Point Prevalence Surveys of Antimicrobial Use among Hospitalized Children in Six Hospitals in India in 2016.

The prevalence of antimicrobial resistance in India is among the highest in the world. Antimicrobial use in inpatient settings is an important driver of resistance, but is poorly characterized, particularly in hospitalized children. In this study, conducted as part of the Global Antimicrobial Resistance, Prescribing, and Efficacy in Neonates and Children (GARPEC) project, we examined the prevalence of and indications of antimicrobial use, as well as antimicrobial agents used among hospitalized children by conducting four point prevalence surveys in six hospitals between February 2016 and February 2017. A total of 681 children were hospitalized in six hospitals across all survey days, and 419 (61.5%) were prescribed one or more antimicrobials (antibacterials, antivirals, antifungals). Antibacterial agents accounted for 90.8% (547/602) of the total antimicrobial prescriptions, of which third-generation cephalosporins (3GCs) accounted for 38.9% (213/547) and penicillin plus enzyme inhibitor combinations accounted for 14.4% (79/547). Lower respiratory tract infection (LRTI) was the most common indication for prescribing antimicrobials (149 prescriptions; 24.8%). Although national guidelines recommend the use of penicillin and combinations as first-line agents for LRTI, 3GCs were the most commonly prescribed antibacterial agents (55/149 LRTI prescriptions; 36.9%). In conclusion, 61.5% of hospitalized children were on at least one antimicrobial agent, with excessive use of 3GCs. Hence there is an opportunity to limit their inappropriate use

Oxygen dependency of mitochondrial metabolism indicates outcome of newborn brain injury

There is a need for a method of real-time assessment of brain metabolism during neonatal hypoxic-ischaemic encephalopathy (HIE). We have used broadband near-infrared spectroscopy (NIRS) to monitor cerebral oxygenation and metabolic changes in 50 neonates with HIE undergoing therapeutic hypothermia treatment. In 24 neonates, 54 episodes of spontaneous decreases in peripheral oxygen saturation (desaturations) were recorded between 6 and 81 h after birth. We observed differences in the cerebral metabolic responses to these episodes that were related to the predicted outcome of the injury, as determined by subsequent magnetic resonance spectroscopy derived lactate/N-acetyl-aspartate. We demonstrated that a strong relationship between cerebral metabolism (broadband NIRS-measured cytochrome-c-oxidase (CCO)) and cerebral oxygenation was associated with unfavourable outcome; this is likely to be due to a lower cerebral metabolic rate and mitochondrial dysfunction in severe encephalopathy. Specifically, a decrease in the brain tissue oxidation state of CCO greater than 0.06 µM per 1 µM brain haemoglobin oxygenation drop was able to predict the outcome with 64% sensitivity and 79% specificity (receiver operating characteristic area under the curve = 0.73). With further work on the implementation of this methodology, broadband NIRS has the potential to provide an early, cotside, non-invasive, clinically relevant metabolic marker of perinatal hypoxic-ischaemic injury

A paleoepidemiological approach to the osteological paradox : Investigating stress, frailty and resilience through cribra orbitalia

Open Access via the Jisc Wiley Agreement Funder: British Academy (GrantNumber(s): GP2\190224)Peer reviewedPublisher PD

Suppression of HBV by Tenofovir in HBV/HIV coinfected patients : a systematic review and meta-analysis

Background: Hepatitis B coinfection is common in HIV-positive individuals and as antiretroviral therapy has made death due to AIDS less common, hepatitis has become increasingly important. Several drugs are available to treat hepatitis B. The most potent and the one with the lowest risk of resistance appears to be tenofovir (TDF). However there are several questions that remain unanswered regarding the use of TDF, including the proportion of patients that achieves suppression of HBV viral load and over what time, whether suppression is durable and whether prior treatment with other HBV-active drugs such as lamivudine, compromises the efficacy of TDF due to possible selection of resistant HBV strains. Methods: A systematic review and meta-analysis following PRISMA guidelines and using multilevel mixed effects logistic regression, stratified by prior and/or concomitant use of lamivudine and/or emtricitabine. Results: Data was available from 23 studies including 550 HBV/HIV coinfected patients treated with TDF. Follow up was for up to seven years but to ensure sufficient power the data analyses were limited to three years. The overall proportion achieving suppression of HBV replication was 57.4%, 79.0% and 85.6% at one, two and three years, respectively. No effect of prior or concomitant 3TC/FTC was shown. Virological rebound on TDF treatment was rare. Interpretation: TDF suppresses HBV to undetectable levels in the majority of HBV/HIV coinfected patients with the proportion fully suppressed continuing to increase during continuous treatment. Prior treatment with 3TC/FTC does not compromise efficacy of TDF treatment. The use of combination treatment with 3TC/FTC offers no significant benefit over TDF alone

Predictors of HBeAg status and hepatitis B viraemia in HIV-infected patients with chronic hepatitis B in the HAART era in Brazil

<p>Abstract</p> <p>Background</p> <p>HBV-HIV co-infection is associated with an increased liver-related morbidity and mortality. However, little is known about the natural history of chronic hepatitis B in HIV-infected individuals under highly active antiretroviral therapy (HAART) receiving at least one of the two drugs that also affect HBV (TDF and LAM). Information about HBeAg status and HBV viremia in HIV/HBV co-infected patients is scarce. The objective of this study was to search for clinical and virological variables associated with HBeAg status and HBV viremia in patients of an HIV/HBV co-infected cohort.</p> <p>Methods</p> <p>A retrospective cross-sectional study was performed, of HBsAg-positive HIV-infected patients in treatment between 1994 and 2007 in two AIDS outpatient clinics located in the São Paulo metropolitan area, Brazil. The baseline data were age, sex, CD4 T+ cell count, ALT level, HIV and HBV viral load, HBV genotype, and duration of antiretroviral use. The variables associated to HBeAg status and HBV viremia were assessed using logistic regression.</p> <p>Results</p> <p>A total of 86 HBsAg patients were included in the study. Of these, 48 (56%) were using combination therapy that included lamivudine (LAM) and tenofovir (TDF), 31 (36%) were using LAM monotherapy, and 7 patients had no previous use of either one. Duration of use of TDF and LAM varied from 4 to 21 and 7 to 144 months, respectively. A total of 42 (48. 9%) patients were HBeAg positive and 44 (51. 1%) were HBeAg negative. The multivariate analysis revealed that the use of TDF for longer than 12 months was associated with undetectable HBV DNA viral load (serum HBV DNA level < 60 UI/ml) (<it>p </it>= 0. 047). HBeAg positivity was associated with HBV DNA > 60 UI/ml (p = 0. 001) and ALT levels above normality (<it>p </it>= 0. 038).</p> <p>Conclusion</p> <p>Prolonged use of TDF containing HAART is associated with undetectable HBV DNA viral load. HBeAg positivity is associated with HBV viremia and increased ALT levels.</p

The Meningococcal Vaccine Candidate Neisserial Surface Protein A (NspA) Binds to Factor H and Enhances Meningococcal Resistance to Complement

Complement forms an important arm of innate immunity against invasive meningococcal infections. Binding of the alternative complement pathway inhibitor factor H (fH) to fH-binding protein (fHbp) is one mechanism meningococci employ to limit complement activation on the bacterial surface. fHbp is a leading vaccine candidate against group B Neisseria meningitidis. Novel mechanisms that meningococci employ to bind fH could undermine the efficacy of fHbp-based vaccines. We observed that fHbp deletion mutants of some meningococcal strains showed residual fH binding suggesting the presence of a second receptor for fH. Ligand overlay immunoblotting using membrane fractions from one such strain showed that fH bound to a ∼17 kD protein, identified by MALDI-TOF analysis as Neisserial surface protein A (NspA), a meningococcal vaccine candidate whose function has not been defined. Deleting nspA, in the background of fHbp deletion mutants, abrogated fH binding and mAbs against NspA blocked fH binding, confirming NspA as a fH binding molecule on intact bacteria. NspA expression levels vary among strains and expression correlated with the level of fH binding; over-expressing NspA enhanced fH binding to bacteria. Progressive truncation of the heptose (Hep) I chain of lipooligosaccharide (LOS), or sialylation of lacto-N-neotetraose LOS both increased fH binding to NspA-expressing meningococci, while expression of capsule reduced fH binding to the strains tested. Similar to fHbp, binding of NspA to fH was human-specific and occurred through fH domains 6–7. Consistent with its ability to bind fH, deleting NspA increased C3 deposition and resulted in increased complement-dependent killing. Collectively, these data identify a key complement evasion mechanism with important implications for ongoing efforts to develop meningococcal vaccines that employ fHbp as one of its components

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

The snow must go on: Ground ice encasement, snow compaction and absence of snow differently cause soil hypoxia, CO2 accumulation and tree seedling damage in boreal forest

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Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112