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Impact of high-dose vitamin D and calcium carbonate supplementation on bone density in adolescents living with HIV: a randomised, placebo-controlled trial.
Get PDFBACKGROUND: HIV has adverse impact on skeletal development in children despite antiretroviral therapy (ART). We investigated the effect of high-dose (20 000 IU) weekly vitamin D3 and daily calcium carbonate (500 mg) supplementation for 48 weeks on bone density and muscle strength and power among peripubertal individuals (11-19 years) with perinatally acquired HIV. METHODS: We conducted an individually randomised, double-blind, placebo-controlled trial. Individuals taking ART for at least 6 months who had a defined caregiver, and knew their HIV status (in those aged >12 years) were recruited from HIV clinics in Harare, Zimbabwe and Lusaka, Zambia. The primary outcome was total body less-head bone mineral density (TBLH-BMD) Z score and secondary outcome was lumbar spine bone mineral apparent density (LS-BMAD) Z score (both measured by dual-energy x-ray absorptiometry). Linear regression was used to compare arms adjusting for country and baseline value of the measure. Pre-specified subgroup analyses by country, age-group, sex, pubertal stage, calcium intake, tenofovir disproxil fumarate use, and baseline vitamin D insufficiency (defined as 25[OH]D <75 nmol/L), and a post-hoc subgroup analysis by viral suppression, were performed. A Participant Advisory Board that included adolescents with HIV, their guardians, and health providers guided study conduct. The trial is registered with the Pan African Clinical Trials Registry, PACTR20200989766029. FINDINGS: Of 842 participants (median age 15 years [IQR 13-17], 448 [53%] female and 394 [47%] male) enrolled between Feb 4 to Nov 23, 2021, 639 (76%) were vitamin D insufficient. At 48 weeks, outcomes were available for 751 (89%) participants. There was no difference by arm in TBLH-BMD Z score (intervention vs control: mean -1·53 [SD 1·18] vs -1·56 [1·12], adjusted mean difference -0·04 [95% CI -0·01 to 0·09]) or in LS-BMAD Z score (intervention vs control: -0·64 [1·17] vs -0·71 [SD 1·16], adjusted mean difference -0·05 [95% CI -0·01 to 0·12]). However, among participants with vitamin D insufficiency at baseline, there was a significantly higher LS-BMAD Z score (adjusted mean difference 0·09 [95% CI 0·02 to 0·16], pinteraction=0·025) in the intervention arm than in the control arm. The corresponding adjusted mean difference in TBLH-BMD Z score was 0·06 (0·00-0·11), pinteraction=0·15. There was no statistical evidence of interaction in other subgroups. No drug-related severe adverse events were observed. INTERPRETATION: There was no difference in bone density between arms overall, but among those with vitamin D insufficiency the intervention improved bone density. High-dose vitamin D3 and calcium supplementation, a safe and cheap intervention, during adolescence might promote bone accrual and mineralisation in those with vitamin D insufficiency, which could increase peak bone mass. FUNDING: European Developing Country Clinical Trials Partnership
How does the internal family systems model of psychotherapy support clients in the integration of their psychedelic experiences? An interpretative phenomenological analysis of clients' testimonies
Get PDFAbstract
Background and aims
An increasing number of individuals seek psychedelics for mental illness, and when seeking psychotherapy in the aftermath, psychotherapists have an ethical duty to attempt to reduce harms and maximise benefits from these experiences. The Internal Family Systems (IFS) model of therapy is sometimes chosen as the therapeutic approach in psychedelic-assisted psychotherapy. This qualitative, exploratory study aimed to understand the extent to which IFS therapy can support clients in the integration of their psychedelic experiences.
Methods
In-depth interviews were conducted with four individuals who attended IFS therapy as part of their psychedelic integration. Data were analysed using an Interpretative Phenomenological Analysis.
Results
Psychedelic integration was described as a transformational process that begins with preparation, takes time, needs space and attention, and that can be challenging. Finding people to integrate with and someone to talk to were reported as important practices to support integration. Participants also alluded to a transformational process when describing their experiences of IFS therapy as “
a pathway towards wholeness
”. Their testimonies shed light on ways IFS therapy supported them: IFS creates “
a forum to take those parts seriously
”, gives a language to narrate internal experiences, is not only a talking therapy, and is “
all about self-love
”. Most participants however warned that one can “
lose sight of where that Self might be
”. The therapeutic relationship also emerged as an important enabling factor.
Conclusions
This study provided initial insights into ways IFS therapy can support psychedelic integration. IFS offers tailored interventions to revisit psychedelic experiences, find meanings and work through difficulties encountered during the integration process. Further phenomenological research is warranted to elaborate on the emerging themes identified in this study through the inclusion of more diverse experiences, perspectives on IFS, and participant backgrounds
SIGNIFIED: whole-body MRI screening in Li-Fraumeni syndrome in the UK.
Get PDFBACKGROUND: Li-Fraumeni syndrome (LFS), caused by a pathogenic germline variant of the TP53 tumour suppressor gene, is an autosomal dominant condition that predisposes affected individuals to multiple cancers at a young age. International guidelines recommend yearly screening to identify cancers: in addition to annual breast magnetic resonance imaging (MRI) in female patients and full dermatological skin check, patients should undergo whole-body imaging. Whole-body MRI (WB-MRI) can image from vertex to toes in a single examination, without the use of ionising radiation. We aimed to assess the utility of WB-MRI in detecting malignancies in LFS patients. MATERIALS AND METHODS: SIGNIFIED was a prospective, exploratory and observational study. Patients with LFS were identified and invited to undergo two WB-MRIs 12 months apart. WB-MRI was carried out at 1.5 T from vertex to toes without contrast, including axial T1-, T2- and diffusion-weighted imaging. Images were reviewed independently by two experienced oncological radiologists. Suspicious lesions and incidental findings were discussed in a multidisciplinary meeting, with further investigation and management carried out on a case-by-case basis. RESULTS: Between July 2022 and August 2023, 54 individuals (14 males, 40 females) with LFS underwent a baseline WB-MRI within the study. Fifty patients had a second scan ∼12 months later. Following the first WB-MRI, nine patients underwent biopsy/excision (16.7%), and four cancers were diagnosed (7.4%). Five patients developed interval cancer between the first and second WB-MRI. These were either outside of the initial WB-MRI field of view (i.e. upper limb sarcoma, breast carcinoma) or had developed clinically since the initial scan. Six patients (12%) were diagnosed with a cancer following the second WB-MRI. Seven (70%) out of the 10 cancers detected overall by both scans were in an early stage, and the remaining 3 (30%) were locally advanced or metastatic. CONCLUSION: WB-MRI can identify early cancers in the high-risk setting of LFS screening, with cancers detected at both baseline and 12-month follow-up screenings. The burden of additional investigations for incidental findings decreases with repeat imaging
Navigating power hierarchies in the "field": A qualitative exploration of researcher experiences.
Get PDFDespite increasing focus on the broad topic of power hierarchies within research partnerships, scholarly analysis and guidance within global health tends to focus on partnership-building, governance structures and authorship, while the interactions occurring between researchers in settings where a project or community are located, often referred to as the "field", remains a neglected topic. This study applies an intersectional lens to explore how to tackle power hierarchies (including race, gender, age, education/expertise) during visits in the "Global South", based on a case study of an academic institution in the United Kingdom. It involves interviews with staff and research degree students, as well as research partners, and feedback workshops. The study finds that positionality influences how participants view the role of power hierarchies in shaping research dynamics. Senior staff tended to be less critical of power hierarchies, while early-career researchers were more inclined to feel power hierarchies needed to be challenged. Across multiple types of research relationships we find that seniority is a powerful dynamic that shapes interactions during visits. Institutional power is also an overarching force that often limits individual researcher efforts to shift power. Our study identifies five key recommendations for Northern-based institutions in particular: 1) challenge extractive practices and assumptions associated with research in the "field"; 2) advocate for more equitable institutional policies and practices on contracting and budgeting in Northern institutions that constrain efforts to shift power; 3) build in time for ongoing reflection on power and positionality within research teams; 4) ensure visits to "the field" are planned with Global South partners; 5) conduct further research on power hierarchies to tackle specific dimensions of power
All-cause and cause-specific mortality trends among people with and without HIV in the Siaya health and demographic surveillance system, Kenya, 2011-2018.
Get PDFBACKGROUND: All-cause mortality among people with HIV (PWH) in sub-Saharan Africa declined after antiretroviral therapy's introduction, but data in rural settings on evolving causes of death as this population age remain limited.
OBJECTIVES: To compare all-cause and cause-specific mortality trends among PWH and people without HIV (PWOH) in western Kenya using a prospective cohort study.
METHODS: Data from the Siaya Health and Demographic Surveillance System were used to estimate mortality rates from 2011 to 2018 among persons aged 15-64 years, with the study population (PWH/PWOH) determined through HIV testing. InterVA-4 was used to ascertain the cause of death.
RESULTS: 45,581 individuals with an HIV test result contributed 209,078 person-years (py) of follow-up. The HIV prevalence was 14.5%. Median age among PWH increased from 37 to 42 years from 2011 to 2018. For PWOH, this was between 29 and 31 years. 1386 individuals died, 48.8% were PWH. HIV/AIDS/tuberculosis (319 deaths; 58.2%) was the leading mortality cause for PWH and non-communicable diseases (NCDs) (235; 40.9%) for PWOH. From 2011 to 2017, HIV/AIDS/tuberculosis mortality rates declined among PWH from 19.0 to 7.0 deaths/1,000py, and mortality due to NCDs increased from 3.7 in 2014 to 5.1/1,000py in 2017. For PWOH, cause-specific mortality trends were stable over time.
CONCLUSION: Among PWH, HIV/AIDS/tuberculosis mortality decreased from 2011 to 2017, while mortality rates due to NCDs rose over time as the population aged. Among PWOH, NCDs were the leading cause of death. Managing HIV and the increasing burden of NCDs in this community requires education on prevention, active screening, and delivery of treatment and palliative care services
Development of a Self-Reported Measure of Academic Pressure Among Secondary-School Students: The Academic Pressure Questionnaire.
Get PDFPurposeThere is evidence that academic pressure has been rising among adolescents in the UK. While this may be a modifiable risk factor for mental health problems, there are few validated measures of academic pressure and all have limitations.MethodsWith secondary-school students, we co-produced a student-reported measure of academic pressure, the 7-item Academic Pressure Questionnaire (APQ). This was included in the baseline survey of students aged 12-13 within the Positive Choices trial, a whole-school intervention to promote sexual health in English secondary schools. We ran factor analyses and assessed internal consistency, associations with sex and depressive symptoms, and variation in academic pressure between schools.ResultsWe extracted one factor (Cronbach's alpha 0.76). Female students had higher APQ scores than males (mean difference = 2.18, 95% CI: 1.88 to 2.49). Higher APQ scores were associated with more depressive symptoms (coefficient = 0.51, 95% CI: 0.48 to 0.55) and associations were larger in female than male students (p value for interaction <0.001). School-level factors explained 2.6% of variation in APQ scores after adjusting for individual-level factors (ICC = 0.026, 95% CI: 0.01 to 0.06).ConclusionThe APQ is a valid and reliable tool to investigate academic pressure in secondary-school adolescents
DoxyPEP for cisgender women and people assigned female at birth
Get PDFResponding to the continued rise of bacterial sexually transmitted infections (STIs), in June 2025, the British Association for Sexual Health and HIV (BASHH) published a UK-first guideline on the use of doxycycline as post-exposure prophylaxis (DoxyPEP) for syphilis and chlamydia prevention.1 However, in the new guidelines, DoxyPEP is not recommended for cisgender women and people who were assigned female at birth, regardless of gender. In August 2025, an expert roundtable was held at University College London (London, UK) to discuss the next steps for STI prevention for this group, from a clinical, ethical, and policy perspective. In response to an earlier published Correspondence in The Lancet Infectious Diseases,2 we suggest that although guidelines cannot explicitly recommend DoxyPEP for all cisgender women and people who were assigned female at birth due to scarce efficacy data, clinician guidance on when and how to recommend DoxyPEP should be clarified to better raise awareness and address unmet need for this group
Diabetes management using a clinical guideline versus usual practice: a feasibility trial-based qualitative study among Ayurvedic practitioners and patients in Nepal.
Get PDFBACKGROUND: Type 2 diabetes mellitus (T2DM) is common in Nepal, where many people seek primary care through Ayurveda, a widely practiced traditional medical system. However, concerns remain about variability in clinical practice and the quality of care provided by Ayurvedic practitioners. No evidence-based clinical practice guideline (EB-CPG) currently exists for managing T2DM in Ayurveda. To address this, an EB-CPG was developed, and a feasibility trial was conducted to inform a future definitive cluster randomized controlled trial evaluating whether the EB-CPG would improve T2DM management compared to usual clinical practice. OBJECTIVES: To explore the experiences and perspectives of Ayurvedic practitioners and patients regarding the two treatment groups (EB-CPG-based care versus usual clinical practice) and participation in the feasibility trial. DESIGN: Constructivist qualitative study. METHODS: Semistructured interviews were conducted with Ayurvedic practitioners and patients. Data were analyzed thematically using an inductive approach and the framework method. RESULTS: A total of 41 Ayurvedic practitioners and patients were interviewed. Common themes identified across both groups included facilitators and challenges in the trial patient recruitment, challenges in usual clinical care, experiences with EB-CPG-based care (predominantly positive), ease and difficulties of monthly follow-ups, and pros and cons of patient diaries for assessing medication compliance. Practitioner-specific themes included the diverse populations they serve; patients' motivations for choosing Ayurveda over Western medicine; their motivations for trial participation; balancing clinical duties with the trial demands; confusion about trial roles and responsibilities; and other trial-related issues such as understanding processes and documentation, support and communication, coordination with data collectors, and finances and other resources. CONCLUSION: The EB-CPG-based approach for managing T2DM by Ayurvedic practitioners in Nepal was well-received and perceived as more beneficial than usual clinical practice. Trial experiences and perspectives were largely positive; however, several challenges related to trial conduct should be addressed in future studies, including the definitive cluster trial
Genomic diversity and clade clustering of Burkholderia pseudomallei and B. thailandensis prophages with soil-derived phages.
No full textMost studies on bacteriophages (phages) of the Gram-negative bacterium Burkholderia pseudomallei rely on in silico predictions and thus underestimate the true diversity of phages. Analysis of the whole genome sequences of culturable prophages induced from B. pseudomallei and B. thailandensis, along with their free Burkholderia phages isolated from soils in Thailand, identified six novel groups of Burkholderia phages, surpassing in silico expectations. The analysis also indicated that soil-dwelling phages may have originated from lysogenic B. pseudomallei strains. Free phages isolated from soil showed high nucleotide similarity to prophage sequences in B. pseudomallei, including phages previously cultured from melioidosis patients' hemocultures, indicating that similar phage types occur in both environmental and clinical sources. Phylogenomic analysis also revealed close genomic relatedness between prophages from B. thailandensis and B. pseudomallei, although the biological significance remains unknown. Together, these findings refine our understanding of the genomic diversity and ecological patterns of Burkholderia phages
Malaria-GENOMAP: a web-based tool for exploring genomic variation of malaria parasites.
No full textMOTIVATION: Malaria, caused by Plasmodium parasites, imposes a significant public health burden. While Plasmodium falciparum remains the primary target of elimination strategies due to its high mortality rate, lesser-known species such as P. malariae, P. vivax, and P. knowlesi continue to contribute to substantial human morbidity. Genomic approaches, including whole-genome sequencing, offer powerful tools for understanding the biology, transmission, and emerging drug resistance of these neglected Plasmodium species. However, there is an urgent need for informatic tools to summarize and visualize the high-dimensional and complex genomic data generated.
RESULTS: We developed Malaria-GENOMAP, a user-friendly web-based tool, which integrates genomic variant data, such as allele frequencies, with geographical maps and chromosome-wide to gene views for in-depth exploration. The tool includes variation from P. knowlesi (n = 139), P. malariae (n = 158), P. ovale curtisi (n = 36), P. ovale wallikeri (n = 47), P. simium (n = 38), and P. vivax (n = 1359). It enables the investigation of population structure, geographic associations of mutations, and putative drug resistance markers, offering valuable insights for malaria control efforts.
AVAILABILITY AND IMPLEMENTATION: Malaria-GENOMAP is available online at https://genomics.lshtm.ac.uk/malaria-genomaps