Interventions in adult patients with multimorbidity in low-income and middle-income countries: protocol for a mixed-methods systematic review.

INTRODUCTION: Multimorbidity, the coexistence of two or more chronic conditions in the same individual, is a major public health problem in low-income and middle-income countries (LMICs). The use of single-disease guidelines contributes to polypharmacy, fragmented care and increased treatment burden. Health systems in LMICs are very different from those in high-income countries, and adapting interventions from one to the other may not be feasible. This review aims to systematically present the current evidence for interventions for multimorbidity in the LMIC setting. METHODS AND ANALYSIS: In this mixed-methods systematic review, we will include all studies of interventions for the care of adults (>18 years of age) with multimorbidity (defined as the presence of two or more chronic illnesses in an individual) in any healthcare organisation (primary, secondary or tertiary care) in an LMIC (as defined by the World Bank), published between 2000 and March 2023. All primary study designs will be included. Studies reported in languages other than English and those describing interventions classified as 'financial' or 'governance arrangement' according to the Cochrane Effective Practice and Organisation of Care classification will be excluded. MEDLINE, PubMed, Cochrane Library, TRIP, SCOPUS and the 3ie databases will be searched. The titles will be screened by one author, and two authors will independently screen all included abstracts and full texts. A third author will resolve conflicts at every stage. Studies will be reviewed for quality of evidence using appropriate tools. Epidemiological, intervention and outcome data will be extracted and summarised. Outcomes of interest for LMICs defined by the Global Alliance for Chronic Diseases research group will be analysed. Subgroup analysis according to study types and study settings will be done. ETHICS AND DISSEMINATION: No ethics approval is required for this systematic review. Results will be disseminated through publication in an open-access journal and presentation at conferences. PROSPERO REGISTRATION NUMBER: CRD42023391897.

Teleradiology and technology innovations in radiology: status in India and its role in increasing access to primary health care.

Background: There is an inequitable distribution of radiology facilities in India. This scoping review aimed at mapping the available technology instruments to improve access to imaging at primary health care; to identify the facilitators and barriers, and the knowledge gaps for widespread adaptation of technology solutions. Methods: A search was conducted using broad inclusive terms non-specific to subtypes of medical imaging devices or informatics. Work published in the English language between 2005 and 2022, conducted primarily in India, and with full manuscripts were included. Two authors independently screened the abstracts against the inclusion criteria for full-text review and a senior author settled discrepancies. Data were extracted using DistillerSR software. Findings: 43 original articles and 52 non-academic materials were finally reviewed. The data was from 10 Indian states with n = 9 from rural settings. The broad trends in original articles were: connectivity using teleradiology (n = 7), mobile digital imaging units (n = 9), artificial intelligence (n = 16); mobile devices and smartphone applications (n = 7); data security (n = 7) and web-based technology (n = 2); public-private partnership (n = 9); cost (n = 2); concordance (n = 19); evaluation (n = 4); implementation (n = 2). Interpretation: Available evidence suggests that teleradiology when combined with AI and mobile digital imaging units can address radiologist shortages; strengthen programs aimed at population screening and emergency care. However, there is insufficient data on the scale of teleradiology networks within India; needs assessment; cost; facilitators, and barriers for implementation of technologies solutions in primary healthcare settings. Regulations governing quality standards, data protection, and confidentiality are unclear. Funding: The authors are The Lancet Citizen's Commission fellows. The Lancet Commission has received financial support from the Lakshmi Mittal and Family South Asia Institute, Harvard University; Christian Medical College, Vellore (CMC), Vellore; Azim Premji Foundation, Infosys; Kirloskar Systems Ltd.; Mahindra & Mahindra Ltd.; Rohini Nilekani Philanthropies; and Serum Institute of India. The views expressed are those of the author(s) and not necessarily those of the Lancet Citizens' Commission or its partners.

Clinical features, outcomes and predictors of drug resistance and complications in patients admitted with pyelonephritis.

Drug resistance and the presence of structural complications have significant implications for the treatment of acute pyelonephritis. We aimed to examine the predictors of drug resistance and complications in a retrospective cohort of patients admitted with pyelonephritis. 188 patients were included in this study. Patients who had had a urinary catheterization in the previous month and who lived outside the district in which the hospital was located were more likely to have ESBL infections. Carbapenem resistance was associated with recent urinary catheterization, a positive urine nitrate test, hypotension requiring vasopressors and the need for intensive care. A history of flank pain, urea level >13.3 mmol/L, a differential neutrophil count >75% and a urinalysis with >1000 leucocytes per high power field was associated with an increased risk of complications. A score derived from these variables to predict structural complications of infection had a sensitivity of 77.8% and a specificity of 67.1.

Absence of posterior pituitary bright spot in adults with CNS tuberculosis: A case-control study.

INTRODUCTION: Current diagnostic methods used in Central Nervous System Tuberculosis (CNS TB) are limited by the paucibacillary nature of this form of tuberculosis. Posterior pituitary bright spot (PPBS) refers to an area of T1 hyperintensity in the posterior pituitary in MR imaging of the brain. It is found in 80-90% of healthy children and adults. In children with CNS TB, nearly half have absence of PPBS. This finding has not been described in adults. Our study looked for absence of PPBS in MR imaging and its association with CNS tuberculosis. OBJECTIVE: To study prevalence of the absence of PPBS in patients with CNS tuberculosis when compared to a control group of normal patients. METHODS: This was a retrospective case-control study of 100 patients with CNS tuberculosis and 200 controls (matched in 1:2 ratio) of patients with normal MRI brain. The MRI images were presented to a blinded radiologist in a randomised sequence to report for absence of PPBS. The data was subsequently analysed to look for association of absence of PPBS with CNS tuberculosis. RESULTS: Absence of PPBS (cases (47%), controls (8.5%)) was significantly associated with CNS tuberculosis in (Odds ratio-7.90, 95%CI 4.04-15.44, P-value<0.0001). The specificity, sensitivity, positive predictive value and positive likelihood ratio are 91.5%, 47%, 73.4% and 5.53 respectively. Adding of absence of PPBS as an additional radiological feature in diagnosis of CNS TB increased the sensitivity from 77% to 84%. CONCLUSION: Absence of PPBS is significantly associated with CNS tuberculosis and could be a relatively simple diagnostic aid in the diagnosis of CNS tuberculosis.

ZFTA (Zinc Finger Translocation Associated) Fusion in Supratentorial Ependymomas: Low Prevalence in South Asians and No Correlation with Survival.

BACKGROUND: Supratentorial ependymomas (STEs) are an aggressive group of ependymomas, topographically distinct from their posterior fossa and spinal counterparts. Zinc finger translocation associated (ZFTA) fusion-positive cases have been reported to account for the majority of STEs, although data on its association with poorer outcomes are inconsistent. MATERIALS AND METHODS: We assessed the prevalence of the ZFTA fusion by reverse-transcription polymerase chain reaction and fluorescence in situ hybridization in a cohort of 61 patients (68 samples) with STE. Our primary outcome was to determine the role of the ZFTA fusion on progression-free and overall survival of patients with STE. Our secondary objectives were to assess the impact of ZFTA fusion on nuclear factor (NF)-kB pathway signaling via surrogate markers of this pathway, namely COX-2, CCND1, and L1 cell adhesion molecule. RESULTS: ZFTA fusion was noted in 21.3% of STEs in our cohort. The presence of this rearrangement did not significantly impact the progression-free or overall survival of patients with STEs and was not associated with upregulation of markers of the NF-kB pathway. Only gross total resection was significantly associated with better progression-free survival. CONCLUSIONS: In contradiction to previous reports from across the world, the ZFTA fusion is far less prevalent among our population. It does not appear to drive NF-kB signaling or significantly affect outcomes. Gross total resection must be attempted in all cases of STE and adjuvant radiation and/or chemotherapy employed when gross total resection is not achieved.

Good survival rate, moderate overall and good respirator quality of life, near normal pulmonary functions, and good return to work despite catastrophic economic costs 6 months following recovery from Acute Respiratory Distress Syndrome.

Introduction: Long-term quality of life, return to work, economic consequences following Acute Respiratory Distress Syndrome (ARDS) are not well described in India. This study was aimed to address the question. Methods: A prospective cohort study of 109 ARDS survivors were followed up for a minimum of 6 months following discharge. Quality of life was assessed using the SF-36 questionnaire. Respiratory quality was assessed using the St Georges Respiratory Questionnaire. Time to return to work was documented. Costs-direct medical, as well as indirect were documented up to 6 months. Results: At 6 months, 6/109 (5.5%) had expired. Low energy/vitality and general heath were noted in the SF-36 scores at 6 months; overall a moderate quality of life. Pulmonary function tests had mostly normalized. Six-min walk distance was 77% of predicted. Respiratory quality of life was good. It took at the median of 111 days to go back Interquartile range (55-193.5) to work with 88% of previously employed going back to work. There were no significant differences in the severity of ARDS and any of these outcomes at 6 months. The average total cost from the societal perspective was ₹ 231,450 (standard deviation 146,430-, 387,300). There was a significant difference between the 3-ARDS severity groups and costs (P < 0.01). There were no independent predictors of return to work. Conclusion: ARDS survivors have low 6-month mortality. Pulmonary physiology and exercise capacity was mostly normal. Overall, quality of life is average was moderate, while respiratory quality of life was good. Return to work was excellent, while cost of care falls under a catastrophic heath expense.

Bedside lung ultrasonography: comparison with chest radiography (BLUR), a diagnostic study in a developing country.

BACKGROUND: This study determines the diagnostic utility of lung ultrasonography (LUS) in a medical ward in a developing country. In a low resource country like India, we hope that use of lung ultrasound in primary and secondary hospitals will assist in earlier and better bedside diagnosis. METHODS: This prospective diagnostic study was done to test the diagnostic accuracy of LUS against a composite reference standard, which included clinical history and examination, basic laboratory investigations, imaging and the diagnosis at discharge. We evaluated 321 consecutive patients, admitted in our medical wards with an LUS within 24 hours of the chest radiograph being done. FINDINGS: Between August 2016 and August 2017, we enrolled 321 patients. The sensitivity and specificity of the LUS for all pathologies were found to be 82.5% (76.50 to 87.20) and 78.2% (69.09 to 85.26) respectively. A subgroup analysis including the patients in whom CT was part of the composite reference standard showed sensitivity and specificity of 87.9% and 92.9% for all lung pathologies. It was found that there was superior sensitivity and specificity of LUS compared with chest radiograph in a subgroup analysis of pulmonary oedema and acute respiratory distress syndrome (ARDS). INTERPRETATION: We found that the LUS was better than chest radiograph and as good as CT in most pathologies, especially pulmonary oedema and ARDS. We believe that training in the basics of bedside LUS must be part of the medical curriculum and a low-cost ultrasound machine must be made available in medical wards, so that clinical diagnosis can be supplemented with this tool. In a low resource setting like India, where access to chest radiograph and CT may be difficult particularly in a rural setup, expertise in LUS would be helpful in easy bedside diagnosis and saving cost on a CT scan.

Heart failure among patients admitted with Influenza. The influenza subtypes, seasonality and mortality: A case series.

Respiratory infections like influenza infections have been found to increase the risk of coronary artery disease and precipitate cardiac failure. However, Indian data is lacking. A retrospective observational study was done to describe patients with influenza infection who had concomitant heart failure (HF) requiring admission over 5 years (January 2013-December 2017). A total of 93 influenza cases were hospitalised during this time, of which 14 (15%) also had features of HF. Among them, the types of influenza infection were AH1N1 (6,43%), BH1N1 (4,29%), AH3N2 (3,21%) with one patient having both strains. Two-thirds of the HF were new onset (10, 71%), whereas rest were due to acute worsening of pre-existing HF (4, 29%). Ten (64.3%) of the patients had HF with reduced ejection fraction (HFrEF). The average hospital stay was 10 days with 2 (14%) deaths. The peak of influenza in August and September preceded the peak admission for HF. A total of 15% of influenza admissions have concomitant HF. They are predominantly due to influenza A H1N1 (43%), influenza A H3N2 (21%) and influenza B (29%). Only 7% had preceding influenza vaccination. Influenza during August and September appears to precede the peak of HF admissions which happen in October and November. Overall mortality was 14.

Intravenous Mannitol reduces intracompartmental pressure following tibia fractures: A randomized controlled trial.

PURPOSE: Impending compartment syndrome is a common event following closed tibia fractures, which can progress to sinister compartment syndrome. Fasciotomy is the only definitive treatment available, though it has its own drawbacks and complications. Medical management at present consists of limb elevation and adequate hydration. This study aims at determining whether intravenous administration of Mannitol reduced the intracompartmental pressure in patients with closed tibial fractures. METHODS: This is a double blinded, randomized control trial done in a single tertiary care center in India. Forty-five patients were recruited between February 2012 and October 2012. Forty patients who presented to the emergency department with isolated, closed, high velocity, and proximal 2/3 tibia fractures were included in this study. Patients with contraindication to Mannitol were excluded. They were allocated into 2 groups by the investigator using computer generated randomization. The pressure in the anterior compartment of the leg was measured with a handheld Stryker pressure monitor. Then either 20% Mannitol or 0.9% normal saline as given intravenously in a blinded manner, based on the randomization. The intracompartmental pressure was measured at 0, 1 and 3 h after the infusion. The participant, investigator and statistician were masked to the group assessment. RESULTS: There was no difference in intracompartmental pressures at 1 or 3 h, between the groups. However, in patients with the baseline of compartmental pressures ≥30 mmHg, Mannitol showed a marked reduction in pressure of 8.5 mmHg at 1 h compared to almost no change in pressure in the saline group. There were no adverse events with the use of Mannitol. CONCLUSIONS: This preliminary study appears to show that Mannitol is useful in the management of the increased compartment pressure. The limitations of this study were that it only involved a small group of patients and the baseline pressures in both the groups were not comparable. More studies are required before the use of Mannitol as a standard of care in the management of compartment syndrome can be established.

Is BCG associated with reduced incidence of COVID-19? A meta-regression of global data from 160 countries.

BACKGROUND: Global research is running towards to find a vaccine to stop the threat of the COVID-19. The Bacillus Calmette-Guérin (BCG) vaccine that prevents severe forms of tuberculosis is getting more attention in this scenario. The objective of our study was to determine the association between BCG vaccine coverage and incidence of COVID-19 at a national-level across the Globe. METHODS: The data of 160 countries were included in the study. Meta-regression was done to estimate the difference in the incidence of COVID-19 cases between countries with BCG vaccination coverage. BCG coverage was categorized as ≤70%, >70% and no vaccination. The analyses were carried out by adjusting for factors such as population density, income group, latitude, and percentage of the total population under age groups 15-64 and above 65 years of each country. RESULTS: The countries that had ≤70% coverage of BCG vaccine reported 6.5 (95% CI: -8.4 to -4.5) less COVID-19 infections per 10,000 population as compared to countries that reported no coverage. Those that had >70% coverage reported 10.1 (95% CI: -11.4 to -8.7) less infections per 10,000 population compared to those with no BCG countries. CONCLUSION: Our analysis suggests that BCG is associated with reduced COVID-19 infections if the BCG vaccine coverage is over 70%. The region-wise analyses also suggested similar findings, except the Middle East and North African region.

Acute kidney injury is an independent predictor of in-hospital mortality in a general medical ward: A retrospective study from a tertiary care centre in south India.

BACKGROUND & OBJECTIVES: : Acute kidney injury (AKI) has been identified as an independent risk factor for mortality in intensive care units. This retrospective study was conducted to determine the effect of AKI on in-hospital mortality in a general medical ward of a tertiary care hospital and risk factors for mortality in patients with AKI. METHODS: : Demographic and clinical details, and outcome data were collected from case records of patients. In all hospitalized patients, factors associated with increased in-hospital mortality, such as AKI, inotrope requirement, mechanical ventilation and primary disease were compared between patients who died during their hospital stay and those who were discharged alive. Among the hospitalized patients, who had AKI, likely predictors of in-hospital mortality were compared between dead and alive patients at discharge. Factors that were significant in univariate analysis were tested by multivariate regression analysis to identify those that independently predicted poor outcomes. RESULTS: : Of the 1150 patients admitted in a general medical ward in a year, 220 patients were identified to have AKI. In-hospital mortality rate among patients with AKI was 19.09 per cent as compared to 1.8 per cent without AKI [adjusted odds ratio (OR) 5.7 (95% CI: 1.56-20.74)]. The presence of AKI was an independent risk factor for death, with an adjusted OR of 6.0 [95% CI: 1.67-21.6]. Among patients with AKI, the presence of haematological malignancy, adjusted OR 25.86 (95% CI: 1.81-369.58), requirement of inotrope, adjusted OR 126.5 (95% CI: 19.39-825.93) and serum creatinine at admission (P<0.001) were found to be independent predictors of death. The presence of underlying chronic kidney disease and hospital-acquired AKI were not found to have an association with mortality. INTERPRETATION & CONCLUSIONS: : The study showed the in-hospital mortality rate among patients with AKI in a general medical ward was 19.09 per cent. The occurrence of AKI was an independent risk factor for death, with haematological malignancy, use of vasopressors and higher serum creatinine at admission, significantly associated with death among patients with AKI. Large prospective studies need to be done to better understand the outcomes in AKI and the ways to present and manage AKI.

Feasibility of computer-generated telephonic message-based follow-up system among healthcare workers with diabetes: a randomized controlled trial.

INTRODUCTION: To assess the feasibility of computer-generated educational messaging system in healthcare workers of a tertiary care hospital. The secondary objectives were glycemic control, patient satisfaction and adherence to lifestyle modifications. RESEARCH DESIGN AND METHODS: Single-center parallel-group open-labeled randomized controlled trial with computer generated block randomization. SETTING: Healthcare workers with diabetes working in Christian Medical College Vellore, Tamil Nadu. PARTICIPANTS: 431 assessed, 341 met the selection criteria, 320 participants were randomized and 161 were taken into intervention arm and 159 in the control arm. INTERVENTION: Computer-generated short message service (SMS) based on transtheoretical model of behavioral change, 2 messages per week for 3 months, along with standard of care diabetic care. Messages had educational material regarding healthy eating habits and exercise and these messages were sent twice weekly. The messages were scheduled via an automatic calendar in a way that each subject in the intervention arm received 15 educational messages per month.Control group received only standard of care diabetic care which included dietary advice, exercise regimen and diabetic medications under supervision of their physician every 3 months. FOLLOW-UP: 6 months. RESULTS: 95.65% of people in the intervention arm (n=154) received regular messages, out of which 93.17% read the messages regularly. 80.12% acted on the messages. 93.17% felt more satisfied with their healthcare.While both groups showed improvement in body mass index (BMI) and hemoglobin A1c (HbA1c), the difference was greater in the intervention with regard to both decrease in BMI (-0.6, p<0.001) and HBA1c (-0.48, p<0.001). CONCLUSIONS: SMS-based education system is feasible in improving healthcare among healthcare workers with diabetes. It improves patient satisfaction, adherence and improves healthcare among individuals with diabetes by decreasing their BMI and decreasing HbA1c.

Clinical and Immunological Profile of Mixed Connective Tissue Disease and a Comparison of Four Diagnostic Criteria.

Mixed connective tissue disease (MCTD) was initially described as a chronic immune-mediated disease with overlapping features of systemic lupus erythematosus, scleroderma, and polymyositis. We conducted a cross-sectional study to describe the clinical and immunological profile of patients with MCTD and to compare the four diagnostic criteria, namely, Sharp, Kasukawa, Alarcón-Segovia, and Khan criteria. A total of 291 patients who were admitted from June 2007 to June 2017 and fulfilled the inclusion criteria were included in the study. A clinical diagnosis of MCTD was made in 111 patients, of whom 103 (92.8%) were women. The mean age at presentation was 39.3 years (SD ± 11.6). The most common organ systems that were involved were musculoskeletal system (95.5%), skin and mucosa (78.4%), and the gastrointestinal and hepatobiliary systems (56%). The maximum sensitivity was for the Kasukawa criteria with a sensitivity of 77.5% (95% CI 68.4-84.6) and specificity of 92.2% (95% CI 87-95.5). The Kahn criteria and Alarcón-Segovia criteria had the maximum specificity; the Alarcón-Segovia criteria had a sensitivity of 69.4% (95% CI 59.8-77.6) and a specificity of 99.4% (95% CI 96.5-99.9), while the Kahn criteria had a sensitivity of 52.3% (95% CI 42.6-61.7) and a specificity of 99.4% (95% CI 96.5-99.9). The sensitivity and specificity of Sharp criteria were 57.7% (95% CI 47.9-66.87) and 90% (95% CI 84.4-93.8), respectively.

Predictors of mortality, strategies to reduce readmission, and economic impact of acute decompensated heart failure: Results of the Vellore Heart Failure Registry.

AIM: Heart failure is a global problem that is increasing in prevalence. We undertook the initiative to compile the Vellore Heart Failure Registry (VHFR) to assess the clinical profile, mortality, risk factors and economic burden of heart failure by conducting a prospective, observational, hospital-based cohort study in Vellore, Tamil Nadu. METHODS AND RESULTS: This study was a prospective observational cohort study conducted at the Christian Medical College and Hospital, Vellore, between January 2014 and December 2016. A total of 572 patients who satisfied the Boston criteria for "definite heart failure" were included and the primary outcome was all-cause mortality. The median duration of hospital stay was eight days and the in-hospital, one, three and six month mortalities were 13.25%, 27.3%, 32.53% and 38.15%, respectively. The median duration of survival was 921 days. Readmission for heart failure constituted 42%, and the most common cause of decompensation was an infection(31.5%). The presence of cyanosis at admission, history of previous stroke or transient ischemic attack, and American College of Cardiology (ACC)/American Heart Association (AHA) stage D at the time of discharge were independently associated with mortality at six months. The median total direct cost of admission was INR 84,881.00 ($ 1232.34) CONCLUSION: The VHFR cohort had younger, more diabetic, and fewer hypertensive subjects than most cohorts. Admission for heart failure is a catastrophic health expenditure. Attempts should be made to ensure a reduction in readmission rates by targeting goal-directed therapy. As the most common cause of acute decompensation is pneumonia, vaccinating all patients before discharge may also help in this regard.

Time to debridement in open high-grade lower limb fractures and its effect on union and infections: A prospective study in a tropical setting.

PURPOSE: To prospectively evaluate whether time to debridement has any correlation with union, infection, and quality of life in high-grade lower limb fractures in a tropical setting. METHODS: A prospective cohort study was conducted at a tertiary care center in South India. Two hundred fifty-four adult skeletally mature patients with 301 grade 3 fractures involving the femur, tibia, or fibula were recruited. The cohort was empirically divided into two groups (early and late) based on the time to debridement (less than or more than 12 h from injury). OUTCOME: The primary outcome was nonunion. Secondary outcomes were deep infection rates and patients' quality of life. Short form-36 (SF-36) and short musculoskeletal functional assessment (SMFA) questionnaires were also used. Patients were followed up for 9 months. RESULTS: The follow-up rate was 93%. The late group had a significantly higher risk of nonunion (odds ratio(OR): 6.5, 95% confidence interval (CI): 2.82-14.95) and infections (OR: 6.05, 95% CI: 2.85-12.82). There was a 4% increase in the infection risk for each hour of delay for the initial 50 h (p < 0.0001). SF-36 and SMFA scores were superior in the early group (p < 0.0001). CONCLUSION: The study contradicts findings reported in the literature from the West. Our study was in agreement with our hypothesis and proved that debridement within 12 h resulted in significantly lower rates of nonunion and infections and an overall improved quality of life in high-grade open lower limb fractures in a developing country. LEVEL OF EVIDENCE: Level II. TRIAL REGISTRATION: German Clinical Trials Register DRKS00015186.

Susceptibility profile, resistance mechanisms & efficacy ratios of fosfomycin, nitrofurantoin & colistin for carbapenem-resistant Enterobacteriaceae causing urinary tract infections.

Background & objectives: The escalation in carbapenem resistance among Enterobacteriaceae has resulted in a lack of effective therapeutic alternatives. Older antimicrobials, fosfomycin, nitrofurantoin and colistin for urinary tract infections (UTIs) caused by carbapenem-resistant Enterobacteriaceae (CRE) may be effective treatment options. The objectives of this study were to evaluate the utility of fosfomycin, nitrofurantoin and colistin in treating UTI caused by CRE and molecular characterization of the plasmid-mediated carbapenem resistance mechanisms. Methods: Consecutive, non-duplicate isolates of CR Escherichia coli and Klebsiella spp. from urine cultures were included (n=150). Minimum inhibitory concentrations (MIC) were determined by E-test (fosfomycin and nitrofurantoin) and broth microdilution (colistin). Efficacy ratios were derived by dividing susceptibility breakpoints by observed MIC values of the drugs for the isolates. Isolates were screened for genes coding for carbapenemases using multiplex PCR. Fosfomycin, nitrofurantoin and colistin-resistant isolates were screened for plasmid-borne resistance genes fos A3, oqx AB and mcr-1, respectively using PCR. Results: Among E. coli, 98.9, 56 and 95 per cent isolates were susceptible to fosfomycin, nitrofurantoin and colistin, respectively, while 94 and 85 per cent of Klebsiella spp. were susceptible to fosfomycin and colistin, respectively. The efficacy ratios indicated fosfomycin as the drug of choice for UTI caused by CR E. coli and Klebsiella spp., followed by colistin. The blaNDM gene was most common, followed by blaOXA48-like. Plasmid-borne genes encoding resistance to fosfomycin, nitrofurantoin and colistin were absent. Interpretation & conclusions: With increasing resistance against the current treatment options, older drugs may emerge as effective options. Molecular screening of resistant isolates is essential to prevent the spread of plasmid-borne resistance against these drugs.

End-of-life decisions: A retrospective study in a tertiary care teaching hospital in India.

Background & objectives: In developing countries like India, there is a lack of clarity regarding the factors that influence decisions pertaining to life supports at the end-of-life (EOL). The objectives of this study were to assess the factors associated with EOL-care decisions in the Indian context and to raise awareness in this area of healthcare. Methods: This retrospectively study included all patients admitted to the medical unit of a tertiary care hospital in southern India, over one year and died. The baseline demographics, economic, physiological, sociological, prognostic and medical treatment-related factors were retrieved from the patient's medical records and analysed. Results: Of the 122 decedents included in the study whose characteristics were analyzed, 41 (33.6%) received full life support and 81 (66.4%) had withdrawal or withholding of some life support measure. Amongst those who had withdrawal or withholding of life support, 62 (76.5%) had some support withheld and in 19 (23.5%), it was withdrawn. The documentation of the disease process, prognosis and the mention of imminent death in the medical records was the single most important factor that was associated with the EOL decision (odds ratio - 0.08; 95% confidence interval, 0.01-0.74; P=0.03). Interpretation & conclusions: The documentation of poor prognosis was the only factor found to be associated with EOL care decisions in our study. Prospective, multicentric studies need to be done to evaluate the influence of various other factors on the EOL care.

Slow parasite clearance, absent K13-propeller gene polymorphisms and adequate artesunate levels among patients with malaria: A pilot study from southern India.

Background: Artemisinin-based combination therapy (ACT) is widely used in India and many generic preparations are available. Delayed response has been reported, suggesting inadequate response to artesunate (AS) or genotypic resistance. We designed a prospective observational study to assess the therapeutic response, elaborate pharmacokinetics of AS and identify Plasmodium falciparum kelch 13 (pfk13) propeller gene polymorphisms among hospitalized Indian patients with severe malaria. Methods: We collected blood samples from adult patients with severe P. falciparum or mixed (P. falciparum and P. vivax) malaria on ACT. We calculated the parasite clearance (CL) half-life using the Worldwide Antimalarial Resistance Network (WWARN) online parasite clearance estimator (PCE). We used the liquid chromatography tandem mass spectrophoto-metry method for simultaneous quantification of AS and dihydroartemisinin. We genotyped longitudinally archived DNA samples obtained pre-treatment (day 0) to study the point mutations in the pfk13 propeller domain. Results: A total of 54 patients with malaria were included, with a majority fulfilling the definitions of severe malaria. The median parasite CL slope half-life was estimated to be 6.44 hours (interquartile range 4.79-10.24). AS pharmacokinetics, assessed in 17 patients, were found to be similar in the groups with rapid (<48 hours) and slow CL (>48 hours) of parasites. No known mutations associated with artemisinin resistance in Southeast Asia were observed in our study participants. Conclusions: Slow parasite CL was seen with a high parasite burden without genotypic evidence of AS resistance. There is a need to standardize definitions of therapeutic efficacy of AS in cases of severe malaria.

Extended-Spectrum Beta-lactamase Producers: Detection for the Diagnostic Laboratory.

BACKGROUND AND OBJECTIVES: Discovered in 1983, Extended spectrum beta-lactamase (ESBL) producers are still the leading cause of infections in India. Its prompt detection is crucial to the clinical management. The Clinical Laboratory Standards Institute (CLSI) recommends phenotypic screening and confirmatory tests to identify the ESBL producer making it cost and time consuming for the diagnostic laboratory. We compare here the screening and confirmatory tests offering a solution to the CLSI recommendation. METHODS: Nosocomial isolates E. coli (71) and K. pneumoniae (25) resistant to cefotaxime and ceftazidime were included. CLSI recommended testing with cefotaxime, ceftazidime and in combination with clavulanic acid by disk diffusion and agar dilution methods were performed. E-test was performed on discrepant results. To determine the genetic relatedness of the organisms, 22 Medical and Surgical ICU isolates were genotyped by PFGE. Dendrogram was constructed using dice co-efficient, UPGMA method with diversity database software. RESULTS AND CONCLUSIONS: Phenotypic screening disk diffusion test versus the confirmatory agar dilution MIC tests with cefotaxime and ceftazidime correlated well with the final ESBL status (kappa 0.852 and 0.905 P < 0.001) and (kappa 0.911 and 0.822 P < 0.001). The tests show 99-100% sensitivity, 75-83.3% specificity, and positive likelihood ratios between 4.0 -5.9. E-test confirmed 6 of 12 discordant results as ESBLs. Of the 96 nosocomial isolates screened as possible ESBL producers by the Kirby-Bauer disk diffusion test, 86.5% were confirmed ESBL producers. Genotyping on the ICU isolates by PFGE revealed a genetically diverse population suggesting no transmission of phenotypically similar ESBL strains within the ICUs.