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Optimising healthcare workforce training and deployment: qualitative experiences from stakeholders in Tanzania

Por: Nyongole · O. V. · Sirili · N. · Mwakilasa · M. T. · Temba · P. · Mkoka · D. A. · Akoko · L. · August · F. · Kiwango · G. · Kaale · E. · Kamori · D. · Mbawala · H. · Sangeda · R. Z. · Mbugi · E. V. · Balandya · E. · Kamuhabwa · A. A. R. · Kakoko · D.
Objective

To explore the experiences of different stakeholders on the balance of package training and deployment of highly skilled Human Resources for Health for specialised services in Tanzania.

Design

An exploratory qualitative case study was used as part of a larger tracer study conducted by Muhimbili University of Health and Allied Sciences (MUHAS) for its postgraduate programmes being a requirement for quality assurance. Semi-structured interview guides were used for in-depth interviews (IDIs) and focus group discussions (FGDs). Qualitative content analysis was adopted to analyse the data.

Setting

The trace study was carried out in all seven geopolitical zones of the Tanzania mainland and Unguja in Zanzibar.

Participants

We conducted 14 FGDs and 301 IDIs. Participants included alumni, immediate supervisors at employment sites, MUHAS faculty, continuing students at MUHAS and management of professional councils in Tanzania.

Results

Key findings revealed variations in demands and recognition within the scheme of services, even after registration by professional councils. Five main themes emerged from the qualitative interviews: Package training to improve service provision, Unprofessional collegial relationships or issues related to professionalism within interdisciplinary teams, Silence of scheme services on super specialisation in the medical cadre, Silence of scheme services on specialisation in the nursing cadre, Integrated scheme of services for specialties in pharmacy.

Conclusion

The findings highlight the demand for specialised training, challenges with professionalism and inconsistencies in the recognition and remuneration of specialists across medical, nursing and pharmacy cadres within existing service schemes. There is a need for harmonisation between specialisation/super specialisation and the scheme of services. This harmonisation is crucial to ensure the provision of quality healthcare services. Furthermore, harmonisation requires multistakeholder engagement to realise universal health coverage strategies.

Associations between heart failure-related quality of life and clinical parameters in patients with hypertrophic cardiomyopathy: a cross-sectional analysis of data from a multicentre Japanese registry

Por: Saotome · M. · Akita · K. · Kageyama · S. · Suzuki · S. · Ohno · K. · Kamakura · M. · Nawada · R. · Takanaka · C. · Wakabayashi · Y. · Kanda · T. · Tawarahara · K. · Muto · M. · Matsunaga · M. · Suwa · S. · Takeuchi · Y. · Sakamoto · H. · Saito · H. · Hayashi · K. · Wakahara · N. · Unno · K.
Objective

To investigate the relationship between a quality of life (QOL) score and clinical parameters in patients with hypertrophic cardiomyopathy (HCM).

Design

A multicentre cross-sectional study.

Setting

We analysed data from the Searching for Atrial Fibrillation and Early Recruitment of Heart Failure in HCM registry, collected between 2018 and 2023.

Participants

Patients with HCM (n=499) aged ≥18 years from 12 institutions (Shizuoka Prefecture, Japan) were consecutively enrolled.

Outcome measures

Clinical parameters, along with data from a short form of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12), were collected. The association between each clinical parameter and the KCCQ-12 score was analysed. Clinical parameters with a significant univariable association (p

Results

In the univariable analysis, KCCQ-12 scores exhibited significant associations with 21 clinical parameters, including sex, left ventricular morphology and the Pittsburgh Sleep Quality Index (PSQI). The multiple regression model with 12 parameters that had a significant univariable association exhibited an adjusted R2 of 0.48. In this model, the PSQI (standardised coefficient –0.39; p

Conclusions

In patients with HCM, we investigated the association between the KCCQ-12 score and various clinical parameters. PSQI, as well as known heart failure-related clinical parameters, was significantly associated with the KCCQ-12 score. Visualising the associations of various clinical parameters with the KCCQ-12 score will help physicians to consider factors linked to the decline in QOL in patients with HCM.

Three infections, one fight: an implementation study to map needle prevalence and evaluate HIV, syphilis and hepatitis C prevention interventions in Regina, Saskatchewan - a protocol

Por: Eaton · A. D. · Rowe · M. W. · Varghese · S. M. · House · H. · Pang · N. · Kwan · S. · Ford · P. · Reddy · V. D. · Acoose · T. · Littleford · J. · Lang · K. · Foreman · E. S. · Sasakamoose · J. · Pandey · M. · Medeiros · P. · Loutfy · M. R. · Grace · D. · Brennan · D. J. · Zhao · K. · Shuper
Introduction

Saskatchewan is facing a public health crisis driven by high rates of HIV, syphilis and hepatitis C virus (HCV) infections, particularly among people who use drugs. Injection drug use is a major contributor to these syndemic infections, exacerbated by structural barriers such as stigma, poverty and limited culturally safe healthcare. Innovative, community-informed approaches are urgently needed to improve prevention, testing and linkage to care.

Methods and analysis

This study will implement a rapid assessment and response system in Regina, Saskatchewan, Canada, integrating geospatial mapping of community needle prevalence with pop-up interventions. Needle hotspot maps will be used to guide the deployment of community-based pop-up events offering point-of-care testing for HIV, syphilis and HCV, alongside education on pre-exposure prophylaxis (PrEP) and postexposure prophylaxis (PEP). A convergent participatory mixed-methods design will be used to evaluate feasibility, acceptability and effectiveness, guided by the Reach, Effectiveness, Adoption, Implementation and Maintenance framework. Quantitative data will assess changes in knowledge of PrEP and PEP, satisfaction with the intervention and report new diagnoses and participant demographics descriptively. A qualitative substudy will include 30 participants and will explore experiences with the intervention, barriers to care and perceptions of service delivery.

Ethics and dissemination

Ethical approval has been obtained from the research ethics board of the Saskatchewan Health Authority (#24–91). Findings will be disseminated through peer-reviewed publications, conference presentations and community reporting. This study may provide a model of community-based geospatial testing and education that could be scaled up and adapted elsewhere.

Registration

Open Science Framework https://doi.org/10.17605/OSF.IO/HVK3B

Identification of natural Zika virus peptides presented on the surface of paediatric brain tumour cells by HLA class I

by Matt Sherwood, Ben Nicholas, Alistair Bailey, Thiago Giove Mitsugi, Carolini Kaid, Oswaldo K. Okamoto, Paul Skipp, Rob M. Ewing

Despite decades of research, survival from brain cancer has scarcely improved and is drastically lower than that of other cancers. Novel therapies, such as immunotherapy, hold great promise for treating brain tumours and are desperately needed. Zika virus (ZIKV) infects and kills aggressive cancer cells with stem-like properties (CSCs) from both paediatric and adult brain tumours. Whilst T cell recruitment into ZIKV-infected brain tumours is becoming well documented, the specific mechanisms through which they are activated are poorly understood. We address this by employing a combined global proteome and immunopeptidome mass spectrometry approach to describe, for the first time, human leukocyte antigen (HLA) presentation of ZIKV peptides on the surface of infected brain tumour cells. We first show that antigen processing and presentation by HLA class I (HLA-I) is the top enriched immune response pathway in the global proteome of aggressive paediatric USP7-ATRT brain tumour cells following ZIKV infection. We identify USP7-ATRT cells as a desirable immunopeptidome model as they express the globally common HLA-A allotype (A*02:01). We predict the majority of our 19 identified ZIKV peptides to strongly bind and be presented by HLA-A*02:01. We observe a trend between immunopeptide presentation and cellular ZIKV protein abundance, with nearly half of the peptides arising from the most abundant viral protein; non-structural protein 3 (NS3). We show the ZIKV NS3 helicase domain to be a particularly rich source of peptides. Finally, we verify that the 19 ZIKV peptides identified here are not predicted to mimic peptides of the human proteome. The ZIKV peptides we identify here are novel targets for immunotherapy, and our findings provide potential insight into the efficacious cytotoxic T cell response that oncolytic ZIKV virotherapy can induce against brain tumours.

Autologous peripheral blood mononuclear cell-loaded injectable cell scaffold (ICS-001) for revolutionising angiogenic therapy: a study protocol for an exploratory clinical trial

Por: Yamahara · K. · Akahori · H. · Kawai · K. · Suna · S. · Yoshihara · S. · Ishihara · M. · Kakibuchi · M. · Furukawa · M. · Kogai · Y. · Sato · H. · Fukumoto · S. · Furuzono · T. · Tani-Yokoyama · A. · Okamoto · R. · Fujita · Y. · Kawamoto · A.
Introduction

This research paper presents a study protocol for an exploratory clinical trial evaluating the safety and potential efficacy of autologous peripheral blood mononuclear cell (PBMNC)-loaded injectable cell scaffold (ICS-001) for angiogenic therapy in chronic limb-threatening ischaemia (CLTI). CLTI, the advanced stage of peripheral artery disease, presents significant therapeutic challenges.

Methods and analysis

Angiogenic therapy using ICS-001 with PBMNCs—a novel approach designed to enhance local cell retention and promote neovascularisation—will be explored. The study will address the pathophysiology of CLTI, the limitations of current treatments and the rationale for cell-based therapies, alongside the clinical trial design for evaluating the safety and efficacy of ICS-001. We hypothesise that ICS-001 will improve ulcer healing and reduce ischaemic rest pain in patients with CLTI. This paper outlines the methodology, including patient selection, CD34+ cell mobilisation, scaffold preparation, injection protocols, clinical assessments, data collection and safety monitoring. The anticipated results, discussion and conclusion will offer insight into the clinical significance and potential impact of ICS-001 as a pioneering angiogenic therapy for CLTI.

Ethics and dissemination

The institutional review boards of all participating hospitals approved this study protocol (latest version V.6.0, 5 June 2025). Final data will be made publicly available. A report detailing the study results will be submitted for publication in an appropriate peer-reviewed journal.

Data availability statement

Data are available on reasonable request. Technical appendix, statistical code is available by contacting the corresponding author. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) licence, which permits others to distribute, remix, adapt, build on this work non-commercially, and licence their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

Trial registration number

jRCT2052230115, Japan Registry of Clinical Trials.

Randomised, double-blind, placebo-controlled, parallel-group study to assess the efficacy and safety of antibiotic faecal microbiota transplantation in patients with Parkinsons disease (FLORA-PD): a study protocol

Por: Takeshige-Amano · H. · Igami · E. · Okuzumi · A. · Kamo · R. · Iseki · M. · Tsuyama · K. · Wakamori · R. · Okada · H. · Taniguchi · D. · Ueno · S.-I. · Oji · Y. · Ishikawa · K.-i. · Nishikawa · N. · Orikasa · M. · Odakura · R. · Koma · M. · Maruyama · T. · Nomura · K. · Ishikawa · D. · Shibu
Introduction

The intestinal microbiota of people with Parkinson’s disease (PwP) differs significantly from that of healthy individuals. Given that altered microbiota may play a role in the pathogenesis of Parkinson’s disease, faecal microbiota transplantation (FMT) has been proposed as a potential therapeutic approach. However, the efficacy of FMT in improving motor symptoms in PwP has been inconclusive in some pilot randomised controlled trials (RCT). Previous RCTs on PwP employed simple FMT, but our modified approach—pretreatment with antibiotics before FMT (A-FMT)—has been shown to improve the engraftment rate of given species and the beneficial effects of FMT. This study aims to evaluate the efficacy and safety of A-FMT for PwP, particularly in those with motor fluctuations.

Methods and analysis

This study is a randomised, double-blind, placebo-controlled, parallel-group study with an 8-week observation period following a single A-FMT. Thirty clinically established PwP with prominent motor fluctuation episodes will be randomised 1:1 to FMT or placebo. Participants in both groups will receive antibiotic treatment prior to colonoscopy for FMT or placebo treatment. Primary and secondary endpoints will include subjective and objective evaluations of motor and non-motor symptoms and will be evaluated before and after antibiotic treatment and at 4 and 8 weeks after the procedure. Exploratory endpoints will include blood and faecal sample analyses, advanced brain MRI and pharmacokinetic assessment of levodopa concentrations during a levodopa challenge test.

Ethics and dissemination

This study has been approved by the ethical committee of Juntendo University in August 2024 (J24-005) and will be conducted in accordance with the Declaration of Helsinki, the Japan Ministry of Health, Labour and Welfare Clinical Trials Act and related laws and regulations. All patient data will be anonymised to protect privacy and used solely for study purposes. Results will be published in academic journals and presented at conferences.

Trial registration number

jRCTs031240344.

Differential regulation of the eicosanoid biosynthesis pathway in response to <i>Enterocytozoon hepatopenaei</i> infection in <i>Litopenaeus vannamei</i>

by Wananit Wimuttisuk, Pisut Yotbuntueng, Pacharawan Deenarn, Punsa Tobwor, Kamonluk Kittiwongpukdee, Surasak Jiemsup, Rapeepun Vanichviriyakit, Chanadda Kasamechotchung, Suganya Yongkiettrakul, Natthinee Munkongwongsiri, Siriwan Khidprasert, Vanicha Vichai

The microsporidian Enterocytozoon hepatopenaei (EHP) is a highly contagious pathogen that causes severe growth retardation in penaeid shrimp. EHP infection damages the hepatopancreatic tubules, causes hematopoietic infiltration, and recruits granulocytes and inflammatory cells to the shrimp stomach and intestine. In this study, we investigated whether EHP infection induced the eicosanoid biosynthesis pathway in the gastrointestinal tract of the Pacific white shrimp Litopenaeus vannamei. Shrimp hepatopancreases, stomachs, and intestines were collected on days 0, 7, and 21 of the EHP cohabitation experiment for analysis. On day 7, the levels of cyclooxygenase (COX) and prostaglandin F synthase (PGFS) enzymes, which catalyze the production of prostaglandins, were elevated in the hepatopancreas of EHP-infected shrimp. The stomach of EHP-infected shrimp also contained higher levels of 12-hydroxyeicosatetraenoic acid (12-HETE) and 12-hydroxyeicosapentaenoic acid (12-HEPE) than the control shrimp. Nevertheless, the most significant impact of EHP infection on day 7 was observed in shrimp intestines, in which the levels of prostaglandin F (PGF), 8-HETE, and four isomers of HEPEs were higher in the EHP-infected shrimp than in the control shrimp. As the EHP infection progressed to day 21, the upregulation of COX and PGFS persisted in the EHP-infected hepatopancreas, leading to increasing levels of PGF and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2). The upregulation of prostaglandins was in contrast with the decreasing levels of HETEs and HEPEs in the hepatopancreas of EHP-infected shrimp. Meanwhile, the stomach of EHP-infected shrimp contained higher levels of prostaglandin D2, PGF, 15d-PGJ2, and most of the hydroxy fatty acids than the control shrimp. The levels of eicosanoid precursors, namely arachidonic acid and eicosapentaenoic acid, were upregulated in the shrimp gastrointestinal tract collected on days 7 and 21, suggesting that substrate availability contributes to the increasing levels of eicosanoids after EHP infection. Our study provides the first comprehensive analysis of the eicosanoid biosynthesis pathway in response to EHP infection. Moreover, the results indicate that eicosanoids are part of the host-pathogen interactions in crustaceans.

Prospective, multicentre trial on preoperative biliary drainage by endoscopic ultrasound-guided hepaticogastrostomy for resectable/borderline resectable pancreatic cancer with biliary obstruction: the PROLOGUE study - a study protocol

Por: Yagi · S. · Hijioka · S. · Nagashio · Y. · Harai · S. · Agarie · D. · Yamashige · D. · Okamoto · K. · Fukuda · S. · Kuwada · M. · Komori · Y. · Kurita · Y. · Hasegawa · S. · Kubota · K. · Ishida · Y. · Ushio · J. · Takeshita · K. · Yoshino · K. · Ishiwatari · H. · Okusaka · T.
Introduction

Preoperative biliary drainage (PBD) is often required for patients with pancreatic cancer accompanied by biliary obstruction to ensure the safe administration of neoadjuvant chemotherapy or to manage cholangitis and jaundice. Although endoscopic retrograde cholangiopancreatography (ERCP) is the standard approach for PBD, it carries a significant risk of post-ERCP pancreatitis. Endoscopic ultrasound-guided biliary drainage (EUS-BD), particularly via hepaticogastrostomy (EUS-HGS), offers a promising alternative that avoids papillary manipulation. However, the clinical utility of EUS-BD as primary drainage for PBD remains unclear due to a lack of prospective studies. This multicentre prospective trial aims to evaluate the safety and efficacy of EUS-HGS as primary drainage for PBD in patients with resectable or borderline resectable pancreatic cancer.

Methods and analysis

This multicentre prospective study involves seven institutions in Japan. Eligible patients will undergo EUS-HGS using a 7Fr plastic stent. The primary endpoint is clinical success, defined by improvements in bilirubin or liver enzyme levels within 14 days postprocedure. Secondary endpoints include technical success rate, adverse event incidence, stent patency and surgical outcomes. A total of 30 patients will be enrolled, considering an expected clinical success rate of 90% and a 10% dropout allowance.

Ethics and dissemination

This study has been approved by the National Cancer Center Institutional Review Board (Research No. 2024-084). The results of this study will be reported at an international conference and published in an international peer-reviewed journal.

Trial registration number

UMIN ID: 000055173.

Anticholinergic burden and clinical outcomes among older adults admitted in a tertiary hospital: a prospective cohort study

by Pornkamol Tiranaprakij, Sahaphume Srisuma, Krongtong Putthipokin, Sirasa Ruangritchankul

Background

Anticholinergic medication use is associated with adverse clinical outcomes, especially in older adults. However, few studies have assessed the anticholinergic burden in the Thai geriatric population. Hence, we aimed to evaluate the impact of anticholinergic burden on clinical outcomes in older patients after discharge from the hospital.

Methods

A prospective cohort study was conducted between January 1 to December 31, 2023. The prescribed medications were assessed at admission and discharge to determine the anticholinergic cognitive burden (ACB) scores. Participants were classified into three groups according to the ACB score at discharge: none (score 0), moderate (score 1–2), and severe (score ≥ 3) anticholinergic burden. The Cox proportional hazard model was used to determine the marker risk of high anticholinergic burden to adverse outcomes.

Results

This study involved 290 older patients admitted to general internal medicine wards. At discharge, 37.9% (n = 110) of the patients had a high anticholinergic burden (ACB score ≥ 3), and 50% (n = 145) had a higher ACB score than at admission. The three most commonly prescribed anticholinergics at discharge were benzodiazepines (20.3%), corticosteroids (20.0%), and antihistamines (15.9%). During the one-year follow-up period, 16.6% (n = 48) of the patients died. The incidence rate of all-cause mortality in hospitalized older patients with an ACB score ≥ 3 was 0.65 cases per 1000-person day during a one-year follow-up period. After adjusting for potential factors, an ACB score of ≥ 3 at discharge was marginally associated with one-year mortality post discharge [hazard ratio: 2.98, 95% confidence interval (0.96–9.28)].

Conclusions

The exposure to high anticholinergic burden (ACB scores ≥ 3) at discharge was slightly associated with an increased risk of one-year mortality post discharge. The cautious use of benzodiazepines may assist to reduce the anticholinergic burden in this vulnerable population.

Association of dropout history and HbA1c levels with subsequent dropout risk in patients with diabetes: a secondary analysis of the Japan Diabetes Outcome Intervention Trial-2 Large-Scale Trial 008 (J-DOIT2-LT008)

Por: Goto · A. · Hayashino · Y. · Takamoto · I. · Suzuki · H. · Yamazaki · K. · Izumi · K. · Noda · M.
Objectives

Adherence to treatment strategies is essential for preventing future complications during diabetes management. This study evaluated the association between dropout history, glycated haemoglobin (HbA1c) levels and subsequent risks of dropout (missed appointment)in patients with type 2 diabetes.

Design

This was a secondary analysis of a cluster-randomised trial (the Japan Diabetes Outcome Intervention Trial 2 Large-Scale Trial), focusing on the non-intervention group over the study period.

Setting

Data were obtained from a multisite trial conducted in Japan, encompassing patients with type 2 diabetes who received routine clinical care at participating clinics.

Participants

A total of 996 patients with type 2 diabetes from the non-intervention group were included in the analysis. Baseline characteristics (eg, age, sex, smoking status, occupational status and diabetes medication use) were recorded at study entry.

Outcome measures

The primary outcome measure was subsequent treatment dropout. The Cox proportional hazards model with the Huber/White method was used to estimate HRs and 95% CIs, with adjustment for age, sex, smoking status, occupational status and diabetes medication use at baseline.

Results

Participants with treatment dropout history had a higher dropout rate than those without dropout history (multivariable-adjusted HR=3.59; 95% CI=2.25 to 5.71). Overall, HbA1c levels were not significantly associated with dropout risk. However, among the 855 participants without dropout history, the dropout risk was higher in the group with HbA1c level ≥10.0% (HR=3.76; CI=1.29 to 10.9) than in the group with HbA1c level of 6.0–6.9%.

Conclusions

This prospective cohort study of Japanese patients with type 2 diabetes suggests that dropout history is strongly associated with a higher subsequent dropout risk. High HbA1c levels (≥10%) may be related to a higher dropout risk in patients without a dropout history. These findings may provide actionable indicators for tailored interventions, enhancing targeted healthcare strategies and improving continuity of care.

Trial registration number

UMIN000002186.

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