of Medicine, All India Institute of Medical Sciences, a tertiary care apex institute in north India. Prospective audit and feedback were conducted by the team, and the following outcome variables were recorded and analyzed: the practice of sending cultures, appropriateness of prescribed empiric antibiotics, gross antimicrobial consumption and mortality. ASP intervention led to an increase in blood culture positivity rates by two folds (p<0.001). The trend of empiric prescription choices gradually shifted over time towards the use of more effective antibiotics according to the local antibiogram. Redundant usage of antibiotics substantially reduced over time. There was no impact of the antimicrobial stewardship program on the all-cause mortality rate. ASP had a significant effect on the practice of sending cultures and appropriateness of antibiotic usage. In resource-limited settings, trainee-driven antimicrobial stewardship program can succeed in inculcating rational practices among fellow residents and practicing physicians.

Background and Aim: There is a paucity of data on the clinical presentations and outcomes of Corona Virus Disease-19 (COVID-19) in patients with underlying liver disease. We aimed to summarize the presentations and outcomes of COVID-19-positive patients and compare with historical controls., Methods: Patients with known chronic liver disease who presented with superimposed COVID-19 (n = 28) between 22 April 2020 and 22 June 2020 were studied. Seventy-eight cirrhotic patients without COVID-19 were included as historical controls for comparison., Results: A total of 28 COVID-19 patients (two without cirrhosis, one with compensated cirrhosis, sixteen with acute decompensation [AD], and nine with acute-on-chronic liver failure [ACLF]) were included. The etiology of cirrhosis was alcohol (n = 9), non-alcoholic fatty liver disease (n = 2), viral (n = 5), autoimmune hepatitis (n = 4), and cryptogenic cirrhosis (n = 6). The clinical presentations included complications of cirrhosis in 12 (46.2%), respiratory symptoms in 3 (11.5%), and combined complications of cirrhosis and respiratory symptoms in 11 (42.3%) patients. The median hospital stay was 8 (7-12) days. The mortality rate in COVID-19 patients was 42.3% (11/26), as compared with 23.1% (18/78) in the historical controls (p = 0.077). All COVID-19 patients with ACLF (9/9) died compared with 53.3% (16/30) in ACLF of historical controls (p = 0.015). Mortality rate was higher in COVID-19 patients with compensated cirrhosis and AD as compared with historical controls 2/17 (11.8%) vs. 2/48 (4.2%), though not statistically significant (p = 0.278). Requirement of mechanical ventilation independently predicted mortality (hazard ratio 13.68). Both non-cirrhotic patients presented with respiratory symptoms and recovered uneventfully., Conclusion: COVID-19 is associated with poor outcomes in patients with cirrhosis, with worst survival rates in ACLF. Mechanical ventilation is associated with a poor outcome.

The aim of the study was to determine the clinical spectrum and outcome of invasive fungal infections (IFIs) in hospitalized patients. A prospective study was conducted in a teaching hospital in North India between December 2016 and December 2018. Patients diagnosed with IFIs were enrolled. Their clinical and laboratory parameters were recorded using a pre-defined clinical report form. They were followed up till discharge or death and a 60-day outcome was recorded. A total of 110 IFI cases were identified, which included invasive aspergillosis (39%), invasive candidiasis (16%), cryptococcosis (14%) and mucormycosis (12%). Pneumonia (63%) was the most common final diagnosis in these patients. Diabetes mellitus, chronic kidney disease and chronic obstructive pulmonary disease were the most common risk factor for all four diseases. Additionally, most patients with cryptococcosis had human immunodeficiency virus infection. Mortality was observed in 73% of the patients. Overall, IFIs are an important cause of morbidity and mortality in critically ill patients admitted to medical wards and ICUs.

With significant advancement in the tools and strategies available for diagnosis and management, there is an expected change in the epidemiological profile of patients living with HIV/AIDS (Human immunodeficiency syndrome/Acquired immunedeficiency syndrome). We retrospectively analyzed the changing epidemiological pattern of HIV infection over a period of 13 years in the anti-retroviral (ART) center of a tertiary care hospital in India. The study included a total of 9419 patients (8811 adults and 608 children) who were registered at our ART center between 2005 and 2017. Among adult patients, 68.9% patients were males and the mean age of presentation was 35.6±9.9 years. Heterosexual route was the most common route of transmission (95.5%). A total of 97.4% of pediatric patients acquired HIV infection via vertical transmission from their mothers. Most of the adult patients (77.1%) were educated only to primary level. Despite the economic growth in the country over the years, the monthly income of these patients has not significantly changed. The median CD4 count at the time of eligibility for starting ART was 244/μl of blood. An increasing trend in the baseline CD4 count was noticed from 2005 to 2017. Also, improved outcomes with less loss to follow up were noticed in the latter years. However, an increasing trend was also noted in the time gap between registration at the ART center and initiation of ART. Improvement in the baseline CD4 count and better treatment outcomes are indicators of a well-functioning national program. However, continued programmatic interventions are needed to further tackle the menace of HIV/AIDS in India.

Introduction: Dengue fever management is guided by WHO guideline, the recent one being 2009; however, compliance to the guideline is difficult to assess and in India there is no data on it. The present study, a longitudinal pre-post interventional quality improvement study, was done to determine the compliance to the guideline on dengue patients before and after resident physicians' training during two peak seasons and their impact on survival., Methods: This study was conducted in a tertiary health care centre in North India over 18 months. Data of hospitalized patients who admitted with dengue fever diagnosis in a peak season was collected in the form of quality indicators as described by the WHO-2009 guideline on dengue. Resident physicians were then given appropriate training about the guideline during the off season. Data of new dengue patients in next peak season after resident training was collected and compared with the baseline by standard statistical tests., Results: The post-intervention compliances of all components increased (total mean score by giving one point to each of the quality indicators reached 7.9 from 6.4). The compliance to individual indicator also increased: the admission criteria (baseline, 44% to post-intervention, 52%, p = 0.37), classification criteria (91.7% to 96%, p = 0.33), correct staging/triage (42.9% to 86%, p <0.001), vitals monitoring (85.7% to 92%, p = 0.28), correct usage of bolus fluids (34.3% to 69.5%, p <0.001), crystalloid as choice of fluid (100% in both groups), proper fluid titration (26.2% to 56%, p <0.001), hematocrit monitoring (95.2% to 98%, p = 0.42), platelet transfusion when indicated (65.5% to 58%, p = 0.39), antibiotic use when required (61.5% to 80%, p = 0.03), and discharge criteria (100% in both groups). The mortality decreased from 7.1% (baseline) to zero (post-intervention). The median duration of hospital stay also reduced by 1 day., Conclusion: The study affirms that the compliance to WHO guideline on dengue management in India can be further improved by regular physician training on the guideline. Simultaneously, this educational intervention not only improves patient outcomes but also direct proper resource utilization especially platelet transfusion and antibiotic use. Furthermore, every hospital/institute should have an internal quality improvement program like this to improve the management of dengue patients. Future studies are needed to understand various barriers to 100% implementation of the guideline., (© Journal of the Association of Physicians of India 2011.)

Introduction: Central venous catheter (CVC) associated infection are many times higher in India compared to western countries. A group of interventions called as CVC bundle, if implemented effectively prevents CVC related complication., Methodology: Our study was a prospective quasi-experimental study. The study evaluated the level of compliance with the central venous catheter bundle in the management of patients in our Medicine wards and Intensive care unit (ICU)., Results: :In the study, the incidence of central line associated bloodstream infection (CLABSI) was zero and the incidence of pneumothorax was 5%. Most of the patients had higher Acute physiology and chronic health evaluation (APACHE II) at baseline and multi organ dysfunction. The compliance with whole CVC bundle improved from 0% at baseline to 10% in post-intervention phase. Compliance of many components increased significantly in the post intervention period. These were Hand washing before insertion (15% to 72.5%, p<0.001), Maintenance (0% to 52.5%, p<0.001), Prompt removal of catheters (40% to 70%, p=0.007), Skin antisepsis with chlorhexidine increased approaching significance (0% to 12.5%, p=0.055). Avoidance of femoral catheters was done in more than 95% of the cases. The predictors of mortality were higher APACHE II (OR 1.23 [CI 1.03-1.47], p=0.020) and duration of hospital stay (OR 0.87 [CI 0.78-0.97], p=0.022)., Conclusion: This study done at All India Institute of Medical Sciences showed improved outcome in terms of catheter infection and mechanical complications. CVC bundle compliance increased significantly though adherence to full bundle was less. In future, with rectification of barriers to bundle completion, the compliance with CVC bundle can be further improved., (© Journal of the Association of Physicians of India 2011.)

Invasive fungal infections (IFI) are commonly seen in immunosuppressed individuals but their epidemiology in critically ill patients has not been well described. The aim of this study was to determine the frequency, risk factors and outcome of invasive fungal infections in a medical intensive care unit. A prospective observational study was carried out between August 2016 and March 2018 in the medical intensive care unit. Patients above the age of 14 years with endotracheal intubation and/or central venous catheter for at-least three days and sepsis (not responding to 48 hours of intravenous antibiotic therapy) were included in the study. Suitable samples were collected and were subjected to fungal diagnostics. Invasive fungal disease was defined according to standard guidelines. Of the 100 recruited patients, a total of 11 patients had invasive aspergillosis, three patients had invasive candidiasis and one patient had both invasive aspergillosis and mucormycosis. IFI was more commonly seen in patients with auto-immune diseases (p = 0.002, odds ratio-10.13 (95% CI: 2.3-44)). A mortality of 73% was observed in patients with IFI. In conclusion, IFI, especially aspergillosis is grossly under-reported in critical settings. Early suspicion, thorough investigation and timely diagnosis may alleviate patients of significant mortality and morbidity.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are the backbone of effective anti-retroviral therapy in the developing world. Efavirenz is the current NNRTI of choice due to reports of higher incidence of serious adverse events with nevirapine. Majority of patients with Human immunodeficiency virus (HIV) infection in India are still on nevirapine based therapy. The aim of the study was to evaluate the need of shifting these patients to efavirenz based therapy. A cross-sectional study was conducted on adult patients, who were on NNRTI based regimen for more than one year with good adherence. The patients were divided into efavirenz or nevirapine groups based on the treatments they were receiving at the time of study. The different arms were compared based on their clinical and laboratory profile, adverse events and immunological response. A total of 244 patients were recruited. A total of 125 patients were receiving nevirapine based regimen while 119 patients were receiving efavirenz based regimen. There was no significant difference in the frequency of hematological and biochemical derangements between the two groups. There was no difference in the median highest CD4 count achieved during therapy between the two groups. Clinically observed side effects were more common in the efavirenz group. These results suggest that there isn't enough evidence to shift patients tolerating long term nevirapine based therapy to efavirenz based therapy.

Background & Objectives: Acute respiratory distress syndrome (ARDS) is a common disorder in critically ill patients and is associated with high mortality. There is a paucity of literature on this condition from developing countries. This prospective observational study was designed to find out the aetiology, outcomes and predictors of mortality in ARDS., Methods: Sixty four consecutive patients who satisfied American-European Consensus Conference (AECC) definition of ARDS from medical Intensive Care Unit (ICU) of a tertiary care centre in New Delhi, India, were enrolled in the study. Demographic, biochemical and ventilatory variables were recorded for each patient. Baseline measurements of serum interleukin (IL)-1β, IL-6, tumour necrosis factor-alpha (TNF-α), procalcitonin (PCT) and high sensitivity C-reactive protein (hsCRP) were performed., Results: Common causes of ARDS included pneumonia [44/64 (68.7%)], malaria [9/64 (14.1%)] and sepsis [8/64 (12.5%]. Eight of the 64 (12.5%) patients had ARDS due to viral pneumonia. The 28-day mortality was 36/64 (56.2%).Independent predictors of mortality included non-pulmonary organ failure, [Hazard ratio (HR) 7.65; 95% CI 0.98-59.7, P=0.05], Simplified Acute Physiology Score (SAPS-II) [HR 2.36; 95% CI 1.14-4.85, P=0.02] and peak pressure (P peak ) [HR 1.13; 95% CI 1.00-1.30, P = 0.04] at admission., Interpretation & Conclusions: Bacterial and viral pneumonia, malaria and tuberculosis resulted in ARDS in a considerable number of patients. Independent predictors of mortality included non-pulmonary organ failure, SAPS II score and P peak at baseline. Elevated levels of biomarkers such as TNF-α, PCT and hsCRP at admission might help in identifying patients at a higher risk of mortality., Competing Interests: None.

Aims: To determine the incidence of central line associated bloodstream infections (CLABSIs) in the medical intensive care unit (ICU) and ward setting at All India Institute of Medical Sciences (AIIMS), New Delhi., Settings and Design: The study was conducted in the medical ICU, a 9-bedded ICU at the AIIMS, a tertiary care teaching hospital. The study design was a prospective observational study., Methods: One hundred patients admitted to medical ICU and the ward at AIIMS with an indwelling, non-tunnelled central venous catheter (CVC) in place at admission and those with a hospital stay with indwelling CVC for more than 48 hours were monitored. These patients were followed daily for the development of new onset sepsis 48 hours after insertion of CVC, in which case three sets of blood samples for culture were drawn over a span of 24 hours., Statistical Methods: Incidence of CLABSIs was measured per 1000 central line days., Results: One hundred patients hospitalised for an aggregate 1119 days acquired 29 hospital-acquired infections (HAIs), a rate of 38.8% or 31.2 HAIs per 1000 hospital days. The incidence of bloodstream infections (BSIs) in this group was 6.8%. No case of laboratory confirmed CLABSIs could be demonstrated. Incidence of clinical sepsis was 27.6% or 8.2 per 1000 CVC days. There were 9 cases out of the 29 patients (39.7%) who had evidence of HAIs with no apparent focus of infection. Only one of these cases had evidence of BSI with isolation of Staphylococcus aureus in both CVC tip culture and the simultaneous blood culture; however the antibiograms were different., Conclusions: The low rate of BSIs in the present study and the absence of occurrence of a laboratory confirmed CLABSI should be interpreted in the light of the small sample size of the study and the multitude of antibiotics received before the development of HAI.

One approach to the development of an HIV vaccine is to design a protein template which can present gp120 epitopes inducing cross-neutralizing antibodies. To select a V3 sequence for immunogen design, we compared the neutralizing activities of 18 anti-V3 monoclonal antibodies (mAbs) derived from Cameroonian and Indian individuals infected with clade AG and C, respectively. It was found that V3 mAbs from the Cameroonian patients were significantly more cross-neutralizing than those from India. Interestingly, superior neutralizing activity of Cameroonian mAbs was also observed among the nine VH5-51/VL lambda genes encoding V3 mAbs which mediate a similar mode of recognition. This correlated with higher relative binding affinity to a variety of gp120s and increased mutation rates in V3 mAbs from Cameroon. These results suggest that clade C V3 is probably weakly immunogenic and that the V3 sequence of CRF02&#95;AG viruses can serve as a plausible template for vaccine immunogen design., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Telemedicine is an essential technology for providing high-quality health care to rural people. Though India has not yet passed any legislation on telemedicine related issues, a beginning has however been made. Guidelines and Standards for Practice of Telemedicine in India have already been recommended by the Ministry of Information Technology, Govt. of India.

Background: Analysis of human monoclonal antibodies (mAbs) developed from HIV-1 infected donors have enormously contributed to the identification of neutralization sensitive epitopes on the HIV-1 envelope glycoprotein. The third variable region (V3) is a crucial target on gp120, primarily due to its involvement in co-receptor (CXCR4 or CCR5) binding and presence of epitopes recognized by broadly neutralizing antibodies., Methods: Thirty-three HIV-1 seropositive drug naive patients (18 males and 15 females) within the age range of 20-57 years (median = 33 years) were recruited in this study for mAb production. The mAbs were selected from EBV transformed cultures with conformationally constrained Cholera-toxin-B containing V3C (V3C-CTB) fusion protein. We tested the mAbs for their binding with HIV-1 derived proteins and peptides by ELISA and for neutralization against HIV-1 viruses by TZM-bl assays., Results: We isolated three anti-V3 mAbs, 277, 903 and 904 from the cells of different individuals. The ELISA binding revealed a subtype-C and subtype-A specific binding of antibody 277 and 903 while mAb 904 exhibited cross reactivity also with subtype-B V3. Epitope mapping of mAbs with overlapping V3 peptides showed exclusive binding to V3 crown. The antibodies displayed high and low neutralizing activity against 2/5 tier 1 and 1/6 tier 2 viruses respectively. Overall, we observed a resistance of the tier 2 viruses to neutralization by the anti-V3 mAbs, despite the exposure of the epitopes recognized by these antibodies on two representative native viruses (Du156.12 and JRFL), suggesting that the affinity of mAb might equally be crucial for neutralization, as the epitope recognition., Conclusions: Our study suggests that the anti-V3 antibodies derived from subtype-C infected Indian patients display neutralization potential against tier 1 viruses while such activity may be limited against more resistant tier 2 viruses. Defining the fine epitope specificities of these mAbs and further experimental manipulations will be helpful in identification of epitopes, unique to clade C or shared with non-clade C viruses, in context of V3 region.

We assessed the anti-V3 antibody content and viral neutralization potential of the plasma of 63 HIV-1-infected patients (antiretroviral naïve=39, treated=24) against four primary isolates (PIs) of clade C and a tier 1 clade B isolate SF162. Depletion and inhibition of anti-V3 antibodies in the plasma of five patients with high titers of anti-V3 antibodies led to modest change in the neutralization percentage against two PIs (range 0-21%). The plasma of antiretroviral-treated patients exhibited higher neutralization potential than that of the drug-naïve plasmas against the four PIs tested which was further evidenced by a follow-up study.

Background & Objective: IRIS is an important complication that occurs during management of HIV-TB coinfection and it poses difficulty in diagnosis. Previous studies have reported variable incidence of IRIS. The present study was undertaken to describe the pattern of TB-associated IRIS using recently proposed consensus case-definitions for TB-IRIS for its use in resource-limited settings., Methods: A prospective analysis of ART-naïve adults started on HAART from November, 2008 to May, 2010 was done in a tertiary care hospital in north India. A total 224 patients divided into two groups, one with HIV-TB and the other with HIV alone, were followedup for a minimum period of 3 months. The diagnosis of TB was categorised as ''definitive" and ''probable"., Results: Out of a total of 224 patients, 203 completed followup. Paradoxical TB-IRIS occurred in 5 of 123 (4%) HIV-TB patients while 6 of 80 (7.5%) HIV patients developed ART-associated TB. A reduction in plasma viral load was significantly (P = .016) associated with paradoxical TB-IRIS. No identifiable risk factors were associated with the development of ART-associated TB., Conclusion: The consensus case-definitions are useful tools in the diagnosis of TB-associated IRIS. High index of clinical suspicion is required for an early diagnosis.

Objectives: To describe the pattern of adherence to Highly Active Antiretroviral therapy (HAART) and ascertain the factor(s) associated with nonadherence., Methods: This was a cross-sectional, two-site, hospital-based study. The study was undertaken in 2005; as a result of phased roll out of free HAART as part of National AIDS Control Program, patients at Lok Nayak Jai Prakash (LNJP) hospital were receiving free HAART, while patients at All India Institute of Medical Sciences (AIIMS) had to bear out-of-pocket expenses for HAART. Adherence was defined as not having missed even a single pill over the previous 4-day period on self-reporting., Results: Adherence at AIIMS was 47%, whereas it was 90% at LNJP. The difference was statistically significant. Multivariate analysis showed that nonadherence was associated with not having been told about the importance of HAART, having to pay out-of-pocket for HAART and reported continued risk behavior post HAART., Conclusion: With the provision of free HAART, adherence is likely to be high. Emphasis should be given on simultaneous recruitment of counselors, and physicians should be made aware about the need to inquire and counsel patients against continued risk behavior.

The viral reverse transcriptase gene was amplified from the plasma of 27 drug-naïve and five drug-experienced HIV patients in Northern India. Follow-up samples of naïve patients after antiretroviral therapy initiation were collected in six patients at 3 months and three patients at 6 months. Phylogenetic analysis revealed two new recombinant forms, CRF&#95;CH and CRF&#95;CK, and an accessory non-nucleoside reverse transcriptase inhibitor mutation E138A, not previously reported from India. The major DRMs found in two 6-month follow-up samples were absent in their baseline blood samples. This is the first follow-up study to determine anti-retroviral drug resistance mutations in Indian HIV patients.