Search Results (180)

The designs of clinical trials of drugs for rare diseases are challenged by health technology assessment organisations and payers. Phase II pivotal studies, single-arm or open-label designs, the extensive use of non-final endpoints, and the limited use of patient-reported outcomes (PROs) are the main points of contention. The evidence on the actual design of these trials is limited, but corroborates the concerns of the above. Our aim is to scrutinise whether the design of pivotal studies of drugs for rare diseases to be launched into the Italian market by 2026 present similar issues. The drugs and the relevant pivotal studies were retrieved from Biomedtracker and US and European clinical trial databases. We identified 154 new drugs for rare diseases. Single-arm designs account for 36% of trials. Almost 50% of randomised control trials (RCTs) are designed using an active comparator and 61% are double-blinded. Primary endpoints are mostly (82%) surrogate. A total of 59% of studies include PROs. Our findings were partially expected (e.g., extensive use of surrogate endpoints) and partially not (e.g., RCTs and an active comparator), considering previous studies on the same topic. Having more head-to-head studies may reduce uncertainty concerning evidence at market launch, but different issues persist, including the still limited role of PROs. Full article

Organisations have provided health and safety (H&S) control measures for construction activities, but the literature suggests that implementing these measures in the construction industry remains a challenge. This study aims to explore the factors impeding the implementation of H&S control measures (barriers). The study followed a qualitative research approach using interview form as a data collection tool designed to collect qualitative data on the factors impeding the implementation of H&S control measures. Purposive sampling method was adopted. The content analysis method was used to analyse the collected data. The findings reveal that the implementation of H&S control measures is affected by different barriers. The study uncovered eight main barriers (lack of management support and commitment, implementation costs, lack of training and education, language and cultural differences, time pressure, prioritisation of production over H&S issues, lack of worker involvement and participation and lack of communication) to the implementation of H&S control measures. Respondents were mainly from H&S background; it would be interesting to explore the perceptions of site managers, engineers, designers, supervisors and field workers through the use of a quantitative approach involving a larger sample. By identifying and understanding these barriers to the implementation of H&S control measures, construction organisations could be in a better position to control construction hazards. This paper adds value to construction organisations and professionals’ understanding of barriers to the implementation of H&S control measures on construction sites. The study also recommends measures to remove barriers or facilitate better implementation of H&S control measures on construction sites. Full article

Background/Objectives: Porcine Circovirus Type 2 (PCV2) impairs pigs’ immune systems and increases susceptibility to co-infections, including Classical Swine Fever (CSF), a highly contagious disease listed by the World Organisation for Animal Health (WOAH) as notifiable. Therefore, swine operations in CSF-endemic regions are encouraged to immunize piglets with both PCV2 and CSFV vaccinations. Currently, there is no commercially available bivalent vaccine for PCV2/CSFV. Methods: In this study, a total of twenty 4-week-old SPF pigs were administered our formulated PCV2/CSFV bivalent subunit vaccine, containing soluble CSFV-E2 (50 µg) and PCV2-ORF2 (100 µg) antigens with a porcine-specific CpG adjuvant. After 4 weeks of vaccination, all pigs were evaluated for efficacy against PCV2 and CSFV. Results: Pigs were only immunized once and showed significantly increased neutralizing or ELISA antibody titers against both viruses four weeks post-vaccination. After viral challenges, vaccinated pigs displayed no clinical signs or lesions and had markedly reduced CSFV and PCV2 viral loads in the serum and tissues compared to controls. Conclusions: These results demonstrate that a single dose of the PCV2/CSFV bivalent subunit vaccine is safe and effective in young pigs, induces strong antibody responses, and suppresses viral replication, making it a promising tool for swine disease control and cost-effective vaccination strategies. Full article

Background: Antimicrobial resistance (AMR) poses a critical global health challenge, particularly in resource-limited settings. A hub-and-spoke model, decentralising expertise and distributing resources to peripheral facilities, has been proposed as a strategy to enhance the antimicrobial stewardship (AMS) capacity in low- and middle-income countries. Aim: This study sought to understand healthcare professionals’ experiences of a hub-and-spoke AMS model in the Volta Region of Ghana and its influence on clinical practice, leadership, and collaborative endeavours to address AMR. Methods: A qualitative descriptive design was adopted. In-depth interviews were conducted with 11 healthcare professionals who participated in the AMS program. Thematic analysis was used to identify key themes related to the knowledge and skills that were gained, clinical and leadership practice changes, capacity building, and challenges. Results: Participants reported an increased awareness of AMR, particularly regarding the scale and clinical implications of antimicrobial misuse. The clinical practice improvements included more judicious prescribing and enhanced adherence to infection prevention and control measures. Many respondents highlighted stronger leadership skills and a commitment to capacity building through AMS committees, multidisciplinary collaboration, and cross-organisational knowledge exchange. Despite resource constraints and logistical hurdles, participants expressed optimism, citing data-driven approaches such as point prevalence surveys to track progress and inform policy. Engagement with hospital management and public outreach were viewed as essential to sustaining AMS efforts and curbing over-the-counter antibiotic misuse. Conclusions: The hub-and-spoke model caused observable improvements in AMS knowledge, clinical practice, and leadership capacity among healthcare professionals in Ghana. While challenges remain, particularly in securing sustainable resources and shifting community behaviours, these findings underscore the potential of network-based programs to catalyse systemic changes in tackling AMR. Future research should explore long-term outcomes and strategies for embedding AMS practices more deeply within healthcare systems and communities. Full article

Background: Salmonella infections impose a substantial global health burden, with an estimated 95.1 million cases occurring annually. Pregnant women exhibit a heightened vulnerability due to pregnancy-specific immune adaptations and dietary habits that increase their risk of Salmonella exposure, facilitating possible damage to the placental barrier. Despite this significant burden, Salmonella-associated placental pathology remains poorly understood, particularly its impact on foetal development through microstructural alterations. Aim: This study utilised stereology to assess histomorphological and functional alterations in term placentae of Salmonella Typhi-exposed placentae, compared to unexposed controls. Methods: A hospital-based case-control study was conducted in Ghana. Of 237 screened women, 62 placentae were selected for analysis, comprising 31 Salmonella-exposed cases (IgG/IgM-positive in placental and cord blood) and 31 gestational age-matched controls (IgG/IgM-negative). Placental tissues were processed for histology and stereology. Neonatal birthweights were also compared. Results: Stereological assessment revealed significantly higher mean volume densities of syncytial knots in the study group (0.4755 ± 0.04) compared to the controls (0.3342 ± 0.04, p = 0.0219). Syncytial denudation was increased in the study group (0.8113 ± 0.09) relative to the controls (0.1975 ± 0.08, p < 0.0001). Foetal capillary volume density was also significantly elevated in the study group (5.1010 ± 0.32) compared to the controls (3.562 ± 0.47, p < 0.0001). In contrast, intervillous space volume was significantly reduced in the study group (9.5810 ± 0.05) compared to the controls (11.593 ± 0.26, p = 0.0053). Neonates of exposed mothers showed a non-significant reduction in birthweight. Conclusion: Salmonella Typhi exposure in pregnancy induces subtle, yet significant alterations in placental architecture, compromising villous integrity and vascular organisation. Although birthweight may appear unaffected, the observed changes point to reduced placental efficiency and merit further research into their developmental consequences and long-term effects on babies. Full article

In recent years, an increasing number of case reports have mentioned the presence of illicit nootropics, smart drugs or mind doping products on the market. To better understand the extent of the problem, a market surveillance study was organised by the General European Official Medicines Control Laboratory Network and associated member Australia to detect substandard, falsified or illegal medicines or dietary supplements containing unauthorised nootropic molecules of natural or synthetic origin. From January 2020 to September 2024, 159 different samples were documented, which yielded a comprehensive dataset of 166 molecular identification entries. Within this dataset, 34 distinct molecules were identified. Most samples were sold or presented as dietary supplements (49%) or medicines (32%). The vast majority (69%) were collected from the illegal market. Prescription drugs and non-authorised drugs only available on prescription in Russia were found in pharmacological quantities; some of the latter (noopept, phenylpiracetam and phenibut) were intercepted as large bulk quantities of raw material. Unauthorised novel foods, prescription or higher amounts of melatonin, and clinically uncharacterised research molecules were also reported. This study highlights the need for more active monitoring and screening of such products, as consumption of some of the reported samples could have detrimental health effects. Furthermore, as a large number of the samples were presented as dietary supplements, consumers may not be aware of the possible dangers and side-effects of these products. Full article

This article examines Healthy Homes, a program intended to initiate a new approach to housing repairs and maintenance in remote communities in the Northern Territory of Australia. It argues that while the evidence for associations between poor housing and poor health outcomes is clear, greater attention should be paid to the implementation of health-focused housing interventions. Healthy Homes was examined through interviews with public servants, Aboriginal community-controlled organisation staff, and householders, alongside participant observation during maintenance projects and Condition Assessment Tool inspections. Routine housing, inspections, and expenditure datasets were also analysed. Across 5498 houses subject to Healthy Homes and over a twenty-month period, only 1315 Condition Assessment Tool inspections were completed, which is the key mechanism for generating preventive maintenance work. Expenditure on repairs and maintenance was stable between the old maintenance model and under Healthy Homes. Most Healthy Homes remote housing maintenance contracts were awarded to Aboriginal business enterprises. This article finds that Healthy Homes did not effectively shift remote property management to prioritise preventive maintenance. Issues with data collection and monitoring, program implementation, and contractual arrangements impeded more consistent and effective attention paid to the condition of housing health hardware. Future investment into the implementation of health-focused remote housing preventive maintenance programs must attend to the details of program design, including the data collection processes and contractual terms for service providers. Full article

Obesity is a significant global health issue, profoundly affecting metabolic and cardiovascular health and other related chronic conditions. In Chile, the prevalence of obesity is among the highest within the Organisation for Economic Cooperation and Development (OECD) countries, highlighting a critical public health challenge. This narrative review examines current evidence on the independent and potential synergistic roles of omega-3 fatty acids and exercise in managing obesity-related metabolic dysfunction. Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA), have been shown to lower triglyceride levels, enhance lipid metabolism, and modulate inflammation via pathways involving peroxisome proliferator-activated receptors (PPARs) and sterol regulatory element-binding protein-1c (SREBP-1c). Exercise interventions, such as moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT), provide distinct yet complementary metabolic benefits. Specifically, MICT improves body fat distribution and mitochondrial efficiency, whereas HIIT has notable effects on metabolic adaptability and insulin signaling. Additionally, emerging evidence points toward a potential role of the kinin-kallikrein system, particularly kallikrein 7 (KLK7), in obesity-associated insulin resistance. Despite these promising findings, several knowledge gaps persist regarding optimal dosing, intervention timing, population-specific effects, and the exact mechanisms behind the potential synergistic interactions between omega-3 supplementation and structured exercise. This review emphasizes the importance of conducting further research, particularly controlled clinical trials, to clarify these combined interventions’ effectiveness and establish targeted therapeutic strategies tailored to individual metabolic profiles. Full article

Listeria monocytogenes is an intracellular, Gram-positive, non-spore-forming, non-encapsulated, facultative anaerobic, rod-shaped, and psychrotrophic food-borne pathogen that causes the infection, listeriosis, thus it attracts great attention following listeriosis outbreaks, which are often associated with high mortality rates. The prevalence of listeriosis is quite low globally; however, the most recent and deadliest outbreak occurred in South Africa, during which 216 persons lost their lives. L. monocytogenes is endowed with the potential to multiply through a wide range of harsh environmental conditions, forming biofilms on varying surfaces in the food industry, as well as having persistent and antibiotic-resistant cells, which pose a major threat and burden to the ready-to-eat food industry. A more frustrating characteristic of this bacterium is its strain divergence, alongside an increased level of antibiotic resistance registered among the strains of L. monocytogenes recovered from food, humans, and environmental sources, especially to those antibiotics involved in the treatment of human listeriosis. Antibiotic resistance exerted by and among pathogenic food-borne microbes is an ongoing public health menace that continues to be an issue. Against this background, a thorough search into different databases using various search engines was performed, which led to the gathering of salient information that was organised, chronologically, based on Listeria monocytogenes and listeriosis. Altogether, the findings elaborated in this study present up-to date knowledge on different aspects of this pathogen which will improve our understanding of the mystery associated with it and the ways to prevent and control its dissemination through ready-to-eat foods. In addition, constant monitoring of the antibiotic resistance profiles of strains of L. monocytogenes from varying sources detected changes, giving an update on the trend in antibiotic resistance. Overall, monitoring of bacterial contamination serves as the key aspect in the control of the food safety output in the food industry. Full article

Wildfires threaten human health, economies and the environment. Fuel management is a core activity of land managers to reduce the detrimental impacts of wildfires. Land managers also seek to conserve biodiversity within their fuel management programs. We sought to understand how fuel management could be implemented to achieve fire risk reduction and biodiversity conservation in the same landscape. Specifically, we asked: (1) what vegetation attributes are desirable for wildfire risk reduction and biodiversity conservation, and are they compatible? and (2) what combinations of management actions could achieve both objectives? We used structured decision-making with 23 stakeholders from eight organisations to elicit means objectives and management actions for fire risk reduction and biodiversity conservation in dry eucalypt forests and woodlands. Vegetation attributes identified as desirable to reduce fire risk were often compatible with those desired for biodiversity conservation, suggesting management actions could achieve both objectives in the same landscape. Workshop participants often selected prescribed burning as a management action, and specifically, mixed severity, patchy burns for biodiversity conservation. Predator control, habitat creation and revegetation were coupled with burning and mechanical treatments to improve outcomes for biodiversity. There was uncertainty around the likelihood of success for most management actions, highlighting the need for adaptive management to test and refine management over time. Overall, structured decision-making allowed for integration of a range of stakeholder perspectives into the development of multi-objective fuel management pathways. This approach forms a basis for designing more socially acceptable fuel management programs. Full article

Voluntary HIV testing and counselling (VCT) in the workplace could reach population groups who may be at risk for HIV but may not readily seek out testing from other services. We conducted a scoping review to understand (a) the nature of evidence related to initiatives and interventions for vocationally active adults on VCT in occupational settings, and (b) any facilitators and barriers to the delivery of and/or engagement with VCT initiatives/interventions in the workplace. JBI scoping review methodology was followed. The protocol was pre-registered. Included studies focused on vocationally active adults (population), VCT interventions or initiatives (concept), and workplaces in any sector or country (context). The review included studies published after 2000, in English, and of any research design. Studies relating to mandatory workplace HIV screening were excluded. MEDLINE, CINAHL, Scopus, PsycINFO, and the Cochrane Central Register of Control Trials were searched. Sources of grey literature included Google Scholar and governmental and organisational websites. One reviewer screened titles and abstracts; a second reviewer independently screened 10%. Data extraction utilised a modified JBI data extraction tool. We identified 17 studies reporting on 12 workplace VCT interventions (20,985 participants, 15–70 years). Studies were conducted in eight countries between 2001 and 2022. Interventions were delivered in organisations of different types, sizes and sectors. Testing included rapid blood tests and oral fluid self-tests. Where reported, the average on-site HIV testing uptake rate was 63%, and the average linkage to care rate was 86.85%. Views of workers, employers and service providers were largely positive. Barriers included being male, masculinity-driven workplace culture, HIV-related stigma, poor knowledge, low risk perceptions, lack of time and low support. Facilitators included on-site testing for convenience and accessibility, rapid and free tests, organisational, managerial and peer support, and embedding HIV tests within general health checks. Evaluation methods varied, although randomised trial designs were uncommon. Despite the limited number of studies, the workplace appears to be a viable route to the delivery of community-based VCT, albeit barriers should be addressed. Reporting quality of interventions and associated evaluations is variable and could be improved with the use of appropriate checklists. Full article

Animal care workers in sheltering, rescue, and management are exposed to occupational stressors which negatively impact health. While the negative mental health impacts have been previously documented in this population, physical health, and its contributing factors, have not. This study investigated how job demands, job resources, and organisational justice relate to mental and physical health, and how they subsequently affect turnover intentions. Of the 285 participants, aged 19 to 94 years, who completed the online anonymous questionnaire, below average mental and physical health was reported. Mental health, but not physical health, was inversely related to intentions to leave. After controlling for age, hierarchical multiple regressions showed high emotional demands and direct euthanasia exposure significantly predicted poorer mental and physical health, while high levels of social support predicted better mental and physical health. No additional variance in either health domain was accounted for by organisational justice. It was concluded that both physical and mental health may be negatively impacted in those who work in shelter, rescue, and management environments which could lead to high turnover and poor outcomes for individuals and organisations. Monitoring through ongoing health records to enable early intervention and accommodations should be considered to promote the health of these workers. Full article

Background: Parkinson’s disease (PD) is a neurodegenerative disorder that is predominantly controlled through pharmacotherapy. People with PD have highly complex medication regimens that are often poorly managed during hospital admissions. This project aims to understand the issues experienced by patients with PD and healthcare staff that impacted their medication management during their hospital admission at a tertiary metropolitan hospital in New South Wales, Australia. Methods: This project focuses on the mixed-methods diagnostics phase of the healthcare redesign approach to health service improvement, utilising organisational data, online surveys, interviews, and focus groups. Results: The findings from this project highlight key areas to address to improve the medication management of patients with PD admitted to hospital. The organisational data (n = 222) showed that the identification of PD patients, untimely medication reviews, prescribing errors, and untimely medication administration all contributed to poor patient experience. The staff surveys (n = 81) highlighted that a lack of knowledge of PD medications and poor patient identification impacted patient experience. The patient surveys (n = 18) and patient interviews (n = 16) suggested that confidence around medication management and administration timing could be improved. Conclusions: Poor PD medication management in hospital impacts the patient experience and should be improved to ensure better outcomes for patients and the health services. Full article

Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) continue to be global public health issues. Globally, about 39.9 million persons live with HIV in 2023, according to the Joint United Nations Programme on HIV/AIDS (UNAIDS) 2024 Fact Sheet. Consequently, the World Health Organisation (WHO) reported that about 1.5 million new cases of HBV occur, with approximately 820 thousand mortalities yearly. Conversely, the lower percentage of HBV (30%) cases that receive a diagnosis is a setback in achieving the WHO 2030 target for zero HBV globally. This has necessitated a public health concern to repurpose antiretroviral (ARV) drugs for the treatment of HBV diseases. This review provides an introductory background, including the pros and cons of repurposing antiretrovirals (ARVs) for HBV treatment. We examine the similarities in replication mechanisms between HIV and HBV. We further investigate some clinical studies and trials of co-infected and mono-infected patients with HIV–HBV. The topical keywords including repurposing ARV drugs, repurposing antiretroviral therapy, Hepatitis B drugs, HBV therapy, title, and abstracts are searched in PubMed, Web of Science, and Google Scholar. The advanced search includes the search period 2014–2024, full text, clinical trials, randomized control trials, and review. The search results filtered from 361 to 51 relevant articles. The investigations revealed that HIV and HBV replicate via a common route known as ‘reverse transcription’. Clinical trial results indicate that an early initiation of ARVs, particularly with tenofovir disoproxil fumarate (TDF) as part of a regimen, significantly reduced the HBV viral load in co-infected patients. In mono-infected HBV, timely and correct precise medication is essential for HBV viral load reduction. Therefore, genetic profiling is pivotal for successful ARV drug repurposing in HBV treatment. Pharmacogenetics enables the prediction of the right dosages, specific individual responses, and reactions. This study uniquely explores the intersection of pharmacogenetics and drug repurposing for optimized HBV therapy. Additional in vivo, clinical trials, and in silico research are important for validation of the potency, optimum dosage, and safety of repurposed antiretrovirals in HBV therapy. Furthermore, a prioritization of research collaborations comprising of regulators and funders to foster clinically adopting and incorporating repurposed ARVs for HBV therapy is recommended. Full article

Background: The World Health Organisation (WHO) included silver diamine fluoride (SDF) in the WHO Model List of Essential Medicines for the management of early childhood caries. SDF is typically available as a 38% aqueous solution, which is watery to apply. A 38% SDF gel has recently been developed, but its caries-arrest effectiveness remains unsubstantiated. The objective of this study is to determine whether the efficacy of a 38% SDF gel is non-inferior to a 38% SDF solution in arresting early childhood caries. Methods: This is a 30-month, randomised, active-controlled, parallel-group non-inferiority pragmatic clinical trial with two arms. The hypothesis is that the 38% SDF gel is not worse than the 38% SDF solution by a non-inferiority margin of 10% caries-arrest rate when applied semi-annually to preschool children. This trial will recruit 630 3-year-old kindergarten children through block randomisation to receive either an application of SDF gel or SDF solution on cavitated carious lesions in their primary teeth every 6 months. The primary outcome is the proportion of soft (active) carious tooth surfaces that turn hard (arrested) at the 30-month follow-up. The same calibrated dentist will conduct 6-monthly dental examinations in the kindergartens to assess the status of carious lesions over 30 months. The examiner, the children, and parents will be blinded to treatments. The parents will be surveyed on their child’s oral health-related behaviours and socioeconomic background to allow adjustment for effect modification. Results: If the anticipated results are obtained, clinicians can use the 38% SDF gel as an alternative of the 38% SDF solution in arresting early childhood caries. Conclusions: As SDF gel is cost-effective, non-invasive, and non-aerosol-generating, it can be widely recommended for caries control. Trial registration: ClinicalTrials.gov NCT06241261. Registered on 7 February 2024. Full article