Renewing Felsenstein's phylogenetic bootstrap in the era of big data.

Felsenstein's application of the bootstrap method to evolutionary trees is one of the most cited scientific papers of all time. The bootstrap method, which is based on resampling and replications, is used extensively to assess the robustness of phylogenetic inferences. However, increasing numbers of sequences are now available for a wide variety of species, and phylogenies based on hundreds or thousands of taxa are becoming routine. With phylogenies of this size Felsenstein's bootstrap tends to yield very low supports, especially on deep branches. Here we propose a new version of the phylogenetic bootstrap in which the presence of inferred branches in replications is measured using a gradual 'transfer' distance rather than the binary presence or absence index used in Felsenstein's original version. The resulting supports are higher and do not induce falsely supported branches. The application of our method to large mammal, HIV and simulated datasets reveals their phylogenetic signals, whereas Felsenstein's bootstrap fails to do so.

Did school characteristics affect the uptake of meningococcal quadrivalent vaccine in Greater Manchester, United Kingdom?

OBJECTIVES: The objective of this study was to assess if school characteristics were associated with the uptake of the meningococcal ACWY (MenACWY) vaccine in Greater Manchester in 2017/18. STUDY DESIGN: This is an ecological cross-sectional study. METHODS: We analysed data on all 129 schools in seven local authorities in Greater Manchester from the Department for Education and from local child health information systems to determine whether school characteristics, including school type and Ofsted effectiveness score, were associated with vaccine uptake. Schools with no eligible pupils were excluded. We undertook single-variable and multivariable analysis and considered key interactions. RESULTS: The overall uptake rate was 80.7%, with a median uptake per school of 80.6% (interquartile range, 69.0%-87.4%). Lower vaccination rates were associated with lower overall effectiveness scores (odds ratio [OR]: 3.54, 95% confidence interval [CI]: 3.00-4.19) and lower numbers of pupils eligible for vaccination (OR: 1.39, 95% CI: 1.28-1.51). Schools with a lower percentage of pupils for whom English is a second language and high deprivation were associated with lower uptake (OR: 1.58, 95% CI: 1.41-1.78). In addition, community schools (the schools with the most local authority oversight) had lower vaccination rates than other categories of schools. CONCLUSIONS: In this study, uptake rates of the MenACWY vaccine were associated with all five school characteristics considered. Effectiveness scores for schools had the largest association with vaccine uptake, with poorer schools having lower uptake. These characteristics should be used by vaccination providers to prioritise their interventions to increase immunisation rates.

A pilot randomized controlled trial of time-intensive cognitive-behaviour therapy for postpartum obsessive-compulsive disorder: effects on maternal symptoms, mother-infant interactions and attachment.

BACKGROUND: There is increasing recognition that perinatal anxiety disorders are both common and potentially serious for mother and child. Obsessive-compulsive disorder (OCD) can be triggered or exacerbated in the postpartum period, with mothers reporting significant effects on parenting tasks. However, there is little evidence concerning their effective treatment or the impact of successful treatment on parenting. METHOD: A total of 34 mothers with OCD and a baby of 6 months old were randomized into either time-intensive cognitive-behaviour therapy (iCBT) or treatment as usual (TAU). iCBT took place after randomization at 6 months postpartum and was completed by 9 months. Maternal symptomatology, sensitivity in mother-infant interactions and parenting were assessed at baseline and reassessed at 12 months postpartum. At 12 months attachment was also assessed using Ainsworth's Strange Situation Procedure. A healthy control group of mothers and infants (n = 37) underwent the same assessments as a benchmark. RESULTS: iCBT was successful in ameliorating maternal symptoms of OCD (controlled effect size = 1.31-1.90). However, mother-infant interactions were unchanged by treatment and remained less sensitive in both OCD groups than a healthy control group. The distribution of attachment categories was similar across both clinical groups and healthy controls with approximately 72% classified as secure in each group. CONCLUSIONS: iCBT is an effective intervention for postpartum OCD. Sensitive parenting interactions are affected by the presence of postpartum OCD and this is not improved by successful treatment of OCD symptoms. However, the overall attachment bond appears to be unaffected. Longitudinal studies are needed to explore the impact of postpartum OCD as the child develops.

Temporal Progression of Lesions in Guinea Pigs Infected With Lassa Virus.

Lassa virus (LASV) infection causes an acute, multisystemic viral hemorrhagic fever that annually infects an estimated 100 000 to 300 000 persons in West Africa. This pathogenesis study evaluated the temporal progression of disease in guinea pigs following aerosol and subcutaneous inoculation of the Josiah strain of LASV as well as the usefulness of Strain 13 guinea pigs as an animal model for Lassa fever. After experimental infection, guinea pigs ( Cavia porcellus; n = 67) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and serum chemistry and hematologic changes. Guinea pigs developed viremia on day 5 to 6 postexposure (PE), with clinical signs appearing by day 7 to 8 PE. Complete blood counts revealed lymphopenia and thrombocytopenia. Gross pathologic findings included skin lesions and congested lungs. Histologic lesions consisted of cortical lymphoid depletion by day 6 to 7 PE with lymphohistiocytic interstitial pneumonia at 7 to 8 days PE. Scattered hepatocellular degeneration and cell death were also noted in the liver and, to a lesser extent, in other tissues including the haired skin, lung, heart, adrenal gland, lymph nodes, thymus, and spleen. The first cell types to demonstrate staining for viral antigen were fibroblastic reticular cells and macrophages/dendritic cells in the lymph nodes on day 5 to 6 PE. This study demonstrates similarities between Lassa viral disease in human infections and experimental guinea pig infection. These shared pathologic characteristics support the utility of guinea pigs as an additional animal model for vaccine and therapeutic development under the Food and Drug Administration's Animal Rule.

Pathogenesis of Bolivian Hemorrhagic Fever in Guinea Pigs.

Machupo virus, the cause of Bolivian hemorrhagic fever, is a highly lethal viral hemorrhagic fever with no Food and Drug Administration-approved vaccines or therapeutics. This study evaluated the guinea pig as a model using the Machupo virus-Chicava strain administered via aerosol challenge. Guinea pigs (Cavia porcellus) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and sequential changes in serum chemistry and hematology. The incubation period was 5 to 12 days, and complete blood counts revealed leukopenia with lymphopenia and thrombocytopenia. Gross pathologic findings included congestion and hemorrhage of the gastrointestinal mucosa and serosa, noncollapsing lungs with fluid exudation, enlarged lymph nodes, and progressive pallor and friability of the liver. Histologic lesions consisted of foci of degeneration and cell death in the haired skin, liver, pancreas, adrenal glands, lymph nodes, tongue, esophagus, salivary glands, renal pelvis, small intestine, and large intestine. Lymphohistiocytic interstitial pneumonia was also present. Inflammation within the central nervous system, interpreted as nonsuppurative encephalitis, was histologically apparent approximately 16 days postexposure and was generally progressive. Macrophages in the tracheobronchial lymph node, on day 5 postexposure, were the first cells to demonstrate visible viral antigen. Viral antigen was detected throughout the lymphoid system by day 9 postexposure, followed by prominent spread within epithelial tissues and then brain. This study provides insight into the course of Machupo virus infection and supports the utility of guinea pigs as an additional animal model for vaccine and therapeutic development.

Pathology of experimental Machupo virus infection, Chicava strain, in cynomolgus macaques (Macaca fascicularis) by intramuscular and aerosol exposure.

Machupo virus, the causative agent of Bolivian hemorrhagic fever (BHF), is a highly lethal viral hemorrhagic fever of which little is known and for which no Food and Drug Administration-approved vaccines or therapeutics are available. This study evaluated the cynomolgus macaque as an animal model using the Machupo virus, Chicava strain, via intramuscular and aerosol challenge. The incubation period was 6 to 10 days with initial signs of depression, anorexia, diarrhea, mild fever, and a petechial skin rash. These were often followed by neurologic signs and death within an average of 18 days. Complete blood counts revealed leukopenia as well as marked thrombocytopenia. Serum chemistry values identified a decrease in total protein, marked increases in alanine aminotransferase and aspartate aminotransferase, and moderate increases in alkaline phosphatase. Gross pathology findings included a macular rash extending across the axillary and inguinal regions beginning at approximately 10 days postexposure as well as enlarged lymph nodes and spleen, enlarged and friable liver, and sporadic hemorrhages along the gastrointestinal mucosa and serosa. Histologic lesions consisted of foci of degeneration and necrosis/apoptosis in the haired skin, liver, pancreas, adrenal glands, lymph nodes, tongue, esophagus, salivary glands, stomach, small intestine, and large intestine. Lymphohistiocytic interstitial pneumonia was also present. Inflammation within the central nervous system (nonsuppurative encephalitis) was histologically apparent approximately 16 days postexposure and was generally progressive. This study provides insight into the course of Machupo virus infection in cynomolgus macaques and supports the usefulness of cynomolgus macaques as a viable model of human Machupo virus infection.

Netmums: a phase II randomized controlled trial of a guided Internet behavioural activation treatment for postpartum depression.

BACKGROUND: Despite the high prevalence of postnatal depression (PND), few women seek help. Internet interventions may overcome many of the barriers to PND treatment use. We report a phase II evaluation of a 12-session, modular, guided Internet behavioural activation (BA) treatment modified to address postnatal-specific concerns [Netmums Helping With Depression (NetmumsHWD)]. METHOD: To assess feasibility, we measured recruitment and attrition to the trial and examined telephone session support and treatment adherence. We investigated sociodemographic and psychological predictors of treatment adherence. Effectiveness outcomes were estimated with the Edinburgh Postnatal Depression Scale (EPDS), Generalized Anxiety Disorder-7, Work and Social Adjustment Scale, Postnatal Bonding Questionnaire, and Social Provisions Scale. RESULTS: A total of 249 women were recruited via a UK parenting site, Netmums.com. A total of 83 women meeting DSM-IV criteria for major depressive disorder were randomized to NetmumsHWD (n = 41) or treatment-as-usual (TAU; n = 42). Of the 83 women, 71 (86%) completed the EPDS at post-treatment, and 71% (59/83) at the 6-month follow-up. Women completed an average of eight out of 12 telephone support sessions and five out of 12 modules. Working women and those with less support completed fewer modules. There was a large effect size favouring women who received NetmumsHWD on depression, work and social impairment, and anxiety scores at post-treatment compared with women in the TAU group, and a large effect size on depression at 6 months post-treatment. There were small effect sizes for postnatal bonding and perceived social support. CONCLUSIONS: A supported, modular, Internet BA programme can be feasibly delivered to postpartum women, offering promise to improve depression, anxiety and functioning.

What do the revised UK standards of proficiency mean for diagnostic radiography training? A regional radiographer focus group study.

INTRODUCTION: Revisions to the UK Health and Care Professions Council (HCPC) standards of proficiency for diagnostic radiographers came into effect on September 1st 2023. Changes include an increase of proficiencies in CT and extended to MRI imaging. As workforce support the development of learners to meet stage outcomes in practice, this study aimed to understand the radiographers' expectations of future learners' training to meet the new standards of proficiency. METHODS: Snowball sampling was used to invite practice educators/student supervisors and department leads within the 21 NHS Trusts in the North East and Yorkshire region providing diagnostic radiography practice placements. Online focus groups used a semi structured topic guide to explore the expectations of student performance during different stages of their training, and on different types of pre-registration programmes. Participants views were sought on considerations for appropriate assessment. Thematic analysis was supported by NVivo software. RESULTS: Fifteen diagnostic radiographers across 11 NHS trusts participated in 5 focus groups in November 2022. The findings showed consistency in expectations of student performance in projectional radiography, patient care and communication. Participants felt some standards of proficiency were beyond threshold competency, or current practices were a barrier in supporting learning. Participants felt assessment over a period and range of examinations in the clinical environment gave a fairer picture of student performance. CONCLUSION: There is uncertainty and perceived barriers in supporting future diagnostic radiography training in the practice setting. IMPLICATIONS FOR PRACTICE: Further work will be needed to identify and support appropriate learning opportunities and stage outcomes if learners are to meet the breadth of HCPC standards of proficiency with some consistency.

Mapping the migrant diagnostic radiographers in the UK: A national survey.

INTRODUCTION: The international recruitment of healthcare workers remains a UK strategy to manage workforce gaps and maintain service delivery. Although not a new phenomenon, this has been exacerbated by chronic shortages. There is a need to profile the current international recruits and identify individual motivators to understand the opportunities for future recruitment and retention initiatives. METHOD: A UK-wide electronic survey was conducted using the Jisc platform. The survey was promoted using social media and researcher networks. Eligibility criteria were diagnostic radiographers, internationally educated, and currently working in the UK. RESULTS: 226 responses were received. Most were working in England (90.7%) and 58.0% were under 35 years of age. The majority had migrated having moved to the UK since 2020 (63.7%) and the main drivers were career and/or training opportunities. Initial education was in 30 different countries, the highest number originating from Africa and Asia, with a median of 6 years post-qualification experience (IQR 4-11yrs). Despite experience, most were employed in band 5 (n = 72) or band 6 posts (n = 95). 56% had postgraduate qualifications on entry and a third had undertaken postgraduate study in the UK. CONCLUSION: Based on the survey responses, the profile of internationally recruited diagnostic radiographers is relatively young but with pre-migration experience originating all over the globe. They are motivated to work in the UK particular for career progression opportunities. IMPLICATIONS FOR PRACTICE: This study provides an insight into the motivations, demographics and employment patterns of internationally recruited radiographers working in the UK.

Survey of clinical placements within pre-registration diagnostic radiography programmes in the UK and Ireland.

INTRODUCTION: Placement capacity is a challenge in supporting the clinical education of diagnostic radiography students within the UK at a time where growth in the workforce is required if service delivery needs are to be met. COVID-19 has been one of the catalysts in the growth of innovative and simulated clinical placement models. This survey seeks to understand the current picture of clinical education models and the drivers for it. METHODS: A short online MS Forms survey with mixed question types was distributed to higher education institutions (HEIs) delivering pre-registration diagnostic radiography programmes in the UK and Ireland. Descriptive and thematic analysis of data was undertaken to gain insight into the clinical placement models used. RESULTS: Responses related to 24 programmes from 17 HEIs were collated. Capacity issues, increased student numbers and ability to achieve the learning outcomes were the drivers for the model and arrangement of clinical placements. Clinical practice hours varied widely across programmes as did the proportion of simulation-based education. Respondents felt an increase in the use of placements in modalities and other settings could further increase training capacity. CONCLUSION: Opportunities to further change the clinical placement model have been identified which may alleviate some pressure points on capacity. Guidance around clinical practice hours may facilitate a sustainable approach to workforce training. Innovative placement models will require assessment strategies that align in order that students demonstrate relevant capabilities in a range of settings and value varied learning opportunities. IMPLICATIONS FOR PRACTICE: The collective engagement and innovation of higher education institutions and service providers will be needed to create sustainable quality models of clinical training and assessment to meet diagnostic radiography workforce requirements.

Radiographers' perceptions of first year diagnostic radiography students' performance following implementation of a simulation-based education model.

INTRODUCTION: Simulation-based education (SBE) partially replaced the clinical placement learning for a cohort of first year students on a BSc (Hons) Diagnostic Radiography programme. This was in response to the pressures on hospital-based training caused by increasing student numbers and following increased capability and positive outcomes for student learning in delivering SBE as a result of the COVID-19 pandemic. METHODS: A survey was distributed to diagnostic radiographers, across five NHS Trusts, involved in the clinical education of first year diagnostic radiography students at one UK university. The survey sought radiographers' perception of student performance in undertaking radiographic examinations, safety procedures, knowledge of anatomy, professionalism, and the impact of embedding simulation-based education through multichoice and free text questions. Descriptive and thematic analysis of the survey data was undertaken. RESULTS: Twelve survey responses from radiographers across four Trusts were collated. Responses indicated the majority of radiographers perceived students to require the expected level of assistance in undertaking appendicular examinations, applying infection control and radiation safety measures, and had the expected level of radiographic anatomy knowledge. Students also interacted appropriately with service users, demonstrated increased confidence in coming into the clinical environment and were receptive to feedback. Some variation was noted, particularly in professionalism and engagement, though not always attributed to SBE. CONCLUSION: Replacement of clinical placement with SBE was perceived to have provided appropriate learning opportunities and some additional benefits, however it was felt by some radiographers that SBE could not replace the experience of the real imaging environment. IMPLICATIONS FOR PRACTICE: Embedding simulated-based education requires a holistic approach and close collaboration with placement partners to ensure complimentary learning experiences in the clinical placement setting, and support achievement of the learning outcomes.

Multiomics analysis of adaptation to repeated DNA damage in prostate cancer cells.

DNA damage is frequently utilized as the basis for cancer therapies; however, resistance to DNA damage remains one of the biggest challenges for successful treatment outcomes. Critically, the molecular drivers behind resistance are poorly understood. To address this question, we created an isogenic model of prostate cancer exhibiting more aggressive characteristics to better understand the molecular signatures associated with resistance and metastasis. 22Rv1 cells were repeatedly exposed to DNA damage daily for 6 weeks, similar to patient treatment regimes. Using Illumina Methylation EPIC arrays and RNA-seq, we compared DNA methylation and transcriptional profiles between the parental 22Rv1 cell line and the lineage exposed to prolonged DNA damage. Here we show that repeated DNA damage drives the molecular evolution of cancer cells to a more aggressive phenotype and identify molecular candidates behind this process. Total DNA methylation was increased while RNA-seq demonstrated these cells had dysregulated expression of genes involved in metabolism and the unfolded protein response (UPR) with Asparagine synthetase (ASNS) identified as central to this process. Despite the limited overlap between RNA-seq and DNA methylation, oxoglutarate dehydrogenase-like (OGDHL) was identified as altered in both data sets. Utilising a second approach we profiled the proteome in 22Rv1 cells following a single dose of radiotherapy. This analysis also highlighted the UPR in response to DNA damage. Together, these analyses identified dysregulation of metabolism and the UPR and identified ASNS and OGDHL as candidates for resistance to DNA damage. This work provides critical insight into molecular changes which underpin treatment resistance and metastasis.

Concordance facilitates access in diabetes care--service provider perspectives of service improvement and cultural competency.

AIMS: Inequalities between different ethnic groups in diabetes care and outcomes are well documented in the UK. This research sought to explore and understand how national and local policy interventions impacted upon access and the development of culturally competent diabetes services from the care provider perspective. METHODS: This paper describes the care provider perspective of access to diabetes care in ethnically mixed populations from a thematic analysis of 14 semi-structured interviews conducted with professionals, at three study sites, with different roles in the diabetes care pathway. RESULTS: National policy level initiatives to improve quality have led to quality improvements at a practical level. These achievements, however, have been unable to address all aspects of care that service providers identified as important in facilitating access for all patient groups. Concordance emerged as a key process in improving access to care within local systems and barriers to this exist at different levels and are greater for some groups of patients compared with others. CONCLUSIONS: Concordance is a key concept that underpins access and cultural competency in diabetes service improvement. A focus on concordance at different levels within local systems may improve access to quality diabetes care for ethnic minority groups.

A single-centre experience of implementing a rapid CXR reporting and CT access pathway for suspected lung cancer: Initial outcomes.

INTRODUCTION: Lung cancer remains a major cause of preventable death and early diagnosis is critical to improving survival chances. The chest X-ray (CXR) remains the most common initial investigation, but clinical pathways need to support timely diagnosis through, where necessary, escalation of abnormal findings to ensure priority reporting and early CT scan. METHODS: This single-centre study included a retrospective evaluation of a rapid lung cancer CXR pathway in its first year of operation (May 2018-April 2019). The pathway was initially designed for primary care referrals but could also be used for any CXR demonstrating abnormal findings. A parallel cross-sectional survey of radiographers explored their understanding, adherence and concerns regarding their role in the pathway operation. RESULTS: Primary care referrals on the rapid diagnostic pathway were low (n = 51/21,980; 0.2%), with 11 (21.6%) requiring a CT scan. A further 333 primary care CXR were escalated by the examining radiographer, with 100 (30.0%) undergoing a CT scan. Overall, 64 of the CT scans (57.7%) were abnormal or demonstrated suspicious findings warranting further investigation. There were 39 confirmed primary lung carcinomas, most with advanced disease. Survey responses showed that most radiographers were familiar with the pathway but some expressed concerns regarding their responsibilities and limited knowledge of CXR pathologies. CONCLUSION: This baseline evaluation of the rapid lung cancer pathway demonstrated poor referral rates from primary care and identified the need for improved engagement. Radiographer escalation of abnormal findings is an effective adjunct but underlines the need for appropriate awareness, training, and ongoing support. IMPLICATIONS FOR PRACTICE: Engagement of the multiprofessional team is critical in new pathway implementation. Rapid diagnostic pathways can enable early diagnosis and the radiographer has a key role to play in their success.

A role for the medial preoptic area in CGRP-induced suppression of pulsatile LH secretion in the female rat.

Calcitonin gene-related peptide (CGRP) is involved in a variety of stress responses and plays a pivotal role in stress-induced suppression of the GnRH pulse generator in the rat. Intracerebroventricular administration of CGRP suppresses luteinizing hormone (LH) pulses and increases Fos expression within the medial preoptic area (mPOA) and paraventricular nucleus (PVN). The aims of the present study were to investigate whether the mPOA or PVN are sites of action for CGRP-induced suppression of LH pulses and whether lipopolysaccharide (LPS), restraint or insulin-induced hypoglycaemia, stressors known to suppress LH pulses, affect mRNA expression for CGRP and its receptor subunits (calcitonin receptor-like receptor (CL) and RAMP-1) in the mPOA and PVN. Micro-infusion of CGRP (50, 250 or 500 pmol) into the mPOA, but not the PVN, dose-dependently suppressed LH pulse frequency. LPS, restraint and hypoglycaemia suppressed RAMP-1 mRNA, but not CL or CGRP mRNA expression in the mPOA. In the PVN, all three stressors suppressed CL mRNA expression, but only LPS or restraint suppressed RAMP-1 mRNA, and CGRP mRNA was unaffected. These results provide evidence that, unlike the PVN, the mPOA might play an important role in the inhibitory effect of CGRP on pulsatile LH secretion. Additionally, CGRP receptor function may be involved in this brain region in stress-induced suppression of the GnRH pulse generator.

Reversible cleavage and formation of the dioxygen O-O bond within a dicopper complex.

A key step in dioxygen evolution during photosynthesis is the oxidative generation of the O-O bond from water by a manganese cluster consisting of M2(mu-O)2 units (where M is manganese). The reverse reaction, reductive cleavage of the dioxygen O-O bond, is performed at a variety of dicopper and di-iron active sites in enzymes that catalyze important organic oxidations. Both processes can be envisioned to involve the interconversion of dimetal-dioxygen adducts, M2(O2), and isomers having M2(mu-O)2 cores. The viability of this notion has been demonstrated by the identification of an equilibrium between synthetic complexes having [Cu2(mu-eta2:eta2-O2)]2+ and [Cu2(mu-O)2]2+ cores through kinetic, spectroscopic, and crystallographic studies.

Adapting the Structured Operational Research Training Initiative (SORT IT) for high-income countries.

SORT IT (Structured Operational Research Training InitiaTive) is a successful capacity building programme started 10 years ago to develop operational research skills in low- and middle-income countries. Public Health England (PHE) aims to embed a culture of research in front-line staff, and SORT IT has been adapted to train frontline health protection professionals at PHE North West (PHE NW) to collate, analyse and interpret routinely collected data for evidence-informed decision-making. Six participants from the PHE NW Health Protection team were selected to attend a two-module course in Liverpool, UK, in May and in November 2018. Five participants finished the course with completed papers on characteristics and burden of influenza-like illness in elderly care homes (two papers), use of dried blood spots for blood-borne virus screening in prisons, uptake of meningococcal ACWY (groups A, C, W-135 and Y) vaccine in schoolchildren and fires in waste management sites. The SORT IT course led to 1) new evidence being produced to inform health protection practice, and 2) agreement within PHE NW to continue SORT IT with two courses per year, and 3) showed how a research capacity building initiative for low- and middle-income countries that combines 'learning with doing' can be adapted and used in a high-income country.

SORT IT (Structured Operational Research Training InitiaTive) est un programme fructueux de renforcement des capacités qui a démarré il y a 10 ans afin de développer des compétences en recherche opérationnelle dans les pays à revenu faible et moyen. Public Health England (PHE) vise à incorporer une culture de recherche au sein du personnel de première ligne. SORT IT a été adapté afin de former les professionnels de protection de la santé de première ligne à PHE-North West (PHE-NW) pour compiler, analyser et interpréter les données recueillies en routine en vue de prises de décisions basées sur des preuves. Six participants de l'équipe de PHE-NW Health Protection ont été choisis pour participer à un cours de deux modules à Liverpool, Royaume-Uni, en mai 2018 et en novembre 2018 respectivement. Cinq participants ont terminé le cours avec des articles achevés sur les caractéristiques et le fardeau des syndromes grippaux dans les maisons de retraite (deux articles), l'utilisation de gouttes de sang séché pour le dépistage des virus transmis par le sang dans les prisons, la couverture du vaccin anti-méningococcique ACWY (groupes A, C, W-135 and Y) chez les écoliers et les incendies dans les dépôts d'ordures. Les résultats et l'impact de cette approche incluent 1) la production de nouvelles preuves visant à informer les pratiques de protection de la santé ; 2) un accord au sein de PHE-NW pour poursuivre SORT IT avec deux cours par an ; et 3) la démonstration de la manière dont une initiative de renforcement des capacités de recherche destinée aux pays à revenu faible et moyen, qui combine « l'apprentissage par la pratique ¼, peut être adaptée et utilisée dans un pays à haut revenu.

El programa SORT IT (por Structured Operational Research Training InitiaTive) es una iniciativa eficaz de fortalecimiento de la capacidad, orientada a crear competencias en investigación operativa en los países de ingresos bajos y medianos, que se inició hace 10 años. La finalidad del organismo inglés de salud pública (PHE, por Public Health England) consiste en incorporar la cultura de la investigación en la práctica del personal de primera línea; el programa SORT IT se adaptó con miras a capacitar a los profesionales que prestan directamente la protección de la salud en el PHE-NW (noroccidente) para recopilar, analizar e interpretar los datos recogidos de manera sistemática y fundamentar así la adopción de decisiones basadas en la evidencia. Se escogieron seis participantes del equipo de protección de salud del PHE-NW para que asistieran a un curso en dos módulos en Liverpool, RU, en mayo del 2018 y noviembre del 2018. Cinco de los participantes terminaron el curso con la elaboración de artículos sobre las características y la carga de morbilidad por síndrome gripal en los hogares de ancianos (dos artículos), la utilización en las prisiones de muestras de manchas de sangre seca para el tamizaje de los virus de transmisión sanguínea, la aceptación de la vacuna ACWY (grupos A, C, W-135 and Y) contra el meningococo en los niños de edad escolar y los incendios en los centros de gestión de desechos. Los resultados y el impacto de esta iniciativa fueron los siguientes 1) se obtuvo nueva evidencia para fundamentar las prácticas de la protección de la salud; 2) se acordó continuar el programa SORT IT en el PHE-NW con dos cursos por año; y 3) se demostró cómo se puede adaptar una iniciativa de fortalecimiento de la capacidad en investigación dirigida a países de ingresos bajos y medianos, que asocia "aprender con hacer" para utilizarla en un país de ingresos altos.

Tuberculosis-diabetes screening: how well are we doing? A mixed-methods study from North India.

SETTING: Public health care facilities in Sonipat District, Haryana State, India. OBJECTIVES: To assess 1) the proportion of tuberculosis (TB) patients screened for diabetes mellitus (DM) and vice versa, 2) factors associated with screening, and 3) the enablers, barriers and solutions related to screening. DESIGN: A mixed-methods study with quantitative (cohort study involving record reviews of patients registered between November 2016 and April 2017) and qualitative (interviews of patients, health care providers [HCPs] and key district-level staff) components. RESULTS: Screening for TB among DM patients was not implemented, despite documents indicating that it had been. Of 562 TB patients, only 137 (24%) were screened for DM. TB patients registered at tertiary and secondary health centres were more likely to be screened than primary health centres. Low patient awareness, poor knowledge of guidelines among HCPs, lack of staff and inadequate training were barriers to screening. Enablers were the positive attitude of HCPs and programme staff. The key solutions suggested were to improve awareness of HCPs and patients regarding the need for screening, training of HCPs and wider availability of DM testing facilities. CONCLUSION: The implementation of bidirectional screening was poor. Adequate staffing, regular training, continuous laboratory supplies for DM diagnosis and widespread publicity should be ensured.

A comparison of the yield and relative cost of active tuberculosis case-finding algorithms in Zimbabwe.

SETTING: Ten districts and three cities in Zimbabwe. OBJECTIVE: To compare the yield and relative cost of identifying a case of tuberculosis (TB) using the three WHO-recommended algorithms (WHO2b, symptom inquiry only; WHO2d, chest X-ray [CXR] after a positive symptom inquiry; WHO3b, CXR only) and the Zimbabwe active case finding (ZimACF) algorithm (symptom inquiry plus CXR) to everyone. DESIGN: Cross-sectional study using data from the ZimACF project. RESULTS: A total of 38 574 people were screened from April to December 2017; 488 (1.3%) were diagnosed with TB using the ZimACF algorithm. Fewer TB cases would have been diagnosed with the WHO-recommended algorithms. This ranged from 7% fewer (34 cases) with WHO3b, 18% fewer (88 cases) with WHO2b and 25% fewer (122 cases) with WHO2d. The need for CXR ranged from 36% (WHO2d) to 100% (WHO3b). The need for bacteriological confirmation ranged from 7% (WHO2d) to 40% (ZimACF). The relative cost per case of TB diagnosed ranged from US$180 with WHO3b to US$565 for the ZimACF algorithm. CONCLUSION: The ZimACF algorithm had the highest case yield, but at a much higher cost per case than the WHO algorithms. It is possible to switch to algorithm WHO3b, but the trade-off between cost and yield needs to be reviewed by the Zimbabwean National TB Programme.

Influence of Ebola on tuberculosis case finding and treatment outcomes in Liberia.

Setting: National Leprosy and Tuberculosis (TB) Control Programme, Liberia. Objectives: To assess TB case finding, including human immunodeficiency virus (HIV) associated interventions and treatment outcomes, before (January 2013-March 2014), during (April 2014-June 2015) and after (July-December 2015) the Ebola virus disease outbreak. Design: A cross-sectional study and retrospective cohort analysis of outcomes. Results: The mean quarterly numbers of individuals with presumptive TB and the proportion diagnosed as smear-positive were: pre-Ebola (n = 7032, 12%), Ebola (n = 6147, 10%) and post-Ebola (n = 6795, 8%). For all forms of TB, stratified by category and age group, there was a non-significant decrease in the number of cases from the pre-Ebola to the Ebola and post-Ebola periods. There were significant decreases in numbers of cases with smear-positive pulmonary TB (PTB) from the pre-Ebola period (n = 855), to the Ebola (n = 640, P < 0.001) and post-Ebola (n = 568, P < 0.001) periods. The proportions of patients tested for HIV, found to be HIV-positive and started on antiretroviral therapy decreased as follows: pre-Ebola (respectively 72%, 15% and 34%), Ebola (69%, 14% and 30%) and post-Ebola (68%, 12% and 26%). Treatment success rates among TB patients were: 80% pre-Ebola, 69% Ebola (P < 0.001) and 73% post-Ebola (P < 0.001). Loss to follow-up was the main contributing adverse outcome. Conclusion: The principal negative effects of Ebola were the significant decreases in diagnoses of smear-positive PTB, the declines in HIV testing and antiretroviral therapy uptake and poor treatment success. Ways to prevent these adverse effects from recurring in the event of another Ebola outbreak need to be found.

Contexte : Programme national de la tuberculose (TB), Liberia.Objectifs : Evaluer la détection des cas de TB, y compris les interventions associées au virus de l'immunodéficience humaine (VIH) et les résultats du traitement, avant (1 janvier 2013­31 mars 2014), pendant (1 avril 2014­30 juin 2015) et après la flambée d'Ebola (1 juillet­31 décembre 2015).Schéma : Une etude transversale et analyse de cohorte rétrospective des résultats.Résultats : Le nombre moyen mensuel par trimestre de présomptions de TB et de pourcentages de frottis positifs détectés était : pré-Ebola (n = 7032, 12%), pendant Ebola (n = 6147, 10%) et post-Ebola (n = 6795, 8%). Pour les TB toutes formes, stratifiées par catégorie et groupe d'âge, il y a eu une diminution non significative des nombres des périodes pré-Ebola à pendant Ebola et post-Ebola. Il y a eu une diminution significative des TB pulmonaire à frottis positif : pré-Ebola (855), pendant-Ebola (640, P < 0,001) et post-Ebola (568, P < 0,001). Les proportions de patients testés pour le VIH, trouvés VIH positifs et mis sous traitement antirétroviral (TAR) ont diminué : pré-Ebola (respectivement 72%, 15% et 34%), Ebola (69%, 14% et 30%) et post-Ebola (68%, 12% et 26%). Les taux de succès du traitement des patients TB ont été 80% pré-Ebola, 69% pendant Ebola (P < 0,001) et 73% post-Ebola (P < 0,001), avec les pertes de vue comme contributions principales aux résultats défavorables.Conclusion : Les principaux effets négatifs d'Ebola ont été des diminutions significatives du diagnostic de TBP à frottis positif, des déclins du test VIH et de la prise du TAR et un résultat médiocre du traitement. Il faut trouver des moyens d'éviter que ces effets négatifs ne surviennent à nouveau en cas de nouvelle épidémie.

Marco de referencia: El programa nacional contra la tuberculosis (TB) de Liberia.Objetivos: Evaluar la búsqueda de casos de TB teniendo en cuenta las intervenciones asociadas con el virus de la inmunodeficiencia humana (VIH) y examinar los desenlaces terapéuticos antes del brote epidémico de fiebre hemorrágica del Ébola (de 1 enero del 2013 a 31 marzo del 2014), durante el brote (del 1 abril del 2014 a 30 junio del 2015) y después del mismo (de 1 julio a 31 diciembre del 2015).Método: Un estudio transversal con análisis de cohortes retrospectivo de los desenlaces terapéuticos.Resultados: Antes de la epidemia, el promedio mensual por trimestres de los casos con presunción de TB fue 7032 (12% de baciloscopias positivas), durante el brote fue 6147 (10%) y después de la epidemia fue 6795 (8%). En todos los casos de TB, estratificados por categorías y grupos de edad, durante la epidemia y después de ella se observó una disminución no significativa de las cifras, en comparación con el período anterior a la epidemia. Ocurrió una neta disminución de los casos de TB pulmonar con baciloscopia positiva, a saber: antes de la epidemia del Ébola n = 855, durante el brote n = 640 (P < 0,001) y después del mismo n = 568 (P < 0,001). Se observó una disminución de la proporción de pacientes en quienes se practicó la prueba del VIH, que obtuvieron un resultado positivo y que iniciaron el tratamiento antirretrovírico (ART), respectivamente como sigue: antes del brote del Ébola 72%, 15% y 34%, durante la epidemia 69%, 14% y 30% y después del brote 68%, 12% y 26%. La tasa de éxito del tratamiento antituberculoso fue 80% antes del brote, 69% durante la epidemia (P < 0,001) y 7% después de la misma (P < 0,001); el desenlace desfavorable predominante fue la pérdida durante el seguimiento.Conclusión: Las principales consecuencias negativas de la epidemia del Ébola fueron una disminución considerable en el diagnóstico de TB pulmonar con baciloscopia positiva, una reducción de la práctica de la prueba del VIH y de la iniciación del ART y tasas insuficientes de éxito terapéutico. Se recomienda definir las medidas que puedan evitar estas consecuencias adversas, en la eventualidad de una futura epidemia.