The Feasibility of C-Reactive Protein Point-of-Care Testing to Reduce Overuse of Antibiotics in Children with Acute Respiratory Tract Infections in Rural Kyrgyzstan: A Pilot Study.

Background: In Kyrgyzstan, the morbidity prevalence of and morbidity from acute respiratory tract infections (ARTI) in children is high. Local healthcare workers (HCW) often prescribe antibiotics that are not indicative due to a mix of professional and societal factors. It is suggested to precede with a decision on antibiotics by a point-of-care test (POCT) on the appropriateness of the treatment, eg, a measurement of C-reactive protein (CRP). CRP-guided antibiotic stewardship in children with ARTI has not previously been studied in Central Asia. Purpose: This pilot study was conducted to examine the feasibility of the methods and procedures to be used in the upcoming randomised controlled COORDINATE clinical trial (NCT05195866) and in daily clinical practice in primary care. Patients and methods: HCWs from three selected rural healthcare facilities were trained in the CRP POCT and in interpretation of results. Children aged 6 months to 12 years attending the primary healthcare facilities with respiratory symptoms were randomly assigned to CRP-guided management or standard care, guided by clinical findings only. Children were followed up for 14 days by scheduled telephone calls to caregivers. Results: Eighty-one children participated in this pilot study. The CRP POCT and the trial procedures were acceptable to the target group as well as to the HCWs. Children from both groups recovered equally well, with an observed significant lower use of antibiotics in the CRP group. HCWs generally adhered to the CRP guidelines, and only once was an antibiotic prescribed despite low CRP results. No safety concerns were observed. Four parents provided wrong phone numbers impeding follow-up. We will collect all mobile phone numbers in the household for the main trial. Conclusion: The pilot provided satisfactory results, suggesting that the COORDINATE trial of CRP POCT is effective, feasible with minor adjustments and without apparent safety concerns for the participants.

C reactive protein-guided prescription of antibiotics for children under 12 years with respiratory symptoms in Kyrgyzstan: protocol for a randomised controlled clinical trial with 14 days follow-up.

INTRODUCTION: While lower respiratory tract infections are the main cause of death for children under 5 globally, only a small proportion of children with respiratory tract infections need antibiotics. Overuse of antibiotics globally is leading to increasing rates of antibiotic resistance. In Kyrgyzstan, healthcare workers regularly prescribe antibiotics when clinical uncertainty is present to err on the side of caution. Targeting antibiotic use with biomarkers of inflammation such as C reactive protein (CRP) testing at the point-of-care test (POCT) has been shown to reduce antibiotic use in general, but only few studies have been done in children and no studies exist from Central Asia. This study aims to assess whether the use of a CRP POCT can safely decrease prescription of antibiotics for children with acute respiratory symptoms in primary level healthcare centres in Kyrgyzstan. METHODS AND ANALYSIS: Multicentre, open-label, individually randomised, controlled clinical trial with 14 days follow-up (follow-up by phone on days 3, 7 and 14) in rural lowland Chui and highland Naryn regions of Kyrgyzstan. The population are children aged 6 months to 12 years attending the primary level healthcare centres during normal business hours with acute respiratory symptoms. CRP POCT equipment will be supplied to healthcare centres, along with a short training session in CRP use, including the interpretation of results to support the clinical evaluation of the child with acute respiratory infection. The primary outcomes are the proportion of patients prescribed an antibiotic within 14 days of index consultation (superiority analysis) and days to recovery (non-inferiority analysis). Secondary outcomes are antibiotics prescribed at index consultation, reconsultations, hospital admission and vital status within 14 days. Analysis of the first primary outcome, antibiotic use, will be intention to treat using a logistic regression model. Analysis of the second primary outcome, days to recovery, will be per protocol using a linear regression model and a non-inferiority margin of 1 day. ETHICS AND DISSEMINATION: The study was approved on 18 June 2021 by the Ethics Committee (ref: no. 1) of the National Centre of Maternity and Childhood Care, Bishkek, Kyrgyzstan. The results of the study regardless of the conclusion will be presented at international conferences and published in peer-reviewed scientific medical journals along with policy briefs and technical reports. TRIAL REGISTRATION NUMBER: NCT05195866.

Mitigating antimicrobial resistance (AMR) using implementation research: a development funder's approach.

Despite the escalating burden of antimicrobial resistance (AMR), the global response has not sufficiently matched the scale and scope of the issue, especially in low- and middle-income countries (LMICs). While many countries have adopted national action plans to combat AMR, their implementation has lagged due to resource constraints, dysfunctional multisectoral coordination mechanisms and, importantly, an under-recognized lack of technical capacity to adapt evidence-based AMR mitigation interventions to local contexts. AMR interventions should be tailored, context-specific, cost-effective and sustainable. The implementation and subsequent scale-up of these interventions require multidisciplinary intervention-implementation research (IIR). IIR involves both quantitative and qualitative approaches, occurs across a three-phase continuum (proof of concept, proof of implementation and informing scale-up), and across four context domains (inner setting, outer setting, stakeholders and the implementation process). We describe the theoretical underpinnings of implementation research (IR), its various components, and how to construct different IR strategies to facilitate sustainable uptake of AMR interventions. Additionally, we provide real-world examples of AMR strategies and interventions to demonstrate these principles in practice. IR provides a practical framework to implement evidence-based and sustainable AMR mitigation interventions.

Health Workers' Practices in Assessment and Management of Children with Respiratory Symptoms in Primary Care Facilities in Uganda: A FRESH AIR Descriptive Study.

INTRODUCTION: Globally, acute lower respiratory infections are the leading cause of mortality among children under 5 years. Following World Health Organization primary care guidelines, pneumonia is diagnosed based on cough/difficult breathing and fast breathing. We aimed to describe the practices of healthcare workers in primary care health facilities in Uganda in the management of young children with respiratory symptoms especially regarding asthma as opposed to pneumonia. METHODS: Health workers were observed during clinical consultations with children 1-59 months of age presenting with cough and/or difficult breathing at recruitment. Afterward, an exit interview with the caregiver was conducted. Health center availability of clinical guidelines, equipment and supplies for management of children with respiratory symptoms was assessed systematically. RESULTS: A total of 218 consultations with 50 health workers at six health centers were included. Median consultation time was 4 min. Health workers asked history relevant to distinguishing asthma from pneumonia in 16% of consultations. The respiratory rate was counted in 10%. Antibiotics were prescribed to 32% of all the children and to 39% of children diagnosed with pneumonia. Caregivers reported being informed of findings and possible diagnosis in 5% of cases. Medicine and equipment needed for diagnosing and treating asthma were generally unavailable. CONCLUSION: Clinical practices among Ugandan health workers in primary care are insufficient to distinguish between main causes of respiratory symptoms, especially asthma as opposed to pneumonia, in children under five. Irrational use of antibiotics is widespread. Clear communication with caregivers is lacking. This could be due to lack of relevant competencies, medicines, time and supplies. LAY SUMMARY: Globally, the most frequent cause of death for children under five is infections in the lower airways. The World Health Organization recommends that in local health clinics this is defined as cough/difficult breathing and fast breathing. This article focuses on the practices of local health workers in Uganda and how they in practice diagnose and treat children under five with these symptoms. In addition, we try to estimate how much the caregivers of the children understand from the consultation. This is done by observing the healthcare workers (HCWs) and by interviewing the caregivers. In general, we found that the consultations were too short, that too few of the health workers looked for important signs for lower airways disease such as fast breathing and that antibiotics were prescribed in too many of the consultations. Also, the length and quality of the consultations and the supplies at the local health clinics were not sufficient to diagnose and treat asthma, which can often be mistaken for an infection. We believe that it is an important problem that too few children with asthma are being diagnosed correctly and that antibiotics are being prescribed too frequently, the latter being an important cause of antibiotic resistance. Relevant action must be taken to improve this.

[Indirect effects of the COVID-19 pandemic on mortality of mothers and children in low- and middle-income countries].

The COVID-19 pandemic may not only increase mortality due to the virus but also due to the indirect effects. The disease continues to ravage health and economic metrics globally, which is likely to increase maternal and under five-year child mortality in low- and middle-income countries. This review highlights key areas of concern for maternal and under five-year child mortality due to the indirect effects of the COVID-19 pandemic in low- and middle-income countries.

Children Monosensitized to Can f 5 Show Different Reactions to Male and Female Dog Allergen Extract Provocation: A Randomized Controlled Trial.

BACKGROUND: Dog dander consists of several allergenic molecules including Can f 5, which is a protein expressed in the prostate of male dogs. OBJECTIVE: To investigate whether children monosensitized to Can f 5 show different reactions to provocation tests with male versus female dog dander in a double-blind randomized clinical trial. METHODS: Twenty-two children (15-18 years) with a history of dog sensitization were enrolled from the COpenhagen Prospective Studies on Asthma in Childhood2000 mother-child cohort. Skin prick test, specific IgE levels to dog dander (e5), and dog components Can f 1, 2, 3, and 5 were first assessed. We subsequently performed skin prick test and conjunctival allergen provocation test using dog dander collected separately from male and female dogs. RESULTS: Seven of the 22 children were monosensitized to Can f 5. Eight were sensitized to a mix of the dog components, and 7 were no longer sensitized to dog. Of the children monosensitized to Can f 5, all had a positive skin prick test result to male dog extract and 1 of 7 was also positive to female dog extract (P = .01). Furthermore, 5 of 7 had a positive conjunctival allergen provocation test result to male dog extract and 1 of 7 also reacted to the female dog extract (P = .03). There was no difference between reactions to male and female dog extract provocation in children sensitized to a mix of the dog components. CONCLUSIONS: Children monosensitized to Can f 5 show different reactions to male and female dog extract provocation using both skin prick test and conjunctival allergen provocation test, suggesting tolerance to female dogs.

Community-based interventions for prevention of Type 2 diabetes in low- and middle-income countries: a systematic review.

Type 2 diabetes is an increasing burden in low- and middle-income countries (LMICs). Knowledge of effective prevention programs in LMICs is thus important. The aim of this review was to establish an overview of studies evaluating the effectiveness of community-based interventions for prevention of Type 2 diabetes in LMICs. A literature review with searches in the databases using MEDLINE in Ovid (Ovid MEDLINE® In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, Ovid MEDLINE and Version (R); Embase; PsycINFO; Global Health; and Google Scholar) between 1 January 2000 and 31 December 2015 was conducted. Only 10 studies that met our selection criteria were included; 3 were randomized controlled trials, 2 non-randomized controlled trials and 5 were pre-and post-intervention studies. About 9 of 10 studies reported significant reduction in both the glycated hemoglobin (HbA1c) and fasting blood glucose (FBG) levels as a result of the intervention. A majority of the studies included multicomponent interventions such as education and behavioral encompassing both individual and group work, and included health education, nutrition education, nutrition counseling, exercise and promoting physical activity, psychosocial approaches and lifestyle modification. The interventions were delivered by community health workers, volunteers, social workers, community nutritionists and community nurses. Comparisons between studies, however, was not possible due to substantial heterogeneity in study design. This review contributes to the current literature on community-based interventions for prevention of Type 2 diabetes in LMICs, acknowledging the community-based approach can be effective in prevention and control of Type 2 diabetes. Due to the heterogeneity across study designs, outcomes and in terms of variation and duration of interventions, only limited conclusions can be drawn about the effectiveness of interventions. More evidence from randomized controlled trials on culturally tailored, community-based interventions is needed to compare findings and test implementation in practice.

Awareness, Prevalence, Treatment, and Control of Hypertension in Western Nepal.

BACKGROUND: Hypertension is a significant contributor to cardiovascular and renal diseases. In low-income settings like Nepal, there are few epidemiological studies assessing hypertension burden. Thus, the purpose was to determine prevalence, awareness, treatment, and control of hypertension in Nepal. METHODS: A cross-sectional survey was conducted in semi-urban area of western Nepal among randomly selected participants, aged between 25 and 65 years. Systolic blood pressure (BP) ≥140 mm Hg and/or diastolic BP of ≥90 mm Hg and/or taking current antihypertensive medicine defined as hypertension. RESULTS: Study included 2,815 participants, 1,844 were women. The age- and sex-adjusted prevalence of hypertension was 28%. Of the study participants, 17% were daily smokers, 12% harmful alcohol drinkers, 90% consuming low levels of fruit and/or vegetable, and 7% reported low physical activity. Among hypertensive participants, 46% were aware of their preexisting hypertension, 31% were on hypertensive medication, and 15% met BP control targets. Increasing age (odds ratio [OR]: 1.07, 95% confidence interval [CI]: 1.06; 1.08), higher body mass index (OR: 1.09, 95% CI: 1.06; 1.12), men (OR: 1.63, 95% CI: 1.25; 2.14), harmful alcohol intake (Or: 2.46; 95% CI: 1.73; 3.51), family history of hypertension (OR: 1.42; 95% CI: 1.14; 1.76), and diabetes (OR: 2.08, 95% CI: 1.30; 3.33) were independently associated with hypertension. CONCLUSIONS: The prevalence of hypertension was found high in western Nepal. A number of risk factors were identified as possible drivers of this burden. Thus, there is an urgent need to address modifiable risk factors in semi-urban settings of western Nepal.

[Scientific evidence on treatment and prognosis of childhood absence epilepsy].

Until now, ethosuximide (ESM), sodium valproate (VPA) and lamotrigine have been considered the drugs of choice in the management of childhood absence epilepsy, and there has been no high-validated evidence to distinguish their effects. New research shows, however, that while VPA and ESM are equally effective, ESM is the best tolerated of the two drugs, when considering cognitive adverse effects. This is of major importance, as cognitive comorbidities can be dire in childhood absence epilepsy, possibly affecting the psychosocial prognosis of the patients. More research is needed in this area.

Atopic endotype in childhood.

BACKGROUND: The term atopic disorder is an early attempt to define specific endotypes of children with asthma, eczema, or both and increased IgE levels. OBJECTIVE: We performed a longitudinal analysis of the relevance of the atopic endotype from birth to age 13 years. METHODS: Allergic sensitization against 28 inhalant and food allergens was assessed at ½, 1½, 4, 6, and 13 years of age in 399 children from the Copenhagen Prospective Study on Asthma in Childhood2000 birth cohort by using both skin prick test responses and specific IgE levels. Asthma and eczema were diagnosed longitudinally by strictly adhering to predefined algorithms. Associations between allergic sensitization, asthma, and eczema were estimated by means of logistic regression, and a machine learning approach was used to identify temporal phenotype clusters of these traits. RESULTS: Allergic sensitization showed no association with asthma through early childhood (0-6 years) when analyzed as any sensitization (odds ratio [OR] range, 0.78-1.29; P ≥ .48). However, at 13 years of age, any sensitization was associated with asthma (OR range, 4.02-5.94; all P < .001). In contrast, any sensitization was associated with eczema at ½, 1½, and 6 years of age (OR range, 2.06-6.02; P ≤ .01) and borderline associated at 4 years of age (OR, 1.61 [95% CI, 0.96-2.69]; P = .07) but not at 13 years of age (OR, 1.57 [95% CI, 0.78-3.16]; P = .21). We identified 4 latent patterns of disease development that were either dominated by sensitization (37%), eczema (26%), asthma (14%), or healthy status (24%). CONCLUSION: We found very little interdependency between asthma, eczema, and allergic sensitization through childhood. The associations between those entities were strongly dependent on age, type of allergens, and method of testing for sensitization. Therefore, atopy in children is unlikely to represent a true endotype.

[Avoidable loss of vision in a global perspective]. / Undgåeligt synstab i et globalt perspektiv.

WHO estimates that in 2010 there were 39 million blind people and 246 million living with moderate to severe vision impairment globally. 90% of the disease burden is found in developing countries, and most of it is due to preventable or treatable eye conditions. Many of these, such as uncorrected refractive errors, can be prevented with the integration of simple primary health measures. However, as a result of an ageing population, the prevalence of chronic diseases such as diabetic retinopathy and age-related macular degeneration is on the rise. This calls for more focus on specialized treatment.