Continuous quality improvement in a community-wide TB screening and prevention programme in Papua New Guinea.

SETTING: Daru Island in Papua New Guinea (PNG) has a high prevalence of TB and multidrug-resistant TB (MDR-TB). OBJECTIVE: To evaluate the early implementation of a community-wide project to detect and treat TB disease and infection, outline the decision-making processes, and change the model of care. DESIGN: A continuous quality improvement (CQI) initiative used a plan-do-study-act (PDSA) framework for prospective implementation. Care cascades were analysed for case detection, treatment, and TB preventive treatment (TPT) initiation. RESULTS: Of 3,263 people screened for TB between June and December 2023, 13.7% (447/3,263) screened positive (CAD4TB or symptoms), 77.9% (348/447) had Xpert Ultra testing, 6.9% (24/348) were diagnosed with TB and all initiated treatment. For 5-34-year-olds without active TB (n = 1,928), 82.0% (1,581/1,928) had tuberculin skin testing (TST), 96.1% (1,519/1,581) had TST read, 23.0% (350/1,519) were TST-positive, 95.4% (334/350) were TPT eligible, and 78.7% (263/334) initiated TPT. Three PDSA review cycles informed adjustments to the model of care, including CAD4TB threshold and TPT criteria. Key challenges identified were meeting screening targets, sputum unavailability from asymptomatic individuals with high CAD4TB scores, and consumable stock-outs. CONCLUSION: CQI improved project implementation by increasing the detection of TB disease and infection and accelerating the pace of screening needed to achieve timely community-wide coverage.

CONTEXTE: L'île de Daru en Papouasie-Nouvelle-Guinée (PNG) présente une forte prévalence de la TB et de la TB multirésistante (MDR-TB). OBJECTIF: Évaluer la mise en œuvre précoce d'un projet à l'échelle de la communauté pour détecter et traiter la TB et l'infection, décrire les processus de prise de décision et changer le modèle de soins. CONCEPTION: Une initiative d'amélioration continue de la qualité (CQI, pour l'anglais « continuous quality improvement ¼) a utilisé un cadre de planification, d'action, d'étude, d'action (PDSA, pour l'anglais «plan-do-study-act ¼) pour la mise en œuvre prospective. Les cascades de soins ont été analysées pour la détection des cas, le traitement et l'initiation du traitement préventif de la TB. RÉSULTATS: Sur 3 263 personnes dépistées pour la TB entre juin et décembre 2023, 13,7% (447/3 263) ont été dépistées positives (CAD4TB ou symptômes), 77,9% (348/447) ont subi un test Xpert Ultra, 6,9% (24/348) ont reçu un diagnostic de TB et toutes ont commencé un traitement. Chez les 5 à 34 ans sans TB active (n = 1 928), 82,0% (1 581/1 928) ont subi un test cutané à la tuberculine (TCT), 96,1% (1 519/1 581) ont eu un test de dépistage du TCT, 23,0% (350/1 519) étaient positifs au TCT, 95,4% (334/350) étaient éligibles au TPT et 78,7% (263/334) ont initié le TPT. Trois cycles d'examen PDSA ont permis d'ajuster le modèle de soins, y compris le seuil CAD4TB et les critères TPT. Les principaux défis identifiés étaient l'atteinte des objectifs de dépistage, l'indisponibilité des expectorations chez les personnes asymptomatiques avec des scores CAD4TB élevés et les ruptures de stock de consommables. CONCLUSION: L'ACQ a amélioré la mise en œuvre du projet en augmentant la détection de la TB et de l'infection et en accélérant le rythme de dépistage nécessaire pour atteindre une couverture à l'échelle de la communauté en temps opportun.

Operational research highlights ongoing challenges for comprehensive TB services in Papua New Guinea.

Papua New Guinea (PNG) is a high-burden country for TB, with an estimated annual TB incidence rate of 432 per 100,000 population. There are major challenges to the provision of quality care for TB patients with high rates of loss to follow-up, and multidrug-resistant TB is increasingly detected. In 2022-2023, the second Structured Operational Research Training IniTiative (SORT-IT) for TB was undertaken. Eight participants completed the course, and the outputs from these research projects highlight important current operational issues for the PNG TB programme in a range of settings. The first four articles in the series are published in this issue of Public Health Action, with the remainder to follow in subsequent issues.

Loss to follow-up among adults with drug-resistant TB in Papua New Guinea.

SETTING: Multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB) is now endemic in the National Capital District (NCD), Papua New Guinea. Loss to follow-up (LTFU) is a challenge. OBJECTIVE: To evaluate and identify risk factors for LTFU, including pre-treatment LTFU, in adults with MDR/RR-TB at Port Moresby General Hospital (PMGH). DESIGN: A retrospective analysis of treatment initiation in adults diagnosed with MDR/RR-TB (2018-2022) and outcomes for a cohort treated for MDR/RR-TB (2014-2019). We assessed the factors associated with LTFU using multivariate logistic regression. RESULTS: Of 95 patients diagnosed with MDR/RR-TB at PMGH from 2018 to 2022, 21 (22%) were lost to follow-up before treatment. Of the 658 adults who initiated treatment for MDR/RR-TB at PMGH from 2014 to 2019, 161 (24%) were lost to follow-up during treatment. A higher proportion of patients on injectable-containing long regimens (110/404, 27%) were lost to follow-up than those on the all-oral regimen containing bedaquiline (13/66, 12%). Treatment loss to follow-up was associated with age (35-54 years age group: aOR 0.49, 95% CI 0.32-0.77; 55-75 years age group: aOR 0.42, 95% CI 0.19-0.90; compared to the 15-34 years age group), residence outside of NCD (aOR 1.79, 95% CI 1.04-3.06), and year of treatment initiation. CONCLUSION: Pre-treatment LTFU requires programmatic focus. Shorter oral regimens and decentralised services may address the reasons for higher LTFU in younger people and people living outside NCD.

CONTEXTE: La TB multirésistante/résistante à la rifampicine (MDR-TB/RR-TB, pour l'anglais « multidrug/rifampicin-resistant TB ¼) est maintenant endémique dans le district de la capitale nationale (NCD, pour l'anglais « National Capital District ¼), en Papouasie-Nouvelle-Guinée. La perte de suivi (LTFU, pour l'anglais « loss to follow-up ¼) est un défi. OBJECTIF: Évaluer et identifier les facteurs de risque de LTFU, y compris le LTFU avant le traitement, chez les adultes atteints de MDR-TB/RR-TB à Port Moresby General Hospital (PMGH). CONCEPTION: Une analyse rétrospective de l'initiation du traitement chez les adultes diagnostiqués avec une MDR-TB/RR-TB (2018­2022) et des résultats pour une cohorte traitée pour la MDR-TB/RR-TB (2014­2019). Nous avons évalué les facteurs associés au LTFU à l'aide d'une régression logistique multivariée. RÉSULTATS: Sur les 95 patients diagnostiqués avec une MDR-TB/RR-TB à PMGH de 2018 à 2022, 21 (22%) ont été perdus de vue avant le traitement. Sur les 658 adultes qui ont commencé un traitement pour la MDR-TB/RR-TB à PMGH entre 2014 et 2019, 161 (24%) ont été perdus de vue pendant le traitement. Une proportion plus élevée de patients recevant des régimes longs contenant des injectables (110/404 ; 27%) ont été perdus de vue que ceux recevant un régime entièrement oral contenant de la bédaquiline (13/66 ; 12%). La perte de traitement au suivi était associée à l'âge (groupe d'âge de 35 à 54 ans : aOR 0,49 ; IC à 95% 0,32 à 0,77 ; groupe d'âge de 55 à 75 ans : aOR 0,42 ; IC à 95% 0,19 à 0,90 ; par rapport au groupe d'âge de 15 à 34 ans), à la résidence en dehors des NCD (aOR 1,79 ; IC à 95% 1,04 à 3,06) et à quelques années de début de traitement. CONCLUSION: Le LTFU avant le traitement nécessite une orientation programmatique. Des régimes oraux plus courts et des services décentralisés peuvent s'attaquer aux raisons de l'augmentation du LTFU chez les jeunes et les personnes vivant en dehors des NCD.

High rates of unfavourable TB treatment outcomes observed in Madang Province, Papua New Guinea.

SETTING: Madang Province is located on the northern coast of Papua New Guinea (PNG), a critical mixing point between the populous highlands and more remote regions. Madang Province faces challenges with limited capacity to diagnose and treat TB. OBJECTIVE: To describe the TB caseload and investigate factors associated with known unfavourable treatment outcomes. DESIGN: This is a retrospective cohort study using routinely collected TB programmatic data for treatments commenced 1 January 2019 to 31 December 2021. Using multivariable logistic regression, factors associated with known unfavourable treatment outcomes-death, failure after treatment, and loss to follow-up (LTFU)-were evaluated. RESULTS: Of the 4,668 registered and treated, 3,755 had an evaluated outcome, and 33% had unfavourable outcomes, most commonly LTFU (23%). Unfavourable treatment outcomes were significantly associated with HIV-untested (aOR 2.82 compared to HIV-negative; 95% CI 2.39-3.33), having drug-resistant TB (aOR 3.26 compared to drug-susceptible TB, 95% CI 1.18-9.00), and travel time to the health facility 1-<3 hours by foot (aOR 3.53 compared to <1 hour by foot; 95% CI 1.04-12.06). CONCLUSION: High LTFU from TB treatment was associated with factors that indicate barriers to access to care and treatment completion. Decentralisation and strengthening of TB services for improved person-centred care and treatment support are urgently required in Madang Province.

CADRE: La province de Madang est située sur la côte nord de la Papouasie-Nouvelle-Guinée (PNG), un point de mélange essentiel entre les hauts plateaux peuplés et les régions plus éloignées. La province de Madang est confrontée à des défis avec des capacités limitées pour diagnostiquer et traiter la TB. OBJECTIF: Décrire le nombre de cas de TB et enquêter sur les facteurs associés aux résultats défavorables connus du traitement. METHODE: Il s'agit d'une étude de cohorte rétrospective utilisant des données programmatiques de lutte contre la TB collectées en routine pour les traitements commencés du 1er janvier 2019 au 31 décembre 2021. À l'aide d'une régression logistique multivariée, les facteurs associés aux résultats défavorables connus du traitement (décès, échec après le traitement et perte de suivi [LTFU, pour l'anglais « loss to follow-up ¼) ont été évalués. RÉSULTATS: Sur les 4668 personnes enregistrées et traitées, 3755 ont eu un résultat évalué et 33% ont eu des résultats défavorables, le plus souvent des LTFU (23%). Les résultats défavorables du traitement étaient significativement associés au fait que les personnes n'ayant pas fait l'objet d'un test de dépistage du VIH (OR ajusté [ORa] 2,82 par rapport aux personnes séronégatives ; IC à 95% 2,39­3,33), ayant une TB pharmacorésistante (ORa 3,26 par rapport à la TB sensible aux médicaments, IC à 95% 1,18­9,00) et le temps de déplacement jusqu'à l'établissement de santé étant de 1 à <3 h à pied (ORa 3,53 contre <1 h à pied ; IC à 95% 1,04­12,06). CONCLUSION: Un taux élevé dee LTFU provenant du traitement de la TB était associé à des facteurs indiquant des obstacles à l'accès aux soins et à l'achèvement du traitement. La décentralisation et le renforcement des services de lutte contre la TB pour améliorer les soins centrés sur la personne et le soutien au traitement sont nécessaires de toute urgence dans la province de Madang.

TB burden and diagnostic challenges at Sandaun Provincial Hospital in West Sepik Province of PNG, 2016-2021.

SETTING: Bacteriological confirmation of TB diagnosis remains a key operational challenge in Papua New Guinea. Sandaun Provincial Hospital (SPH) is the main TB diagnostic and treatment centre of West Sepik Province. OBJECTIVE: To evaluate TB caseload, patient characteristics, and quality of diagnosis at SPH between 2016 and 2021. DESIGN: A retrospective descriptive study using TB treatment, laboratory, and presumptive TB registers to collect data on all TB patients. We used multivariable logistic regression to determine factors associated with bacteriological confirmation. RESULTS: Of 1,305 TB patients registered, 25% were children (<15 years) and 30% had extrapulmonary TB. The quality of sputum was associated with a positive smear microscopy result (P = 0.002). The proportion bacteriologically confirmed was low (37.3%), being higher in young adults 15-44 years (50.6%, 377/745) than in children <15 years (6.3%, 20/319) or older adults ≥45 years (37.6%, 68/181). Bacteriological confirmation was less likely in people travelling ≥3 hours to a health facility (adjusted OR 0.58, 95% CI 0.34-0.97) and extrapulmonary TB (aOR 0.01, 95% CI 0.00-0.03) but more likely for retreatment cases (aOR 1.59, 95% CI 1.00-2.51). CONCLUSION: Diagnostic services in West Sepik Province need strengthening to achieve a higher proportion of bacteriological confirmation in new pulmonary and extrapulmonary TB cases of all ages and improve access for the rural population.

CONTEXTE: La confirmation bactériologique du diagnostic de la TB reste un défi opérationnel majeur en Papouasie-Nouvelle-Guinée. L'hôpital provincial de Sandaun (SPH) est le principal centre de diagnostic et de traitement de la TB de la province du Sepik occidental. OBJECTIF: Évaluer le nombre de cas de TB, les caractéristiques des patients et la qualité du diagnostic à SPH entre 2016 et 2021. MÉTHODE: Une étude descriptive rétrospective utilisant le traitement de la TB, les registres de laboratoire et les registres de la TB présumée pour recueillir des données sur tous les patients atteints de TB. Nous avons utilisé la régression logistique multivariée pour déterminer les facteurs associés à la confirmation bactériologique. RÉSULTATS: Sur les 1 305 patients atteints de TB enregistrés, 25% étaient des enfants (<15 ans) et 30% avaient une TB extrapulmonaire. La qualité des expectorations a été associée à un résultat positif à la microscopie (P = 0,002). La proportion de bactéries confirmées était faible (37,3%), plus élevée chez les jeunes adultes de 15 à 44 ans (50,6% ; 377/745) que chez les enfants <15 ans (6,3% ; 20/319) ou les adultes plus âgés ≥45 ans (37,6% ; 68/181). La confirmation bactériologique était moins probable chez les personnes voyageant ≥3 h pour se rendre dans un établissement de santé (OR ajusté [ORa] 0,58 ; IC à 95% 0,34­0,97) et la TB extrapulmonaire (ORa 0,01 ; IC à 95% 0,00­0,03) mais plus probable pour les cas de retraitement (ORa 1,59 ; IC à 95% 1,00­2,51). CONCLUSION: Les services de diagnostic dans la province du Sepik occidental doivent être renforcés afin d'atteindre une proportion plus élevée de cas de TB pulmonaire et extrapulmonaire de tous âges et d'améliorer l'accès pour la population rurale.

Standards for clinical trials for treating TB.

BACKGROUND: The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice.METHODS: A global panel of experts participated in a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached.RESULTS: Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.CONCLUSION: These standards should improve the efficiency and effectiveness of evidence generation, as well as the translation of research into policy and practice.

Knowledge and attitudes towards TB among healthcare workers in Yogyakarta, Indonesia.

SETTING: Healthcare workers (HCWs) are at an increased risk of TB worldwide. Individual knowledge and attitudes may influence HCW behaviour, and subsequently, TB risk. Indonesia has the second highest case-load globally. OBJECTIVE: To measure TB knowledge and attitudes among a subsection of HCWs in Yogyakarta, Indonesia, and to explore factors associated with knowledge. DESIGN: A cross-sectional study using an online survey targeting all HCW staff was conducted among HCWs from four pre-selected healthcare facilities in Yogyakarta. Descriptive analysis and a multivariable linear regression were undertaken. RESULTS: Of 792 HCWs, 290 (37%) completed the survey; 64% (n = 185) were medical staff, 33% (n = 95) reported previously being tested for active TB and 8% (n = 24) for latent TB. The mean knowledge score was 7.2/11 (SD 1.5): this was higher among medical staff and those with university education (average score increase: 0.53, 95% CI 0.15 to 0.90; and 0.38, 95% CI 0.01 to 0.74, respectively). Participants agreed that free access to TB screening (93%) and treatment (93%) should be available, and 57% of medical and 77% of non-medical staff would take preventive therapy if eligible. CONCLUSION: Participants had practical understanding of TB; however, gaps were identified in knowledge about TB disease progression and prevention. Prevention programmes were viewed positively. We suggest further TB education and engagement programmes for HCWs.

CONTEXTE: Les travailleurs de la santé (HCW) sont exposés à un risque accru de TB dans le monde entier. Les connaissances et les attitudes individuelles peuvent influencer le comportement des HCW et, par conséquent, le risque de TB. L'Indonésie a le deuxième plus grand nombre de cas dans le monde. OBJECTIF: Mesurer les connaissances et les attitudes à l'égard de la TB parmi un sous-groupe de HCW à Yogyakarta, en Indonésie, et explorer les facteurs associés aux connaissances de la TB. MÉTHODE: Une étude transversale a été menée à l'aide d'un sondage en ligne ciblant tous les HCW de quatre établissements de santé présélectionnés à Yogyakarta. Une analyse descriptive et une régression linéaire multivariable ont été effectuées. RÉSULTATS: Sur 792 HCW, 290 (37%) ont répondu à l'enquête ; 62% (n = 181) étaient des membres du personnel médical, 33% (n = 95) ont déclaré avoir déjà été testés pour la TB active et 8% (n = 24) pour la TB latente. Le score moyen de connaissances était de 7,2/11 (SD 1,5) : il était plus élevé parmi le personnel médical et les personnes ayant une formation universitaire (augmentation moyenne du score : 0,53 ; IC 95% 0,11­0,93 et 0,38 ; IC 95% 0,01­0,74, respectivement). Les participants étaient d'accord pour dire que l'accès au dépistage (93%) et au traitement (93%) de la TB devrait être gratuit, et 57% du personnel médical et 77% du personnel non médical suivraient un traitement préventif s'ils étaient éligibles. CONCLUSION: Les participants avaient une compréhension pratique de la TB ; cependant, des lacunes ont été identifiées dans les connaissances sur la progression de la maladie et la prévention de la TB. Les programmes de prévention ont été perçus positivement. Nous suggérons d'autres programmes d'éducation et d'engagement sur la TB pour les HCW.

Methods for generating hypotheses in human enteric illness outbreak investigations: a scoping review of the evidence.

Enteric illness outbreaks are complex events, therefore, outbreak investigators use many different hypothesis generation methods depending on the situation. This scoping review was conducted to describe methods used to generate a hypothesis during enteric illness outbreak investigations. The search included five databases and grey literature for articles published between 1 January 2000 and 2 May 2015. Relevance screening and article characterisation were conducted by two independent reviewers using pretested forms. There were 903 outbreaks that described hypothesis generation methods and 33 papers which focused on the evaluation of hypothesis generation methods. Common hypothesis generation methods described are analytic studies (64.8%), descriptive epidemiology (33.7%), food or environmental sampling (32.8%) and facility inspections (27.9%). The least common methods included the use of a single interviewer (0.4%) and investigation of outliers (0.4%). Most studies reported using two or more methods to generate hypotheses (81.2%), with 29.2% of studies reporting using four or more. The use of multiple different hypothesis generation methods both within and between outbreaks highlights the complexity of enteric illness outbreak investigations. Future research should examine the effectiveness of each method and the contexts for which each is most effective in efficiently leading to source identification.

Inflammatory cytokines in type 2 diabetes mellitus as facilitators of hypercoagulation and abnormal clot formation.

BACKGROUND: The global burden of type 2 diabetes mellitus (T2DM), together with the presence of cardiovascular risk in this population, is reaching pandemic levels. A prominent feature of T2DM is chronic and systemic inflammation, with the accompanying presence of circulating and dysregulated inflammatory biomarkers; which in turn is associated with abnormal clot formation. METHODS: Here, we investigate the correlation between abnormal blood clotting, using thromboelastography (TEG), clot ultrastructure using scanning electron microscopy (SEM) and the presence of a dysregulated inflammatory cytokine profile, by examining various circulating biomarkers. RESULTS: Our results show that many biomarkers, across TEG, cytokine and lipid groups, were greatly dysregulated in the T2DM sample. Furthermore, our T2DM sample's coagulation profiles were significantly more hypercoagulable when compared to our heathy sample, and ultrastructural analysis confirmed a matted and denser clot structure in the T2DM sample. CONCLUSIONS: We suggest that dysregulated circulating molecules may in part be responsible for a hypercoagulable state and vascular dysfunction in the T2DM sample. We propose further that a personalized approach could be of great value when planning treatment and tracking the patient health status after embarking on a treatment regimes, and that looking to novel inflammatory and vascular biomarkers might be crucial.

Serum amyloid A binds to fibrin(ogen), promoting fibrin amyloid formation.

Complex associations exist between inflammation and thrombosis, with the inflammatory state tending to promote coagulation. Fibrinogen, an acute phase protein, has been shown to interact with the amyloidogenic ß-amyloid protein of Alzheimer's disease. However, little is known about the association between fibrinogen and serum amyloid A (SAA), a highly fibrillogenic protein that is one of the most dramatically changing acute phase reactants in the circulation. To study the role of SAA in coagulation and thrombosis, in vitro experiments were performed where purified human SAA, in concentrations resembling a modest acute phase response, was added to platelet-poor plasma (PPP) and whole blood (WB), as well as purified and fluorescently labelled fibrinogen. Results from thromboelastography (TEG) suggest that SAA causes atypical coagulation with a fibrin(ogen)-mediated increase in coagulation, but a decreased platelet/fibrin(ogen) interaction. In WB scanning electron microscopy analysis, SAA mediated red blood cell (RBC) agglutination, platelet activation and clumping, but not platelet spreading. Following clot formation in PPP, the presence of SAA increased amyloid formation of fibrin(ogen) as determined both with auto-fluorescence and with fluorogenic amyloid markers, under confocal microcopy. SAA also binds to fibrinogen, as determined with a fluorescent-labelled SAA antibody and correlative light electron microscopy (CLEM). The data presented here indicate that SAA can affect coagulation by inducing amyloid formation in fibrin(ogen), as well as by propelling platelets to a more prothrombotic state. The discovery of these multiple and complex effects of SAA on coagulation invite further mechanistic analyses.

La Crosse virus: a scoping review of the global evidence.

Urbanisation and climate change are altering the pattern of California serogroup viruses in North America. As La Crosse virus (LACV) is the most pathogenic of the California serogroup, it is important to identify changes in distribution, transmission and pathogenesis. A scoping review (ScR) was prioritised to summarise the global evidence on LACV. A comprehensive search strategy was used, identified references were screened for relevance and relevant articles were characterised. Each step was conducted by two independent reviewers using pre-tested forms. Analysis identified areas of research saturation and gaps. The ScR included 481 research articles that were mostly journal articles (78.2%) conducted in North America (90.9%) from 1969 to 2016. Most evidence focused on epidemiology (44.9%), virus characteristics (25.8%), transmission conditions (18.7%) and pathogenesis of LACV in hosts (18.3%). Fewer studies evaluated the accuracy of diagnostic tests (8.7%), the efficacy of treatments (3.5%), prevention and control strategies (3.1%), the economic burden of infection (0.6%) and social impact (0.2%) of LACV. None of the literature predicted the impact of climate change on LACV, nor were any cases reported in Canada. These findings are intended to guide research to close knowledge gaps and inform evidence-based decisions surrounding activities for the prevention and control of LACV.

Platelet activity and hypercoagulation in type 2 diabetes.

BACKGROUND: A strong correlation exists between type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), with CVD and the presence of atherosclerosis being the prevailing cause of morbidity and mortality in diabetic populations. T2DM is accompanied by various coagulopathies, including anomalous clot formation or amyloid fibrin(ogen), the presence of dysregulated inflammatory molecules. Platelets are intimately involved in thrombus formation and particularly vulnerable to inflammatory cytokines. METHODS: The aim of this current study was therefore to assess whole blood (hyper)coagulability, platelet ultrastructure and receptor expression, as well as the levels of IL-1ß, IL-6, IL-8 and sP-selectin in healthy and diabetic individuals. Platelet morphology was assessed through scanning electron microscopy (SEM), while assessment of GPIIb/IIIa receptor expression was performed with confocal microscopy and flow cytometry with the addition of FITC-PAC-1 and CD41-PE antibodies. IL-1ß, IL-6 and IL-8 and sP-selectin levels were assessed using a multiplex assay. RESULTS: In T2DM there is significant upregulation of circulating inflammatory markers, hypercoagulation and platelet activation, with increased GPIIb/IIIa receptor expression, as seen with flow cytometry and confocal microscopy. Analyses showed that these receptors were additionally shed onto microparticles, which was confirmed with SEM. CONCLUSIONS: Cumulatively, this provides mechanistic evidence that pathological states of platelets together with amyloid fibrin(ogen) in T2DM, might underpin an increased risk for cardiovascular events.

Impact of pyrazinamide resistance on multidrug-resistant tuberculosis in Karakalpakstan, Uzbekistan.

SETTING: The World Health Organization (WHO) recommends the inclusion of pyrazinamide (PZA) in treatment regimens for multidrug-resistant tuberculosis (MDR-TB) unless resistance has been confirmed. OBJECTIVE: To investigate the association between PZA susceptibility and MDR-TB treatment outcome among patients treated with a PZA-containing regimen and whether the duration of the intensive phase of the PZA-containing regimen affected treatment outcome. DESIGN: We conducted a retrospective cohort study including all eligible MDR-TB patients starting treatment in 2003-2013 in the TB programme in Karakalpakstan, Uzbekistan. PZA drug susceptibility testing (DST) using liquid culture was performed, and outcomes were classified according to the WHO 2013 definitions. RESULTS: Of 2446 MDR-TB patients included, 832 (34.0%) had an available baseline PZA DST result, 612 (73.6%) of whom were PZA-resistant. We found no association between treatment success and PZA susceptibility (adjusted odds ratio [aOR] 0.86, 95%CI 0.51-1.44, P = 0.6) in patients treated with PZA. Furthermore, among patients with no baseline PZA DST result, no evidence was seen of an association between treatment success and PZA treatment duration (aOR 0.86, 95%CI 0.49-1.51, P = 0.6). CONCLUSION: Treatment of MDR-TB with a standard PZA regimen does not appear to improve treatment outcomes, regardless of PZA susceptibility or duration of treatment.

The Anatomical Society's core anatomy syllabus for undergraduate nursing.

The Anatomical Society has developed a series of learning outcomes in consultation with nursing educators delivering anatomical content to undergraduate (preregistration) nursing students. A Delphi panel methodology was adopted to select experts within the field that would recommend core anatomical content in undergraduate nursing programmes throughout the UK. Using the Anatomical Society's Core Gross Anatomy Syllabus for Medical Students as a foundation, a modified Delphi technique was used to develop discipline-specific outcomes to nursing graduates. The Delphi panel consisted of 48 individuals (n = 48) with a minimum of 3 years' experience teaching anatomy to nursing students, representing a broad spectrum of UK Higher Education Institutions. The output from this study was 64 nursing specific learning outcomes in anatomy that are applicable to all undergraduate (preregistration) programmes in the UK. The new core anatomy syllabus for Undergraduate Nursing offers a basic anatomical framework upon which nurse educators, clinical mentors and nursing students can underpin their clinical practice and knowledge. The learning outcomes presented may be used to develop anatomy teaching within an integrated nursing curriculum.

Current evidence on the transmissibility of chronic wasting disease prions to humans-A systematic review.

A number of prion diseases affect humans, including Creutzfeldt-Jakob disease; most of these are due to genetic mutations in the affected individual and occur sporadically, but some result from transmission of prion proteins from external sources. Of the known animal prion diseases, only bovine spongiform encephalopathy prions have been shown to be transmissible from animals to humans under non-experimental conditions. Chronic wasting disease (CWD) is a prion disease that affects cervids (e.g., deer and elk) in North America and isolated populations in Korea and Europe. Systematic review methodology was used to identify, select, critically appraise and analyse data from relevant research. Studies were evaluated for adherence to good conduct based on their study design following the Cochrane collaboration's approach to grading the quality of evidence and the strength of recommendations (GRADE). Twenty-three studies were included after screening 800 citations from the literature search and evaluating 78 full papers. Studies examined the transmissibility of CWD prions to humans using epidemiological study design, in vitro and in vivo experiments. Five epidemiological studies, two studies on macaques and seven studies on humanized transgenic mice provided no evidence to support the possibility of transmission of CWD prions to humans. Ongoing surveillance in the United States and Canada has not documented CWD transmission to humans. However, two studies on squirrel monkeys provided evidence that transmission of CWD prions resulting in prion disease is possible in these monkeys under experimental conditions and seven in vitro experiments provided evidence that CWD prions can convert human prion protein to a misfolded state. Therefore, future discovery of CWD transmission to humans cannot be entirely ruled out on the basis of current studies, particularly in the light of possible decades-long incubation periods for CWD prions in humans. It would be prudent to continue CWD research and epidemiologic surveillance, exercise caution when handling potentially contaminated material and explore CWD management opportunities.

A scoping review of Lyme disease research relevant to public health.

Lyme disease (LD) is an emerging infectious disease in Canada associated with expansion of the geographic range of the tick vector Ixodes scapularis in eastern and central Canada. A scoping review of published research was prioritized to identify and characterize the scientific evidence concerning key aspects of LD to support public health efforts. Prior to initiation of this review, an expert advisory group was surveyed to solicit insight on priority topics and scope. A pre-tested search strategy implemented in eight databases (updated September 2016) captured relevant research. Pre-tested screening and data characterization forms were completed by two independent reviewers and descriptive analysis was conducted to identify topic areas with solid evidence and knowledge gaps. Of 19,353 records screened, 2,258 relevant articles were included in the review under the following six public health focus areas: a) surveillance/monitoring in North America (n=809); b) evaluation of diagnostic tests (n=736); c) risk factors (n=545); d) public health interventions (n=205); e) public knowledge, attitudes and/or perceptions in North America (n=202); and f) the economic burden of LD or cost-benefit of interventions (n=32). The majority of research investigated Borrelia burgdorferi (n=1,664), humans (n=1,154) and Ixodes scapularis (n=459). Sufficient research was identified for potential systematic reviews in four topic areas: a) accuracy of diagnostic tests; b) risk factors for human illness; c) efficacy of LD intervention strategies; and d) prevalence and/or incidence of LD in humans or B. burgdorferi sensu stricto in vertebrate reservoirs or ticks in North America. Future primary research could focus on closing knowledge gaps, such as the role of less studied vertebrate reservoirs in the transmission cycle. Results of this scoping review can be used to quickly identify and summarize relevant research pertaining to specific questions about LD or B. burgdorferi sensu lato in humans, vertebrate hosts or vectors, providing evidence-informed information within timelines that are conducive for public health decision-making.

Social and Economic Aspects of the Transmission of Pathogenic Bacteria between Wildlife and Food Animals: A Thematic Analysis of Published Research Knowledge.

Wildlife is a known reservoir of pathogenic bacteria, including Mycobacterium bovis and Brucella spp. Transmission of these pathogens between wildlife and food animals can lead to damaging impacts on the agri-food industry and public health. Several international case studies have highlighted the complex and cross-sectoral challenges involved in preventing and managing these potential transmission risks. The objective of our study was to develop a better understanding of the socio-economic aspects of the transmission of pathogenic bacteria between wildlife and food animals to support more effective and sustainable risk mitigation strategies. We conducted qualitative thematic analysis on a purposive sample of 30/141 articles identified in a complementary scoping review of the literature in this area and identified two key themes. The first related to the framing of this issue as a 'wicked problem' that depends on a complex interaction of social factors and risk perceptions, governance and public policy, and economic implications. The second theme consisted of promising approaches and strategies to prevent and mitigate the potential risks from transmission of pathogenic bacteria between wildlife and food animals. These included participatory, collaborative and multidisciplinary decision-making approaches and the proactive incorporation of credible scientific evidence and local contextual factors into solutions. The integration of these approaches to address 'wicked problems' in this field may assist stakeholders and decision-makers in improving the acceptability and sustainability of future strategies to reduce the transmission of pathogenic bacteria between wildlife and food animals.

A scoping review of the role of wildlife in the transmission of bacterial pathogens and antimicrobial resistance to the food Chain.

Wildlife can contribute to environmental contamination with bacterial pathogens and their transfer to the human food chain. Global usage and frequent misuse of antimicrobials contribute to emergence of new antimicrobial resistant (AMR) strains of foodborne pathogens. We conducted a scoping review of published research to identify and characterize the evidence on wildlife's role in transmission of AMR and/or bacterial pathogens to the food chain. An advisory group (AG) of 13 North American experts from diverse disciplines was surveyed to solicit insight in the review scope, priority topics and research characteristics. A pre-tested search strategy was implemented in seven bibliographic databases (1990 to January 2013). Citations were relevance screened, and key characteristics on priority topics extracted independently by two reviewers. Analysis identified topic areas with solid evidence and main knowledge gaps. North America reported 30% of 866 relevant articles. The prevalence of five targeted bacterial pathogens and/or AMR in any pathogen in wildlife was reported in 582 articles. Transmission risk factors for selected bacteria or AMR in any bacteria were reported in 300. Interventions to control transmission were discussed in 124 articles and formally evaluated in 50. The majority of primary research investigated birds, cervids, rodents, feral pigs, opossums, E. coli (n = 329), Salmonella (n = 293) and Campylobacter (n = 124). An association between wildlife and transmission of bacterial pathogens and/or AMR to the food chain was supported in 122 studies. The scoping review identified a significant body of research on the role of wild birds in the prevalence and transmission of E. coli, Salmonella and Campylobacter. There was little research employing molecular methods contributing to the evidence concerning the importance and direction of transmission of wildlife/pathogen combinations. Given the advancements of these methods, future research should focus in this area to help prioritize future intervention studies and risk mitigation strategies.

A review of nosocomial Salmonella outbreaks: infection control interventions found effective.

OBJECTIVE: To review nosocomial salmonellosis outbreaks to identify: mode of transmission; morbidity and mortality patterns; and recommendations for control and prevention. DESIGN: Documented nosocomial salmonellosis outbreaks in hospitals published from January 1995 to November 2011, written in the English language, were systematically reviewed. METHODS: The study methodology incorporated steps from the PRISMA statement for a high quality review process. Computer-aided searches of Scopus, CAB Global Health and CINAHL(®), the Cumulative Index to Nursing and Allied Health Literature were completed to identify relevant outbreak reports written in English. To validate the electronic search methodology, bibliographies and reference lists of relevant review articles were hand-searched. Public health and government websites were searched for nosocomial salmonellosis. RESULTS: Fifty-two relevant reports were identified. The most frequently reported routes of transmission were food 31/52 (59.6%) and person-to-person transmission 7/52 (13.5%). Actions taken during the outbreak to control transmission included improvements to: 1) infection control practices (41.8% of actions); isolation or cohorting patients, hand hygiene practices, and enhancing cleaning and disinfection in patient care areas; and 2) food handling practices (24.4% of actions); reviewing food preparation practices, enhancing cleaning and sanitation of the kitchen, and controlling food temperatures. Investigators made recommendations retrospectively in outbreak reports to provide direction to health centees but these recommendations were not statistically evaluated for effectiveness. CONCLUSIONS: More emphasis should be placed on improving food handling practices, such as training food workers, monitoring food temperatures, and not using raw foods of animal origin, to prevent nosocomial salmonellosis outbreaks in hospitals because almost 60% of the outbreaks were foodborne.