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    Age-specific distribution of cervical precancer and cancer among women living with HIV across seven countries: a systematic review and an individual patient data meta-analysis

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    Background Women living with HIV have an elevated risk for cervical cancer, present earlier, and have more recurrent human papillomavirus (HPV) infections compared with women without HIV. To update WHO recommendations on screening and treatment to prevent cervical cancer, we aimed to identify whether women living with HIV should be screened for cervical cancer at a specific age, the optimal screening interval following a negative cervical screen, and the screening interval following treatment. Methods We conducted a systematic literature review on cervical cancer and HIV by searching MEDLINE, Embase, CENTRAL, the Cochrane Library, and clinical trial registries covering Jan 1, 2012, through to Oct 13, 2019, updating a previous systematic review covering database inception to July, 2012. Included articles reported original data and assessed one or more outcomes related to cervical precancer and cancer in women living with HIV; no restrictions on study design or setting were made. Articles were excluded if they did not include any women living with HIV, or if they reported only HPV genotype prevalence without any other relevant data. Two authors extracted data from any study reporting cervical cancer screening tests and histopathologically confirmed disease outcomes, by age. We analysed summary data on optimal age and screening intervals, providing pooled estimates when possible; we then conducted an individual patient data meta-analysis (IPDMA) to analyse age-specific data on cervical cancer and precancer. Authors of studies with 40 or more women living with HIV and cervical intraepithelial neoplasia (CIN) grade 2+ were invited to submit individual patient data for meta-analysis. Random-effects models were used to calculate predicted probabilities for cervical cancer screening results by age, HIV status, and antiretroviral therapy (ART) status. Findings Of the 304 full-text articles screened, 34 studies from 12 countries, with 128 732 women, including 63 790 women living with HIV, were included in the systematic review. Of 55 studies potentially eligible for the IPDMA, eight studies provided data for 72 350 women, 12 527 of whom were living with HIV, from seven countries (Burkina Faso, Cameroon, India, Kenya, South Africa, Thailand, and the USA). In the IPDMA, the pooled predicted probability of CIN2 or CIN3 among women living with HIV increased from 6·0% (95% CI 0·74–64·1) for ages 15–19 years to 32·4% (8·3–72·7) for ages 20–24 years, 42·1% (16·4–80·2) for ages 25–29 years, 50·3% (16·3–80·0) for ages 30–34 years, 47·0% (16·3–80·0) for ages 35–39 years, 49·0% (16·3–80·2) for ages 40–44 years, 58·1% (17·0–81·5) for ages 45–49 years, and 55·3% (21·0–86·6) for age 50 years and older; invasive cervical cancer was uncommon before 30 years of age. In the systematic review, women living with HIV who had a negative baseline cytology result and negative HPV test had a cumulative incidence of developing CIN2+ that ranged from 0·8% to 5% within 4·2–6·4 years and a cumulative incidence of developing of CIN of any grade up to 10% within 12 years. Also in the systematic review, women living with HIV had high recurrence of CIN2+ following treatment (11–27% by 1 year follow-up, 3–64% by 3 years, and 57% by 10 years). No significant evidence of publication bias was found in the data included in the IPDMA (Egger’s test p=0·83). Interpretation Our data show a clear, age-related increase in CIN2 and CIN3 among women living with HIV, with the highest risk occurring in the 45–49-year age group. Our findings informed WHO recommendations to initiate cervical cancer screening for women living with HIV at age 25 years, with regular screening every 3–5 years. Expanding screening and treatment is necessary to reduce cervical cancer incidence towards its elimination. Funding US Agency for International Development and US President’s Emergency Plan for AIDS Relief

    The rise of e-patients in Tanzania: Reflections on the unregulated growth of digital health consultations

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    Background: Digital technologies have significantly transformed healthcare delivery globally, enabling patients to access healthcare services through electronic and mobile platforms. In Tanzania, this transformation has manifested in the rise of “e-patients” — individuals who actively seek health advice, consultation, or treatment through unregulated digital platforms. This paper examines the drivers, patterns, and implications of this trend in Tanzania. Methods: A descriptive approach was employed, synthesising peer-reviewed and grey literature from global and sub-Saharan African sources, with a particular focus on Tanzania. Insights were also drawn from expert discussions, public digital platforms, and the author’s experiential reflections to contextualize findings and guide recommendations. Results: Tanzania has made notable strides in integrating digital health technologies through strategic government and donor-supported initiatives, resulting in widespread use of both formal eHealth and mHealth platforms as well as an emerging ecosystem of unregulated digital services accessed via social media and mobile apps. This dual landscape has fueled the rise of e-patients who seek care outside formal systems, raising critical concerns about safety, regulation, and equity, and underscoring the urgent need for comprehensive governance frameworks to balance innovation with public health safeguards Conclusion: Harnessing the momentum of digital health transformation requires Tanzania to move beyond reactive oversight and toward a proactive, inclusive approach that integrates e-patients into the formal health system. The country can turn the rise of e-patients into a catalyst for equitable and resilient healthcare delivery by embedding regulatory frameworks, promoting digital health literacy, fostering collaboration between formal and informal providers and balancing technological innovation with ethical safeguards and systemic integration

    Acceptability, feasibility and preliminary evaluation of the WHO caregiver skills training for children with developmental disabilities in rural and urban Kenya

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    Background Interventions to improve the developmental outcomes of children with developmental disabilities (DDs) in low-resourced settings such as Kenya are limited. The WHO caregiver skills training (CST) was developed to address social and communication needs of children with DDs through caregiver-mediated engagement strategies. This study investigated CST’s acceptability, feasibility and evaluated its effect on behavioural, communication and quality of life outcomes for children with DDs and their caregivers in Kenya. Methods The settings were rural Kilifi and Korogocho informal settlement in Nairobi, Kenya. A sequential mixed-methods design consisting of three phases. First, CST materials translation to Swahili, stakeholder consultations and pretesting the adapted CST with caregivers. A pilot with 90 caregivers randomly assigned to the CST or non-CST arm followed. Postintervention discussions with caregivers explored CST’s acceptability. Quantitative data were analysed using descriptive statistics and tests of associations. Qualitative data were analysed using thematic analysis. Results The adapted Swahili CST materials were found acceptable. Stakeholders reflected on the appropriateness, potential barriers and recommended approaches to improve CST. CST’s perceived benefits were increased awareness of DDs and support resources, and stigma management. Overall, 86% of caregivers attended two-thirds of CST sessions, though non-attendance was mostly recorded in informal settings. CST’s preliminary evaluation suggested improved scores on child and caregiver outcomes. Conclusion WHO CST is a ‘promising’ intervention that needs adaptations and serves the needs of families of children with DDs in Kenya. Future studies evaluating CST’s efficacy and feasibility for scale-up in health, education and community-based systems are needed

    Maternal iron status and total immunoglobulin-G influence transplacental antibody transfer across eight diverse geographical settings

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    Transfer of antibodies across the placenta provides critical early life protection for neonates against infection. Understanding factors influencing efficient transfer is vital for enhancing neonatal immunity and improving maternal vaccination strategies. Stored maternal and cord serum samples from studies in The Gambia, Guatemala, Mali, The Netherlands, Pakistan, Thailand, UK and Vietnam were processed for measles plaque reduction neutralisation titres (PRNT), and measles, mumps and rubella immunoglobulin G (IgG) (multiplex immunoassay) at a central laboratory (N = 557 pairs). Nutritional indicators (ferritin, soluble transferrin receptor, retinol binding protein) and total IgG, were measured in subsets of maternal serum. Transplacental transfer ratios (TPTRs) were calculated and factors associated with maternal IgG, cord IgG and TPTRs explored in multivariable regression. At delivery, most mothers (range 78 % Guatemala to 100 % Pakistan, Netherlands) and infants (range 86 % Guatemala to 100 % Netherlands, UK) had PRNT above the threshold of clinical protection (0.12 IU/mL). Maternal and cord antibody concentrations across diverse geographical settings were highly correlated. TPTRs were highest in high-income countries; geometric mean range 0.7 (Pakistan) to 2.2 (Netherlands), and were correlated across antigens. However, TPTRs varied widely within low/middle-income countries. In models adjusting for country, higher maternal total IgG was consistently associated with lower TPTR. In multivariable regression, lower iron status, indicated by increasing soluble transferrin receptor concentration, was significantly associated with lower TPTR for measles neutralising antibody. There is marked geographical variation in TPTRs, and following adjustment for this, measurable factors in maternal blood can inform estimates of transplacental transfer efficiency

    Expression of multidrug efflux pump gene acrAB in Escherichia coli: A systematic review and meta analysis

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    Background: Multidrug-resistant (MDR) Escherichia coli (E.coli) is a growing public health concern, largely driven by the overexpression of efflux pumps such as AcrAB-tolC. These efflux systems contribute to resistance against multiple antibiotic classes, including fluoroquinolones, β-lactams, and aminoglycosides. Despite the well-documented role of efflux pumps in resistance, inconsistencies in reported expression levels and regulatory mechanisms complicate the development of targeted therapies. This systematic review and meta-analysis aim to consolidate available evidence on acrAB-tolC expression patterns and evaluate the impact of efflux pump inhibitors (EPIs) on antibiotic susceptibility. Methods: A systematic search was conducted in PubMed, Scopus, Google Scholar, and EBSCO to identify relevant studies examining acrAB expression in E.coli under antibiotic exposure conditions. Inclusion criteria encompassed experimental studies utilizing qPCR, RNA-seq, or microarray techniques to quantify acrAB expression, as well as research assessing the efficacy of EPIs in restoring antibiotic susceptibility. Data synthesis was performed using a random-effects meta-analysis model, and heterogeneity was assessed using the I² statistic. Results: A total of 10 studies were included in the final meta-analysis. Pooled analysis demonstrated a significant increase in acrAB expression (SMD: 3.5, 95% CI: 2.1-4.9) in MDR E.coli isolates compared to susceptible strains. Efflux inhibition resulted in a ≥ 4-fold reduction in minimum inhibitory concentrations (MICs) for fluoroquinolones and β-lactams across multiple studies. Risk ratio analysis showed that EPIs significantly restored antibiotic susceptibility (RR: 4.2, 95% CI: 3.0-5.8). However, substantial heterogeneity was noted among studies due to methodological variations. Conclusion: These findings confirm that acrAB-tolC overexpression is a major contributor to antibiotic resistance in E.coli and that efflux inhibition is a viable strategy for restoring antibiotic susceptibility. However, clinical translation remains a challenge due to toxicity concerns and pharmacokinetic limitations of current EPIs. Future research should focus on developing safer efflux inhibitors, optimizing combination therapies, and standardizing efflux pump expression assays to facilitate their integration into antimicrobial treatment strategies

    CURE Newsletter Volume 4 Issue 3

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    Message from the Chair Advancing Oncology Through Education & Exchange Clinical Conversations & Collaborations Voices from Oncology “Invited Perspectives” Spotlight on Achievements Workshops Spotlight: Nurturing Clinical Excellence Moments That Matter Celebrating Together” Umeed Parr Social Media Spotlight Oncology at CPSP “The Academic Contributions” Resident Reflections Future Leaders in Oncology Nursing Highlights The upcoming Event at Oncology Clinical Wisdom Shared via Grand Rounds Welcoming New Colleagues, “New Strengths” “Climbing Higher”, Promotions at Oncology “Where Research Meets Impact” Oncology Publicationshttps://ecommons.aku.edu/arch_research_publications_university-wide_cure/1010/thumbnail.jp

    Fifth edition WHO classification: mature B-cell neoplasms

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    We present a review of mature B-cell neoplasms as described in the fifth edition of the WHO classification of haematolymphoid tumours (WHO-HAEM5). Entities have expanded, and definitions are increasingly reliant on genomic and other technologies. However, the WHO-HAEM5 employs a hierarchical structure with family (class)-level definitions that group several specific entities. This approach enables the assignment of a family-level diagnosis when criteria for specific entities cannot be met due to resource constraints. To facilitate application in resource-limited settings, WHO-HAEM5 divides diagnostic criteria into ‘essential’ and desirable criteria for most entities. This review focuses on changes and updates in B-cell lymphoma classification, providing guidance on how to apply the WHO classification in resource-limited settings

    Gut microbiota in different stages and subtypes of colorectal cancer in Nairobi, Kenya

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    Background: Sub-Saharan African colorectal cancer (CRC) incidence is rising with delayed diagnosis being common since the population does not have access to many screening programs. Alterations in gut microbiota have been associated with CRC, although not much is known from cohorts in Africa. Aims: To characterized and compare mucosal gut microbiota in Colorectal Cancer (CRC) stages and pathology subtypes to identify the biomarkers. Study Design: A case-control study. Place and Duration of Study: Department of Pathology, Aga Khan University Hospital (AKU) and Jomo Kenyatta University of Agriculture and Technology (JKUAT), between January 2021- December 2023. Methodology: We analyzed 60 Formalin-fixed Paraffin wax-embedded (FFPE) colorectal biopsy samples (30 cases and 30 controls) of patients from Aga Khan University Hospital. We processed the tissues histologically, extracted the DNA and analyzed through 16S rRNA gene PCR amplification and sequencing. Taxonomic assignment was calculated by Biological Locus Alignment Sequence Tool (BLAST) against the NCBI 16S microbial database. Results: Major bacterial species that were found in CRC were Oscillospiraceae bacterium, Clostridales bacterium, Acetivibrio sp., Eubacterium, Texcoconibacillus texcoconensis, and Staphylococcus sp. Stage II CRC was of greater microbial richness than Stage III. Mucinous adenocarcinoma was associated with Firmicutes commensals, and invasive adenocarcinoma with pathogenic members like Bacillus cereus and Staphylococcus spp. Conclusion: Gut microbiota community structure is stage and subtype-specific in CRC. The shift from commensal to pathogenic bacteria suggests that microbial dysbiosis has the potential to contribute to the development of CRC. Microbiota profiling may assist in the early diagnosis of CRC and guide individualized diagnostic strategies in African populations

    Influence of institutional support and organisational culture on HIV and NCD integration

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    Background: The integration of services for human immunodeficiency virus (HIV) and noncommunicable diseases (NCDs) has gained increasing attention in recent years because of the overlapping prevalence and shared risk factors between these health conditions. However, successful integration requires more than just the alignment of clinical practices. The role of institutional support and organisational culture in promoting effective integration remains an underexplored area. Aim: This study aims to fill this gap by examining how institutional structures and organisational values influence the integration of HIV and NCD care. Setting: The study setting was Nakuru County in Kenya. Methods: This study employed a qualitative research design to capture the nuanced experiences and perceptions of healthcare providers involved in HIV and NCD care integration. A total of 99 key informant interviews were conducted with healthcare providers in levels 2 to 5 facilities in Nakuru County. The interviews lasting 45 min – 60 min were conducted sequentially. This study adopted a thematic analysis using NVivo 12. Results: Institutional support, including an improved provider efficiency, support from top management, capacity building, availability of essential commodities, maximum use of facility space, and monitoring of outcomes, has been shown to enhance integration efforts. Additionally, a supportive organisational culture characterised by adaptivity, embracing innovative or new culture, staff empowerment to propose new strategies, teamwork and performance monitoring contributes to successful integration outcomes. These factors improve patient workflow, ensure continuity of care, reduce patient wait times and reduce stigma. Conclusion: The findings highlight the importance of leadership commitment, resource allocation, communication, collaboration, stigma reduction and patient-centredness in achieving successful integration outcomes. Contribution: This study contributes to the body of knowledge surrounding the integration of HIV and NCD services, providing valuable insights that can be applied in other contexts and settings aiming to enhance healthcare delivery and outcomes for individuals living with these conditions

    Management of pediatric brain tumors in low- and middle-income countries

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    Five-year survival rates exceed 70 % for the 10-20 % children with central nervous system (CNS) tumors in high-income countries (HICs) but are less than 30 % for the 80 % children in lower-middle-income countries (LMICs). The management of CNS tumors is complex and multidisciplinary. It requires a minimum of infrastructure and interactive collaboration between the different actors involved in the care of these patients. This chapter addresses the main challenges associated with the management of pediatric CNS tumors in LMIC, and describes examples of successful development, particularly in the context of twinning programs between institutions in HIC and institutions in LMIC

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