Search results

Pharmacometrics of high-dose ivermectin in early COVID-19 from an open label, randomized, controlled adaptive platform trial (PLATCOV)

Background: There is no generally accepted methodology for in vivo assessment of antiviral activity in SARS-CoV-2 infections. Ivermectin has been recommended widely as a treatment of COVID-19, but whether it has clinically significant antiviral activity in vivo is uncertain. Methods: In a multicentre open label, randomized, controlled adaptive platform trial, adult patients with early symptomatic COVID-19 were randomized to one of six treatment arms including high-dose oral ivermectin (600 µg/kg daily for 7 days), the monoclonal antibodies casirivimab and imdevimab (600 mg/600 mg), and no study drug. The primary outcome was the comparison of viral clearance rates in the modified intention-to-treat population. This was derived from daily log 10 viral densities in standardized duplicate oropharyngeal swab eluates. This ongoing trial is registered at https://clinicaltrials.gov/ (NCT05041907). Results: Randomization to the ivermectin arm was stopped after enrolling 205 patients into all arms, as the prespecified futility threshold was reached. Following ivermectin, the mean estimated rate of SARS-CoV-2 viral clearance was 9.1% slower (95% confidence interval [CI] –27.2% to +11.8%; n=45) than in the no drug arm (n=41), whereas in a preliminary analysis of the casirivimab/imdevimab arm it was 52.3% faster (95% CI +7.0% to +115.1%; n=10 (Delta variant) vs. n=41). Conclusions: High-dose ivermectin did not have measurable antiviral activity in early symptomatic COVID-19. Pharmacometric evaluation of viral clearance rate from frequent serial oropharyngeal qPCR viral density estimates is a highly efficient and well-tolerated method of assessing SARS-CoV-2 antiviral therapeutics in vivo. Funding: ‘Finding treatments for COVID-19: A phase 2 multi-centre adaptive platform trial to assess antiviral pharmacodynamics in early symptomatic COVID-19 (PLAT-COV)’ is supported by the Wellcome Trust Grant ref: 223195/Z/21/Z through the COVID-19 Therapeutics Accelerator. Clinical trial number: NCT05041907 .

Clinical Antiviral Efficacy of Remdesivir in Coronavirus Disease 2019: An Open-Label, Randomized Controlled Adaptive Platform Trial (PLATCOV)

Abstract Background Uncertainty over the therapeutic benefit of parenteral remdesivir in coronavirus disease 2019 (COVID-19) has resulted in varying treatment guidelines. Methods In a multicenter open-label, controlled, adaptive, pharmacometric platform trial, low-risk adult patients with early symptomatic COVID-19 were randomized to 1 of 8 treatment arms including intravenous remdesivir (200 mg followed by 100 mg daily for 5 days) or no study drug. The primary outcome was the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance (estimated under a linear model fit to the daily log10 viral densities, days 0–7) in standardized duplicate oropharyngeal swab eluates, in a modified intention-to-treat population. This ongoing adaptive trial is registered at ClinicalTrials.gov (NCT05041907). Results The 2 study arms enrolled 131 patients (remdesivir n = 67, no study drug n = 64) and estimated viral clearance rates from a median of 18 swab samples per patient (a total of 2356 quantitative polymerase chain reactions). Under the linear model, compared with the contemporaneous control arm (no study drug), remdesivir accelerated mean estimated viral clearance by 42% (95% credible interval, 18%–73%). Conclusions Parenteral remdesivir accelerates viral clearance in early symptomatic COVID-19. Pharmacometric assessment of therapeutics using the method described can determine in vivo clinical antiviral efficacy rapidly and efficiently.

Chloroquine/ hydroxychloroquine prevention of coronavirus disease (COVID-19) in the healthcare setting; protocol for a randomised, placebo-controlled prophylaxis study (COPCOV)

There is no proven preventative therapy or vaccine against COVID-19. Theinfection has spread rapidly and there has already been a substantial adverse impact on the global economy. Healthcare workers have been affected disproportionately in the continuing pandemic. Significant infection rates in this critical group have resulted in a breakdown of health services in some countries. Chloroquine, and the closely related hydroxychloroquine, are safe and well tolerated medications which can be given for years without adverse effects. Chloroquine and hydroxychloroquine have significant antiviral activity against SARS-CoV-2, and despite the lack of benefit of hydroxychloroquine treatment in patients hospitalised with severe COVID-19, these drugs could still work in prevention. The emerging infection paradigm of an early viral peak, and late inflammation where there is benefit from corticosteroids. If these direct actiing antivirals are to work, they have the best chance given either early in infection and before infection occurs. We describe the study protocol for a multi-centre, multi-country randomised, double blind, placebo controlled trial to answer the question- can chloroquine/ hydroxychloroquine prevent COVID-19. 40,000 participants working in healthcare facilities or involved in the management of COVID-19 will be randomised 1:1 to receive chloroquine/ hydroxychloroquine or matched placebo as daily prophylaxis for three months. The primary objective is the prevention of symptomatic, virological or serologically proven coronavirus disease (COVID-19). The study could detect a 23% reduction from an incidence of 3% in the placebo group for either drug with 80% power. Secondary objectives are to determine if chloroquine/hydroxychloroquine prophylaxis attenuates severity, prevents asymptomaticCOVID-19 and symptomatic acute respiratory infections of another aetiology (non-SARS-CoV-2).

Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, randomised, controlled, adaptive platform trial

Abstract Brief summary In early symptomatic COVID-19 treatment, high dose oral favipiravir did not accelerate viral clearance. Background Favipiravir, an anti-influenza drug, has in vitro antiviral activity against SARS-CoV-2. Clinical trial evidence to date is inconclusive. Favipiravir has been recommended for the treatment of COVID-19 in some countries. Methods In a multicentre open-label, randomised, controlled, adaptive platform trial, low-risk adult patients with early symptomatic COVID-19 were randomised to one of ten treatment arms including high dose oral favipiravir (3.6g on day 0 followed by 1.6g daily to complete 7 days treatment) or no study drug. The primary outcome was the rate of viral clearance (derived under a linear mixed-effects model from the daily log 10 viral densities in standardised duplicate oropharyngeal swab eluates taken daily over 8 days [18 swabs per patient]), assessed in a modified intention-to-treat population (mITT). The safety population included all patients who received at least one dose of the allocated intervention. This ongoing adaptive platform trial was registered at ClinicalTrials.gov (NCT05041907) on 13/09/2021. Results In the final analysis, the mITT population contained data from 114 patients randomised to favipiravir and 126 patients randomised concurrently to no study drug. Under the linear mixed-effects model fitted to all oropharyngeal viral density estimates in the first 8 days from randomisation (4,318 swabs), there was no difference in the rate of viral clearance between patients given favipiravir and patients receiving no study drug; a -1% (95% credible interval: -14 to 14%) difference. High dose favipiravir was well-tolerated. Interpretation Favipiravir does not accelerate viral clearance in early symptomatic COVID-19. The viral clearance rate estimated from quantitative measurements of oropharyngeal eluate viral densities assesses the antiviral efficacy of drugs in vivo with comparatively few studied patients.

The utility of an AMR dictionary as an educational tool to improve public understanding of antimicrobial resistance

Background: Communicating about antimicrobial resistance (AMR) to the public is challenging. Methods: We developed a dictionary of terms commonly used to communicate about AMR. For each term, we developed learning points to explain AMR and related concepts in plain language. We conducted a pilot evaluation in 374 high school students in Ubon Ratchathani, Thailand. In three 50-minute sessions, students were asked to answer five true/false questions using a paper-based questionnaire. The first session assessed their understanding of AMR at baseline, the second after searching the internet, and the third after the provision of the printed AMR dictionary and its web address. Results: We developed the AMR dictionary as a web-based application (www.amrdictionary.net). The Thai version of the AMR dictionary included 35 terms and associated learning points, seven figures displaying posters promoting AMR awareness in Thailand, and 66 recommended online videos. In the pretest, the proportion of correct responses to each question ranged from 10% to 57%; 10% of the students correctly answered that antibiotics cannot kill viruses and 57% correctly answered that unnecessary use of antibiotics makes them ineffective. After the internet searches, the proportions of correct answers increased, ranging from 62% to 89% (all p<0.001). After providing the AMR dictionary, the proportions of correct answers increased further, ranging from 79% to 89% for three questions (p<0.001), and did not change for one question (p=0.15). Correct responses as to whether taking antibiotics often has side-effects such as diarrhoea reduced from 85% to 74% (p<0.001). The dictionary was revised based on the findings and comments received. Conclusions: Understanding of AMR among Thai high school students is limited. The AMR dictionary can be a useful supportive tool to increase awareness and improve understanding of AMR. Our findings support the need to evaluate the effectiveness of communication tools in the real-world setting.

Protection from UVB Toxicity in Human Keratinocytes by Thailand Native Herbs Extracts.

Thai traditional medicine employs a wide range of indigenous herbs in the forms of tincture or tea for the cure of skin and systemic inflammatory diseases. The protection by Thai plants extracts against UVB DNA damage and cytotoxicity was investigated in human keratinocytes. Petroleum ether, dichloromethane and ethanol extracts were prepared from 15 Thai herb species, and the total phenolic and flavonoid contents, the antioxidant and UV-absorbing properties were assessed by standard procedures. Cytoprotective effects were evaluated on the basis of cell survival, caspase-3 activity and pyrimidine dimers determination. High total phenolic and flavonoid contents were found in the ethanol and dichloromethane fractions. Dichloromethane extract of turmeric was shown to possess the highest antioxidant activity. The maximum UV absorptions were found in the ethanol extract of turmeric and in the dichloromethane extract of ginger. These extracts stimulated the synthesis of Thioredoxin 1, an antioxidant protein, and could protect human HaCaT keratinocytes from UV-induced DNA damage and cytotoxicity. The present data support the utilization of turmeric and ginger extracts in anti-UV cosmetic pharmaceuticals.

Similarities and differences in the biogenesis, processing and lysosomal targeting between zebrafish and human pro-Cathepsin D: functional implications.

The lysosomal protease Cathepsin D (CD) plays a role in neurodegenerative diseases, cancer, and embryo-fetus abnormalities. It is therefore of interest to know how this protein is synthesized in animal species used for modeling human diseases. Zebrafish (Danio rerio) is emerging as a valuable 'in vivo' vertebrate model for several human diseases. We have characterized the biogenetic pathways of zebrafish and human CD transgenically expressed in both human SH-SY5Y cells and zebrafish PAC2 cells. Differently from human CD, zebrafish CD was synthesized as a mono-glycosylated precursor (pro-CD) that was eventually processed into a single-chain mature polypeptide. In PAC2 cells, ammonium chloride and chloroquine impaired the N-glycosylation, and greatly stimulated the secretion, of pro-CD; still, a portion of un-glycosylated pro-CD reached the lysosomes and was processed to mature CD. The treatment with tunicamycin, which abrogates N-glycosylation, resulted in a similar effect. Zebrafish pro-CD was correctly processed when expressed in human cells, and its glycosylation, transport and maturation were not impaired by ammonium chloride. On the contrary, the transport and processing of human pro-CD expressed in zebrafish cells were profoundly altered: while the intermediate single-chain was not detectable, a small amount of double-chain mature CD still formed. This fact indicates that the enzyme machinery for single- to double-chain processing of mammal CD is present in zebrafish. Our data highlight the respective impact of the information imparted by the primary sequence and of the cellular transport and processing machineries in the biogenesis of lysosomal CD.

Labeling and exocytosis of secretory compartments in RBL mastocytes by polystyrene and mesoporous silica nanoparticles.

BackgroundFor a safe 'in vivo' biomedical utilization of nanoparticles, it is essential to assess not only biocompatibility, but also the potential to trigger unwanted side effects at both cellular and tissue levels. Mastocytes (cells having secretory granules containing cytokines, vasoactive amine, and proteases) play a pivotal role in the immune and inflammatory responses against exogenous toxins. Mastocytes are also recruited in the tumor stroma and are involved in tumor vascularization and growth.Aim and methodsIn this work, mastocyte-like rat basophilic leukemia (RBL) cells were used to investigate whether carboxyl-modified 30 nm polystyrene (PS) nanoparticles (NPs) and naked mesoporous silica (MPS) 10 nm NPs are able to label the secretory inflammatory granules, and possibly induce exocytosis of these granules. Uptake, cellular retention and localization of fluorescent NPs were analyzed by cytofluorometry and microscope imaging.ResultsOUR FINDINGS WERE THAT: (1) secretory granules of mastocytes are accessible by NPs via endocytosis; (2) PS and MPS silica NPs label two distinct subpopulations of inflammatory granules in RBL mastocytes; and (3) PS NPs induce calcium-dependent exocytosis of inflammatory granules.ConclusionThese findings highlight the value of NPs for live imaging of inflammatory processes, and also have important implications for the clinical use of PS-based NPs, due to their potential to trigger the unwanted activation of mastocytes.

Biocompatibility, endocytosis, and intracellular trafficking of mesoporous silica and polystyrene nanoparticles in ovarian cancer cells: effects of size and surface charge groups.

Background and methodsNanoparticles engineered to carry both a chemotherapeutic drug and a sensitive imaging probe are valid tools for early detection of cancer cells and to monitor the cytotoxic effects of anticancer treatment simultaneously. Here we report on the effect of size (10-30 nm versus 50 nm), type of material (mesoporous silica versus polystyrene), and surface charge functionalization (none, amine groups, or carboxyl groups) on biocompatibility, uptake, compartmentalization, and intracellular retention of fluorescently labeled nanoparticles in cultured human ovarian cancer cells. We also investigated the involvement of caveolae in the mechanism of uptake of nanoparticles.ResultsWe found that mesoporous silica nanoparticles entered via caveolae-mediated endocytosis and reached the lysosomes; however, while the 50 nm nanoparticles permanently resided within these organelles, the 10 nm nanoparticles soon relocated in the cytoplasm. Naked 10 nm mesoporous silica nanoparticles showed the highest and 50 nm carboxyl-modified mesoporous silica nanoparticles the lowest uptake rates, respectively. Polystyrene nanoparticle uptake also occurred via a caveolae-independent pathway, and was negatively affected by serum. The 30 nm carboxyl-modified polystyrene nanoparticles did not localize in lysosomes and were not toxic, while the 50 nm amine-modified polystyrene nanoparticles accumulated within lysosomes and eventually caused cell death. Ovarian cancer cells expressing caveolin-1 were more likely to endocytose these nanoparticles.ConclusionThese data highlight the importance of considering both the physicochemical characteristics (ie, material, size and surface charge on chemical groups) of nanoparticles and the biochemical composition of the cell membrane when choosing the most suitable nanotheranostics for targeting cancer cells.

cDNA-AFLP analysis of differential gene expression in human hepatoma cells (HepG2) upon dengue virus infection.

In infectious diseases, the disease pathogenesis is the outcome of the interaction between the genome of the host and the genome of the pathogen. Despite the wide distribution of dengue infections in the world, and the large number of annual infections, few studies have investigated how the dengue genome alters the global transcriptional profile of the host cell. To investigate alterations in the liver cell transcriptome in response to dengue virus infection, liver cells (HepG2) were infected with dengue serotype 2 at MOI 5 and at 3 days post-infection RNA extracted and analyzed by cDNA-AFLP in parallel with mock-infected cells. From 73 primer combinations over 5,000 transcription-derived fragments (TDFs) were observed, of which approximately 10% were regulated differentially in response to infection. Sixty-five TDFs were subsequently cloned and sequenced and 27 unique gene transcripts identified. Semi-quantitative reverse transcription (RT)-PCR was used to validate the expression of 12 of these genes and 10 transcripts (CK2, KIAA509, HSP70, AK3L, NIPA, PHIP, RiboS4, JEM-1, MALT1, and HSI12044) were confirmed to be differentially regulated, with four transcripts (HSP70, NIPA, RiboS4, and JEM-1) showing a greater than twofold regulation. These results suggest that the expression of a large number of genes is altered in response to dengue virus infection of liver cells, and that cDNA-AFLP is a useful tool for obtaining information on both characterized and as yet uncharacterized transcripts whose expression is altered during the infection process.

A simplified PCR methodology for semiquantitatively analyzing dengue viruses.

The standard methodology for titrating dengue viruses, the plaque assay, is slow, time consuming and relatively expensive. Other methods require machinery that may not be routinely accessible to all researchers, particularly those in developing nations. We therefore sought to develop a rapid, simplified semiquantitative polymerase chain reaction (PCR) methodology based on the use of a template mimic. In particular, it was desired that the mimic should be applicable for use a DNA template to avoid the requirement for producing an in vitro RNA transcript. A 511 base pair fragment of the capsid-PrM junction of dengue serotype 4 was cloned into pGEM-T Easy vector and subjected to splicing overlap extension-PCR to generate a 160 base pair deletion. The deleted plasmid mimic competed competitively against the parent plasmid as well as the first strand cDNA of all four dengue viruses. The primers used are specific for the dengue virus, and no product was seen with first strand cDNA from a closely related flavivirus, Japanese encephalitis virus. Under the conditions used, accurate quantitation of the dengue viruses in the range of 10(3) to 10(6) pfu can be achieved in a single day, as opposed to the 7 days required for conventional plaque assay.

Antibiotic use in Kenyan public hospitals: Prevalence, appropriateness and link to guideline availability.

ObjectiveTo examine prescription patterns and explore to what extent guidelines are available and how they might influence treatment appropriateness among hospitalised patients in Kenyan hospitals.MethodsData on antimicrobial usage were collected from hospitalised patients across 14 Kenyan public hospitals. For each prescription, appropriateness of treatment was defined using available local and international treatment guidelines and through consensus with local medical specialists. Association between appropriate treatment, guideline availability and other possible explanatory factors was explored using univariate and multiple regression analysis.ResultsThere were 1675 (46.7%) of the 3590 hospitalised patients on antimicrobials with 3145(94%) of the 3363 antimicrobial prescriptions being antibiotics. Two patients (0.1%), had treatment based on available antibiotic susceptibility tests. Appropriate treatment was assessed in 1502 patients who had a single diagnosis. Of these, 805 (53.6%) received appropriate treatment. Physical availability of treatment guidelines increased the odds of receiving appropriate treatment Odds Ratio 6.44[95% CI 4.81-8.64].ConclusionAppropriate antibiotic prescription remains a challenge in Kenyan public hospitals. This may be improved by the availability of context-specific, up-to-date, and readily accessible treatment guidelines across all the departments, and by providing better diagnostic support.

Improving facility-based care: eliciting tacit knowledge to advance intervention design

Attention has turned to improving the quality and safety of healthcare within health facilities to reduce avoidable mortality and morbidity. Interventions should be tested in health system environments that can support their adoption if successful. To be successful, interventions often require changes in multiple behaviours making their consequences unpredictable. Here, we focus on this challenge of change at the mesolevel or microlevel. Drawing on multiple insights from theory and our own empirical work, we highlight the importance of engaging managers, senior and frontline staff and potentially patients to explore foundational questions examining three core resource areas. These span the physical or material resources available, workforce capacity and capability and team and organisational relationships. Deficits in all these resource areas may need to be addressed to achieve success. We also argue that as inertia is built into the complex social and human systems characterising healthcare facilities that thought on how to mobilise five motive forces is needed to help achieve change. These span goal alignment and ownership, leadership for change, empowering key actors, promoting responsive planning and procurement and learning for transformation. Our aim is to bridge the theory—practice gap and offer an entry point for practical discussions to elicit the critical tacit and contextual knowledge needed to design interventions. We hope that this may improve the chances that interventions are successful and so contribute to better facility-based care and outcomes while contributing to the development of learning health systems.

Extending the use of the World Health Organisations’ water sanitation and hygiene assessment tool for surveys in hospitals – from WASH-FIT to WASH-FAST

The CINAMR (Clinical Information Network-Antimicrobial Resistance) Project: A pilot microbial surveillance using hospitals linked to regional laboratories in Kenya: Study Protocol

Background: Antimicrobial resistance (AMR) is a global threat and is thought to be acute in low-and middle-income country (LMIC) settings, including in Kenya, but there is limited unbiased surveillance that can provide reliable estimates of its burden. Current efforts to build capacity for microbiology testing in Kenya are unlikely to result in systematic routine microbiological testing in the near term. Therefore, there is little prospect for microbiological support to inform clinical diagnoses nor for indicating the burden of AMR and for guiding empirical choice of antibiotics. Objective: We aim to build on an existing collaboration, the Clinical Information Network (CIN), to pilot microbiological surveillance using a ‘hub-and-spoke’ model where selected hospitals are linked to high quality microbiology research laboratories. Methods: Children admitted to paediatric wards of 12 participating hospitals will have a sample taken for blood culture at admission before antibiotics are started. Indication for blood culture will be a clinician’s prescription of antibiotics. Samples will then be transported daily to the research laboratories for culture and antibiotic susceptibility testing and results relayed back to clinicians for patient management. The surveillance will take place for 6 months in each hospital. Separately, we shall conduct semi-structured interviews with frontline health workers to explore the feasibility and utility of this approach. We will also seek to understand how the availability of microbiology results might inform antibiotic stewardship, and as an interim step to the development of better national or regional laboratories linked to routine surveillance. Conclusions: If feasible, this approach is less costly and periodic ‘hub-and-spoke’ surveillance can be used to track AMR trends and to broadly guide empirical antibiotic guidance meaning it is likely to be more sustainable than establishing functional microbiological facilities in each hospital in a LMIC setting.

Identifying gaps in global evidence for nurse staffing and patient care outcomes research in low/middle-income countries: an umbrella review

ObjectiveTo identify nurse staffing and patient care outcome literature in published systematic reviews and map out the evidence gaps for low/middle-income countries (LMICs).MethodsWe included quantitative systematic reviews on nurse staffing levels and patient care outcomes in regular ward settings published in English. We excluded qualitative reviews or reviews on nursing skill mix. We searched the Cochrane Register of Systematic Reviews, the Joanna Briggs Institute Database of Systematic Reviews and Implementation Reports, Medline, Embase and Cumulative Index to Nursing and Allied Health Literature from inception until July 2021. We used the A Measurement Tool to Assess Systematic Reviews -2 (AMSTAR-2) criteria for risk of bias assessment and conducted a narrative synthesis.ResultsFrom 843 papers, we included 14 in our final synthesis. There were overlaps in primary studies summarised across reviews, but overall, the reviews summarised 136 unique primary articles. Only 4 out of 14 reviews had data on LMIC publications and only 9 (6.6%) of 136 unique primary articles were conducted in LMICs. Only 8 of 23 patient care outcomes were reported from LMICs. Less research was conducted in contexts with staffing levels that are typical of many LMIC contexts.DiscussionOur umbrella review identified very limited data for nurse staffing and patient care outcomes in LMICs. We also identified data from high-income countries might not be good proxies for LMICs as staffing levels where this research was conducted had comparatively better staffing levels than the few LMIC studies. This highlights a critical need for the conduct of nurse staffing research in LMIC contexts.LimitationsWe included data on systematic reviews that scored low on our risk of bias assessment because we sought to provide a broad description of the research area. We only considered systematic reviews published in English and did not include any qualitative reviews in our synthesis.PROSPERO registration numberCRD42021286908.

Pulse oximetry values of neonates admitted for care and receiving routine oxygen therapy at a resource‐limited hospital in Kenya

AimThere are 2.7 million neonatal deaths annually, 75% of which occur in sub‐Saharan Africa and South Asia. Effective treatment of hypoxaemia through tailored oxygen therapy could reduce neonatal mortality and prevent oxygen toxicity.MethodsWe undertook a two‐part prospective study of neonates admitted to a neonatal unit in Nairobi, Kenya, between January and December 2015. We determined the prevalence of hypoxaemia and explored associations of clinical risk factors and signs of respiratory distress with hypoxaemia and mortality. After staff training on oxygen saturation (SpO2) target ranges, we enrolled a consecutive sample of neonates admitted for oxygen and measured SpO2 at 0, 6, 12, 18 and 24 h post‐admission. We estimated the proportion of neonates outside the target range (≥34 weeks: ≥92%; <34 weeks: 89–93%) with 95% confidence intervals (CIs).ResultsA total of 477 neonates were enrolled. Prevalence of hypoxaemia was 29.2%. Retractions (odds ratio (OR) 2.83, 95% CI 1.47–5.47), nasal flaring (OR 2.68, 95% CI 1.51–4.75), and grunting (OR 2.47, 95% CI 1.27–4.80) were significantly associated with hypoxaemia. Nasal flaring (OR 2.85, 95% CI 1.25–6.54), and hypoxaemia (OR 3.06, 95% CI 1.54–6.07) were significantly associated with mortality; 64% of neonates receiving oxygen were out of range at ≥2 time points and 43% at ≥3 time points.ConclusionThere is a high prevalence of hypoxaemia at admission and a strong association between hypoxaemia and mortality in this Kenyan neonatal unit. Many neonates had out of range SpO2 values while receiving oxygen. Further research is needed to test strategies aimed at improving the accuracy of oxygen provision in low‐resource settings.

Does audit and feedback improve the adoption of recommended practices? Evidence from a longitudinal observational study of an emerging clinical network in Kenya

Background Audit and feedback (A&F) is widely used in healthcare but there are few examples of how to deploy it at scale in low-income countries. Establishing the Clinical Information Network (CIN) in Kenya provided an opportunity to examine the effect of A&F delivered as part of a wider set of activities to promote paediatric guideline adherence. Methods We analysed data collected from medical records on discharge for children aged 2–59 months from 14 Kenyan hospitals in the CIN. Hospitals joined CIN in phases and for each we analysed their initial 25 months of participation that occurred between December 2013 and March 2016. A total of 34 indicators of adherence to recommendations were selected for evaluation each classified by form of feedback (passive, active and none) and type of task (simple or difficult documentation and those requiring cognitive work). Performance change was explored graphically and using generalised linear mixed models with attention given to the effects of time and use of a standardised paediatric admission record (PAR) form. Results Data from 60 214 admissions were eligible for analysis. Adherence to recommendations across hospitals significantly improved for 24/34 indicators. Improvements were not obviously related to nature of feedback, may be related to task type and were related to PAR use in the case of documentation indicators. There was, however, marked variability in adoption and adherence to recommended practices across sites and indicators. Hospital-specific factors, low baseline performance and specific contextual changes appeared to influence the magnitude of change in specific cases. Conclusion Our observational data suggest some change in multiple indicators of adherence to recommendations (aspects of quality of care) can be achieved in low-resource hospitals using A&F and simple job aides in the context of a wider network approach.

A systematic review of neonatal treatment intensity scores and their potential application in low-resource setting hospitals for predicting mortality, morbidity and estimating resource use

Infection prevention and control during the COVID-19 pandemic: challenges and opportunities for Kenyan public hospitals.

Background: Infection prevention and control, and water sanitation and hygiene have an essential role in ensuring the quality of care and patient outcomes in hospitals. Using a modification of the World Health Organization's water sanitation and hygiene facility improvement tool, we undertook assessments in 14 public hospitals in Kenya in 2018. The hospitals received written feedback on areas where they could make improvements. Following the first confirmed cases of COVID-19 in Kenya, we were drawn to ask whether the results of our pre-pandemic survey had led to action, and whether or not the threat of COVID-19 had focused more attention on infection prevention and control and water sanitation and hygiene. Methods: Using a semi-structured interview guide, we carried out phone interviews with key hospital leaders in 11 of the 14 hospitals. The data were transcribed and coded into thematic areas. We draw on these interviews to describe the status and awareness of infection prevention and control. Results: The infection prevention and control committee members are training health workers on infection prevention and control procedures and proper use of personal protective equipment and in addition, providing technical support to hospital managers. While some hospitals have also accessed additional funds to improve infection prevention and control, they tended to be small amounts of money. Long-standing challenges with supplies of infection prevention and control materials and low staff morale persist. Crucially, the reduced supply of personal protective equipment has led to fear and anxiety among health care personnel. Conclusions: As funds are mobilised to support care for COVID-19, we ask that funds prioritise infection prevention and control measures. This would have a profoundly positive effect on within hospital virus transmission, patient and staff safety but also lasting benefits beyond the COVID-19 pandemic.