Improving antibiotic prescribing for children in the resource-poor setting.

Antibiotics are a critically important part of paediatric medical care in low- and middle-income countries (LMICs), where infectious diseases are the leading cause of child mortality. The World Health Organization estimates that >50% of all medicines are prescribed, dispensed or sold inappropriately and that half of all patients do not take their medicines correctly. Given the rising prevalence of antimicrobial resistance globally, inappropriate antibiotic use is of international concern, and countries struggle to implement basic policies promoting rational antibiotic use. Many barriers to rational paediatric prescribing in LMICs persist. The World Health Organization initiatives, such as 'Make medicines child size', the Model List of Essential Medicines for Children and the Model Formulary for Children, have been significant steps forward. Continued strategies to improve access to appropriate drugs and formulations, in conjunction with improved evidence-based clinical guidelines and dosing recommendations, are essential to the success of such initiatives on both a national and an international level. This paper provides an overview of these issues and considers future developments that may improve LMIC antibiotic prescribing

Tonsillectomy among children with low baseline acute throat infection consultation rates in UK general practices: a cohort study.

OBJECTIVE: To investigate the effectiveness of tonsillectomy in reducing acute throat infection (ATI) consultation rates over 6 years' follow-up among children with low baseline ATI consultation rates. DESIGN: Retrospective cohort study. SETTING: UK general practices from the Clinical Practice Research Datalink. PARTICIPANTS: Children aged 4-15 years with ≤3 ATI consultations during the 3 years prior to 2001 (baseline). 450 children who underwent tonsillectomy (tonsillectomy group) and 13 442 other children with an ATI consultation (comparison group) in 2001. MAIN OUTCOME MEASURES: Mean differences in ATI consultation rates over the first 3 years' and subsequent 3 years' follow-up compared with 3 years prior to 2001 (baseline); odds of ≥3 ATI consultations at the same time points. RESULTS: Among children in the tonsillectomy group, the 3-year mean ATI consultation rate decreased from 1.31 to 0.66 over the first 3 years' follow-up and further declined to 0.60 over the subsequent 3 years' follow-up period. Compared with children who had no operation, those who underwent tonsillectomy experienced a reduction in 3-year mean ATI consultations per child of 2.5 (95% CI 2.3 to 2.6, p<0.001) over the first 3 years' follow-up, but only 1.2 (95% CI 1.0 to 1.4, p<0.001) over the subsequent 3 years' follow-up compared with baseline, respectively. This equates to a mean reduction of 3.7 ATI consultations over a 6-year period and approximates to a mean annual reduction of 0.6 ATI consultations per child, per year, over 6 years' follow-up. Children who underwent tonsillectomy were also much less likely to experience ≥3 ATI consultations during the first 3 years' follow-up (adjusted OR=0.12, 95% CI 0.08 to 0.17) and the subsequent 3 years' follow-up (adjusted OR=0.24, 95% CI 0.14 to 0.41). CONCLUSIONS: Among children with low baseline ATI rates, there was a statistically significant reduction in ATI consultation rates over 6 years' follow-up. However, the relatively modest clinical benefit needs to be weighed against the potential risks and complications associated with surgery

Bacterial pathogens and resistance causing community acquired paediatric bloodstream infections in low- and middle-income countries: a systematic review and meta-analysis

Background Despite a high mortality rate in childhood, there is limited evidence on the causes and outcomes of paediatric bloodstream infections from low- and middle-income countries (LMICs). We conducted a systematic review and meta-analysis to characterize the bacterial causes of paediatric bloodstream infections in LMICs and their resistance profile. Methods We searched Pubmed and Embase databases between January 1st 1990 and October 30th 2019, combining MeSH and free-text terms for “sepsis” and “low-middle-income countries” in children. Two reviewers screened articles and performed data extraction to identify studies investigating children (1 month-18 years), with at least one blood culture. The main outcomes of interests were the rate of positive blood cultures, the distribution of bacterial pathogens, the resistance patterns and the case-fatality rate. The proportions obtained from each study were pooled using the Freeman-Tukey double arcsine transformation, and a random-effect meta-analysis model was used. Results We identified 2403 eligible studies, 17 were included in the final review including 52,915 children (11 in Africa and 6 in Asia). The overall percentage of positive blood culture was 19.1% [95% CI: 12.0–27.5%]; 15.5% [8.4–24.4%] in Africa and 28.0% [13.2–45.8%] in Asia. A total of 4836 bacterial isolates were included in the studies; 2974 were Gram-negative (63.9% [52.2–74.9]) and 1858 were Gram-positive (35.8% [24.9–47.5]). In Asia, Salmonella typhi (26.2%) was the most commonly isolated pathogen, followed by Staphylococcus aureus (7.7%) whereas in Africa, S. aureus (17.8%) and Streptococcus pneumoniae (16.8%) were predominant followed by Escherichia coli (10.7%). S. aureus was more likely resistant to methicillin in Africa (29.5% vs. 7.9%), whereas E. coli was more frequently resistant to third-generation cephalosporins (31.2% vs. 21.2%), amikacin (29.6% vs. 0%) and ciprofloxacin (36.7% vs. 0%) in Asia. The overall estimate for case-fatality rate among 8 studies was 12.7% [6.6–20.2%]. Underlying conditions, such as malnutrition or HIV infection were assessed as a factor associated with bacteraemia in 4 studies each. Conclusions We observed a marked variation in pathogen distribution and their resistance profiles between Asia and Africa. Very limited data is available on underlying risk factors for bacteraemia, patterns of treatment of multidrug-resistant infections and predictors of adverse outcomes

Exploring the Impact of a Global Pandemic (COVID-19) on Factors Impacting the Resilience of Top-Tier London Hockey Players

Introduction. The cessation of all professional and amateur sport due to the COVID-19 pandemic had a dramatic effect on the mental and physical capacity of the United Kingdom populace, but its impact was arguably felt more deeply by the athletic population. Thus, this research explored which limiting factors were experienced by team hockey players during the national lockdowns (1.0–3.0) with the objective of enabling coaches and team management to better support and protect players’ physiological and psychological resilience in return to play. Methods. Data were collected over 12 weeks during the 3rd UK lockdown (March 2021) from two top-tier London clubs. Hockey players (n = 63) completed an online questionnaire that included validated tests for self-compassion, sport motivation, and a custom open-ended style qualitative questionnaire on nutrition and lifestyle behaviour. Mean self-compassion, motivation scores, and common indicative limiting factors were evaluated and ranked according to significance. Results. High “rebound resilience” was found with low amotivation scores (m = 8.33) and strong affinity for their sport identifying with the statement “because participation in my sport is an integral part of my life” with correspondingly high integrated regulation scores (m = 21.43). Participants’ self-compassion showed the highest scores in mindfulness (m = 3.66) and lowest in self-kindness (m = 2.84) indicating a common trait in athletes for self-criticism. The highest limiting factor was cited as “no social outlets, social interactions, or seeing friends and family”. Conclusion. This study revealed the critical role that social connectedness plays in promoting resilience and enhancing motivation in return to play during extremely challenging circumstances. When the social outlet is absent, enhancing resilience factors with mindfulness, self-compassion, and the creation of a more facilitative environment where player welfare takes priority are potential strategies to support players when they are unable to participate in their sport

Measuring antibiotic availability and use in 20 low- and middle-income countries

Objective To assess antibiotic availability and use in health facilities in low- and middle-income countries, using the service provision assessment and service availability and readiness assessment surveys. Methods We obtained data on antibiotic availability at 13 561 health facilities in 13 service provision assessment and 8 service availability and readiness assessment surveys. In 10 service provision assessment surveys, child consultations with health-care providers were observed, giving data on antibiotic use in 22 699 children. Antibiotics were classified as access, watch or reserve, according to the World Health Organization’s AWaRe categories. The percentage of health-care facilities across countries with specific antibiotics available and the proportion of children receiving antibiotics for key clinical syndromes were estimated. Findings The surveys assessed the availability of 27 antibiotics (19 access, 7 watch, 1 unclassified). Co-trimoxazole and metronidazole were most widely available, being in stock at 89.5% (interquartile range, IQR: 11.6%) and 87.1% (IQR: 15.9%) of health facilities, respectively. In contrast, 17 other access and watch antibiotics were stocked, by fewer than a median of 50% of facilities. Of the 22 699 children observed, 60.1% (13 638) were prescribed antibiotics (mostly co-trimoxazole or amoxicillin). Children with respiratory conditions were most often prescribed antibiotics (76.1%; 8972/11 796) followed by undifferentiated fever (50.1%; 760/1518), diarrhoea (45.7%; 1293/2832) and malaria (30.3%; 352/1160). Conclusion Routine health facility surveys provided a valuable data source on the availability and use of antibiotics in low- and middle-income countries. Many access antibiotics were unavailable in a majority of most health-care facilities

Using risk adjustment to improve the interpretation of global inpatient pediatric antibiotic prescribing.

Objectives Assessment of regional pediatric last-resort antibiotic utilization patterns is hampered by potential confounding from population differences. We developed a risk-adjustment model from readily available, internationally used survey data and a simple patient classification to aid such comparisons. Design We investigated the association between pediatric conserve antibiotic (pCA) exposure and patient / treatment characteristics derived from global point prevalence surveys of antibiotic prescribing, and developed a risk-adjustment model using multivariable logistic regression. The performance of a simple patient classification of groups with different expected pCA exposure levels was compared to the risk model. Setting 226 centers in 41 countries across 5 continents. Participants Neonatal and pediatric inpatient antibiotic prescriptions for sepsis/bloodstream infection for 1281 patients. Results Overall pCA exposure was high (35%), strongly associated with each variable (patient age, ward, underlying disease, community acquisition or nosocomial infection and empiric or targeted treatment), and all were included in the final risk-adjustment model. The model demonstrated good discrimination (c-statistic = 0.83) and calibration (p = 0.38). The simple classification model demonstrated similar discrimination and calibration to the risk model. The crude regional pCA exposure rates ranged from 10.3% (Africa) to 67.4% (Latin America). Risk adjustment substantially reduced the regional variation, the adjusted rates ranging from 17.1% (Africa) to 42.8% (Latin America). Conclusions Greater comparability of pCA exposure rates can be achieved by using a few easily collected variables to produce risk-adjusted rates

Development of a Novel Multipenicillin Assay and Assessment of the Impact of Analyte Degradation: Lessons for Scavenged Sampling in Antimicrobial Pharmacokinetic Study Design

Penicillins are widely used to treat infections in children, however the evidence is continuing to evolve in defining optimal dosing. Modern paediatric pharmacokinetic study protocols frequently favour opportunistic, “scavenged” sampling. This study aimed to develop a small volume single assay for five major penicillins and to assess the influence of sample degradation on inferences made using pharmacokinetic modelling, to investigate the suitability of scavenged sampling strategies. Using a rapid ultra-high performance liquid chromatographic-tandem mass spectrometric method, an assay for five penicillins (amoxicillin, ampicillin, benzylpenicillin, piperacillin and flucloxacillin) in blood plasma was developed and validated. Penicillin stabilities were evaluated under different conditions. Using these data, the impact of drug degradation on inferences made during pharmacokinetic modelling was evaluated. All evaluated penicillins indicated good stability at room temperature (23 ± 2°C) over 1 hour remaining in the range of 98-103% of the original concentration. More rapid analyte degradation had already occurred after 4 hours with stability ranging from 68% to 99%. Stability over longer periods declined: degradation of up to 60% was observed with delayed sample processing of up to 24 hours. Modelling showed that analyte degradation can lead to a 30% and 28% bias in clearance and volume of distribution, respectively, and falsely show nonlinearity in clearance. Five common penicillins can now be measured in a single low volume blood sample. Beta-lactam chemical instability in plasma can cause misleading pharmacokinetic modelling results, which could impact upon model-based dosing recommendations and the forthcoming era of beta-lactam therapeutic drug monitoring

Research activity among UK social work academics

Summary: The research activity of social work academics in the UK has been of interest and concern amongst academics and research funders. Multiple initiatives have been implemented to develop social work research activity, yet research by social work academics remains limited, hindered by lack of time, support infrastructures, funding and training. Through the use of a mixed-methods cross-sectional survey (N = 200) and follow-up individual interviews (N = 11), this study reports on the factors that were found to contribute to or impede the amount of time that social work academics reported spending on research. Findings: The results from the survey indicated that 73% of respondents were research active. Bivariate analysis revealed that academics spent less time on research and teaching, and more time on administration than expected by their employing universities. Multivariate analysis found that less time spent on administration and teaching, more university supports, and being from a pre-1992 university predicted more time spent on research. Applications: The findings indicate that the administrative burdens associated with teaching and assessment in social work education result in academics struggling to fit research into their busy lives, despite initiatives to raise the profile and productivity of social work research. Research support infrastructures and strategies should be reviewed in light of such findings