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Background: Moringa oleifera Lam. (Moringaceae) leaves are commonly used for diabetes in Mali. This pilot clinical study aimed to evaluate its effect on post-prandial blood glucose in preparation for a larger trial. Methods: Diabetic patients and non-diabetic healthy volunteers (35 each) were asked to fast for 13 hours on three occasions. Blood glucose was measured before and after eating 100g of white bread (at 30, 60, 90, 120, 150 and 180 minutes). On their second and third study visits, they were given 1g and 2g respectively, of M. oleifera leaf powder, 30 minutes after eating the bread. The mean paired reduction in blood glucose at each time interval and the incremental area under the curve were calculated. Results: Ingestion of Moringa powder had no effect on blood glucose in non-diabetic participants, but in diabetic patients, it lowered blood glucose at 90 minutes. There was a trend towards lower incremental area under the curve when diabetic patients took 2g of Moringa. No side-effects were reported by any participant. Conclusions: Moringa oleifera leaf powder reduced post-prandial glycaemia in diabetic patients. A larger study is needed to define the optimal dose and to assess whether this translates into longer-term benefits.

The discovery of compounds and proteins from plants has greatly contributed to modern medicine. Vernonia amygdalina Del. (Compositae) is used by humans and primates for a variety of conditions including parasitic infection. This paper describes the serendipitous discovery that V. amygdalina extract was able to bind to, and functionally inhibit, active TGFβ1. The binding agent was isolated and identified as chlorophyll a-b binding protein AB96. Given that active TGFβ1 contributes to the pathology of many infectious diseases, inhibiting these processes may explain some of the benefits associated with the ingestion of this species. This is the first plant-derived cytokine-neutralizing protein to be described and paves the way for further such discoveries.

BackgroundDoctors can be victim-survivors of domestic abuse (DA), but how this impacts their work and wellbeing, and whether they face barriers to seeking help is not well understood.AimTo understand single doctor mothers’ lived experience of DA, barriers to seeking help, and impact on their work.Design and settingIndividual qualitative interviews with female doctors in the UK who had left an abusive relationship. Interviews were conducted between August 2019 and March 2020.MethodParticipants were invited via a closed online forum for female doctors who are single parents. In total, 114 females expressed interest. In-depth semi-structured telephone interviews were audiorecorded and transcribed. Transcripts were uploaded to NVivo and analysed using inductive thematic analysis.ResultsA total of 21 participants were interviewed. The internalised stigma of DA affected participants’ sense of identity and belonging as a doctor, causing social and professional isolation. Many participants felt that the acute stress of DA had an impact on their work, yet often felt unable to take time off. Barriers to seeking help included lack of confidentiality, especially where the abusive partner was also a doctor (sometimes accusing the victim-survivor of mental illness or threatening to report them to the General Medical Council). Participants found peer support helpful, as well as consulting health professionals who were empathic towards them. After they had left the abusive relationship victim-survivors felt better equipped to support patients going through DA.ConclusionDomestic abuse impacts on the work and wellbeing of female doctors, who face unique barriers to help seeking and reporting DA. An online peer support group can help to break the sense of isolation, but specialised confidential support services are also required to help doctors experiencing DA.

Background Chinese herbal medicine is widely used in combination with usual care for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in China. Chinese patent medicine Shufeng Jiedu (SFJD) capsules is widely used for respiratory infectious diseases. This review aims to evaluate effectiveness and safety of SFJD for AECOPD. Methods A systematic review of randomised controlled trials (RCTs) in patients with AECOPD, who received SFJD as a single intervention or as add-on treatment to usual care. PubMed, the Cochrane Library, EMBASE, Scopus, Web of Science and four Chinese databases were searched from inception to April 2019. Two authors screened trials, extracted data, and assessed risk of bias, independently. Meta-analysis was performed using RevMan 5.3 software. We performed subgroup analyses and sensitivity analyses according to the predefined protocol. Quality of evidence was assessed using GRADE. Results Thirteen RCTs (1036 patients, with 936 inpatients) were included, all compared SFJD in combination with usual care (including antibiotics) to usual care alone. The mean age of participants ranged from 52 to 67 years, with approximately 60% male. Due to lack of blinding and other factors, all trials were of high risk of bias. SFJD was associated with a significant reduction in treatment failure, from 20.1 to 8.3% (11 trials; 815 patients; relative risk 0.43, 95% confidence interval [CI] 0.30 to 0.62), and duration of hospital stay (2 trials; 79 patients; mean difference − 4.32 days, 95% CI − 5.89 to − 2.75 days). No significant difference in adverse events was found between SFJD and control groups. Conclusion Low certainty evidence suggests SFJD may bring additional benefit in reducing treatment failure, shorten hospital stay, and improving symptoms. Further large, high quality RCTs are needed to confirm its benefit and safety. Trial registration PROSPERO CRD42019133682.

BackgroundConsultations for self-limiting infections in children are increasing. It has been proposed that digital technology could be used to enable parents’ decision making in terms of self-care and treatment seeking.AimTo evaluate the evidence that digital interventions facilitate parents deciding whether to self-care or seek treatment for acute illnesses in children.Design and settingSystematic review of studies undertaken worldwide.MethodSearches of MEDLINE and EMBASE were made to identify studies (of any design) published between database inception and January 2019 that assessed digital interventions for parents of children (from any healthcare setting) with acute illnesses. The primary outcome of interest was whether the use of digital interventions reduced the use of urgent care services.ResultsThree studies were included in the review. They assessed two apps and one website: Children’s On-Call — a US advice-only app; Should I See a Doctor? — a Dutch self-triage app for any acute illness; and Strategy for Off-Site Rapid Triage (SORT) for Kids — a US self-triage website for influenza-like illness. None of the studies involved parents during intervention development and it was shown that many parents did not find the two apps easy to use. The sensitivity of self-triage interventions was 84% for Should I See a Doctor? compared with nurse triage, and 93.3% for SORT for Kids compared with the need for emergency-department intervention; however, both had lower specificity (74% and 13%, respectively). None of the interventions demonstrated reduced use of urgent-care services.ConclusionThere is little evidence to support the use of digital interventions to help parent and/or carers looking after children with acute illness. Future research should involve parents during intervention development, and adequately powered trials are needed to assess the impact of such interventions on health services and the identification of children who are seriously ill.

BackgroundThe current GP workforce is insufficient to manage rising demand in patient care within out-of-hours (OOH) primary care services. To meet this challenge, non-medical practitioners (NMPs) are employed to fulfil tasks traditionally carried out by GPs. It is important to learn from experiences of task-shifting in this setting to inform optimal delivery of care.AimTo synthesise qualitative evidence of experiences of task-shifting in the OOH primary care setting.Design & settingSystematic review of qualitative studies and thematic synthesis.MethodElectronic searches were conducted across CINAHL (Cumulative Index of Nursing and Allied Health Literature), PsychINFO, Cochrane, MEDLINE, Embase, and OpenGrey for qualitative studies of urgent or OOH primary care services, utilising task-shifting or role delegation. Included articles were quality appraised and key findings collated through thematic synthesis.ResultsA total of 2497 studies were screened, of which six met the inclusion criteria. These included interviews with 15 advanced nurse practitioners (ANPs), three physician assistants (PAs), two paramedics, and a focus group of 22 GPs, and focus groups with 33 nurses. Key findings highlight the importance of clearly defining and communicating the scope of practice of NMPs, and of building their confidence by appropriate training, support, and mentoring.ConclusionWhile NMPs may have the potential to make a substantial contribution to OOH primary care services, there has been very little research on experiences of task-shifting. Evidence to date highlights the need for further training specific to OOH services. Mentorship and support to manage the sometimes challenging cases presenting to OOH could enable more effective OOH services and better patient care.

Background: Acute lower respiratory tract infection is a common acute infection managed in primary care. The current dominant management strategy in the UK is antibiotics, despite widespread publicity regarding antimicrobial resistance and evidence that the small benefits of antibiotics do not outweigh the harms. There is a need to address the rising problem of antibiotic resistance by providing credible alternative strategies, which reduce symptom burden. There is sufficient evidence to recommend the use of Pelargonium sidoides root extract in order to warrant undertaking an independent clinical trial.We propose a feasibility study to demonstrate our ability to recruit and retain patients and conduct a placebo-controlled trial of Pelargonium sidoides extract EPs®7630 in lower respiratory tract infection where pneumonia is not suspected. Both the tablet and liquid formulations will be included.Methods: The HATRIC trial is a double-blind randomised placebo-controlled feasibility study aiming to determine the potential to conduct a fully powered trial of Pelargonium sidoides root extract as an alternative to the inappropriate use of antibiotics for acute bronchitis in UK primary care.Primary care sites will be equally randomised to one of two formulation groups (tablet or liquid preparation). Additionally, within each site, patients will be evenly randomised to active or placebo treatment. Antibiotic consumption will be monitored during the trial, but the use of a delayed prescription strategy is encouraged. The target sample size for this study is 160 patients overall or 40 per arm, recruited from approximately 20 primary care sites. The analysis will be descriptive focusing on estimation with no formal comparison of groups taking place.Discussion: If this trial demonstrates the feasibility of recruitment and delivery, we will seek funding for a fully powered placebo-controlled trial of Pelargonium sidoides root extract for the treatment of lower respiratory tract infections in primary care.Trial registration: HATRIC was registered on the ISRCTN registry (ISRCTN17672884) on 16 August 2018.

BackgroundSore throat resulting from pharyngotonsillitis is one of the commonest reasons for primary care consultation and inappropriate antibiotic prescription and finding effective alternative treatments is important.ObjectivesTo review the evidence for using the probiotic Streptococcus salivarius K12 (SsK12) for the prevention or treatment of pharyngotonsillitis.Data SourcesPubMed, Embase, CINAHL and Cochrane Library.Study eligibility criteriaRandomized controlled trials (RCTs).ParticipantsAdults or children.InterventionsSsK12 as active treatment or prophylaxis, against pharyngotonsillitis.MethodsLiterature search.ResultsFour articles were identified (1846 participants). All were deemed to be of poor quality using the Cochrane risk-of-bias assessment. Two trials studied SsK12 prophylaxis for streptococcal pharyngitis (children without history of recurrence). One compared daily administration of SsK12 to no treatment over 6 months (n = 222, age 33–45 months), reporting significantly lower incidence in the SsK12 group (16.2% vs. 48.6%, p n = 1314, 5–14 years) found no significant difference (7.8% vs. 8.8%, p 0.34) with SsK12 (administered on school days). Another trial found daily SsK12 to significantly protect children (n = 250, 6–7 years) against chronic adenoiditis exacerbation over 3 months compared to no treatment (71.7% vs. 100%, p SsK12 for acute pharyngotonsillitis (concurrently with penicillin) showed no significant benefit. In all trials, SsK12 was safe and well tolerated.ConclusionsSsK12 appears safe and well tolerated. However, further RCTs are required to establish its role as a prophylactic therapy, particularly among patients experiencing frequent exacerbations of pharyngitis. In the acute setting, SsK12 is unlikely to be effective if given concurrently with antibiotics; however, further RCTs should establish its role as an alternative to antibiotics in nonsevere cases or when prescribed after antibiotic therapy for the prevention of disease recurrence and/or secondary infection.

Background Digital interventions have potential to efficiently support improved hygiene practices to reduce transmission of COVID-19. Objective To evaluate the evidence for digital interventions to improve hygiene practices within the community. Methods We reviewed articles published between 01 January 2000 and 26 May 2019 that presented a controlled trial of a digital intervention to improve hygiene behaviours in the community. We searched MEDLINE, Embase, PsycINFO, Cochrane Controlled Register of Trials (CENTRAL), China National Knowledge Infrastructure and grey literature. Trials in hospitals were excluded, as were trials aiming at prevention of sexually transmitted infections; only target diseases with transmission mechanisms similar to COVID-19 (e.g. respiratory and gastrointestinal infections) were included. Trials had to evaluate a uniquely digital component of an intervention. Study designs were limited to randomised controlled trials, controlled before-and-after trials, and interrupted time series analyses. Outcomes could be either incidence of infections or change in hygiene behaviours. The Risk of Bias 2 tool was used to assess study quality. Results We found seven studies that met the inclusion criteria. Six studies reported successfully improving self-reported hygiene behaviour or health outcomes, but only one of these six trials, Germ Defence, confirmed improvements using objective measures (reduced consultations and antibiotic prescriptions). Settings included kindergartens, workplaces, and service station restrooms. Modes of delivery were diverse: WeChat, website, text messages, audio messages to mobiles, electronic billboards, and electronic personal care records. Four interventions targeted parents of young children with educational materials. Two targeted the general population; these also used behaviour change techniques or theory to inform the intervention. Only one trial had low risk of bias, Germ Defence; the most common concerns were lack of information about the randomisation, possible bias in reporting of behavioural outcomes, and lack of an analysis plan and possible selective reporting of results. Conclusion There was only one trial that was judged to be at low risk of bias, Germ Defence, which reduced incidence and severity of illness, as confirmed by objective measures. Further evaluation is required to determine the effectiveness of the other interventions reviewed. Trial registration PROSPERO CRD42020189919.

Funder: UKAID, Background: Although health workers have been trained to provide post-partum family planning (PPFP), uptake remains low in Uganda. An important reason is that women want the agreement of their partner, who is often absent at the time of delivery. In order to address this, we aimed to understand the views of couples and explore barriers and facilitators to implementation of antenatal couples’ counselling on PPFP in Uganda. Methods: We conducted individual interviews with a purposive sample of 12 postpartum and 3 antenatal couples; and 34 focus groups with a total of 323 participants (68 adolescent women, 83 women aged 20–49, 79 men, 93 health workers) in four contrasting communities (urban and rural) in South-West and Central Uganda. These were recorded, transcribed, translated, and analysed thematically. Results: Although most participants felt that it is important for partners to discuss family planning, half of the couples were unaware of each other’s views on contraception. Most had similar views on motivation to use family planning but not on preferred contraceptive methods. Most liked the idea of antenatal couples’ counselling on PPFP. The main barrier was the reluctance of men to attend antenatal clinics (ANC) in health facilities. Respondents felt that Village Health Teams (VHTs) could provide initial counselling on PPFP in couples’ homes (with telephone support from health workers, if needed) and encourage men to attend ANC. Suggested facilitators for men to attend ANC included health workers being more welcoming, holding ANC clinics at weekends and “outreach” clinics (in rural villages far from health facilities). Conclusion: Antenatal couples’ counselling has the potential to facilitate agreement PPFP, but some men are reluctant to attend antenatal clinics. Counselling at home by VHTs as well as simple changes to the organisation of antenatal clinics, could make it possible to deliver antenatal couples’ counselling on PPFP.

ObjectivesThis study aimed to better understand reasons why children in South Africa die at home, including caregivers’ care-seeking experiences, decision-making, choice of treatment provider and barriers to accessing care during a child’s final illness.DesignThis qualitative study included semi-structured in-depth interviews and focus group discussions with caregivers of children who died below the age of 5 years. Data were thematically analysed, and key findings compared with the Pathways to Survival Framework—a model frequently used in the study of child mortality. An adapted model was developed.SettingTwo rural health and demographic surveillance system (HDSS) sites in South Africa—the Agincourt HDSS and the Africa Health Research Institute.ParticipantsThirty-eight caregivers of deceased children (29 participated in in-depth interviews and 9 were participants in two focus group discussions). Caregivers were purposively sampled to ensure maximum variation across place of death, child age at death, household socioeconomic status, maternal migration status and maternal HIV status.FindingsAlthough caregivers faced barriers in providing care to children (including insufficient knowledge and poor transport), almost all did seek care from the formal health system. Negative experiences in health facilities did not deter care-seeking, but most respondents still received poor quality care and were not given adequate safety-netting advice. Traditional healers were only consulted as a last resort when other approaches had failed.ConclusionBarriers to accessing healthcare disrupt the workings of previously accepted care-seeking models. The adapted model presented in this paper more realistically reflects care-seeking experiences and decision-making during severe childhood illness in rural South Africa and helps explain both the persistence of home deaths despite seeking healthcare, and the impact of a child’s death on care-seeking in future childhood illness. This model can be used as the basis for developing interventions to reduce under-5 mortality.

Background: A rigorous approach is needed to inform rapid adaptation and optimisation of behavioral interventions in evolving public health contexts, such as the Covid-19 pandemic. This helps ensure that interventions are relevant, persuasive, and feasible while remaining evidence-based. This paper provides a set of iterative methods to rapidly adapt and optimize an intervention during implementation. These methods are demonstrated through the example of optimizing an effective online handwashing intervention called Germ Defense.Methods: Three revised versions of the intervention were rapidly optimized and launched within short timeframes of 1–2 months. Optimisations were informed by: regular stakeholder engagement; emerging scientific evidence, and changing government guidance; rapid qualitative research (telephone think-aloud interviews and open-text surveys), and analyses of usage data. All feedback was rapidly collated, using the Table of Changes method from the Person-Based Approach to prioritize potential optimisations in terms of their likely impact on behavior change. Written feedback from stakeholders on each new iteration of the intervention also informed specific optimisations of the content.Results: Working closely with clinical stakeholders ensured that the intervention was clinically accurate, for example, confirming that information about transmission and exposure was consistent with evidence. Patient and Public Involvement (PPI) contributors identified important clarifications to intervention content, such as whether Covid-19 can be transmitted via air as well as surfaces, and ensured that information about difficult behaviors (such as self-isolation) was supportive and feasible. Iterative updates were made in line with emerging evidence, including changes to the information about face-coverings and opening windows. Qualitative research provided insights into barriers to engaging with the intervention and target behaviors, with open-text surveys providing a useful supplement to detailed think-aloud interviews. Usage data helped identify common points of disengagement, which guided decisions about optimisations. The Table of Changes was modified to facilitate rapid collation and prioritization of multiple sources of feedback to inform optimisations. Engagement with PPI informed the optimisation process.Conclusions: Rapid optimisation methods of this kind may in future be used to help improve the speed and efficiency of adaptation, optimization, and implementation of interventions, in line with calls for more rapid, pragmatic health research methods.

Background To control the COVID-19 pandemic, people should adopt protective behaviors at home (self-isolation, social distancing, putting shopping and packages aside, wearing face coverings, cleaning and disinfecting, and handwashing). There is currently limited support to help individuals conduct these behaviors. Objective This study aims to report current household infection control behaviors in the United Kingdom and examine how they might be improved. Methods This was a pragmatic cross-sectional observational study of anonymous participant data from Germ Defence between May 6-24, 2020. Germ Defence is an open-access fully automated website providing behavioral advice for infection control within households. A total of 28,285 users sought advice from four website pathways based on household status (advice to protect themselves generally, to protect others if the user was showing symptoms, to protect themselves if household members were showing symptoms, and to protect a household member who is at high risk). Users reported current infection control behaviors within the home and intentions to change these behaviors. Results Current behaviors varied across all infection control measures but were between sometimes (face covering: mean 1.61, SD 1.19; social distancing: mean 2.40, SD 1.22; isolating: mean 2.78, SD 1.29; putting packages and shopping aside: mean 2.75, SD 1.55) and quite often (cleaning and disinfecting: mean 3.17, SD 1.18), except for handwashing (very often: mean 4.00, SD 1.03). Behaviors were similar regardless of the website pathway used. After using Germ Defence, users recorded intentions to improve infection control behavior across all website pathways and for all behaviors (overall average infection control score mean difference 0.30, 95% CI 0.29-0.31). Conclusions Self-reported infection control behaviors other than handwashing are lower than is optimal for infection prevention, although handwashing is much higher. Advice using behavior change techniques in Germ Defence led to intentions to improve these behaviors. Promoting Germ Defence within national and local public health and primary care guidance could reduce COVID-19 transmission.

BackgroundPelargonium sidoides DC (Geraniaceae) root extract, EPs®7630 or “Kaloba®”, is a widely used herbal remedy for respiratory infections, with some evidence of effectiveness for acute bronchitis. However, it is not yet widely recommended by medical professionals in the UK. There is a need to undertake appropriately designed randomised trials to test its use as an alternative to antibiotics. The aim was to assess the feasibility of conducting a double-blind randomised controlled trial of Pelargonium sidoides root extract for treatment of acute bronchitis in UK primary care, investigating intervention compliance, patient preference for dosage form and acceptability of patient diaries.Study designFeasibility double-blind randomised placebo-controlled clinical trial.MethodsWe aimed to recruit 160 patients with cough (≤ 21 days) caused by acute bronchitis from UK general practices. Practices were cluster-randomised to liquid or tablet preparations and patients were individually randomised to Kaloba® or placebo. We followed participants up for 28 days through self-reported patient diaries with telephone support and reviewed medical records at one month. Outcomes included recruitment, withdrawal, safety, reconsultation and symptom diary completion rates. We also assessed treatment adherence, antibiotic prescribing and consumption, mean symptom severity (at days 2–4 after randomisation) and time to symptom resolution. We interviewed 29 patients and 11 health professionals to identify barriers and facilitators to running such a randomised trial.ResultsOf 543 patients screened, 261 were eligible, of whom 134 (51%) were recruited and 103 (77%) returned a completed diary. Overall, 41% (41/100) of patients took antibiotics (Kaloba® liquid group: 48% [15/31]; placebo liquid group: 23% [6/26]; Kaloba® tablet group: 48% [9/21]; placebo tablet group: 50% [11/22]). Most patients adhered to the study medication (median 19 out of 21 doses taken in week 1, IQR 18–21 - all arms combined). There were no serious adverse events relating to treatment. Most patients interviewed found study recruitment to be straightforward, but some found the diary too complex.ConclusionsIt was feasible and acceptable to recruit patients from UK primary care to a double-blind placebo-controlled trial of herbal medicine (Kaloba®) for the treatment of acute bronchitis, with good retention and low data attrition.Trial registrationHATRIC was registered on the ISRCTN registry (ISRCTN17672884) on 16 August 2018, retrospectively registered. The record can be found at http://www.isrctn.com/ISRCTN17672884.

BackgroundAlthough rarely indicated, antibiotics are commonly used for acute diarrhoea in China. We conducted a randomised, double blind exploratory clinical trial of loperamide, berberine and turmeric for treatment of acute diarrhoea.MethodsAdults with acute uncomplicated diarrhoea aged 18 to 70 were randomised to 4 groups: (A) loperamide; (B) loperamide and berberine; (C) loperamide and turmeric; (D) loperamide, berberine and turmeric. All participants were given rescue ciprofloxacin for use after 48 h if symptoms worsened or were unimproved. Primary endpoints were feasibility and ciprofloxacin use during the 2-week follow-up period. Semi-structured interviews were conducted following recruitment and were analysed thematically. Recruiting doctors, delivery pharmacists and research assistants were blinded to treatment allocation.ResultsOnly 21.5% (278/1295) of patients screened were deemed eligible, and 49% (136/278) of these consented and were entered into the final analysis. Most participants had mild symptoms, because most patients with moderate or severe symptoms wanted to be given antibiotics. Follow-up was good (94% at 2 weeks). Only three participants used rescue antibiotics compared to 67% of acute diarrhoea patients in the hospital during the recruitment period. The median symptom duration was 14 h in group B (interquartile range (IQR) 10-22), 16 h in group D (IQR 10-22), 18 h in group A (IQR 10-33) and 20 h in group C (IQR 16-54). Re-consultation rates were low. There were no serious treatment-related adverse events. Most interviewed participants said that although they had believed antibiotics to be effective for diarrhoea, they were surprised by their quick recovery without antibiotics in this trial.ConclusionAlthough recruitment was challenging because of widespread expectations for antibiotics, patients with mild diarrhoea accepted trying an alternative. The three nutraceuticals therapy require further evaluation in a fully powered, randomised controlled trial among a broader sample.Trial registrationChiCTR-IPR-17014107

Background The World Health Organization characterized the Coronavirus disease 2019 (COVID-19) as a pandemic on March 11th. Many clinical trials on COVID-19 have been registered, and we aim to review the study characteristics and provide guidance for future trials to avoid duplicated effort. Methods Studies on COVID-19 registered before March 3rd, 2020 on eight registry platforms worldwide were searched and the data of design, participants, interventions, and outcomes were extracted and analyzed. Results Three hundred and ninety-three studies were identified and 380 (96.7%) were from mainland China, while 3 in Japan, 3 in France, 2 in the US, and 3 were international collaborative studies. Two hundred and sixty-six (67.7%) aimed at therapeutic effect, others were for prevention, diagnosis, prognosis, etc. Two hundred and two studies (51.4%) were randomized controlled trials. Two third of therapeutic studies tested Western medicines including antiviral drugs (17.7%), stem cell and cord blood therapy (10.2%), chloroquine and derivatives (8.3%), 16 (6.0%) on Chinese medicines, and 73 (27.4%) on integrated therapy of Western and Chinese medicines. Thirty-one studies among 266 therapeutic studies (11.7%) used mortality as primary outcome, while the most designed secondary outcomes were symptoms and signs (47.0%). Half of the studies (45.5%) had not started recruiting till March 3rd. Conclusion Inappropriate outcome setting, delayed recruitment and insufficient numbers of new cases in China implied many studies may fail to complete. Strategies and protocols of the studies with robust and rapid data sharing are warranted for emergency public health events, helping the timely evidence-based decision-making.

Background The United Nations' Sustainable Development Goals (SDGs) include reducing the global maternal mortality rate to less than 70 per 100,000 live births and ending preventable deaths of newborns and children under five years of age, in every country, by 2030. Maternal and perinatal death audit and review is widely recommended as an intervention to reduce maternal and perinatal mortality, and to improve quality of care, and could be key to attaining the SDGs. However, there is uncertainty over the most cost‐effective way of auditing and reviewing deaths: community‐based audit (verbal and social autopsy), facility‐based audits (significant event analysis (SEA)) or a combination of both (confidential enquiry). Objectives To assess the impact and cost‐effectiveness of different types of death audits and reviews in reducing maternal, perinatal and child mortality. Search methods We searched the following from inception to 16 January 2019: CENTRAL, Ovid MEDLINE, Embase OvidSP, and five other databases. We identified ongoing studies using ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform, and searched reference lists of included articles. Selection criteria Cluster‐randomised trials, cluster non‐randomised trials, controlled before‐and‐after studies and interrupted time series studies of any form of death audit or review that involved reviewing individual cases of maternal, perinatal or child deaths, identifying avoidable factors, and making recommendations. To be included in the review, a study needed to report at least one of the following outcomes: perinatal mortality rate; stillbirth rate; neonatal mortality rate; mortality rate in children under five years of age or maternal mortality rate. Data collection and analysis We used standard Cochrane Effective Practice and Organisation of Care (EPOC) group methodological procedures. Two review authors independently extracted data, assessed risk of bias and assessed the certainty of the evidence using GRADE. We planned to perform a meta‐analysis using a random‐effects model but included studies were not homogeneous enough to make pooling their results meaningful. Main results We included two cluster‐randomised trials. Both introduced death review and audit as part of a multicomponent intervention, and compared this to current care. The QUARITE study (QUAlity of care, RIsk management, and TEchnology) concerned maternal death reviews in hospitals in West Africa, which had very high maternal and perinatal mortality rates. In contrast, the OPERA trial studied perinatal morbidity/mortality conferences (MMCs) in maternity units in France, which already had very low perinatal mortality rates at baseline. The OPERA intervention in France started with an outreach visit to brief obstetricians, midwives and anaesthetists on the national guidelines on morbidity/mortality case management, and was followed by a series of perinatal MMCs. Half of the intervention units were randomised to receive additional support from a clinical psychologist during these meetings. The OPERA intervention may make little or no difference to overall perinatal mortality (low certainty evidence), however we are uncertain about the effect of the intervention on perinatal mortality related to suboptimal care (very low certainty evidence).The intervention probably reduces perinatal morbidity related to suboptimal care (unadjusted odds ratio (OR) 0.62, 95% confidence interval (CI) 0.40 to 0.95; 165,353 births; moderate‐certainty evidence). The effect of the intervention on stillbirth rate, neonatal mortality, mortality rate in children under five years of age, maternal mortality or adverse effects was not reported. The QUARITE intervention in West Africa focused on training leaders of hospital obstetric teams using the ALARM (Advances in Labour And Risk Management) course, which included one day of training about conducting maternal death reviews. The leaders returned to their hospitals, established a multidisciplinary committee and started auditing maternal deaths, with the support of external facilitators. The intervention probably reduces inpatient maternal deaths (adjusted OR 0.85, 95% CI 0.73 to 0.98; 191,167 deliveries; moderate certainty evidence) and probably also reduces inpatient neonatal mortality within 24 hours following birth (adjusted OR 0.74, 95% CI 0.61 to 0.90; moderate certainty evidence). However, QUARITE probably makes little or no difference to the inpatient stillbirth rate (moderate certainty evidence) and may make little or no difference to the inpatient neonatal mortality rate after 24 hours, although the 95% confidence interval includes both benefit and harm (low certainty evidence). The QUARITE intervention probably increases the percent of women receiving high quality of care (OR 1.87, 95% CI 1.35 ‐ 2.57, moderate‐certainty evidence). The effect of the intervention on perinatal mortality, mortality rate in children under five years of age, or adverse effects was not reported. We did not find any studies that evaluated child death audit and review or community‐based death reviews or costs. Authors' conclusions A complex intervention including maternal death audit and review, as well as development of local leadership and training, probably reduces inpatient maternal mortality in low‐income country district hospitals, and probably slightly improves quality of care. Perinatal death audit and review, as part of a complex intervention with training, probably improves quality of care, as measured by perinatal morbidity related to suboptimal care, in a high‐income setting where mortality was already very low. The WHO recommends that maternal and perinatal death reviews should be conducted in all hospitals globally. However, conducting death reviews in isolation may not be sufficient to achieve the reductions in mortality observed in the QUARITE trial. This review suggests that maternal death audit and review may need to be implemented as part of an intervention package which also includes elements such as training of a leading doctor and midwife in each hospital, annual recertification, and quarterly outreach visits by external facilitators to provide supervision and mentorship. The same may also apply to perinatal and child death reviews. More operational research is needed on the most cost‐effective ways of implementing maternal, perinatal and paediatric death reviews in low‐ and middle‐income countries., Plain language summary Reviewing deaths to prevent mothers and children from dying in the future What was the aim of this review? This Cochrane Review aimed to assess if 'death audits and reviews' (exploring why people have died and what could have been done to prevent these deaths) can prevent mothers and children from dying. The review authors collected and analysed all relevant studies to answer this question and found two studies. Key messages In a study from West African hospitals, where death rates among women and babies were high, reviewing deaths probably led to fewer deaths among pregnant women, new mothers and newborn babies. In French hospitals, where death rates among babies were low, it may have made little or no difference to death rates among newborn babies . What did the review study? Every year, millions of babies and children die. Many women also die while they are pregnant or giving birth, or shortly afterwards. More than half of these deaths happen in sub‐Saharan Africa. In many settings, health facilities or communities carry out 'death audits and reviews'. Here, people explore why a person died, what could have been done to avoid this death and what could be done better in the future. Death audits and reviews could potentially help improve the quality of care and prevent new deaths among mothers and children. But they could also cost money, be based on wrong information and take health workers away from other important tasks. If they are done badly, they could also make health workers feel blamed and humiliated, which could lead to poorer care. We need to find out if audits and reviews work and which approach works best. The review authors searched for studies where people from health facilities or the community carried out audits or reviews of deaths of pregnant women, women who had recently given birth, newborn babies or children under five years of age. The studies had to compare places or times where death audits and reviews were used to places or times where they were not. What were the main results of the review? The review authors found two relevant studies. Both studies assessed death audits at health facilities. The first study took place in West African hospitals with high death rates among women and babies. In this study, doctors and midwives were given extra training in pregnancy and childbirth care. This included one day of training in how to carry out death audits of women who had died during pregnancy or childbirth. They then returned to their hospitals and held audits at monthly meetings, with support from an expert from a different hospital. These hospitals were compared to hospitals without the training and audit meetings. For mothers and babies who were in hospital, this approach: ‐ probably led to fewer pregnant women and new mothers dying, and probably led to slightly better care for mothers; ‐ probably led to fewer babies dying during the first 24 hours. However, it may have made no difference to the number of babies who died after their first 24 hours, although the range where the actual effect may be (the "margin of error") includes both an increase and a decrease in the number of babies who died. ‐ probably made no difference to the number of stillbirths. The second study took place in French hospitals that already had very few deaths among newborns. In this study, doctors and midwives were given information about pregnancy and childbirth guidelines. They then held audit meetings in their hospitals where they discussed stillbirths and newborn babies who had become sick or died. These hospitals were compared to hospitals without the information and the meetings. This approach: ‐ may have made little or no difference to the number of babies who died during their first week ‐ probably reduced the number of babies who were sick because they received poor quality care. We don't know what the effect was on stillbirths or on the number of mothers or older babies and children who died because the study did not measure this. How up‐to‐date was this review? The review authors searched for studies that had been published up to 16 January 2019.

Background Ill health associated with household air pollution (HAP) is increasingly recognized as a public health problem in sub-Saharan Africa. To date, attempts to reduce HAP have focussed on smoke from cooking fires and have ignored traditional cultural practices which generate purposely produced smoke (PPS). This study aimed to investigate PPS prevalence, reasons for use and safety perceptions. Methods The study was conducted in Wollo, Ethiopia, and used a mixed methods approach of quantitative surveys (analysed descriptively) and qualitative interviews with householders and healthcare workers (analysed thematically). Results PPS use was reported by 99% of survey respondents and it was considered a fundamental part of life. Although reasons for use included housekeeping, culture/religion and well-being, coffee ceremony was most commonly cited (44% of respondents). Both householders and healthcare workers appeared to assume PPS is safe, except for people with certain underlying conditions. Healthcare workers felt the lack of evidence of harm from PPS meant there was no justification for intervention. Conclusion This study, the first in-depth study of PPS, has shown its use to be widespread, with many perceived benefits and thus a very important part of local culture in this sample Ethiopian community. Consequently, any public health interventions aimed at reducing HAP in this setting need to consider PPS.

Antenatal vaccination is usually delivered in primary care, yet a recent survey highlighted that many UK GPs are not confident discussing vaccination with pregnant women, and would value concise guidelines.1 Antenatal vaccination boosts maternal antibody levels and therefore the amount of antibody transferred to the fetus. ### Pertussis (whooping cough) #### Recommendation: between 16–32 weeks of gestation The UK antenatal pertussis vaccination programme was introduced following the 2012 pertussis outbreak, when >9000 individuals were infected and 14 infants died.2 Although numbers of cases have since reduced, rates of pertussis remain significantly higher than prior to 2012. A similar trend has been observed globally, and at least 14 countries have implemented similar recommendations.2 Pertussis disproportionately affects young infants, who have the highest rates of disease, and are at highest risk of severe disease and death. Most cases occur in early childhood before completion of primary immunisation, and therefore antenatal vaccination provides effective protection during this ‘window-period’ of …

Background: Ethnopharmacological research aims at gathering information on local and traditional uses of plants and other natural substances. However, the approaches used and the methods employed vary, and while such a variability is desirable in terms of scientific diversity, research must adhere to well defined quality standards and reproducible methods. Objectives: With ConSEFS (the Consensus Statement on Ethnopharmacological Field Studies) we want to define best-practice in developing, conducting and reporting field studies focusing on local and traditional uses of medicinal and food plants, including studies using a historical approach. Methods: After first developing an initial draft the core group invited community-wide feedback from researchers both through a web-based consultation and a series of workshops at conferences during 2017. Outcomes:The consultation resulted in a large number of responses. Feedback was received via a weblink on the Journal of Ethnopharmacology´s website (ca. 100 responses), other oral and written responses (ca. 50) and discussions with stakeholders at four conferences. The main outcome is a checklist, covering best practice for designing, implementing and recording ethnopharmacological field studies and historical studies. Conclusions: Prior to starting ethnopharmacological field research, it is essential that the authors are fully aware of the best practice in the field. For the first time in the field of ethnopharmacology a community-wide document defines guidelines for best practice on how to conduct and report such studies. It will need to be updated and further developed. While the feedback has been based on responses by many experienced researchers, there is a need to test it in practice by using it both in implementing and reporting field studies (or historical studies), and peer-review. Fil: Heinrich, Michael. University of London; Reino Unido Fil: Lardos, Andreas. No especifíca; Fil: Leonti, Marco. Università Degli Studi Di Cagliari.; Italia Fil: Weckerle, Caroline. Universitat Zurich; Suiza Fil: Willcox, Merlin. University of Southampton; Reino Unido Fil: Applequist, Wendy. Missouri Botanical Garden; Estados Unidos Fil: Ladio, Ana Haydee. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina Fil: Lin Long, Chun. Minzu University Of China; China Fil: Mukherjee, Pulok. Jadavpur University; India Fil: Stafford, Gary. Stellenbosch University; Sudáfrica

Background: Half of all under-5 deaths occur in sub-Saharan Africa. Reducing child mortality requires understanding of the modifiable factors that contribute to death. Social autopsies collect information about place of death, care-seeking and care-provision, but this has not been pooled to learn wider lessons. We therefore undertook a systematic review to collect, evaluate, map, and pool all the available evidence for sub-Saharan Africa. Methods: We searched PubMed, Embase, Global Health, the Cochrane Library and grey literature for studies relating to under-5 deaths in sub-Saharan Africa with information on place of death and/or care-seeking during a child’s final illness. We assessed study quality with a modified Axis tool. We pooled proportions using random effects meta-analysis for place of death and for each stage of the Pathways to Survival framework. Pre-specified subgroup analysis included age group, national income and user-fee policy. We explored heterogeneity with meta-regression. Our protocol was published prospectively (CRD42018111484). Results: We included 34 studies from 17 countries. Approximately half of the children died at home, irrespective of age. More children died at home in settings with user-fees (69.1%, 95% confidence interval (CI) = 56.2-80.6, I2 = 98.4%) compared to settings without user-fees (43.8%, 95% CI = 34.3-53.5, I2 = 96.7%). Signs of illness were present in over 95% of children but care-seeking differed by age. 40.1% of neonates (95% CI = 20.7-61.3, I2 = 98.0%) died without receiving any care, compared to 6.4% of older children (95% CI = 4.2%-9.0%, I2 = 90.6%). Care-seeking outside the home was less common in neonatal deaths (50.5%, 95% CI = 35.6-65.3, I2 = 98.3%) compared to infants and young children (82.4%, 95% CI = 79.4%-85.2%, I2 = 87.5%). In both age groups, most children were taken for formal care. Healthcare facilities discharged 69.6% of infants and young children who arrived alive (95% CI = 59.6-78.7, I2 = 95.5%), of whom only 34.9% were referred for further care (95% CI = 15.1-57.9, I2 = 98.7%). Conclusions: Despite similar distributions in place of death for neonates and infants and young children, care-seeking behaviour differed by age groups. Poor illness recognition is implicated in neonatal deaths, but death despite care-seeking implies inadequate quality care and referral for older children. Understanding such care-seeking patterns enables targeted interventions to reduce under-5 mortality across the region.

ObjectivesTo explore doctors’ knowledge, willingness, concerns and the countermeasures to the most stringent antimicrobial stewardship regulations of China which implemented in August 2012.DesignCross-sectional survey. A pretested 32-point structured questionnaire was distributed to doctors by sending a web link via the mobile phone application WeChat through snowball sampling methods and email groups of medical academic societies.SettingChina.ParticipantsDoctors.Primary and secondary outcome measuresThe questionnaire inquired about the doctors’ experiences, knowledge, willingness, concerns and the countermeasures to the stewardship policies.ResultsTotal of persons in the groups was 19 791, among them 1194 submitted the answers, within them, 807 were doctors. Doctors had a mean age of 39.0 years. The majority (78.9% in 2012, 89.1% in 2016) reported that they were willing or very willing to accept the regulations. Almost all respondents (93.2%) felt the stewardship regulations had the potential to adversely affect the prognosis of patients who would have been prescribed antimicrobials before they were implemented, and >65% (65.7% in 2012, 66.9% in 2016) of doctors were often or always concerned about the prognosis of these patients. In 2012, 32% of doctors prescribed restricted antimicrobials or suggested patient self-medication with restricted antimicrobials to address doctors’ concerns, and this number decreased to 22.6% in 2016. Although compulsory antimicrobial stewardship training was frequent, less than half of respondents (46.8%) responded correctly to all three knowledge questions.ConclusionAntimicrobial stewardship regulations had some positive effect on rational antimicrobial use. Willingness and practice of doctors towards the regulations improved from 2012 to 2016. Knowledge about rational antimicrobial use was still lacking. Doctors found ways of accessing restricted antibiotics to address their concerns about the prognosis of patients, which undermined the implementation of the stewardship regulations.

To determine the proportion of under-5 deaths that occurred at home in rural South Africa, whether care was sought prior to death, and determinants of home deaths amongst those who sought care.Verbal autopsy data were used for all under-5 deaths, 2000-2015, in two health and demographic surveillance system sites. Trends in place of death and care-seeking were assessed. Associations between sociodemographic factors and home death despite seeking care were assessed by multivariate logistic regressions.There were 3760 under-5 deaths; 1954 (53%) at home and 1510 (41%) in health facilities. Eighty-four per cent of children who died at home accessed healthcare during their final illness. Amongst neonates for whom care was sought, those who were 8-27 days old were more likely to die at home than those who were 0-7 days old (OR = 5.56, 95%CI 2.69-11.55, P 0.001). Factors associated with home death of infants and young children despite seeking care included low maternal education (OR = 1.71, 95%CI 1.31-2.24, P 0.001), larger household size (OR = 1.56, 95%CI 1.17-2.06, P = 0.002), traditional medicine use (OR = 2.33, 95%CI 1.75-3.12, P 0.001) and Mozambican descent (OR = 1.47, 95%CI 1.06-2.03, P = 0.020). The proportion of HIV-related deaths that occurred at home fell from 60% in 2008-2011 to 39% in 2012-2015 ( χMore than half of under-5 deaths in rural South Africa occurred at home although healthcare was sought for most children, highlighting that home deaths are not simply a function of poor care-seeking. Interventions should target high-risk sociodemographic groups.Déterminer la proportion de décès d'enfants de moins de 5 ans survenus à domicile dans les zones rurales d'Afrique du Sud, si des soins ont été recherchés avant le décès et les déterminants des décès à domicile chez ceux qui ont recherché des soins. MÉTHODES: Les données d'autopsie verbale ont été utilisées pour tous les décès d'enfants de moins de 5 ans entre 2000 et 2015, dans deux sites du système de surveillance démographique et de santé. Les tendances en matière de lieu de décès et de recherche de soins ont été évaluées. Les associations entre les facteurs sociodémographiques et le décès à domicile malgré les soins recherchés ont été évaluées par des régressions logistiques multivariées. RÉSULTATS: Il y a eu 3.760 décès de moins de 5 ans; 1.954 (53%) à domicile et 1.510 (41%) dans les établissements de santé. 84% des enfants décédés à domicile ont eu accès à des soins de santé au cours de leur dernière maladie. Parmi les nouveau-nés pour lesquels des soins ont été recherchés, ceux âgés de 8 à 27 jours étaient plus susceptibles de mourir à domicile que ceux âgés de 0 à 7 jours (OR = 5,56; IC95% 2,69-11,55; p0,001). Les facteurs associés au décès des nourrissons et des jeunes enfants à domicile malgré la recherche de soins comprenaient un niveau d’éducation maternelle faible (OR = 1,71; IC95%: 1,31-2,24; p0,001), une taille du ménage plus grande (OR = 1,56; IC95%: 1,17-2,06; p = 0,002), l'utilisation de la médecine traditionnelle (OR = 2,33; IC95%: 1,75-3,12; p0,001) et l'origine mozambicaine (OR = 1,47; IC95%: 1,06-2,03; p = 0,020). La proportion de décès liés au VIH survenus à domicile est passée de 60% en 2008-2011 à 39% en 2012-2015 (ChiPlus de la moitié des décès des moins de 5 ans dans les zones rurales d'Afrique du Sud sont survenus à domicile bien que pour la plupart des enfants une recherche de soins de santé a été effectuée, soulignant que les décès à domicile ne sont pas simplement liés à un mauvais recours aux soins. Les interventions devraient cibler les groupes sociodémographiques à haut risque.

Health workers have received training on delivering postpartum long‐acting reversible contraceptives (LARCs) through several projects in Uganda, yet uptake still remains poor. To understand the reasons, and to gather suggestions for improving uptake, we conducted individual semi‐structured interviews with a total of 80 postpartum parents, antenatal parents, health workers, and village health teams in rural south‐west Uganda. Interviews were recorded, transcribed, translated, and analyzed using qualitative thematic analysis. Specific barriers to uptake of immediate postpartum contraception for women included: the need to discuss this option with their husband, the belief that time is needed to recover before insertion of a LARC, and fear that the baby might not survive. Furthermore, social consequences of side‐effects are more serious in low‐income settings. Suggestions for improving uptake of postpartum contraception included health education by “expert users,” couples counseling during antenatal care, and improved management of side‐effects.

Objectives The aim was to investigate if offering symptomatic therapy (Uva-ursi or ibuprofen) alongside a delayed prescription would relieve symptoms and reduce the consumption of antibiotics for adult women presenting with acute uncomplicated urinary tract infection (UTI). Methods A 2 × 2 factorial placebo controlled randomized trial in primary care. The participants were 382 women aged 18–70 years with symptoms of dysuria, urgency, or frequency of urination and suspected by a clinician to have a lower UTI. The interventions were Uva-ursi extract and/or ibuprofen advice. All women were provided with a delayed or ‘back-up' prescription for antibiotics. Missing data were imputed using multiple imputation methods (ISRCTN registry: ISRCTN43397016). Results An ITT analysis of mean score for frequency symptoms assessed on Days 2–4 found no evidence of a difference between Uva-ursi vs. placebo –0.06 (95% CI –0.33 to 0.21; p 0.661), nor ibuprofen vs. no ibuprofen advice –0.01 (95% CI –0.27 to 0.26; p 0.951). There was no evidence of a reduction in antibiotic consumption with Uva-ursi (39.9% vs. placebo 47.4%; logistic regression odds ratio (OR) 0.59 (95% CI 0.22–1.58; p 0.293) but there was a significant reduction for ibuprofen advice (34.9% vs. no advice 51.0%; OR 0.27 (95% CI 0.10 to 0.72; p 0.009). There were no safety concerns and no episodes of upper tract infection were recorded. Conclusions We found no evidence of an effect of either intervention on the severity of frequency symptoms. There is evidence that advice to take ibuprofen will reduce antibiotic consumption without increasing complications. For every seven women given this advice, one less will use antibiotics.

Background: Half of under-5 deaths in South Africa occur at home, however the reasons remain poorly described and data on the care pathways during fatal childhood illness is limited. This study aimed to better describe care-seeking behavior in fatal childhood illness and to assess barriers to healthcare and modifiable factors that contribute to under-5 deaths in rural South Africa. Methods: We conducted a social autopsy study on all under-5 deaths in two rural South African health and demographic surveillance system sites. Descriptive analyses based on the Pathways to Survival Framework were used to characterise how caregivers move through the stages of seeking and providing care for children during their final illness and to identify modifiable factors that contributed to death. Findings: Of 53 deaths, 40% occurred outside health facilities. Rates of antenatal and perinatal preventative care-seeking were high: over 70% of mothers had tested for HIV, 93% received professional assistance during delivery and 79% of children were reportedly immunised appropriately for age. Of the 48 deaths tracked through the stages of the Pathways to Survival Framework, 10% died suddenly without any care, 23% received home care of whom 80% had signs of severe or possibly severe illness, and 85% sought or attempted to seek formal care outside the home. Although half of all children left the first facility alive, only 27% were referred for further care.Conclusions: Modifiable factors for preventing deaths during a child’s final illness occur both inside and outside the home. The most important modifiable factors occurring inside the home relate to caregivers’ recognition of illness and appreciation of urgency in response to the severity of the child’s symptoms and signs. Outside the home, modifiable factors relate to inadequate referral and follow-up by health professionals. Further research should focus on identifying and overcoming barriers to referral.

Aim. The aim of this narrative review was to explore the potential contributions of CAM to reduce antibiotic use. Methods. We searched PubMed, Embase, and Cochrane Database of Systematic Reviews with a specific, limited set of search terms and collected input from a group of expert CAM researchers to answer the question: What is known about the contribution of CAM health and health promotion concepts, infection prevention, and infection treatment strategies to reduce antibiotic use? Results. The worldview-related CAM health concepts enable health promotion oriented infection prevention and treatment aimed at strengthening or supporting the self-regulating ability of the human organism to cope with diseases. There is some evidence that the CAM concepts of health (promotion) are in agreement with current conceptualization of health and that doctors who practice both CAM and conventional medicine prescribe less antibiotics, although selection bias of the presented studies cannot be ruled out. There is some evidence that prevention and some treatment strategies are effective and safe. Many CAM treatment strategies are promising but overall lack high quality evidence. Conclusions. CAM prevention and treatment strategies may contribute to reducing antibiotic use, but more rigorous research is necessary to provide high quality evidence of (cost-)effectiveness.

ObjectiveIdentify predictors of clinical deterioration in a virtual hospital (VH) setting for COVID-19.DesignReal-world prospective observational study.SettingVH remote assessment service in West Hertfordshire NHS Trust, UK.ParticipantsPatients with suspected COVID-19 illness enrolled directly from the community (postaccident and emergency (A&E) or medical intake assessment) or postinpatient admission.Main outcome measureDeath or (re-)admission to inpatient hospital care during VH follow-up and for 2 weeks post-VH discharge.Results900 patients with a clinical diagnosis of COVID-19 (455 referred from A&E or medical intake and 445 postinpatient) were included in the analysis. 76 (8.4%) of these experienced clinical deterioration (15 deaths in admitted patients, 3 deaths in patients not admitted and 58 additional inpatient admissions). Predictors of clinical deterioration were increase in age (OR 1.04 (95% CI 1.02 to 1.06) per year of age), history of cancer (OR 2.87 (95% CI 1.41 to 5.82)), history of mental health problems (OR 1.76 (95% CI 1.02 to 3.04)), severely impaired renal function (OR for eGFR ConclusionsThese predictors may help direct intensity of monitoring for patients with suspected or confirmed COVID-19 who are being remotely monitored by primary or secondary care services. Further research is needed to confirm our findings and identify the reasons for increased risk of clinical deterioration associated with cancer and mental health problems.

Introduction Traditional Chinese medicine (TCM) has been fully committed to the treatment of coronavirus disease 2019 (COVID-19) in China. An increasing number of clinical trials have been registered to evaluate the effects of TCM for COVID-19. The aim of this study was to review the existing TCM clinical trial registrations and identify potentially promising and available TCM therapies, in order to provide a reference for the global management of COVID-19. Methods All clinical trials on TCM for COVID-19 registered in registry platforms worldwide were searched. The data of registration temporal trend, design, objective, interventions, and relevant information were reviewed and summarized. Results 161 TCM trials were identified from three registries (January 26 to May 14 2020,). Of these, 94 (58.4%) were randomized controlled trials and 114 trials (70.8%) assessed therapeutic effects; while the remainder focused on prevention, rehabilitation, and the epidemiology of TCM syndromes. Eight trials (5.0%) had completed their recruitment. TCM interventions with potential for further evaluation in terms of prevention were moxibustion, Huoxiang Zhengqi pill and Jinye Baidu granules. For treatment of COVID-19, Qingfei Paidu decoction, Huashi Baidu decoction, Lianhua Qingwen capsules, Toujie Quwen granules and Xiyanping injection, and Xuebijing injection were to be tested for their therapeutic effects and symptoms relief. For rehabilitation, Tai Chi and Liuzijue were to be tested for improving patients’ lung function. Conclusion Some potentially promising TCM interventions have been identified and deserve further evaluation to establish their evidence base, particularly on populations outside of China.

Introduction: The traditional antimalarial tea Artemisia annua, indicated for centuries in China to treat fevers, is again arousing interest for the treatment of malaria due to improvements attained in the plant composition by a few Institutions throughout the world, including the State University of Campinas (UNICAMP), Brazil, increasing its principal component by more than 100 times as from standard varieties, giving 1% in artemisinin and an expressive biomass yield such as 2 tons of dried leaves/hectare. Clinical trials carried out with this material in African countries have proven its therapeutic potential for a new generation of Artemisia tea in the treatment of falciparum malaria. In addition to artemisinin, recent studies have identified and quantified other compounds present in the crude extract and characterized their contributions to the anti-malarial efficacy, including their action against chloroquine-resistant strains. The majority of the clinical trials carried out with Artemisia tea in African countries have shown that the control of the parasitaemia is efficient in the initial treatment period, but few trials have followed the patients up to the 28th day. This first clinical trial carried out in Brazil with the A. annua infusion, after toxicological trials that defined the safety of this form of medication. Methods: The therapeutic efficacy of the tea was measured in patients with falciparum malaria over 28 days, comparing it with the current first-line treatment namely artemether-lumefantrine (Coartem?). The trial was carried out in controlled groups according to official protocol approved by the National Ethics in Research Committee (CONEP: 77/ 2011) and a rigorous control of the 17 patients with non-serious cases of falciparum malaria, recruited in the following three municipalities of the State of Para, Brazil: Tucurui, Goianesia do Para and Anajas. The tea group received the infusion prepared in the proportion of 1.25 g of dry leaves of the variety CPQBA with 1% artemisinin for 250 mL of just boiled water, taken every 6 hours for 7 days, giving a total of approximately 175 mg of artemisinin, whilst the artemether-lumefantrine (Coartem?) group received a total of 525 mg of artemisinin equivalent to artemether. Results: The parasitaemia by the tea treatment became negative in the first days, even though it was administered with a dose that was one third of the recommended dose of artemisinin. However, as in the case artemisinin or artesunate monotherapies, 57.1% of the patients treated with the A. annua tea presented type I resistance, with a return of the parasitaemia around the 14th or 21st day. The other patients in the tea group showed type II/III resistance without manifestation of any serious signs or symptoms. In these cases, according to the protocol, the patients were redirected for treatment with artemether-lumefantrin (Coartem?) with subsequent negativity of the parisitaemia. Discussion: The fact that the efficacy of the tea with 1/3 of the dose of artemisinin was similar to that of the full dose of this medication infers that other compounds present in the crude extract, probably flavonoids, had contributed to the negativity of the parasitaemia at the start of the treatment. Considering that the positive control group, where the compound derived from artemisinin (artemether) was associated with another antimalarial agent (lumefantrine), presented excellent efficacy throughout the entire control of the cure, future trials with the A. annua tea should use the same strategy of association with another antimalarial agent, preferably from A. annua itself, in order to extend its therapeutic action during the whole control period. The Artemisia annua tea in the form standardized and used in this research, should not substitute the most efficient treatment, but could be considered as an emergency therapeutic resource in the first hours of symptoms as a function of its availability, anti-inflammatory action and lack of side effects. Other regimes and standardizations deserve investigation, mainly those with a high content of arteannuin B, as occurs in the initial cultivation phase.

Background Antibiotics are widely prescribed for acute bronchitis in the UK. Herbal medicine could be used instead to provide symptom relief. Aim To explore the views of patients and health professionals on using herbal medicine for acute bronchitis instead of antibiotics. Design and setting This was a nested qualitative study, conducted alongside a feasibility randomised clinical trial which ran from July 2018 to May 2019 in 20 GP practices in Wessex, UK. Method We conducted telephone semi-structured interviews with patients and with health professionals. The interview data were transcribed and analysed thematically. Results Overall, 40 interviews were conducted with 29 patients, six GPs and five nurses. While some patients believed antibiotics are more effective, most were aware of resistance and were keen to try an alternative, including herbal medicine. Several patients believed herbals would be “less intrusive” than antibiotics, whereas a few disliked the taste or experienced side-effects after taking a herbal. Professionals were concerned about potential interactions with conventional medicines. Many patients trusted herbals because of their long history of use, while some did not understand them. Availability of herbals without a prescription enables patients to use them for self-care, but their cost was a barrier for some. Many patients were willing to take a herbal if advised by their GP. Most GPs were happy to recommend a herbal, if endorsed by evidence-based guidelines. Conclusion Many patients and health professionals would consider using herbal medicine for acute bronchitis, if based on trustworthy advice and evidence-based guidelines respectively.

Introduction Most Complementary & Alternative Medicine (CAM) interventions have not been tested in clinical trials and systematic reviews (SRs). It is therefore important to collect knowledge from experienced practitioners to identify (lower level) evidence to support their use and to prioritize interventions for future research. This study aimed to document the CAM treatments for cough and sore throat as part of uncomplicated, acute respiratory tract infections (RTI), most frequently recommended by experienced integrative medical practitioners; and to assess whether these approaches have been tested in clinical trials and SRs. Methods Data on treatment approaches were collected by means of (1) a SR on prescription rates of CAM treatments for RTIs in CAM practice by searching Pubmed and CINAHL databases; and (2) a survey among integrative medical doctors and TCM practitioners in five European countries. Results The SR identified 336 articles. After screening five studies were included (Anthroposophic Medicine (AM): two and homeopathy (HOM): three). The survey resulted in 262 responses (including 99 AM and 95 HOM experts). Of 19 products that were described in both the SR and the survey, two (22%) AM (Hustenelixier, Echinacea) and three (30%) homeopathic products (Belladonna, Hepar sulphuris, Mercurius solubilis) had been studied in a clinical trial and one AM treatment (Echinacea) in a SR for this indication. Conclusions CAM treatments for RTI related cough and sore throat were identified (medicinal products, syrup, external applications, tea and acupuncture). These treatments have hardly been studied in clinical trials (26%) and SRs (5%) and require further evaluation.

Background: unnecessary antibiotic prescribing and use are most common for uncomplicated acute respiratory infections (ARIs). Some Complementary and Alternative Medicine (CAM) treatments have evidence of effectiveness for symptom relief and could be used instead of antibiotics. Aim: to understand views of the general public and health professionals regarding use of CAM for uncomplicated ARIs.Design and Setting: systematic review and thematic synthesis of qualitative studies.Method: we systematically searched MEDLINE, EMBASE, AMED, COREHOM, CINAHL, Dissertation and theses global and Web of Science Core Collection. We included studies which reported qualitative data on the use of CAM for uncomplicated ARIs where participants were either patients or parents of patients, health professionals or the general public. Analysis followed thematic synthesis. Results: twenty-two studies were included from four high-income and ten low-and-middle income countries; almost all focussed on non-White populations. Nineteen concerned parents’ treatment of ARIs in their children. In all settings, treatment decisions were influenced by beliefs about the illness (cause, severity), beliefs about treatments (efficacy, safety), availability of treatments and of trustworthy advice. Participants mostly thought CAM is an acceptable option for treatment of mild ARIs but felt that they need trustworthy advice on which treatments to use and when. Conclusion: treatment decisions depend on beliefs about the illness and treatments, availability of treatments and advice. CAM treatments appear to be acceptable to people from many different settings as a possible alternative to antibiotics for mild ARIs. There is a need for reliable, evidence-based advice on which treatments to use.

Background: in Ethiopia, medicinal plants have been used to treat different diseases, including malaria, for many centuries. People living in rural areas are especially noted for their use of medicinal plants as a major component of their health care. This study aimed to study treatment-seeking and prioritize plants/plant recipes as anti-malarials, in Dembia district, one of the malarious districts in Northwest Ethiopia. Methods: parents of children aged under 5 years who had had a recent episode of fever were interviewed retrospectively about their child’s treatment and self-reported outcome. Treatments and subsequent clinical outcomes were analysed using Fisher’s exact test to elicit whether there were statistically significant correlations between them. Results and discussion: of 447 children with malaria-like symptoms, only 30% took the recommended first-line treatment (ACT) (all of whom were cured), and 47% took chloroquine (85% cured). Ninety-nine (22.2%) had used medicinal plants as their first-choice treatment. Allium sativum (Liliaceae), Justicia schimperiana (Acanthaceae), Buddleja polystachya (Scrophulariaceae) and Phytolacca dodecondra (Phytolaccaceae) were the most frequently used. Justicia schimperiana was the one associated with the best clinical outcomes (69% self-reported cure rate). However, the difference in clinical outcomes between the plants was not statistically significant.Conclusion: in this study, only 30% of children took the recommended first-line treatment. 22% of children with presumed malaria were first treated with herbal medicines. The most commonly used herbal medicine was garlic, but Justicia schimperiana was associated with the highest reported cure rate of the plants. Further research is warranted to investigate its anti-malarial properties.

Ethnopharmacological relevanceChinese herbal medicine (CHM) is a widely used traditional intervention that may have a role to play in addressing the global problem of antimicrobial resistance in conditions such as recurrent urinary tract infections (RUTIs). Aim of the studyTo evaluate the feasibility of administering standardised and individualised formulations of CHM for RUTIs as a Clinical Trial of an Investigational Medicinal Product (CTIMP) within primary care of the UKs National Health Service (NHS).Materials and methodsRegulatory approval was applied for a placebo controlled, double blinded randomised controlled feasibility trial comparing a) standardised CHM vs placebo administered via General practitioners, and b) individualised CHM vs placebo administered by an experienced CHM practitioner. Primary feasibility outcomes included: gaining regulatory approval, recruitment, randomisation, retention, safety and the relevance of outcomes measures. ResultsRegulatory approval for testing CHM as a CTIMP was successfully obtained. Recruitment to the trial was slow and non-NHS self-help networks were required to find participants for the individualised arm (n=31). Retention and data collection in the standardised arm (n= 30) were problematic, but these were acceptable in the individualised arm. The use of a daily symptom diary was not a suitable outcome measure for women with continuous infection. Other measures showed promising preliminary data for the individualised arm on improvement in symptoms, and reduction in antibiotic use during and after the trial.ConclusionCHM can fulfil the demanding requirements of a CTIMP study but it may not be feasible at this point in time to recruit and treat via NHS primary care. However acceptable rates of recruitment and retention via self-help groups and promising preliminary results in the individualised arm suggest it would be worth testing this approach in a full trial.

OBJECTIVE To compare clinical practice guideline recommendations on the use of oral patent Traditional Chinese Medicines (PTCMs) for uncomplicated acute lower respiratory tract infections (ALRTIs) in adults with the existing evidence using results of a systematic review of randomized controlled trials (RCTs). METHODS A systematic review on RCTs and a systematic review of current guidelines on orally taken PTCMs for uncomplicated ALRTIs were performed. PubMed, Cochrane Library, EMBASE and four Chinese databases were searched from inception to September 2016 for RCTs testing orally taken PTCMs for uncomplicated ALRTIs (excluding pneumonia). Two reviewers independently screened each study, extracted study data, and assessed risk of bias. Disagreements were resolved through discussion or by consultation with a third reviewer. Clinical practice guidelines for uncomplicated ALRTIs containing PTCM recommendations were identified and quality appraised. The quality of pooled evidence of the RCTs and the guidelines was assessed with GRADE and AGREE II respectively. The consistency of the evidence base in RCTs and the guideline recommendations were then compared. RESULTS For the systematic review of RCTs, 4810 papers were identified, among which 29 RCTs (5093 patients) were included in the review. PTCMs compared to placebo increased the effective treatment rate of cough (3 trials, 949 patients, risk ratio (RR) 2.50, 1.16 to 5.43; low certainty); improved assessment of global health (3 trials, 948 patients, RR 1.70, 1.44 to 2.01; low certainty); and increased the effective rate of specific symptom relief (1 trial, 478 patients, RR 4.01, 2.76 to 5.81; moderate certainty). 21 trials (3432 patients) compared effects of different PTCMs. For the guideline evaluation, 29 PTCMs were recommended for the use of uncomplicated ALRTIs, of which27 had no supportive evidence from RCTs. CONCLUSION The evidence base of PTCMs for uncomplicated ALRTIs is weak and the guideline recommendations were based on almost no clinical trial evidence. Rigorous clinical research is urgently needed to inform the clinical use of these herbal medicines. Further training in evidence-based medicine methods for Traditional Chinese Medicine guideline developers is essential.

BackgroundInterventions to reduce child deaths in Africa have often underachieved, causing the Millennium Development Goal targets to be missed. We assessed whether a community enquiry into the circumstances of death could improve intervention effectiveness by identifying local avoidable factors and explaining implementation failures.MethodsDeaths of children younger than 5 years were ascertained by community informants in two districts in Mali (762 deaths) and three districts in Uganda (442 deaths) in 2011–15. Deaths were investigated by interviewing parents and health workers. Investigation findings were reviewed by a panel of local health-care workers and community representatives, who formulated recommendations to address avoidable factors and, subsequently, oversaw their implementation.FindingsAt least one avoidable factor was identified in 97% (95% CI 96–98, 737 of 756) of deaths in children younger than 5 years in Mali and 95% (93–97, 389 of 409) in Uganda. Suboptimal newborn care was a factor in 76% (146 of 194) of neonatal deaths in Mali and 64% (134 of 194) in Uganda. The most frequent avoidable factor in postneonatal deaths was inadequate child protection (mainly child neglect) in Uganda (29%, 63 of 215) and malnutrition in Mali (22%, 124 of 562). 84% (618 of 736 in Mali, 328 of 391 in Uganda) of families had consulted a health-care provider for the fatal illness, but the quality of care was often inadequate. Even in official primary care clinics, danger signs were often missed (43% of cases in Mali [135 of 396], 39% in Uganda [30 of 78]), essential treatment was not given (39% in Mali [154 of 396], 35% in Uganda [27 of 78]), and patients who were seriously ill were not referred to a hospital in time (51% in Mali [202 of 396], 45% in Uganda [35 of 78]). Local recommendations focused on quality of care in health-care facilities and on community issues influencing treatment-seeking behaviour.InterpretationLocal investigation and review of circumstances of death of children in sub-Saharan Africa is likely to lead to more effective interventions than simple consideration of the biomedical causes of death. This approach discerned local public health priorities and implementable solutions to address the avoidable factors identified.FundingEuropean Union's 7th Framework Programme for research and technological development.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:\ud \ud To assess the impact and cost-effectiveness of different types of death review in reducing maternal, perinatal and child mortality.

Background Women with acute uncomplicated urine infection are usually treated with antibiotics. One trial has demonstrated that delayed antibiotic treatment offered without symptom relief results in a modest reduction in antibiotic use. There is some evidence that ibuprofen provides symptom relief and reduces antibiotic use. Uva-ursi, a herbal product, has a traditional use for urinary infection symptom relief. We set out to test: in adult women with suspected UTI who accept the delayed prescription strategy: Do NSAIDs or uva-ursi (a herbal product) provide relief from urinary symptoms and reduce antibiotic use. Methods/design Adult women with suspected urinary tract infection presenting to primary care will be randomised using a factorial trial design in which patients will be randomised to one of two interventions as below:Group 1 – Uva-ursi + advice to take ibuprofenGroup 2 – Placebo + advice to take ibuprofenGroup 3 – Uva-ursi + no advice to take ibuprofenGroup 4 – Placebo + no advice to take ibuprofen Patients and physicians will be blinded to the randomised group for the herb. The main outcome is symptom severity at days 2–4 recorded in a validated, self-report diary used in previous studies. Secondary outcomes include antibiotic use and symptom duration. In total the trial will require 328 patients in order to achieve at least 90% power for the primary endpoint and 80% for the secondary endpoint. In accordance with CONSORT guidelines all comparative analyses will be conducted on an intention-to-treat basis using SPSS or similar package. Discussion The outcomes from this trial have the potential to modify the current approach to the management of acute urinary symptoms with less dependence on the use of antibiotics. Trial registration ISRCTN registry, ID: ISRCTN43397016. Registered on 11 February 2015. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2145-7) contains supplementary material, which is available to authorized users.

Background : Migration of health workers from Africa continues to undermine the universal provision of quality health care. South Africa is an epicentre for migration – it exports more health workers to high-income countries than any other African country and imports health workers from its lower-income neighbours to fill the gap. Although an inter-governmental agreement in 2003 reduced the very high numbers migrating from South Africa to the United Kingdom, migration continues to other high-income English-speaking countries and few workers seem to return although the financial incentive to work abroad has lessened. A deeper understanding of reasons for migration from South Africa and post-migration experiences is therefore needed to underpin policy which is developed in order to improve retention within source countries and encourage return. Methods : Semi-structured interviews were conducted with 16 South African doctors and nurses who had migrated to the United Kingdom. Interviews explored factors influencing the decision to migrate and post-migration experiences. Results : Salary, career progression, and poor working conditions were not major push factors for migration. Many health workers reported that they had previously overcome these issues within the South African healthcare system by migrating to the private sector. Overwhelmingly, the major push factors were insecurity, high levels of crime, and racial tension. Although the wish to work and train in what was perceived to be a first-class care system was a pull factor to migrate to the United Kingdom, many were disappointed by the experience. Instead of obtaining new skills, many (particularly nurses) felt they had become ‘de-skilled’. Many also felt that working conditions and opportunities for them in the UK National Health Service (NHS) compared unfavourably with the private sector in South Africa. Conclusions : Migration from South Africa seems unlikely to diminish until the major concerns over security, crime, and racial tensions are resolved. However, good working conditions in the private sector in South Africa provide an occupational incentive to return if security did improve. Potential migrants should be made more aware of the risks of losing skills while working abroad that might prejudice return. In addition, re-skilling initiatives should be encouraged. Keywords : health worker; migration; brain drain; insecurity; de-skilling; South Africa (Published: 28 July 2014) Citation : Glob Health Action 2014, 7 : 24194 - http://dx.doi.org/10.3402/gha.v7.24194

An electronic survey was used to assess the training needs of clinical and public health researchers who have been involved, and/or plan to become involved, in clinical trials of herbal medicines in Africa. Over 90 researchers were contacted through pre-existing networks, of whom 58 (64%) responded, from 35 institutions in 14 African countries. Over half (57%) had already been involved in a clinical trial of an herbal medicine, and gave information about a total of 23 trials that have already been completed. Of these, only five had been published, and only one had resulted in a licensed product. Fifty-four (54) of the researchers were planning to conduct a clinical trial of an herbal medicine in the future, and gave information about 54 possible trials. Respondents outlined the following most commonly encountered difficulties when conducting clinical trials: resource constraints (including lack of funding, equipment, staff, and infrastructure); social acceptance of the clinical trial (including difficulty recruiting enough patients, poor rapport with traditional healers, and willingness of biomedical staff to be involved); herbal medicine supply (including insufficient cultivation, production, and quality control); lack of trained staff; and logistical issues in conducting trials. The topics in which researchers were least confident were Intellectual Property Rights issues, statistical issues, and issues related to Good Clinical Practice guidelines.

Background : Migration of African-trained health workers to countries with higher health care worker densities adds to the severe shortage of health personnel in many African countries. Policy initiatives to reduce migration levels are informed by many studies exploring the reasons for the original decision to migrate. In contrast, there is little evidence to inform policies designed to facilitate health workers returning home or providing other forms of support to the health system of their home country. Objective : This study explores the links that South African-trained health workers who now live and work in the United Kingdom maintain with their country of training and what their future migration plans may be. Design : Semi-structured interviews were conducted with South African trained health workers who are now living in the United Kingdom. Data extracts from the interviews relating to current links with South Africa and future migration plans were studied. Results : All 16 participants reported strong ongoing ties with South Africa, particularly through active communication with family and friends, both face-to-face and remotely. Being South African was a significant part of their personal identity, and many made frequent visits to South Africa. These visits sometimes incorporated professional activities such as medical work, teaching, and charitable or business ventures in South Africa. The presence and location of family and spouse were of principal importance in helping South African-trained health care workers decide whether to return permanently to work in South Africa. Professional aspirations and sense of duty were also important motivators to both returning and to being involved in initiatives remotely from the United Kingdom. Conclusions : The main barrier to returning home was usually the development of stronger family ties in the United Kingdom than in South Africa. The issues that prompted the original migration decision, such as security and education, also remained important reasons to remain in the United Kingdom as long as they were perceived as unresolved at home. However, the strong residual feeling of identity and regular ongoing communication meant that most participants expressed a sense of duty to their home country, even if they were unlikely to return to live there full-time. This is a resource for training and short-term support that could be utilised to the benefit of African health care systems. Keywords : migration; South Africa; United Kingdom; doctors; nurses (Published: 17 March 2015) Citation : Glob Health Action 2015, 8 : 26125 - http://dx.doi.org/10.3402/gha.v8.26125

Background Unnecessary antibiotic use increases the risk for antibiotic resistance. The rates of antibiotic use for upper respiratory infections are high in hospitals in China. Although most guidelines advise against the use of antibiotics for acute diarrhea, little is known about antibiotic use practices for acute diarrhea in China. Methods A retrospective prescription review from a Shanghai hospital outpatient electronic health records system was conducted from 1 January 2016 to 30 December 2016. Records were included for adult patients. The microbial resistance seasonal data in 2016 were extracted. Chi-squared and multivariable logistic regression and adjusted odd ratio (aOR) were used to assess the relationships between demographic characteristics and antibiotic prescribing. Results In total, there were 16,565 prescriptions, 16,060 prescriptions were included in the final analysis after excluding the follow up visits. There were 12,131 (76%) prescriptions with antibiotics prescribed. 5505 (45%) of the antibiotics prescribed were injectable. Of the antibiotics prescribed, levofloxacin was the most frequent (85%), followed by various cephalosporins (14%). Of the cephalosporin prescriptions, third-generation products were the most common (97%). Treatment with oral rehydration salts (ORS) was prescribed 34 (0.2%) times, probiotics were prescribed 3414 (21%) times and smectite was prescribed 2209 (14%) times. Multivariable regression analysis showed that those more likely to receive antibiotics were age 31–50 aOR 1.3 (1.1–1.4), P < 0.001, evaluated in the late evening (11pm to 7am) aOR 2.6 (2.2–2.9) P < 0.001, in the early evening (6pm-11pm) aOR 2.0 (1.8–2.2) P < 0.001, in the summer (June-August) aOR 1.7 (1.5–1.9) P < 0.001. At the same time, the Gram-positive and Gram-negative resistance rates to levofloxacin exceeded 40%, including 50% of E. coliisolates. Conclusion High rates of antibiotic use were observed for acute diarrhea in this hospital. Given the inappropriateness of antibiotics for acute diarrhea and the nonsensical high rates of of intravenous levofloxacin use and the concurrent high rates of the levofloxacin resistance, a more effective antibiotic stewardship program is needed to improve patient outcomes, reduce costs, reinforce policy and address the underlying causes of antibiotic abuse. Disclosures All authors: No reported disclosures.

BACKGROUND: Africa bears 24% of the global burden of disease but has only 3% of the world's health workers. Substantial variation in health worker performance adds to the negative impact of this significant shortfall. We therefore sought to identify interventions implemented in sub-Saharan African aiming to improve health worker performance and the contextual factors likely to influence local effectiveness. METHODS AND FINDINGS: A systematic search for randomised controlled trials of interventions to improve health worker performance undertaken in sub-Saharan Africa identified 41 eligible trials. Data were extracted to define the interventions' components, calculate the absolute improvement in performance achieved, and document the likelihood of bias. Within-study variability in effect was extracted where reported. Statements about contextual factors likely to have modified effect were subjected to thematic analysis. Interventions to improve health worker performance can be very effective. Two of the three trials assessing mortality impact showed significant reductions in death rates (age

Background Over 1200 plant species are reported in ethnobotanical studies for the treatment of malaria and fevers, so it is important to prioritize plants for further development of anti-malarials. Methods The “RITAM score” was designed to combine information from systematic literature searches of published ethnobotanical studies and laboratory pharmacological studies of efficacy and safety, in order to prioritize plants for further research. It was evaluated by correlating it with the results of clinical trials. Results and discussion The laboratory efficacy score correlated with clinical parasite clearance (rs=0.7). The ethnobotanical component correlated weakly with clinical symptom clearance but not with parasite clearance. The safety component was difficult to validate as all plants entering clinical trials were generally considered safe, so there was no clinical data on toxic plants. Conclusion The RITAM score (especially the efficacy and safety components) can be used as part of the selection process for prioritising plants for further research as anti-malarial drug candidates. The validation in this study was limited by the very small number of available clinical studies, and the heterogeneity of patients included.