Oral versus intravenous empirical antibiotics in children and adolescents with uncomplicated bone and joint infections: a nationwide, randomised, controlled, non-inferiority trial in Denmark.

BACKGROUND: Bone and joint infections (BJIs) are treated with intravenous antibiotics, which are burdensome and costly. No randomised controlled studies have compared if initial oral antibiotics are as effective as intravenous therapy. We aimed to investigate the efficacy and safety of initial oral antibiotics compared with initial intravenous antibiotics followed by oral antibiotics in children and adolescents with uncomplicated BJIs. METHODS: From Sept 15, 2020, to June 30, 2023, this nationwide, randomised, non-inferiority trial included patients aged 3 months to 17 years with BJIs who presented to one of the 18 paediatric hospital departments in Denmark. Exclusion criteria were severe infection (ie, septic shock, the need for acute surgery, or substantial soft tissue involvement), prosthetic material, comorbidity, previous BJIs, or antibiotic therapy for longer than 24 h before inclusion. Patients were randomly assigned (1:1), stratified by C-reactive protein concentration (<35 mg/L vs ≥35 mg/L), to initially receive either high-dose oral antibiotics or intravenous ceftriaxone (100 mg/kg per day in one dose). High-dose oral antibiotics were coformulated amoxicillin (100 mg/kg per day) and clavulanic acid (12·5 mg/kg per day) in three doses for patients younger than 5 years or dicloxacillin (200 mg/kg per day) in four doses for patients aged 5 years or older. After a minimum of 3 days, and upon clinical improvement and decrease in C-reactive protein, patients in both groups received oral antibiotics in standard doses. The primary outcome was sequelae after 6 months in patients with BJIs, defined as any atypical mobility or function of the affected bone or joint, assessed blindly, in all randomised patients who were not terminated early due to an alternative diagnosis (ie, not BJI) and who attended the primary outcome assessment. A risk difference in sequelae after 6 months of less than 5% implied non-inferiority of the oral treatment. Safety outcomes were serious complications, the need for surgery after initiation of antibiotics, and treatment-related adverse events in the as-randomised population. This trial was registered with ClinicalTrials.gov, NCT04563325. FINDINGS: 248 children and adolescents with suspected BJIs were randomly assigned to initial oral antibiotics (n=123) or initial intravenous antibiotics (n=125). After exclusion of patients without BJIs (n=54) or consent withdrawal (n=2), 101 patients randomised to oral treatment and 91 patients randomised to intravenous treatment were included. Ten patients did not attend the primary outcome evaluation. Sequelae after 6 months occurred in none of 98 patients with BJIs in the oral group and none of 84 patients with BJIs in the intravenous group (risk difference 0, one-sided 97·5% CI 0·0 to 3·8, pnon-inferiority=0·012). Surgery after randomisation was done in 12 (9·8%) of 123 patients in the oral group compared with seven (5·6%) of 125 patients in the intravenous group (risk difference 4·2%, 95% CI -2·7 to 11·5). We observed no serious complications. Rates of adverse events were similar across both treatment groups. INTERPRETATION: In children and adolescents with uncomplicated BJIs, initial oral antibiotic treatment was non-inferior to initial intravenous antibiotics followed by oral therapy. The results are promising for oral treatment of uncomplicated BJIs, precluding the need for intravenous catheters and aligning with the principles of antimicrobial stewardship. FUNDING: Innovation Fund Denmark and Rigshospitalets Forskningsfond.

School-Based Serosurveys to Assess the Validity of Using Routine Health Facility Data to Target Malaria Interventions in the Central Highlands of Madagascar.

BACKGROUND: In low-malaria-transmission areas of Madagascar, annual parasite incidence (API) from routine data has been used to target indoor residual spraying at subdistrict commune level. To assess validity of this approach, we conducted school-based serological surveys and health facility (HF) data quality assessments in 7 districts to compare API to gold-standard commune-level serological measures. METHODS: At 2 primary schools in each of 93 communes, 60 students were randomly selected with parents and teachers. Capillary blood was drawn for rapid diagnostic tests (RDTs) and serology. Multiplex bead-based immunoassays to detect antibodies to 5 Plasmodium falciparum antigens were conducted, and finite mixture models used to characterize seronegative and seropositive populations. Reversible catalytic models generated commune-level annual seroconversion rates (SCRs). HF register data were abstracted to assess completeness and accuracy. RESULTS: RDT positivity from 12 770 samples was 0.5%. Seroprevalence to tested antigens ranged from 17.9% (MSP-1) to 59.7% (PF13). Median commune-level SCR was 0.0108 (range, 0.001-0.075). Compared to SCRs, API identified 71% (95% confidence interval, 51%-87%) of the 30% highest-transmission communes; sensitivity declined at lower levels. Routine data accuracy did not substantially affect API performance. CONCLUSIONS: API performs reasonably well at identifying higher-transmission communes but sensitivity declined at lower transmission levels.

The difficult management of persistent, non-focal congenital hyperinsulinism: A retrospective review from a single, tertiary center.

BACKGROUND/OBJECTIVE: Congenital hyperinsulinism (CHI) is a rare, heterogeneous disease with transient or persistent hypoglycemia. Histologically, focal, diffuse, and atypical forms of CHI exist, and at least 11 disease-causing genes have been identified. METHODS: We retrospectively evaluated the treatment and outcome of a cohort of 40 patients with non-focal, persistent CHI admitted to the International Hyperinsulinism Center, Denmark, from January 2000 to May 2017. RESULTS: Twenty-two patients (55%) could not be managed with medical monotherapy (diazoxide or octreotide) and six (15%) patients developed severe potential side effects to medication. Surgery was performed in 17 (43%) patients with resection of 66% to 98% of the pancreas. Surgically treated patients had more frequently KATP -channel gene mutations (surgical treatment 12/17 vs conservative treatment 6/23, P = .013), highly severe disease (15/17 vs 13/23, P = .025) and clinical onset <30 days of age (15/17 vs 10/23, P = .004). At last follow-up at median 5.3 (range: 0.3-31.3) years of age, 31/40 (78%) patients still received medical treatment, including 12/17 (71%) after surgery. One patient developed diabetes after a 98% pancreatic resection. Problematic treatment status was seen in 7/40 (18%). Only 8 (20%) had clinical remission (three spontaneous, five after pancreatic surgery). Neurodevelopmental impairment (n = 12, 30%) was marginally associated with disease severity (P = .059). CONCLUSIONS: Persistent, non-focal CHI remains difficult to manage. Neurological impairment in 30% suggests a frequent failure of prompt and adequate treatment. A high rate of problematic treatment status at follow-up demonstrates an urgent need for new medical treatment modalities.

Employability and career experiences of international graduates of MSc Public Health: a mixed methods study.

OBJECTIVES: This article aims to describe the public health career experiences of international graduates of a Master of Science in Public Health (MSc PH) programme and to contribute to developing the evidence base on international public health workforce capacity development. STUDY DESIGN: A sequential mixed methods study was conducted between January 2017 and April 2017. METHODS: Ninety-seven international graduates of one UK university's MSc PH programme were invited to take part in an online survey followed by semistructured interviews, for respondents who consented to be interviewed. We computed the descriptive statistics of the quantitative data obtained, and qualitative data were thematically analysed. RESULTS: The response rate was 48.5%. Most respondents (63%) were employed by various agencies within 1 year after graduation. Others (15%) were at different stages of doctor of philosophy studies. Respondents reported enhanced roles after graduation in areas such as public health policy analysis (74%); planning, implementation and evaluation of public health interventions (74%); leadership roles (72%); and research (70%). The common perceived skills that were relevant to the respondents' present jobs were critical analysis (87%), multidisciplinary thinking (86%), demonstrating public health leadership skills (84%) and research (77%). Almost all respondents (90%) were confident in conducting research. Respondents recommended the provision of longer public health placement opportunities, elective courses on project management and advanced statistics, and 'internationalisation' of the programme's curriculum. CONCLUSIONS: The study has revealed the relevance of higher education in public health in developing the career prospects and skills of graduates. International graduates of this MSc PH programme were satisfied with the relevance and impact of the skills they acquired during their studies. The outcomes of this study can be used for curriculum reformation. Employers' perspectives of the capabilities of these graduates, however, need further consideration.

Free mass distribution of long lasting insecticidal nets lead to high levels of LLIN access and use in Madagascar, 2010: A cross-sectional observational study.

BACKGROUND: Madagascar conducted the first two phases of a national free mass distribution campaign of long-lasting insecticidal nets (LLINs) during a political crisis in 2009 aiming to achieve coverage of two LLINs per household as part of the National Malaria Control Strategy. The campaign targeted households in 19 out of 91 total health districts. METHODS: A community-based cross-sectional household survey using a three-stage cluster sample design was conducted four months post campaign to assess LLIN ownership, access and use. Multivariable logistic regression analysis was used to identify factors associated with household LLIN access and individual LLIN use. RESULTS: A total of 2211 households were surveyed representing 8867 people. At least one LLIN was present in 93.5% (95% confidence interval [CI], 91.6-95.5%) of households and 74.8% (95% CI, 71.0-78.6%) owned at least two LLINs. Access measured as the proportion of the population that could potentially be covered by household-owned LLINs was 77.2% (77.2% (95% CI, 72.9-81.3%) and LLIN use by all individuals was 84.2% (95% CI, 81.2-87.2%). LLIN use was associated with knowledge of insecticide treated net use to prevent malaria (OR = 3.58, 95% CI, 1.85-6.94), household ownership of more LLINs (OR 2.82, 95% CI 1.85-4.3), presence of children under five (OR = 2.05, 95% CI, 1.67-2.51), having traveled to the distribution point and receiving information about hanging a bednet (OR = 1.56, 95% CI, 1.41-1.74), and having received a post-campaign visit by a community mobilizer (OR = 1.75, 95% CI, 1.26-2.43). Lower LLIN use was associated with increasing household size (OR = 0.81 95% CI 0.77-0.85) and number of sleeping spaces (OR = 0.55, 95% CI, 0.44-0.68). CONCLUSIONS: A large scale free mass LLIN distribution campaign was feasible and effective at achieving high LLIN access and use in Madagascar. Campaign process indicators highlighted potential areas for strengthening implementation to optimize access and equity.

Improved equity in measles vaccination from integrating insecticide-treated bednets in a vaccination campaign, Madagascar.

OBJECTIVE: To evaluate the effect of integrating ITN distribution on measles vaccination campaign coverage in Madagascar. METHODS: Nationwide cross-sectional survey to estimate measles vaccination coverage, nationally, and in districts with and without ITN integration. To evaluate the effect of ITN integration, propensity score matching was used to create comparable samples in ITN and non-ITN districts. Relative risks (RR) and 95% confidence intervals (CI) were estimated via log-binomial models. Equity ratios, defined as the coverage ratio between the lowest and highest household wealth quintile (Q), were used to assess equity in measles vaccination coverage. RESULTS: National measles vaccination coverage during the campaign was 66.9% (95% CI 63.0-70.7). Among the propensity score subset, vaccination campaign coverage was higher in ITN districts (70.8%) than non-ITN districts (59.1%) (RR=1.3, 95% CI 1.1-1.6). Among children in the poorest wealth quintile, vaccination coverage was higher in ITN than in non-ITN districts (Q1; RR=2.4, 95% CI 1.2-4.8) and equity for measles vaccination was greater in ITN districts (equity ratio=1.0, 95% CI 0.8-1.3) than in non-ITN districts (equity ratio=0.4, 95% CI 0.2-0.8). CONCLUSION: Integration of ITN distribution with a vaccination campaign might improve measles vaccination coverage among the poor, thus providing protection for the most vulnerable and difficult to reach children.

Malaria prevention during pregnancy: assessing the disease burden one year after implementing a program of intermittent preventive treatment in Koupela District, Burkina Faso.

The World Health Organization recommends that pregnant women in malaria-endemic areas receive >or= 2 doses of intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp/SP) in the second and third trimesters of pregnancy to prevent maternal anemia, placental parasitemia, and low birth weight (LBW). In 2001, a program evaluation in Koupéla District, Burkina Faso demonstrated that despite widespread use of chloroquine chemoprophylaxis, the burden of malaria during pregnancy remained high. In 2003, the Burkina Faso Ministry of Health piloted a program of IPTp/SP (three doses) and accelerated distribution of insecticide-treated nets (ITN) to pregnant women in Koupéla District. In 2004, a follow-up program evaluation was conducted. Coverage with >or= 1 doses of IPTp/SP was high among women attending antenatal clinics (ANCs) (96.2%) and delivery units (DUs) (93.5%); ITN ownership was moderately high (ANC = 53.9%, DU = 61.6%). In multivariate analysis, >or= 1 dose of IPTp/SP was associated with a significant reduction in the prevalence of peripheral parasitemia at ANCs (risk ratio [RR] = 0.49, P = 0.008), >or= 2 doses of IPTp/SP were associated with a reduction in the prevalence of placental parasitemia (RR = 0.56, P = 0.02), and three doses of IPTp/SP were associated with a reduced risk of LBW (RR = 0.51, P = 0.04). The proportions of women at ANCs with peripheral parasitemia and anemia were significantly lower in 2004 than in 2001 (RR = 0.53, P = 0.001 and RR = 0.78, P = 0.003, respectively). The proportions of women at DUs with peripheral and placental parasitemia were also significantly lower in 2004 than in 2001 (RR = 0.66, P < 0.0001 and RR = 0.71, P = 0.0002, respectively). These data suggest that a package of IPTp/SP and ITNs is effective in reducing the burden of malaria during pregnancy in Burkina Faso.

Going beyond triage in Tajikistan. Health reform in the former Soviet Union.

Tajikistan is among the few countries where life expectancy diminished during the 1990's. To rebuild a health system fractured by economic collapse, political disintegration and civil war, the Essential Hospital Services Project was initiated to restore essential hospital services, encourage structural reform and build the health system's capacity to sustain itself. The article provides an overview of these reform efforts, outlines some of the challenges of health reform in Tajikistan and illustrates the benefits global partnerships can achieve when sharing creative new approaches to health reform.

What can information systems do for primary health care? An international perspective.

The reform of health information systems has been made a priority by health managers, public health specialists and technocrats. While each of these groups has promised major benefits from improvements in information systems, insufficient attention has been paid to the limitations placed upon the theoretical possibilities of information technology by the characteristics of the health system of which the information system is but a part. Managers anticipate improved efficiency and rational allocation of resources, but rational decision making does not automatically follow from improvements in information. Epidemiologists and public health specialists seek more effective and equitable health systems but methodological problems and the expense of many conventional epidemiological approaches continue to limit the usefulness of disease surveillance, programme monitoring and evaluation. Both managers and epidemiologists are confronted with the conflicts which arise in seeking to create locally sensitive information systems within centralised health systems. Technocrats see microcomputers as essential for information systems to be truly effective and as a means of liberating health workers from the drudgery of form filling. However, the rate of organisational evolution in the health system has not kept pace with the rapid development of information technology. There are good prospects for considerable health gain to be wrought from reforms in health information systems but to realise these it is necessary that this process be 'action-led' rather than, as is conventional, 'data-led'. The latter approach sees data as the end in itself; the 'action-led' approach, in contrast, regards information as needs to interventions with a focus on how information will influence decisions. For improvements in information to result in improved health, strategies must be adopted which will ensure that information routinely informs decisions and is seen as a means to the end of improving health.

Information support for urban primary health care.

PIP: The Kampung Improvement Project in Indonesia and slum improvement projects in Lusaka, Zambia and in Calcutta, Hyderabad, Indore, Visakhapatnam, and Vijayawada, India are examples of multidisciplinary projects that emphasize primary health care (PHC) and are designed to meet the needs of low income people. A case study of such a project in a developing country city reveals that each health center had filed 7770 pieces of data each month from 105 slums yet no one had analyzed the data. Health managers believed computers were needed to evaluate the health information system but the problems were greater than just the lack of computers. They included the considerable time taken to complete forms, unreliable accuracy of data, and not using the data to make decisions at the local or municipal level. So consultants set up a rationalization of indicators system to guide health managers on what type of data to include and exclude into the health information system. The 1st step involved reviewing each proposed indicator using 5 steps for decision making purposes. For example, they advised exclusion of number of households with latrines and vague and complicated variables such as number of 1-year old children who were fully immunized and whose mothers had had all prenatal immunizations. The next step was ranking the indicators based on ease of collection, accuracy, and value to managers. The final step was eliminating unsuitable indicators (low scoring ones). Decentralization of management of the slums into 4 regions also occurred which resulted in monthly meetings with health workers to review activities and increased morale. A computer programmer became responsible for data entry into the new system. This case study demonstrated the difficulty of a health information system steered by data instead of the need for data to use for decision-making purposes.^ieng

Rapid appraisal in an urban setting, an example from the developed world.

Rapid Appraisal has been used as a method to understand communities' own perceptions of their priority needs. It can be used as a tool for formulating joint action plans between communities and service planners and managers. It can also be used to complement quantitative methods of assessing needs by more in-depth qualitative understanding of socio-cultural perspectives. In the example described in this paper Rapid Appraisal is used both as action research and as a qualitative tool in order to define health and social needs of an urban, deprived community in England.