Pre-admission antibiotics for suspected cases of meningococcal disease.

BACKGROUND: Meningococcal disease can lead to death or disability within hours after onset. Pre-admission antibiotics aim to reduce the risk of serious disease and death by preventing delays in starting therapy before confirmation of the diagnosis. OBJECTIVES: To study the effectiveness and safety of pre-admission antibiotics versus no pre-admission antibiotics or placebo, and different pre-admission antibiotic regimens in decreasing mortality, clinical failure, and morbidity in people suspected of meningococcal disease. SEARCH METHODS: We searched CENTRAL (6 January 2017), MEDLINE (1966 to 6 January 2017), Embase (1980 to 6 January 2017), Web of Science (1985 to 6 January 2017), LILACS (1982 to 6 January 2017), and prospective trial registries to January 2017. We previously searched CAB Abstracts from 1985 to June 2015, but did not update this search in January 2017. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing antibiotics versus placebo or no intervention, in people with suspected meningococcal infection, or different antibiotics administered before admission to hospital or confirmation of the diagnosis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data from the search results. We calculated the risk ratio (RR) and 95% confidence interval (CI) for dichotomous data. We included only one trial and so did not perform data synthesis. We assessed the overall quality of the evidence using the GRADE approach. MAIN RESULTS: We found no RCTs comparing pre-admission antibiotics versus no pre-admission antibiotics or placebo. We included one open-label, non-inferiority RCT with 510 participants, conducted during an epidemic in Niger, evaluating a single dose of intramuscular ceftriaxone versus a single dose of intramuscular long-acting (oily) chloramphenicol. Ceftriaxone was not inferior to chloramphenicol in reducing mortality (RR 1.21, 95% CI 0.57 to 2.56; N = 503; 308 confirmed meningococcal meningitis; 26 deaths; moderate-quality evidence), clinical failures (RR 0.83, 95% CI 0.32 to 2.15; N = 477; 18 clinical failures; moderate-quality evidence), or neurological sequelae (RR 1.29, 95% CI 0.63 to 2.62; N = 477; 29 with sequelae; low-quality evidence). No adverse effects of treatment were reported. Estimated treatment costs were similar. No data were available on disease burden due to sequelae. AUTHORS' CONCLUSIONS: We found no reliable evidence to support the use pre-admission antibiotics for suspected cases of non-severe meningococcal disease. Moderate-quality evidence from one RCT indicated that single intramuscular injections of ceftriaxone and long-acting chloramphenicol were equally effective, safe, and economical in reducing serious outcomes. The choice between these antibiotics should be based on affordability, availability, and patterns of antibiotic resistance.Further RCTs comparing different pre-admission antibiotics, accompanied by intensive supportive measures, are ethically justified in people with less severe illness, and are needed to provide reliable evidence in different clinical settings.

Caregiver perceptions on intensive care: A qualitative study from southern India.

BACKGROUND: Admission of a patient to an intensive care unit (ICU) can result in tremendous stress to family caregivers not only because of the need to provide physical and emotional support to the sick relative, but also due to the burden of decision-making on behalf of the critically ill person. We enquired about family caregivers' perspectives on intensive care, the challenges they faced with decision-making and their perceptions on the nature of their interactions with healthcare providers. METHODS: We used maximum variation sampling and enrolled 20 consenting caregivers for semi-structured interviews. Each interview, based on an interview guide, took 30-40 minutes and was conducted in a private place within the hospital premises. All interviews were recorded, transcribed verbatim and entered into a qualitative software (NVivo) for analysis. RESULTS: The three emergent themes of analysis were (i) understanding about ICU, (ii) decision-making concerning ongoing treatment; and (iii) relationship with healthcare-providers. Some respondents saw the intensive care as an expensive facility for seriously ill patients while others were not so clear. The family's relationship with the patient and their financial status were seen as important deciding factors in continuing treatment. Decision-making was a complex and emotional issue and doctors were held in awe and seen as the main deciding authority. The importance of doctors being compassionate and communicative was stressed. CONCLUSION: Our study highlights the problems faced by family caregivers and of the need to improve their satisfaction through clear and simple communication strategies.

Risk Factors of Clinical and Immunological Failure in South Indian Cohort on Generic Antiretroviral Therapy.

Background: Since the time of NACO Antiretroviral (ART) roll-out, generic ART has been the mainstay of therapy. There are many studies documenting the efficacy of generic ART but with the passage of time, failure of therapy is on the rise. As institution of second line ART has significant financial implications both for a program and for an individual it is imperative that we determine factors which contribute towards treatment failure in a cohort of patients on generic antiretroviral therapy. Methodology: This was a nested matched case-control study assessing the predictors for treatment failure in our cohort who had been on Anti-retroviral therapy for at least a year. We identified 42 patients (Cases) with documented treatment failure out of our cohort of 823 patients and 42 sex, age and duration of therapy-matched controls. Using a structured proforma, we collected information from the out-patient and in-patient charts of the Infectious Diseases clinic Cohort in CMC, Vellore. A set of predetermined variables were studied as potential risk factors for treatment failure on ART. Results: Univariate analysis showed significant association with 1) Self-reported nonadherence<95% [OR 12.81 (95%CI 1.54-281.45)]. 2) Treatment interruptions in adherent cases (OR 9.56 (95% CI 1.11-213.35)]. 3) Past inappropriate therapies [OR 9.65 (95% CI 1.12-215.94)]. 4) Diarrhoea [OR 16.40 (95% CI 2.02-3.55.960]. 5) GI opportunistic infections (OR 11.06 (95% CI 1.31 -244.27)] and 6) Drug Toxicity [OR 3.69 (95% CI 1.15-12.35).In multiple logistic regression analysis, we found independent risk factors of treatment failure to be: Self-reported non-adherence (<95%) with OR 15.46(95%CI 1.55 - 154.08), drug toxicity - OR 4.13(95%CI 1.095 - 15.534) and history of diarrhoea - OR 23.446(95%CI 2.572 - 213.70). Conclusion: This study reveals that besides adherence to therapy, presence of diarrhoea and occurrence of drug toxicity are significant risk factors associated with failure of anti-retroviral therapy. There is a need for further prospective studies to assess their role in development of treatment failure on ART and thus help development of targeted interventions.

COST OF INTENSIVE CARE IN INDIA.

OBJECTIVES: The majority of patients in India access private sector providers for curative medical services. However, there is scanty information on the cost of treatment of critically ill patients in this setting. The study evaluates the cost and extent of financial subsidy required for patients admitted to an intensive care unit (ICU) in India. METHODS: Data on direct medical, direct nonmedical, and indirect cost were prospectively collected from critically ill patients admitted to a tertiary teaching hospital in India. Willingness-to-pay (WTP) amount was obtained from the next-of-kin following admission and the actual cost paid by the family at discharge was recorded. RESULTS: The main diagnoses (n = 499) were infection (26 percent) and poisoning (21 percent). The mean APACHE-II score was 13.9 (95 percent confidence interval [CI], 13.3-14.5); 86 percent were ventilated. ICU stay was 7.8 days (95 percent CI, 7.3-8.3). Hospital mortality was 27.9 percent. Direct medical cost accounted for 77 percent (US$ 2164) of the total treatment cost (US$ 2818). Indirect cost and direct nonmedical cost contributed to 19 percent (US$ 547.5) and 4 percent (US$ 106.5), respectively. Average total and daily ICU cost were US$ 1,897 and US$ 255, respectively. Although the family's WTP was 53 percent (US$ 1146; 95 percent CI, 1090-1204) of direct medical cost, their final contribution was 67.7 percent (US$ 1465; 95 percent CI, 1327-1604). CONCLUSIONS: The cost of an ICU admission in our setting is US$ 2818. Although the family's contribution to expenses exceeded their initial WTP, a substantial subsidy (33 percent) is still required. Alternate financing strategies for the poor and optimization of ICU resources are urgently required.

Supraphysiological 25-hydroxy vitamin D3 level at admission is associated with illness severity and mortality in critically ill patients.

We studied the association between admission serum 25-hydroxy vitamin D3 level and in-hospital mortality in a prospective cohort of critically ill patients admitted to the medical intensive care unit of a tertiary care referral center. Of the 180 patients enrolled, 129 were included. Vitamin D3 deficiency was observed in 37% (n = 48) and supra-physiological levels (≥250 nmol/L) in 15.5% (n = 20). Patients with supraphysiological vitamin D3 levels were grouped as outliers. There was no difference in mortality (p = 0.41) between vitamin D3 deficient (21/48) and non-deficient (36/81) patients in analysis with and without outliers. Patients with vitamin D3 ≥250 nmol/L had a significantly higher (p = 0.02) Simplified Acute Physiology Score (SAPS) II and mortality (p = 0.003) [mean (SD) 60.1 ± 17.1 and 75% (15/20), respectively] when compared with the rest [45.6 ± 18 and 38.5% (42/109), respectively]. The sensitivity, specificity and SAPS II independent odds ratio to predict mortality in patients with supraphysiological vitamin D3 levels were 26.3, 93.1 and 3.7% (95% confidence interval 1.2-11.4; p = 0.03), respectively. In conclusion, vitamin D3 deficiency in our cohort was not associated with mortality. A patient subset with supra-physiological vitamin D levels had higher illness severity scores and mortality. Extrinsic factors interfering with test results were ruled out. A biological hypothesis to explain this observation is proposed. Further clarification of mechanisms leading to this observation is warranted.

Competency Based Medical Education (CBME) in India: Clinicians' Multifaceted Challenges.

In the recent past, in order to achieve our national goal of 'health for all', National Medical Commission and Government of India made competency based medical education (CBME) mandatory in all Indian medical colleges. By undergoing CBME, the Indian Medical Graduate is expected to achieve the five roles of Clinician, Communicator, Leader and Member of the health care, Professional and Lifelong learner. This article is an overview of CBME, its relevant terminologies and knowledge-gaps. The purpose is to share these changes in medical education with practicing Otolaryngologists of India. It also discusses the various challenges regarding this already- suggested implementation process for clinical academicians, which could be counterproductive to the expected national aim and goal.

Calcitriol in Sepsis-A Single-Centre Randomised Control Trial.

Background/Objectives: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis is a significant cause of hospital admission and the leading reason for admission to the ICU and is associated with high mortality. Vitamin D has shown promising immunomodulatory effects by upregulating the antimicrobial peptide, cathelicidin. However, previous studies analysing the use of calcitriol in sepsis have shown variable results and did not utilise APACHE II (Acute Physiology and Chronic Health Evaluation II) scores as endpoints. This study evaluates the efficacy of intramuscular calcitriol in patients admitted to the ICU with sepsis, focusing on its impact on APACHE II scores. The primary aim was to determine if intramuscular calcitriol improved APACHE II scores from day 1 to day 7 or discharge from the ICU, whichever was earlier. Secondary outcomes included 28-day mortality, ventilator days, vasopressor days, ICU stay length, adverse events, and hospital-acquired infections in ICU patients. Methods: This was a triple-blinded phase III randomised control trial. A total of 152 patients with suspected sepsis were block-randomised to receive either intramuscular calcitriol (300,000 IU) (n = 76) or a placebo (n = 76). The trial was registered with the Clinical Trials Registry-India (CTRI No: CTRI 2019/01/17066) following ethics committee approval and was not funded. Results: There was no significant difference in APACHE II scores between the calcitriol and placebo groups from day 1 to day 7 (p = 0.382). There were no significant changes in 28-day mortality (14.4% vs. 17%, p = 0.65), number of days on a ventilator (5 vs. 5, p = 0.84), number of days on vasopressors (3 vs. 3, p = 0.98), length of ICU stay (10 days vs. 11 days, p = 0.78), adverse events (27.6% vs. 19.7%, p = 0.25), and hospital-acquired infections (17.1% vs. 15.8%, p = 0.82). Conclusions: There was no effect of intramuscular calcitriol in patients admitted to the ICU with sepsis.

Patterns of antibiotic use in the community and challenges of antibiotic surveillance in a lower-middle-income country setting: a repeated cross-sectional study in Vellore, South India.

OBJECTIVES: There is considerable evidence linking antibiotic usage to bacterial resistance. Intervention strategies are needed to contain antibiotic use and thereby resistance. To plan appropriate strategies, it is imperative to undertake surveillance in the community to monitor antibiotic encounters and drivers of specific antibiotic misuse. Such surveillance is rarely in place in lower-middle-income countries (LMICs). This study describes antibiotic patterns and challenges faced while developing such surveillance systems in an LMIC. PATIENTS AND METHODS: Surveillance of antibiotic encounters (prescriptions and dispensations) was carried out using a repeated cross-sectional design for 2 years in Vellore, south India. Every month, patients attending 30 health facilities (small hospitals, general practitioner clinics and pharmacy shops) were observed until 30 antibiotic encounters were attained in each. Antibiotic use was expressed as the percentage of encounters containing specific antibiotics and defined daily doses (DDDs)/100 patients. Bulk antibiotic sales data were also collected. RESULTS: Over 2 years, a total of 52,788 patients were observed and 21,600 antibiotic encounters (40.9%) were accrued. Fluoroquinolones and penicillins were widely used. Rural hospitals used co-trimoxazole more often and urban private hospitals used cephalosporins more often; 41.1% of antibiotic prescriptions were for respiratory infections. The main challenges in surveillance included issues regarding sampling, data collection, denominator calculation and sustainability. CONCLUSIONS: Patterns of antibiotic use varied across health facilities, suggesting that interventions should involve all types of health facilities. Although challenges were encountered, our study shows that it is possible to develop surveillance systems in LMICs and the data generated may be used to plan feasible interventions, assess impact and thereby contain resistance.

Pre-admission antibiotics for suspected cases of meningococcal disease.

BACKGROUND: Meningococcal disease can lead to death or disability within hours after onset. Pre-admission antibiotics aim to reduce the risk of serious disease and death by preventing delays in starting therapy before confirmation of the diagnosis. OBJECTIVES: To study the effectiveness and safety of pre-admission antibiotics versus no pre-admission antibiotics or placebo, and different pre-admission antibiotic regimens in decreasing mortality, clinical failure and morbidity in people suspected of meningococcal disease. SEARCH METHODS: We updated searches of CENTRAL (2013, Issue 4), MEDLINE (1966 to April week 4, 2013), EMBASE (1980 to May 2013), Web of Science (1985 to May 2013), CAB Abstracts (1985 to May 2013), LILACS (1982 to May 2013) and prospective trials registries to May 2013. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing antibiotics versus placebo or no intervention, in people with suspected meningococcal infection, or different antibiotics administered before admission to hospital or confirmation of the diagnosis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data from the search results. We calculated the risk ratio (RR) and 95% confidence interval (CI) for dichotomous data. We included only one trial so data synthesis was not performed. We assessed the overall quality of the evidence using the GRADE approach. MAIN RESULTS: We found no RCTs that compared pre-admission antibiotics versus no pre-admission antibiotics or placebo. One open-label, non-inferiority RCT, conducted during an epidemic in Niger, evaluated a single dose of intramuscular ceftriaxone versus a single dose of intramuscular long-acting (oily) chloramphenicol. Ceftriaxone was not inferior to chloramphenicol in reducing mortality (RR 1.2, 95% CI 0.6 to 2.6; N = 503; 308 confirmed meningococcal meningitis; 26 deaths; moderate-quality evidence), clinical failures (RR 0.8, 95% CI 0.3 to 2.2; N = 477, 18 clinical failures; moderate-quality evidence) or neurological sequelae (RR 1.3, 95% CI 0.6 to 2.6; N = 477; 29 with sequelae; low-quality evidence). No adverse effects of treatment were reported. Estimated treatment costs were similar. No data were available on disease burden due to sequelae. AUTHORS' CONCLUSIONS: We found no reliable evidence to support or refute the use of pre-admission antibiotics for suspected cases of non-severe meningococcal disease. Evidence of moderate quality from one RCT indicated that single intramuscular injections of ceftriaxone and long-acting chloramphenicol were equally effective, safe and economical in reducing serious outcomes. The choice between these antibiotics would be based on affordability, availability and patterns of antibiotic resistance.Further RCTs comparing different pre-admission antibiotics, accompanied by intensive supportive measures, are ethically justifiable in participants with severe illness, and are needed to provide reliable evidence in different clinical settings.

Prospective multi-centre sentinel surveillance for Haemophilus influenzae type b & other bacterial meningitis in Indian children.

BACKGROUND & OBJECTIVES: Haemophilus influenzae type b (Hib) is one of the leading bacterial causes of invasive disease in populations without access to Hib conjugate vaccines (Hib-CV). India has recently decided to introduce Hib-CV into the routine immunization programme in selected States. Longitudinal data quantifying the burden of bacterial meningitis and the proportion of disease caused by various bacteria are needed to track the impact of Hib-CV once introduced. A hospital-based sentinel surveillance network was established at four places in the country and this study reports the results of this ongoing surveillance. METHODS: Children aged 1 to 23 months with suspected bacterial meningitis were enrolled in Chennai, Lucknow, New Delhi, and Vellore between July 2008 and June 2010. All cerebrospinal fluid (CSF) samples were tested using cytological, biochemical, and culture methods. Samples with abnormal CSF (≥10 WBC per µl) were tested by latex agglutination test for common paediatric bacterial meningitis pathogens. RESULTS: A total of 708 patients with abnormal CSF were identified, 89 of whom had a bacterial pathogen confirmed. Hib accounted for the majority of bacteriologically confirmed cases, 62 (70%), while Streptococcus pneumoniae and group B Streptococcus were identified in 12 (13%) and seven (8%) cases, respectively. The other eight cases were a mix of other bacteria. The proportion of abnormal CSF and probable bacterial meningitis that was caused by Hib was 74 and 58 per cent lower at Christian Medical College (CMC), Vellore, which had a 41 per cent coverage of Hib-CV among all suspected meningitis cases, compared to the combined average proportion at the other three centres where a coverage between 1 and 8 per cent was seen (P<0.001 and P= 0.05, respectively). INTERPRETATION & CONCLUSIONS: Hib was found to be the predominant cause of bacterial meningitis in young children in diverse geographic locations in India. Possible indications of herd immunity was seen at CMC compared to sites with low immunization coverage with Hib-CV. As Hib is the most common pathogen in bacterial meningitis, Hib-CV would have a large impact on bacterial meningitis in Indian children.

Alternate day versus daily oral iron for treatment of iron deficiency anemia: a randomized controlled trial.

Oral iron is the mainstay of treating iron deficiency anemia. Recent studies indicate better fractional iron absorption with alternate day supplementation. However, the optimal supplementation strategy is unclear. We compared effectiveness of daily versus alternate day supplementation of oral iron for treatment of iron deficiency anemia. This double blind, active control, randomized controlled trial was conducted on two hundred adults having hemoglobin 10 g/dL or less with microcytic hypochromic anemia and/or serum ferritin below 50 ng/mL. They were randomized to receive either two Ferrous sulfate tablets containing 60 mg elemental iron (120 mg total) on alternate days or single tablet of 60 mg elemental iron daily for 8 weeks. Primary outcome was mean change in hemoglobin at week 8 from baseline. Mean hemoglobin was 6.53 (± 1.89) and 6.68 (± 1.89) g/dL in the alternate day and daily arms respectively. Mean change in hemoglobin was + 1.05 ± 1.34 g/dL in alternate day arm and + 1.36 ± 1.51 g/dL in daily arm (p = 0.47) at week 8. There were no statistically significant differences between the arms with respect to any secondary outcome. There is no significant difference between alternate day and daily iron administration in improving hemoglobin. Randomized controlled trials enrolling more participants for longer periods of supplementation and evaluating clinically relevant outcomes like change in hemoglobin may be useful in identifying the ideal dosing strategy.Trial Registration: Clinical Trial Registry of India (CTRI/2019/01/017169).

Adenoidectomy: Anatomical Versus Clinical Success.

Endoscopic adenoidectomy with powered instruments,a challenge in resource-constraint developing countries, has been on the rise. To evaluate conventional curettage as compared to endoscopic assisted adenoidectomy in the successful management of adenoid enlargement. A randomized controlled double-blinded study among children undergoing adenoidectomywas done. Primary outcomes were assessed by pre- and postoperative evaluation with a symptoms questionnaire and fiberoptic nasal endoscopy. There were 71 children aged 3-15 years, majority having grade III adenoids. Conventional adenoidectomy was done by the surgeon who was blinded to preoperative adenoid status. Patients were randomized to two groups, 35in conventional curettage where no further on-table intervention was done. Check endoscopyof the remaining 36 patients, formingthe second group, revealed residual grade III adenoidsin 5.6%. They underwentcompletion adenoidectomyendoscopically. By the 12th postoperative week, nasal endoscopy noted that 39.3% had grade I/II and 8.8% had grade I in the conventional and endoscopic groups respectively. Thoughstatistically significant, all pre-op symptoms settled except sleep-related ones which persisted in both groups (25% versus 14.7) with no complications in either group. Relief of all symptoms other than sleep-related ones, was achieved despite residual adenoids being up to grade II in both conventional and endoscopic group. This suggests non-obstructive causes in a subset of these patients. Conventional adenoid curettage is comparable to endoscopic adenoidectomy by cold method among children aged three and above. Complete adenoidclearance for achieving 'anatomical success' appears not to be necessary for 'clinical success'.

Acute kidney injury in tropical acute febrile illness in a tertiary care centre--RIFLE criteria validation.

BACKGROUND: Acute febrile illnesses are a common cause of tropical acute kidney injury (AKI). The incidence and severity of AKI in tropical febrile illnesses and validity of RIFLE classification are unclear. METHODS: Consecutive adult inpatients of a tertiary hospital in southern India with tropical acute febrile illness between January 2007 and January 2008 were prospectively studied for the incidence and severity of AKI based on RIFLE classification and its association with mortality and dialysis requirement. RESULTS: The 367 patients (mean age 39.7±16.9 years; 60% males) with tropical acute febrile illness due to scrub typhus (51.2%), falciparum malaria (10.4%), enteric fever (8.7%), dengue (7.6%), mixed malaria (6.5%), leptospirosis (3.3%), undifferentiated acute febrile illness (8.4%) and others (3.8%) (spotted fever, vivax malaria and Hantaan virus infection) had an overall mortality rate of 12.3%. The incidence of AKI was 41.1%; of which, 17.4%, 9.3% and 14.4% were in the Risk, Injury and Failure classes, respectively. Of the patients, 7.9% required dialysis. Among the Risk, Injury and Failure groups, there was an incremental risk of mortality (OR 6.9, 20.2 and 25.6; P<0.001) and dialysis requirement (OR 3.4, 28.8 and 178.8; P<0.001). CONCLUSIONS: The incidence of AKI in the common tropical acute febrile illnesses in our study such as scrub typhus, falciparum malaria, enteric fever, dengue and leptospirosis is 41.1%. RIFLE classification is valid and applicable in AKI related to tropical acute febrile illnesses, with an incremental risk of mortality and dialysis requirement.

Rationalizing antibiotic use to limit antibiotic resistance in India.

Antibiotic resistance, a global concern, is particularly pressing in developing nations, including India, where the burden of infectious disease is high and healthcare spending is low. The Global Antibiotic Resistance Partnership (GARP) was established to develop actionable policy recommendations specifically relevant to low- and middle-income countries where suboptimal access to antibiotics - not a major concern in high-income countries - is possibly as severe a problem as is the spread of resistant organisms. This report summarizes the situation as it is known regarding antibiotic use and growing resistance in India and recommends short and long term actions. Recommendations aim at (i) reducing the need for antibiotics; (ii) lowering resistance-enhancing drug pressure through improved antibiotic targeting, and (iii) eliminating antibiotic use for growth promotion in agriculture. The highest priority needs to be given to (i) national surveillance of antibiotic resistance and antibiotic use - better information to underpin decisions on standard treatment guidelines, education and other actions, as well as to monitor changes over time; (ii) increasing the use of diagnostic tests, which necessitates behavioural changes and improvements in microbiology laboratory capacity; (iii) setting up and/or strengthening infection control committees in hospitals; and (iv) restricting the use of antibiotics for non-therapeutic uses in agriculture. These interventions should help to reduce the spread of antibiotic resistance, improve public health directly, benefit the populace and reduce pressure on the healthcare system. Finally, increasing the types and coverage of childhood vaccines offered by the government would reduce the disease burden enormously and spare antibiotics.

An External Evaluation on the INCLEN Research Program to Emphasize the Public Health Significance of Childhood Pneumonia in India.

OBJECTIVE: An independent external evaluation of the International Clinical Epidemiology Network (INCLEN) research program to emphasize the public health significance of childhood pneumonia in India. METHOD: An independent evaluation based on desk reviews of available documents and reports, site visits to study sites, and structured interviews with study investigators, technical advisory group (TAG) members, INCLEN staff and the donor agency. FINDINGS: The program elicited responses from a range of investigators across India. The selection process was transparent and objective, and the selected projects were of public health significance. The support provided through the program strengthened research capacity and improved study outputs. However, the available expertise was not fully exploited and protocol deviations in a few studies resulted in suboptimal outputs. CONCLUSIONS: The program represented a new and positive paradigm for research support in India, though a few improvements may result in greater impact for future programs.

Utility of Pecs Block for Perioperative Opioid-Sparing Analgesia in Cancer-Related Breast Surgery: A Randomized Controlled Trial.

Multidisciplinary treatment and multimodal analgesia are the approach to reduce mortality and morbidity of breast cancer. Pectoral nerve block (PECS I and II) is one of the modes of analgesia advocated. The primary aim is to find the risks and benefits of the block in providing analgesia for intraoperative and immediate postoperative cancer-related breast surgery and total morphine consumption. The secondary aim is to evaluate, any additional knowledge acquired, in the reduction of persistent chronic pain state and cancer recurrence, during the time frame studied. The study was conducted after the approval of the ethics committee and National Registry, and included patients of ASA I and II undergoing mastectomy surgery with axillary clearance, under general anesthesia, during the period of 2017 to 2018. A total of 60 patients were recruited, randomizing them into two groups: group 1 (n = 30): ultrasound-guided PECS I (0.2 ml/kg) and PECS II (0.4 ml/kg) block, post-induction with 0.25% levobupivacaine, maximum dose of 2 mg/kg; group 2 (n = 30): no block, only general anesthesia. Intraoperatively, vitals were monitored at regular intervals and analgesics given as per response. Postoperatively, pain was assessed using the numerical pain score and arm abduction score, until discharge. Data collected was analyzed and interpreted using statistical methods. Patients were followed up telephonically, until six months for any chronic pain and cancer recurrence instances. The PECS block group used less morphine intra and postoperatively, which was statistically significant (p = 0.0001). Group 1- Had a significant decrease in the mean intraoperative systolic blood pressure (p = 0.03). There was significant improvement in the arm abduction in the test group as compared to that in the control group (p = 0.001). The average time for block performance was 7.9 min and no complications were observed. No patients in the study groups reported chronic pain or cancer recurrence issues. The two-level PECS block is safe, effective, reliable, and easy to perform. Clinical Trial Registration Number: CTRI/2017/11/010630.

Secreted Wnt antagonists in scrub typhus.

BACKGROUND: The mechanisms that control local and systemic inflammation in scrub typhus have only been partially elucidated. The wingless (Wnt) signaling pathways are emerging as important regulators of inflammation and infection, but have not been investigated in scrub typhus. METHODOLOGY/PRINCIPAL FINDINGS: Plasma levels of secreted Wnt antagonists (i.e. DKK-1, sFRP-3, WIF-1 and SOST) were analyzed in patients with scrub typhus (n = 129), patients with similar febrile illness without O. tsutsugamushi infection (n = 31), febrile infectious disease controls, and in healthy controls (n = 31) from the same area of South India, and were correlated to markers of inflammation, immune and endothelial cell activation as well as for their association with organ specific dysfunction and mortality in these patients. We found i) Levels of SOST and in particular sFRP-3 and WIF-1 were markedly increased and DKK-1 decreased in scrub typhus patients at admission to the hospital compared to healthy controls. ii) In recovering scrub typhus patients, SOST, sFRP-3 and WIF-1 decreased and DKK-1 increased. iii) SOST was positively correlated with markers of monocyte/macrophage and endothelial/vascular activation as well as with renal dysfunction and poor outcome iv) Finally, regulation of Wnt pathways by O. tsutsugamushi in vitro in monocytes and ex vivo in mononuclear cells isolated from patients with scrub typhus, as evaluated by gene expression studies available in public repositories, revealed markedly attenuated canonical Wnt signaling. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that scrub typhus is characterized by attenuated Wnt signaling possibly involving dysregulated levels of several secreted pathway antagonists. The secreted Wnt antagonist SOST was strongly associated with renal dysfunction and poor prognosis in these patients.

Community effect of Haemophilus influenzae type b vaccination in India.

We assessed the effect of distribution of Haemophilus influenzae type b (Hib) vaccine in the private health care sector on Hib meningitis admissions at a referral hospital in India. The annual mean number of Hib cases was 10.7 before Hib vaccine introduction, falling to 3.8 cases following introduction (P < 0.0001). By contrast, the mean of annual numbers of pneumococcal cases were 3.0 and 4.6, (P = 0.55). Even at relatively low coverage through private sector distribution, Hib vaccine has significant community impact on Hib disease.

Invasive pneumococcal disease in Indian adults: 11 years' experience.

PURPOSE: To investigate the epidemiology of invasive pneumococcal disease (IPD), prevalent serotypes, and pattern of antimicrobial resistance (AMR) in Indian adults. METHODS: Prospective laboratory based surveillance of IPD was carried out in >18 years age group between January 2007 and July 2017, from a tertiary care hospital in South India. All Streptococcus pneumoniae culture positives from blood, CSF and sterile body fluids were characterized to identify the serotypes and AMR. RESULTS: A total of 408 IPD cases were characterized in this study. The overall case fatality rate in this study was 17.8% (95% confidence interval (CI): 14.1, 22.4). Pneumonia (39%), meningitis (24.3%), and septicaemia (18.4%) were the most common clinical conditions associated with IPD. Serotypes 1, 3, 5, 19F, 8, 14, 23F, 4, 19A and 6B were the predominant serotypes in this study. Penicillin non-susceptibility was low with 6.4% CONCLUSION: Serotype data from this study helped in accurate estimation of pneumococcal conjugate vaccine-13 and pneumococcal polysaccharide vaccine-23 protective coverage against serotypes causing IPD in India as 58.7% (95% CI: 53.8, 63.4) and 67.4% (95% CI: 62.7, 71.8) respectively. Penicillin non-susceptibility in meningeal IPD cases is 27.4%. Empirical therapy for meningeal IPD must be cephalosporin in combination with vancomycin since cefotaxime non-susceptibility in meningeal IPD is 9.9.

Antimicrobial resistance surveillance among commensal Escherichia coli in rural and urban areas in Southern India.

OBJECTIVE: To assess antimicrobial resistance (AMR) in Tamil Nadu, India. METHODS: Data on AMR of commensal and uropathogenic Escherichia coli were collected from one urban (Christian Medical College Hospital, Vellore) and one rural (CMCH Rural Unit for Health and Social Affairs) centre in Tamil Nadu at monthly intervals for 1 year. RESULTS: Forty-two per cent of commensal E. coli was resistant to one or more of the tested antimicrobials. 8.4% were resistant to three drugs commonly used for the treatment of urinary tract infections, namely ampicillin, co-trimoxazole and nalidixic acid. 1.5% of isolates were resistant to nitrofurantoin. There was no significant difference between resistance rates in commensal E. coli collected in rural and urban areas. Resistance was more common in infecting than commensal strains. DISCUSSION: Resistance to most antimicrobials is high both in urban and rural areas. Higher resistance to antimicrobials used widely for the treatment suggests that drug use contributes to it. Hence unnecessary use of antimicrobials must be avoided. Surveillance among commensal E. coli can be used to monitor changes in AMR over time.