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Background: Telephone and video appointments are still common post-pandemic, with an estimated 25%-50% of kidney appointments in the United Kingdom still conducted remotely. This is important as remote consultations may exacerbate pre-existing inequalities in those from underserved groups. Those from underserved groups are often not represented in health research and include those with learning disability, mental health needs, hearing/sight problems, young/older people, those from ethnic minority groups., Objectives: The aim was to develop a Toolkit to improve the quality of remote kidney care appointments for people from different underserved groups., Design: A parallel mixed methods approach with semistructured interviews/focus groups and survey. We also conducted workshops to develop and validate the Toolkit., Participants: Seventy-five renal staff members completed the survey and 21 patients participated in the interviews and focus groups. Patients (n = 11) and staff (n = 10) took part in the Toolkit development workshop, and patients (n = 13) took part in the Toolkit validation workshop., Results: Four themes from interviews/focus groups suggested areas in which remote appointments could be improved. Themes were quality of appointment, patient empowerment, patient-practitioner relationship and unique needs for underserved groups. Staff reported difficulty building rapport, confidentiality issues, confidence about diagnosis/advice given, technical difficulties and shared decision making., Conclusion: This study is the first to explore experiences of remote appointments among both staff and those from underserved groups living with kidney disease in the United Kingdom. While remote appointments can be beneficial, our findings indicate that remote consultations need optimisation to meet the needs of patients. The project findings informed the development of a Toolkit which will be widely promoted and accessible in the United Kingdom during 2024., (© 2024 The Author(s). Journal of Renal Care published by John Wiley & Sons Ltd on behalf of European Dialysis & Transplant Nurses Association/European Renal Care Association.)

Background: Cervical cancer screening strategies should ideally be informed by population-specific data. Strategies recommended for secondary prevention, are often inadequately studied in populations with high cervical disease burdens. This report describes the test performance measured against CIN2 + /CIN3 + histology in HIV-positive women (HPW) and HIV-negative women (HNW) with the aim to determine the most effective strategies to identify South African women at risk., Methods: Primary screening using visual inspection, cytology and HPV DNA (cobas®) was performed in two South African provinces on 456 HPW and 639 HNW participating in the multicentric DiaVACCS trial. Histology was obtained for 91.7% screen-positive and 42.7% screen-negative participants, and unavailable histology was determined by multiple imputation to adjust for verification bias. Cross-sectional test performance was calculated for single and combination test strategies with and without intermediate risk categories using different cut-offs. Minimum acceptability for sensitivity and specificity, treatment and follow-up numbers were considered to evaluate strategies., Results: The only single test to reach acceptability in HPW was cytology (LSIL) [sensitivity 71.2%; specificity 90.5%; treatment 33.4%]; in HNW only HPV (hr) qualified [sensitivity 68.2%; specificity 85.2%; treatment 23.5%]. The universally best performing strategy which also resulted in smaller treatment numbers without intermediate risk group was primary HPV(hr), with treatment of both HPV(16/18) and cytology (ASCUS +) [HPW: sensitivity 73.6%; specificity 89.7%; treatment 34.7%. HNW: sensitivity 59.1%; specificity 93.6%; treatment 13.9%]. DNA testing for hrHPV (any) and hrHPV (16/18) was the best universally acceptable strategy with an intermediate risk category (early follow-up) in HPW [sensitivity 82.1%; specificity 96.4%; treatment 17.1%; follow-up 31.4%] and HNW [sensitivity 68.2%; specificity 96.7%; treatment 7.6%; follow-up 15.9%]. In comparison, using both HPV (16/18) and cytology (ASCUS +) as secondary tests in hrHPV positive women, decreased follow-up [HPW 13.8%, HNW 9.6%], but increased treatment [HPW 34.7%, HNW 13.9%]., Conclusion: Using hrHPV (any) as primary and both HPV16/18 and cytology as secondary tests, was universally acceptable without an intermediate risk group. Strategies with follow-up groups improved screening performance with smaller treatment numbers, but with effective management of the intermediate risk group as prerequisite., (© 2024. The Author(s).)

Objective: Guidelines for effective triage following positive primary high-risk human papillomavirus (HPV) screening in low- and middle-income countries with high human immunodeficiency virus (HIV)-prevalence have not previously been established. In the present study, we evaluated the performance of three triage methods for positive HPV results in women living with HIV (WLHIV) and without HIV in Botswana., Methods: We conducted baseline enrollment of a prospective cohort study from February 2021 to August 2022 in South-East District, Botswana. Non-pregnant women aged 25 or older with an intact cervix and no prior diagnosis of cervical cancer were systematically consented for enrollment, with enrichment of the cohort for WLHIV. Those who consented completed a questionnaire and then collected vaginal self-samples for HPV testing. Primary HPV testing for 15 individual genotypes was conducted using Atila AmpFire® HPV assay. Those with positive HPV results returned for a triage visit where all underwent visual inspection with acetic acid (VIA), colposcopy, and biopsy. Triage strategies with VIA, colposcopy and 8-type HPV genotype restriction (16/18/31/33/35/45/52/58), separately and in combination, were compared using histopathology as the gold standard in diagnosing cervical intraepithelial neoplasia (CIN) 2 or worse (CIN2+)., Results: Among 2969 women enrolled, 1480 (50%) tested HPV positive. The cohort included 1478 (50%) WLHIV; 99% were virologically suppressed after a mean of 8 years on antiretroviral therapy. In total, 1269 (86%) women had histopathology data for analysis. Among WLHIV who tested positive for HPV, 131 (19%) of 688 had CIN2+ compared with 71 (12%) of 581 in women without HIV. Screening by 8-type HPV genotype restriction was more sensitive as triage to detect CIN2+ in WLHIV 87.79% (95% CI: 80.92-92.85) and women without HIV 85.92% (95% CI: 75.62-93.03) when compared with VIA (WLHIV 62.31% [95% CI: 53.39-70.65], women without HIV 44.29% [95% CI: 32.41-56.66]) and colposcopy (WLHIV 70.77% [95% CI: 62.15-78.41], women without HIV 45.71% [95% CI: 33.74-58.06]). However, 8-type HPV genotype restriction had low specificity in WLHIV of 30.88% (95% CI: 27.06-34.90) and women without HIV 37.06% (95% CI: 32.85-41.41). These results were similar when CIN3+ was used as the outcome. When combining 8-type HPV genotype restriction with VIA as the triage strategy, there was improved specificity to detect CIN2+ in WLHIV of 81.65% (95% CI: 78.18-84.79) but dramatically reduced sensitivity of 56.15% (95% CI: 47.18-64.84)., Conclusions: Eight-type HPV genotype restriction is a promising component of effective triage for HPV positivity. However, novel triage strategies in LMICs with high HIV prevalence may be needed to avoid the trade-off between sensitivity and specificity with currently available options., Clinical Trials Registration: This study is registered on Clinicaltrials.gov no. NCT04242823, https://clinicaltrials.gov/ct2/show/NCT04242823., (© 2023 International Federation of Gynecology and Obstetrics.)

Background:  Infection with the human papillomavirus (HPV) is a necessary cause of cervical cancer and is one of the most prevalent sexually transmitted infections worldwide. Primary prevention strategies target reducing HPV acquisition through vaccination, limiting exposure (e.g. delayed sexual debut, barrier contraception) and health education focusing on sexual behaviour and tobacco use., Methods:  The ImmunoVACCS study, conducted from 2019 to 2022 in two provinces in South Africa, examined sociodemographic characteristics, sexual practices, and knowledge of cervical cancer and the HPV vaccine among young female vaccine recipients. It encompassed participants from the previously conducted vaccine implementation trials, VACCS 1 and VACCS 2 (2011-2014). Recruitment involved telephonic contact with eligible potential participants. Data were collected through self-administered questionnaires., Results:  One hundred and eleven participants took part in the current study (median age: 20 years; age range: 16-22 years). Most sexually active participants had their first engagement in secondary school (96.2%), and 77.2% used contraception during their last sexual activity. Knowledge gaps were evident, with only 13.5% recognising cervical cancer's cervix origin and 3.6% attributing it to a virus. Despite this, 70.3% had heard of a vaccine for cervical cancer. Less than half knew about the importance of regular Pap smears (49.5%), vaccine protection (44.1%) or condom use (20.7%) against HPV and cervical cancer., Conclusion:  The current study demonstrates that young women still lack complete information on cervical cancer and its risk factors even after receiving health education linked with vaccination.Contribution: This study underscores the necessity of ongoing education about HPV, its risks and preventive measures among young women to combat cervical cancer.

Background: Cervical cancer prevention in regions with limited access to screening and HPV vaccination necessitates innovative approaches. This study explored the potential of a test-and-treat strategy using mRNA HPV tests to impact cervical cancer prevention in a high-prevalence HIV population., Methods: A cervical screening study was conducted at three South African hospitals involving 710 under-screened, non-pregnant women (25 to 65 years) without known cervical diseases. Cytology, HPV testing, colposcopy, and biopsies were performed concurrently. Histopathologists determined final histological diagnoses based on biopsy and LLETZ histology. mRNA-HPV-genotyping for 3 (16, 18, 45) to 8 (16, 18, 31, 33, 35, 45, 52, 58) high-risk types was performed on leftover liquid-based cytology material. The preventive potential of the test-and-treat approach was estimated based on published data, reporting the causative HPV types in cervical cancer tissue from South African women. Treatment was provided as needed., Results: The HPV positivity rate more than doubled from 3-type (15.2%; 95% CI: 12.6-17.8) to 8-type mRNA (31.5%; 95% CI: 28.8-34.9) combinations, significantly higher among HIV-positive women. CIN3+ prevalence among HIV-positive women (26.4%) was double that of HIV-negative women (12.9%) ( p < 0.01). The 6-type combination showed the best balance of sensitivity, specificity and treatment group size, and effectiveness to prevent cervical cancer. A 4-type combination (16, 18, 35, 45) could potentially prevent 77.6% (95% CI: 71.2-84.0) of cervical cancer burden by treating 20% and detecting 41.1% of CIN3 cases in the study group. Similarly, a 6-type combination (16, 18, 31, 33, 35, 45), treating 25% and including 62% of CIN3 cases, might prevent 85% of cervical cancer cases (95% CI: 79.6-90.6) among HIV-positive and negative women., Conclusion: Employing mRNA HPV tests within a test-and-treat approach holds huge promise for targeted cervical cancer prevention in under-screened populations. Testing for mRNA of the 6 highest-risk HPV types in this population and treating them all is projected to effectively prevent progression from CIN3 to invasive cervical cancer while reducing overtreatment in resource-constrained settings.

The Eurotransplant Senior Program (ESP) has expedited the chance for elderly patients with kidney failure to receive a timely transplant. This current study evaluated survival parameters of kidneys donated after brain death with or without matching for HLA-DR antigens. This cohort study evaluated the period within ESP with paired allocation of 675 kidneys from donors 65 years and older to transplant candidates 65 years and older, the first kidney to 341 patients within the Eurotransplant Senior DR-compatible Program and 334 contralateral kidneys without (ESP) HLA-DR antigen matching. We used Kaplan-Meier estimates and competing risk analysis to assess all cause mortality and kidney graft failure, respectively. The log-rank test and Cox proportional hazards regression were used for comparisons. Within ESP, matching for HLA-DR antigens was associated with a significantly lower five-year risk of mortality (hazard ratio 0.71; 95% confidence interval 0.53-0.95) and significantly lower cause-specific hazards for kidney graft failure and return to dialysis at one year (0.55; 0.35-0.87) and five years (0.73; 0.53-0.99) post-transplant. Allocation based on HLA-DR matching resulted in longer cold ischemia (mean difference 1.00 hours; 95% confidence interval: 0.32-1.68) and kidney offers with a significantly shorter median dialysis vintage of 2.4 versus 4.1 yrs. in ESP without matching. Thus, our allocation based on HLA-DR matching improved five-year patient and kidney allograft survival. Hence, our paired allocation study suggests a superior outcome of HLA-DR matching in the context of old-for-old kidney transplantation., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Objective: Screening with primary human papillomavirus (HPV) testing has been evaluated in highly prescreened populations with lower HPV and HIV prevalence than what is the case in South Africa. High prevalence of HPV and underlying precancer in women living with HIV (WLWH) affect the clinical performance of screening tests significantly. This study investigates the utility and performance of an extended genotyping HPV test in detection of precancer in a population with a high coinfection rate with HIV., Methods: A total of 1,001 women aged 25 to 65 years with no cervical cancer screening in the preceding 5 years were tested with cytology and primary extended genotyping HPV testing. The cohort of 1,001 women included 430 WLWH (43.0%) and 564 HIV-negative (56.3%) women., Results: Abnormal cytology (atypical squamous cells of undetermined significance or higher) was significantly higher in WLWH (37.2% vs 15.9%) and high-grade squamous intraepithelial lesion or above (23.5% vs 5.2%). The WLWH also tested positive more often for any HPV type (44.3% vs 19.6%; p < .0001) The specificity for cervical intraepithelial neoplasia 2+ at 91.2% of a combination of HPV types, 16/18/45 (very high risk) and 31/33/58/52 (moderate risk), performed better than cytology or any HPV-positive result to predict cervical intraepithelial neoplasia 3+ on histology. The additional genotype information supports direct referral to treatment or colposcopy in a larger proportion of the screen-positive population., Conclusions: The potential contribution of extended genotyping is demonstrated. The ideal choice of sensitivity and specificity ultimately depends on the health budget. More information will allow a screening algorithm, guiding management according to risk., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2023, ASCCP.)

Objectives: Cervical cancer is preventable and caused by persistent infection with oncogenic human papilloma virus (HPV) types. HPV screening is more sensitive and is the preferred screening test. HPV screening data are mainly from developed settings, and the purpose of this study was to investigate the performance of HPV screening in previously unscreened HIV positive and negative women., Methods: In this cross sectional multicenter study, liquid based cytology and HPV testing were performed on women attending different clinics. Patients with positive screening tests had colposcopy and biopsy or large loop excision of the transformation zone. Some women with normal screening had colposcopy and biopsy. Data of women with histology results, and data of HIV positive and negative women were analyzed for comparison. For women without histology results, data were imputed using a statistical model., Results: In 903 women with known HIV status, 683 (75.6%) had negative cytology, 202 women (22.4%) had abnormal cytology, and in 18 patients (2.0%) the results were uncertain. Mean age was 41.4 years (range 25-65). HPV tests were negative in 621 women (68.8%). In HIV positive women, 54.5% tested negative compared with 79.7% HIV negative women (p<0.0001). HPV screening had higher sensitivity (60.9%), but lower specificity (82.4%), compared with cytology (48.6% and 86.7%) for detection of cervical intraepithelial neoplasia (CIN) 2+ in all women. For detection of CIN 3+, HPV screening had higher sensitivity (70.4%) compared with cytology (62.9%), and specificity (75.5%) was lower compared with cytology at a threshold of atypical squamous cells of undetermined significance (ASCUS+) (82.4%)., Conclusion: HPV screening was more sensitive than cytology in HIV positive and HIV negative women, but specificity was lower. Although HPV screening should be the preferred screening test, cytology is a suitable screening test in HIV positive women in low resource settings., Trial Registration Number: NCT02956031., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The main objective of this study was to evaluate the Medically Necessary Time Sensitive (MeNTS) scoring system in triaging gynaecologic oncologic surgery during and beyond the COVID-19 pandemic., Material and Methods: This was a retrospective cross-sectional study including 209 patients who either had surgery (151) or surgery postponed (58) between the 26th March and 30th September 2020 in an academic hospital in South Africa. The MeNTS score was used to independently score each patient three times by two observers., Results: The mean age of the participants was 46.6 ± 15 years and the cumulative mean MeNTS score was 51.0 ± 5.1. Over two-thirds of the cases had surgery. There was no significant difference between the first and second observers' cumulative scores, 51.0 vs 51.1 (p 0.77). The cumulative score among those who had surgery was significantly lower than that for those whose surgeries were postponed, 49.8 vs 54.1 (p <0.0001). The intra-observer and inter-observer reliability were 0.78 and 0.74 respectively. After adjusting for confounding variables, those with low cumulative MeNTS scores were about 5 times more likely to have surgery than those with high scores (Adj. OR = 4.67, 95% CI: 1.92-11.4, p <0.001. Patients with malignant diagnosis were also 5 times more likely to be operated than those with benign diagnosis (Adj. OR = 5.03, 95% CI: 1.73-14.6, p <0.001. The area under the curve (AUC) was 0.85 suggesting an excellent discriminatory power between those who were operated and those who were postponed., Conclusion: The study provided some insight into the potential usefulness of MeNTS score in prioritizing patients for surgery in gynaecologic oncologic sub-specialty. The score performed well across a range of gynaecologic conditions and procedures with good intra-observer and inter-observer consistency and reliability. This is a prioritization tool that is dynamically adaptable to accommodate changes in resources availability and operating theatre capacity., Competing Interests: The authors have declared that no competing interest exists., (Copyright: © 2023 Sajo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Preclinical studies show that the anticancer actions of vitamin D metabolites are mediated by apoptosis, inhibition of cell proliferation and induction of cell cycle arrest. Cervical cancer cells express an autocrine vitamin D metabolising system (VDMS) comprised of a vitamin D receptor, vitamin D catabolic enzyme (CYP24A1), and the activating enzyme of 25-hydroxycholecalciferol (25(OH)D3), CYP27B1. We assessed the anticancer effects of 25(OH)D3 at clinically relevant concentrations on a cervical squamous cell cancer cell line, SiHa. We evaluated cell health parameters (cell count, viability, and cell cycle), cell death modes (apoptosis, autophagic-dependent death, and necrosis by flow cytometry and transmission electron microscopy), and autocrine VDMS gene and protein expression by qPCR and Western blot, respectively. Our study demonstrates that physiological and supraphysiological doses of 25(OH)D3 inhibit cell growth and viability and induce biochemical and morphological apoptosis in SiHa cells. These growth effects are mediated by alteration in the VDMS gene and protein expression, with prominent negative feedback at supraphysiological treatment dose. These data identify promising therapeutic potential of 25(OH)D3 in cervical cancer, which warrants further clinical translational investigations.

Background: Compared with women who are human immunodeficiency virus (HIV) negative, women with human immunodeficiency virus (WWH) have a higher human papillomavirus (HPV) prevalence and increased cervical cancer risk, emphasizing the need for effective cervical cancer screening in this population. The present study aimed to validate methylation markers ASCL1 and LHX8 for primary screening in a South African cohort of WWH., Methods: In this post hoc analysis within the DIAgnosis in Vaccine And Cervical Cancer Screen (DiaVACCS) study, a South African observational multicenter cohort study, cervical scrape samples from 411 HIV-positive women were analyzed for hypermethylation of ASCL1 and LHX8 genes, HPV DNA, and cytology. Sensitivities, specificities, and positive and negative predictive values of primary methylation-based, HPV-based and cytology-based screening were calculated for the detection of cervical intraepithelial neoplasia of grade 3 or higher., Results: Single markers ASCL1 and LHX8 resulted in a good performance for the detection of cervical intraepithelial neoplasia of grade 3 or higher, with sensitivities of 85.9% (95% confidence interval [CI], 78.2%-93.6%) and 89.7% (83.0%-96.5%), respectively, and specificities of 72.9% (67.3%-78.5%) and 75.0% (69.5%-80.5%). Combining markers ASCL1 and LHX8 resulted in a lower sensitivity compared with HPV testing (84.6% vs 93.6%, respectively; ratio, 0.90 [95% CI, .82-.99]) and a higher specificity (86.7% vs 78.3%; ratio 1.11 [1.02-1.20]) and reduced the referral rate from 46.8% to 33.4%. ASCL1/LHX8 methylation had a significantly higher sensitivity than cytology (threshold, high-grade intraepithelial squamous lesion or worse), (84.6% vs 74.0%, respectively; ratio, 1.16 [95% CI, 1.01-1.32]) and similar specificity (86.7% vs 91.0%; ratio, 0.95 [.90-1.003])., Conclusions: Our results validate the accuracy of ASCL1/LHX8 methylation analysis for primary screening in WWH, which offers a full-molecular alternative to cytology- or HPV-based screening, without the need for additional triage testing., Competing Interests: Potential conflicts of interest. C. J. L. M. M., and R. D. M. S. are minority shareholders of Self-screen, a spin-off company of Amsterdam UMC, location Vrije Universiteit; Self-screen develops, manufactures and licenses high-risk HPV and methylation marker assays for cervical cancer screening and holds patents on these tests. A research use only version of the methylation assay has been made available by Self-screen (www.self-screen.nl). C. J. L. M. M. is the part-time chief executive officer of Self-screen and served occasionally on scientific advisory boards and/or speakers bureaus for GlaxoSmithKline (GSK), Qiagen, Sanofi Pasteur MSD/Merck, and Asieris Pharma/Ismar Healthcare. He also reports consulting fees from Qiagen, GSK, Sanofi Pasteur MSD/Merck, Asieris Pharma/Ismar Healthcare, paid to the author, and support for attending meetings and/or travel, paid to the author, from Qiagen, GSK, Sanofi Pasteur MSD/Merck, and Self-screen. He formerly had a very small number of shares of MDXHealth and Qiagen. R. D. M. S. is an inventor on patents on methylation markers for cervical cancer (patents are licensed to Self-screen). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: Patients with advanced chronic kidney disease (CKD) or kidney failure receiving replacement therapy (KFRT) are highly vulnerable to COVID-19 infection, morbidity and mortality. Vaccination is effective, but access differs around the world. We aimed to ascertain the availability, readiness and prioritisation of COVID-19 vaccines for this group of patients globally., Setting and Participants: Collaborators from the International Society of Nephrology (ISN), Dialysis Outcomes and Practice Patterns Study and ISN-Global Kidney Health Atlas developed an online survey that was administered electronically to key nephrology leaders in 174 countries between 2 July and 4 August 2021., Results: Survey responses were received from 99 of 174 countries from all 10 ISN regions, among which 88/174 (50%) were complete. At least one vaccine was available in 96/99 (97%) countries. In 71% of the countries surveyed, patients on dialysis were prioritised for vaccination, followed by patients living with a kidney transplant (KT) (62%) and stage 4/5 CKD (51%). Healthcare workers were the most common high priority group for vaccination. At least 50% of patients receiving in-centre haemodialysis, peritoneal dialysis or KT were estimated to have completed vaccination at the time of the survey in 55%, 64% and 51% of countries, respectively. At least 50% of patients in all three patient groups had been vaccinated in >70% of high-income countries and in 100% of respondent countries in Western Europe.The most common barriers to vaccination of patients were vaccine hesitancy (74%), vaccine shortages (61%) and mass vaccine distribution challenges (48%). These were reported more in low-income and lower middle-income countries compared with high-income countries., Conclusion: Patients with advanced CKD or KFRT were prioritised in COVID-19 vaccination in most countries. Multiple barriers led to substantial variability in the successful achievement of COVID-19 vaccination across the world, with high-income countries achieving the most access and success., Competing Interests: Competing interests: EW, MIAH, AL, GD, FC, AKB, SD, SS, DZ, VAL and DB have no disclosures. Global support for the ongoing DOPPS programme is provided without restriction on publications by a variety of funders. For details see, https://www.dopps.org/AboutUs/Support.aspx. BMR has received consultancy fees or travel reimbursement since 2019 from AstraZeneca, GlaxoSmithKline and Kyowa Kirin Co, all paid directly to his institution of employment. DJ has received consultancy fees, research grants, speaker’s honoraria and travel sponsorships from Baxter Healthcare and Fresenius Medical Care, consultancy fees from AstraZeneca, Bayer and AWAK, speaker’s honoraria from Ono and BI & Lilly, and travel sponsorships from Ono and Amgen. He is a current recipient of an Australian National Health and Medical Research Council Leadership Investigator Grant., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Home dialysis may minimize SARS-CoV2 exposure risks compared to center-based dialysis. We explored how the pandemic may have introduced challenges related to peritoneal dialysis (PD) supply availability, routine patient care, and how facility practices changed during this time., Methods: The PD/Dialysis Outcomes and Practice Patterns Study (PDOPPS/DOPPS) and International Society of Nephrology (ISN) administered a web-based survey from November 2020 to March 2021. Medical director responses were compared across 10 ISN regions., Results: One hundered sixy-five PD facilities in 51 countries returned surveys. During the initial COVID-19 wave, the reported frequency of in-person patient visits decreased in 9 of 10 ISN regions. Before the pandemic, most facilities required a mask during PD exchanges which continued over the course of the pandemic. Although most facilities in different regions did not report PD supply disruptions, sites in Africa and South Asia reported major disruptions. Reductions in laparoscopic surgical procedures for PD catheters were reported by facilities in 9 of 10 regions whereas nonsurgical percutaneous procedures increased in facilities in 6 regions. Training of new PD patients declined in facilities in each region. Increased use of remote technology by patients to communicate with clinics was observed in all regions compared to prepandemic levels., Conclusion: Marked within-region and across-region variability was noted in PD facility burden, clinical practice, and adaptation to the COVID-19 pandemic. This study highlights opportunities to improve routine PD care, adapt to the ongoing pandemic, and increase preparedness for potential future interruptions in PD care., (© 2022 International Society of Nephrology. Published by Elsevier Inc.)

Background: The burden of kidney disease in many African countries is unknown. Equations used to estimate kidney function from serum creatinine have limited regional validation. We sought to determine the most accurate way to measure kidney function and thus estimate the prevalence of impaired kidney function in African populations., Methods: We measured serum creatinine, cystatin C, and glomerular filtration rate (GFR) using the slope-intercept method for iohexol plasma clearance (mGFR) in population cohorts from Malawi, Uganda, and South Africa. We compared performance of creatinine and cystatin C-based estimating equations to mGFR, modelled and validated a new creatinine-based equation, and developed a multiple imputation model trained on the mGFR sample using age, sex, and creatinine as the variables to predict the population prevalence of impaired kidney function in west, east, and southern Africa., Findings: Of 3025 people who underwent measured GFR testing (Malawi n=1020, South Africa n=986, and Uganda n=1019), we analysed data for 2578 participants who had complete data and adequate quality measurements. Among 2578 included participants, creatinine-based equations overestimated kidney function compared with mGFR, worsened by use of ethnicity coefficients. The greatest bias occurred at low kidney function, such that the proportion with GFR of less than 60 mL/min per 1·73 m 2 either directly measured or estimated by cystatin C was more than double that estimated from creatinine. A new creatinine-based equation did not outperform existing equations, and no equation, including the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 race-neutral equation, estimated GFR within plus or minus 30% of mGFR for 75% or more of the participants. Using a model to impute kidney function based on mGFR, the estimated prevalence of impaired kidney function was more than two-times higher than creatinine-based estimates in populations across six countries in Africa., Interpretation: Estimating GFR using serum creatinine substantially underestimates the individual and population-level burden of impaired kidney function in Africa with implications for understanding disease progression and complications, clinical care, and service provision. Scalable and affordable ways to accurately identify impaired kidney function in Africa are urgently needed., Funding: The GSK Africa Non-Communicable Disease Open Lab., Translations: For the Luganda, Chichewa and Xitsonga translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests The Ugandan and Malawian study was funded by a project grant from the GSK Africa Non-Communicable Disease Open Lab (project number 8111). CHH received funding from Medical Research Council (MRC) Grant Reference MR/R010161/1. The South African study was jointly funded by the South African MRC, MRC UK (via the Newton Fund), and GSK Africa Non-Communicable Disease Open Lab (via a supporting grant; project number 074). Additional sources of funding for the South African project were obtained from the International Society for Nephrology Clinical Research Program 15–2-015 (Validation of eGFR equations in South Africans; South Africa); the National Health Laboratory Services; and Faculty of Health Sciences Research Incentive Grant (number 0012838434203512110500000000000000004550), University of the Witwatersrand. Funding supported implementation, execution, and completion of the study in Malawi, South Africa, and Uganda., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Human papillomavirus (HPV)-based primary screening guidelines are based on screening test performance and prevalence data generated in high-resource areas with low HIV infection rates. There is an urgent need for local data on infection and disease prevalence, as well as screening test performance, among both HIV-positive and HIV-negative South African (SA) women, in order to inform updated screening guidelines. Objectives. This study describes the baseline characteristics of participants in the cross-sectional phase of the multicentric DIAgnosis in Vaccine And Cervical Cancer Screen (DiaVACCS) screening trial. The objective was to determine the prevalence of positive screening and pre-invasive disease using different tests and strategies in the SA HIV-positive and HIV-negative population., Methods: A total of 1  104 women aged 25 - 65 years and eligible for screening were included, 465 HIV positive and 639 HIV negative. Visual inspection and molecular and cytological screening tests were done on self-sampled and healthcare worker-collected specimens. All participants who screened positive and 49.1% of those who screened negative were invited for colposcopy and biopsy, and those qualifying for treatment were recalled for large loop excision of the transformation zone as part of the trial. The worst histology result for each participant was used, and for untested women, multiple imputation was used to estimate verification biasadjusted histology values., Results: Visual inspection was positive in 50.4% of HIV-positive v. 20.9% of HIV-negative women, cytology (atypical squamous cells of undetermined significance) in 39.9% v. 17.0%, and high-risk HPV DNA in 41.2% v. 19.6%. Overall, high-grade squamous intraepithelial lesion-positive cytology peaked in the age group 30 - 39 years at 16.7%. After adjustment for verification bias, histological diagnosis of cervical intraepithelial neoplasia (CIN)2+ was suspected in 44.7% v. 23.5% and CIN3+ in 23.3% v. 10.2% of HIV-positive and negative women, respectively. Invasive cancer was diagnosed in 15 women (1.95% of histological studies performed), and verification bias adjustment suggested 20 cases (1.8% of the study population)., Conclusion: The baseline findings from the DiaVACCS trial confirm a high prevalence of HPV-related cervical pathology in the SA HIV-negative screening population, showing a clear need to reach these women with a screening programme. Among HIV-positive women, prevalence values were almost doubled. The prevalence of existing invasive cervical cancer was 1 - 2% of all women. Further analysis of the performance of single and multiple screening tests between the two subgroups will contribute to the choice of the most effective strategies to identify women at risk of developing invasive cancer.

Objective: Women with HIV (WWH) have an increased risk to develop recurrent cervical intraepithelial neoplasia grade 2/3 (rCIN2/3) after treatment compared with HIV-negative women. Therefore, appropriate posttreatment monitoring of WWH is important. This study evaluates the performance of ASCL1 and LHX8 methylation analysis as posttreatment monitoring test in WWH treated for CIN2/3, as alternative to cytology or human papillomavirus (HPV) as follow-up test., Design: Prospective observational cohort study., Methods: WWH treated for CIN2/3 by large loop excision of the transformation zone (LLETZ) (n  = 61) were invited for follow-up study visits at 1, 2.5 and 4 years after baseline. Baseline and follow-up cervical scrapes were tested for cytology, HPV and DNA methylation of ASCL1 and LHX8 genes. The performance of these strategies for the detection of rCIN2/3 was evaluated in the first follow-up cervical scrape., Results: Thirteen (21.3%) rCIN2/3 lesions were detected within 4 years of follow-up. In women without rCIN2/3 in follow-up, methylation levels of ASCL1 and LHX8 decreased significantly after LLETZ treatment (P  = 0.02 and 0.007, respectively). In women with rCIN2/3, methylation levels remained high after LLETZ treatment. The 4-year rCIN2/3 risk was 4.9% (95% CI: 0.6-16.5) for ASCL1/LHX8-negative women, 8.1% (95% CI: 1.7-21.9) for HPV-negative women and 7.7% (95% CI: 2.1-18.5) for cytology-negative women., Conclusion: A negative ASCL1/LHX8 methylation test in follow-up is associated with a low rCIN2/3 risk and could serve as an objective test of cure and well tolerated alternative for HPV and/or cytology screening in the posttreatment monitoring of WWH., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: The platform provided by human papillomavirus (HPV) vaccination for linked public health interventions to improve cervical cancer prevention remains incompletely explored. The Vaccine And Cervical Cancer Screen (VACCS) cross-sectional observation trials aimed to evaluate the efficacy of school-based HPV vaccination linked with maternal cervical cancer screening., Methods: Girls from 29 schools in two provinces in South Africa were invited in writing to receive HPV vaccination. Two approaches to informed consent were compared, namely an audiovisual presentation (VACCS1) and in written format (VACCS2). Markers of vaccine uptake and coverage were calculated, namely uptake among the invited and consented cohorts, and rates of completion and sufficient vaccination. Mothers and female guardians received educational material about cervical cancer, and either a self-sampling device or an invitation to attend existing screening facilities. Knowledge was assessed via structured questionnaires (before and after), and screening uptake was self-reported and directly assessed and compared between these approaches., Results: Vaccine acceptance among 5137 invited girls was similar for the two methods of consent; 99.3% of consented girls received a first dose; overall completion rate was 90.5%. More girls were vaccinated using a two-dose (974/1016 (95.9%)) than a three-dose regimen (1859/2030 (91.6%)). The questionnaire (n=906) showed poor maternal knowledge which improved significantly (p<0.05) after health education; only 54% of mothers reported any previous screening. The offer of a self-sampling device (n=2247) was accepted by 43.9% of mothers, but only 26% of those invited to screen at existing facilities (n=396) reported subsequent screening., Conclusions: Successful linking of primary health interventions to control cervical cancer was demonstrated. School-based HPV vaccination, linked to health education, self-sampling, and molecular screening resulted in significant improvements in knowledge and screening., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: It is unknown how the COVID-19 pandemic has affected the care of vulnerable chronic hemodialysis (HD) patients across regions, particularly in low and lower-middle income countries (LLMICs). We aimed to identify global inequities in HD care delivery during the COVID-19 pandemic., Methods: The ISN and the Dialysis Outcomes and Practice Patterns Study (DOPPS) conducted a global online survey of HD units between March and November, 2020, to ascertain practice patterns and access to resources relevant to HD care during the COVID-19 pandemic. Responses were categorized according to World Bank income classification for comparisons., Results: Surveys were returned from 412 facilities in 78 countries: 15 (4%) in low-income countries (LICs), 111 (27%) in lower-middle income countries (LMICs), 145 (35%) in upper-middle income countries (UMICs), and 141 (34%) in high-income countries (HICs). Respondents reported that diagnostic tests for SARS-CoV-2 were unavailable or of limited availability in LICs (72%) and LMICs (68%) as compared with UMICs (33%) and HICs (20%). The number of patients who missed HD treatments was reported to have increased during the COVID-19 pandemic in LICs (64%) and LMICs (67%) as compared with UMICs (31%) and HICs (6%). Limited access to HD, intensive care unit (ICU) care, and mechanical ventilation among hospitalized patients on chronic dialysis with COVID-19 were also reportedly higher in LICs and LMICs as compared with UMICs and HICs. Staff in LLMICs reported less routine testing for SARS-CoV-2 when asymptomatic as compared with UMICs and HICs-14% in LICs and 11% in LMICs, compared with 26% and 28% in UMICs and HICs, respectively. Severe shortages of personal protective equipment (PPE) were reported by the respondents from LICs and LMICs compared with UMICs and HICs, especially with respect to the use of the N95 particulate-air respirator masks., Conclusion: Striking global inequities were identified in the care of chronic HD patients during the pandemic. Urgent action is required to address these inequities which disproportionately affect LLMIC settings thereby exacerbating pre-existing vulnerabilities that may contribute to poorer outcomes., (© 2022 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: To assess the impact of the COVID-19 pandemic impact on hemodialysis (HD) centers, The Dialysis Outcomes and Practice Patterns Study and ISN collaborated on a web-survey of centers., Methods: A combined approach of random sampling and open invitation was used between March 2020 and March 2021. Responses were obtained from 412 centers in 78 countries and all 10 ISN regions., Results: In 8 regions, rates of SARS-CoV-2 infection were <20% in most centers, but in North East Asia (NE Asia) and Newly Independent States and Russia (NIS & Russia), rates were ≥20% and ≥30%, respectively. Mortality was ≥10% in most centers in 8 regions, although lower in North America and Caribbean (N America & Caribbean) and NE Asia. Diagnostic testing was not available in 33%, 37%, and 61% of centers in Latin America, Africa, and East and Central Europe, respectively. Surgical masks were widely available, but severe shortages of particulate-air filter masks were reported in Latin America (18%) and Africa (30%). Rates of infection in staff ranged from 0% in 90% of centers in NE Asia to ≥50% in 63% of centers in the Middle East and 68% of centers in NIS & Russia. In most centers, <10% of staff died, but in Africa and South Asia (S Asia), 2% and 6% of centers reported ≥50% mortality, respectively., Conclusion: There has been wide global variation in SARS-CoV-2 infection rates among HD patients and staff, personal protective equipment (PPE) availability, and testing, and the ways in which services have been redesigned in response to the pandemic., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Purpose of Review: Although cervical cancer is preventable, it is the leading cancer among women in southern Africa. The association of high-risk human papillomavirus (HR-HPV) with almost all invasive cervical cancers has led to the development of effective primary and secondary prevention measures. This review focuses on updated and new evidence of the epidemiology of HPV and HPV-based secondary prevention in southern Africa., Recent Findings: HR-HPV prevalence in southern Africa differs between regions, and varies most by HIV prevalence and age. HR-HPV prevalence among women living with HIV (WLWH) is reported between 29 and 59.7%, and between 16.2 and 25.2% among women without HIV. HPV16 is the most common HR-HPV type present in invasive cervical cancers in the region; and vaccination may potentially prevent approximately 80% of these cancers. Concerning preliminary data suggests faster development of new cervical precancer within a short follow-up period., Summary: We need tools that identify the small number of women with precancer from the many with transient HR-HPV infection in southern Africa. The high-volume of test-positive women leads to challenges in managing triage in a HR-HPV-based screening program. Longitudinal data from the entire region is urgently needed to guide effective implementation of HPV-based screening programs., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Populations in the high-income countries of Western Europe are aging due to increased life expectancy. As the prevalence of diabetes and obesity has increased, so has the burden of kidney failure. To determine the global capacity for kidney replacement therapy and conservative kidney management, the International Society of Nephrology conducted multinational, cross-sectional surveys and published the findings in the International Society of Nephrology Global Kidney Health Atlas. In the second iteration of the International Society of Nephrology Global Kidney Health Atlas, we aimed to describe the availability, accessibility, quality, and affordability of kidney failure care in Western Europe. Among the 29 countries in Western Europe, 21 (72.4%) responded, representing 99% of the region's population. The burden of kidney failure prevalence varied widely, ranging from 760 per million population (pmp) in Iceland to 1612 pmp in Portugal. Coverage of kidney replacement therapy from public funding was nearly universal, with the exceptions of Germany and Liechtenstein where part of the costs was covered by mandatory insurance. Fourteen (67%) of 21 countries charged no fees at the point of care delivery, but in 5 countries (24%), patients do pay some out-of-pocket costs. Long-term dialysis services (both hemodialysis and peritoneal dialysis) were available in all countries in the region, and kidney transplantation services were available in 19 (90%) countries. The incidence of kidney transplantation varied widely between countries from 12 pmp in Luxembourg to 70.45 pmp in Spain. Conservative kidney care was available in 18 (90%) of 21 countries. The median number of nephrologists was 22.9 pmp (range: 9.47-55.75 pmp). These data highlight the uniform capacity of Western Europe to provide kidney failure care, but also the scope for improvement in disease prevention and management, as exemplified by the variability in disease burden and transplantation rates., (© 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Cervical cancer treatment and care remains limited in Zimbabwe despite the growing burden of the disease among women. This study was aimed at investigating strategies to address barriers in accessing treatment and care by women with cervical cancer in Harare, Zimbabwe., Methods: A qualitative inquiry was conducted to generate evidence for this study. Eighty-four (84) participants were purposively selected for interviews and participation in focus group discussions. The participants were selected from cervical cancer patients, caregivers of cervical cancer patients, health workers involved in the care of cervical cancer patients as well as relevant policy makers in the Ministry of Health and Child Care. Participants were selected in such as a way as to ensure different of characteristics to obtain diverse perspectives about the issues under study. Discussion and interview guides were used as data collection tools and discussions/interviews were audio-recorded, transcribed and translated into English. Inductive thematic analysis was conducted using Dedoose software., Results: Salient sub-themes that emerged in the study at the individual patient level were: provision of free or subsidized services, provision of transport to treating health facilities and provision of accommodation to patients undergoing treatment. At the societal level, the sub-themes were: strengthening of health education in communities and training of health workers and community engagement. Salient sub-themes from the national health system level were: establishment of more screening and treatment health facilities, increasing the capacities of existing facilities, decentralization of some services, building of multidisciplinary teams of health workers, development and rolling out of standardized guidelines and reformation of Acquired Immunodeficiency Virus (AIDS) levy into a fund that would finance priority disease areas., Conclusion: This study revealed some noteworthy strategies to improve access to cervical cancer treatment and care in low-income settings. Improved domestic investments in health systems and reforming health policies underpinned on strong political are recommended.

Background: The prevalence of working-aged stroke survivors is increasing yearly. Stroke is an expensive disease, causing financial burden to the government, the family and caregivers of the patient, thus making it imperative for working-aged stroke survivors to work to remain financially independent. Survivors' need to work necessitates occupational therapists to shift their focus from basic activities of daily living, to rehabilitating work., Objectives: This study aimed to determine the perceptions of occupational therapists working with younger stroke survivors in public hospitals and clinics in Gauteng South Africa, about rehabilitating working-aged stroke survivors' work ability., Methods: Ethical clearance was obtained. A qualitative research design was used to obtain narrative, descriptive data from six focus groups. Therapists from public healthcare settings, who had more than six months' experience and had worked in neurological rehabilitation within the six months preceding the focus group, were invited to participate. Focus groups were audio recorded and transcribed. Inductive content analysis was used to identify themes and categories., Results: Few participants are involved in rehabilitating younger stroke survivors' work ability or facilitating return to work (RTW). The study identified perceived barriers and enablers to rendering OT services that meet working-aged stroke survivors' needs., Conclusions: Despite enabling employment equity laws in South Africa, OTs working in the public sector appear to experience a sense of futility when trying to rehabilitate young stoke survivors to RTW. Fragmentation of the public sector and limited resources impede successful RTW for working-aged stroke survivors. Survivors' employment status and motivation to RTW facilitated rehabilitating work ability.

This study aims to characterize cervical intraepithelial neoplasia (CIN) in women living with HIV using biomarkers. Immunohistochemical (IHC) staining for human papillomavirus (HPV) E4 protein indicates CIN with productive HPV infection, whereas Ki-67 and p16 ink4a indicate CIN with transforming characteristics, which may be further characterized using DNA hypermethylation, indicative for advanced transforming CIN. Cervical biopsies (n = 175) from 102 HPV positive women living with HIV were independently reviewed by three expert pathologists. The consensus CIN grade was used as reference standard. IHC staining patterns were scored for Ki-67 (0-3), p16 ink4a (0-3), and E4 (0-2) and correlated to methylation levels of four cellular genes in corresponding cervical scrapes. Reference standards and immunoscores were obtained from 165 biopsies:15 no dysplasia, 91 CIN1, 31 CIN2, and 28 CIN3. Ki-67 and p16 ink4a scores increased with increasing CIN grade, while E4 positivity was highest in CIN1 and CIN2 lesions. E4 positive CIN1 lesions had higher Ki-67 and p16 ink4a scores and higher methylation levels compared with E4 negative CIN1 lesions. E4 positive biopsies with low cumulative Ki-67/p16 ink4a immunoscores (0-3) had significantly higher methylation levels compared with E4 negative biopsies. No significant differences in Ki-67 and p16 ink4a scores and methylation levels were observed between E4 negative and positive CIN2 or CIN3 lesions. The presence of high methylation levels in scrapes of CIN lesions with IHC characteristics of both productive (E4 positive) and transforming infections (increased Ki-67/p16 ink4a expression) in women living with HIV might indicate a rapid aggressive course of HPV infections towards cancer in these women.

Background: There are a growing number of studies on ethnic differences in progression and mortality for pre-dialysis chronic kidney disease (CKD), but this literature has yet to be synthesised, particularly for studies on mortality., Methods: This scoping review synthesized existing literature on ethnic differences in progression and mortality for adults with pre-dialysis CKD, explored factors contributing to these differences, and identified gaps in the literature. A comprehensive search strategy using search terms for ethnicity and CKD was taken to identify potentially relevant studies. Nine databases were searched from 1992 to June 2017, with an updated search in February 2020., Results: 8059 articles were identified and screened. Fifty-five studies (2 systematic review, 7 non-systematic reviews, and 46 individual studies) were included in this review. Most were US studies and compared African-American/Afro-Caribbean and Caucasian populations, and fewer studies assessed outcomes for Hispanics and Asians. Most studies reported higher risk of CKD progression in Afro-Caribbean/African-Americans, Hispanics, and Asians, lower risk of mortality for Asians, and mixed findings on risk of mortality for Afro-Caribbean/African-Americans and Hispanics, compared to Caucasians. Biological factors such as hypertension, diabetes, and cardiovascular disease contributed to increased risk of progression for ethnic minorities but did not increase risk of mortality in these groups., Conclusions: Higher rates of renal replacement therapy among ethnic minorities may be partly due to increased risk of progression and reduced mortality in these groups. The review identifies gaps in the literature and highlights a need for a more structured approach by researchers that would allow higher confidence in single studies and better harmonization of data across studies to advance our understanding of CKD progression and mortality.

Background: Kidney disease is prevalent in low-resource settings worldwide, but tests for its diagnosis are often unavailable. The saliva urea nitrogen (SUN) dipstick is a laboratory and electricity independent tool, which may be used for the detection of kidney disease. We investigated the feasibility and performance of its use in diagnosing kidney disease in community settings in Africa., Methods: Adult patients at increased risk of kidney disease presenting to three community health centres, a rural district hospital and a central hospital in Malawi were recruited between October 2016 and September 2017. Patients underwent concurrent SUN and creatinine testing at enrolment, and at 1 week, 1 month, 3 months and 6 months thereafter., Results: Of 710 patients who presented at increased risk of kidney disease, 655 (92.3%) underwent SUN testing at enrolment, and were included (aged 38 (29-52) years, 367 (56%) female and 333 (50.8%) with HIV). Kidney disease was present in 482 (73.6%) patients and 1479 SUN measurements were made overall. Estimated glomerular filtration rate (eGFR) correlated with SUN (r=-0.39; p<0.0001). The area under the receiver operating characteristics curve was 0.61 for presenting SUN to detect acute or chronic kidney disease, and 0.87 to detect severe (eGFR <15 mL/min/1.73 m 2 ) kidney disease (p<0.0001; sensitivity 82.3%, specificity 81.8%, test accuracy 81.8%). In-hospital mortality was greater if enrolment SUN was elevated (>test pad #1) compared with patients with non-elevated SUN (p<0.0001; HR 3.3 (95% CI 1.7 to 6.1)., Conclusions: SUN, measured by dipstick, is feasible and may be used to screen for kidney disease in low resource settings where creatinine tests are unavailable., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

It is unclear whether nutritional vitamin D supplementation in vitamin d-deficient persons improves arterial stiffness. To conduct a meta-analysis of the effects of the nutritional vitamin D therapy on arterial stiffness in adults with vitamin D deficiency, the Scopus, PUBMED, EMBASE, and Cochrane databases were searched for systematic reviews conducted up to October 5, 2018. Randomized clinical trials that compared nutritional vitamin D therapy with placebo in adults with vitamin D deficiency were eligible. Two reviewers independently evaluated eligibility of all retrieved studies based on titles and abstracts. Meta-analysis was performed using random effect or fixed effects model and inverse variance method was used to calculate the effect using standardized mean difference (SMD) and weighted mean difference. A leave-one-out method was used for sensitivity analysis. The main outcome was arterial stiffness, indicated by the carotid-femoral pulse wave velocity (PWV). We identified 237 records, of which 9 satisfied the inclusion criteria of the study. Our meta-analysis included relatively high-quality placebo-controlled randomized trials. In a random-effects model, nutritional vitamin D was associated with significant reductions in the pooled difference of PWV [(SMD: -0.29; 95 % CI: -0.51 to -0.06), p = 0.01; Cochran's Q test: chi 2  = 21.85; df = 9; p = 0.009; I 2  = 59 %; n = 909 from 9 studies]. All sensitivity analyses yielded similar results. Nutritional vitamin D supplementation significantly improved arterial stiffness (PWV) in several subgroups by correcting vitamin D deficiency, for a study duration of ≥4 months and a daily dose of vitamin D3 ≥ 2000 IU. The study indicated that the correction of vitamin D deficiency by nutritional vitamin D supplementation may improve arterial stiffness in vitamin d-deficient persons, especially by the correction of vitamin D deficiency with a daily dose of vitamin D3 ≥ 2000 IU. However, further studies are required to confirm this., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Prevention and early detection of kidney diseases in adults and children should be a priority for any government health department. This is particularly pertinent in the low-middle-income countries, mostly in Asia, Africa, Latin America, and the Caribbean, where up to 7 million people die because of lack of end-stage kidney disease treatment. The nephrology workforce (nurses, technicians, and doctors) is limited in these countries and expanding the size and expertise of the workforce is essential to permit expansion of treatment for both chronic kidney disease and end-stage kidney disease. To achieve this will require sustained action and commitment from governments, academic medical centers, local nephrology societies, and the international nephrology community., (© 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

A key component of treatment for all people with advanced kidney disease is supportive care, which aims to improve quality of life and can be provided alongside therapies intended to prolong life, such as dialysis. This article addresses the key considerations of supportive care as part of integrated end-stage kidney disease care, with particular attention paid to programs in low- and middle-income countries. Supportive care should be an integrated component of care for patients with advanced chronic kidney disease, patients receiving kidney replacement therapy (KRT), and patients receiving non-KRT conservative care. Five themes are identified: improving information on prognosis and support, developing context-specific evidence, establishing appropriate metrics for monitoring care, clearly communicating the role of supportive care, and integrating supportive care into existing health care infrastructures. This report explores some general aspects of these 5 domains, before exploring their consequences in 4 health care situations/settings: in people approaching end-stage kidney disease in high-income countries and in low- and middle-income countries, and in people discontinuing KRT in high-income countries and in low- and middle-income countries., (© 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

The prevalence of chronic kidney disease and its risk factors is increasing worldwide, and the rapid rise in global need for end-stage kidney disease care is a major challenge for health systems, particularly in low- and middle-income countries. Countries are responding to the challenge of end-stage kidney disease in different ways, with variable provision of the components of a kidney care strategy, including effective prevention, detection, conservative care, kidney transplantation, and an appropriate mix of dialysis modalities. This collection of case studies is from 15 countries from around the world and offers valuable learning examples from a variety of contexts. The variability in approaches may be explained by country differences in burden of disease, available human or financial resources, income status, and cost structures. In addition, cultural considerations, political context, and competing interests from other stakeholders must be considered. Although the approaches taken have often varied substantially, a common theme is the potential benefits of multistakeholder engagement aimed at improving the availability and scope of integrated kidney care., (© 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Early identification of people with CKD in primary care, particularly those with risk factors such as diabetes and hypertension, enables proactive management and referral to specialist services for progressive disease. The 2019 NHS Long Term Plan endorses the development of digitally-enabled services to replace the 'unsustainable' growth of the traditional out-patient model of care.Shared views of the complete health data available in the primary care electronic health record (EHR) can bridge the divide between primary and secondary care, and offers a practical solution to widen timely access to specialist advice., Methods: We describe an innovative community kidney service based in the renal department at Barts Health NHS Trust and four local clinical commissioning groups (CCGs) in east London. An impact evaluation of the changes in service delivery used quantitative data from the virtual CKD clinic and from the primary care electronic health records (EHR) of 166 participating practices. Survey and interview data from health professionals were used to explore changes to working practices., Results: Prior to the start of the service the general nephrology referral rate was 0.8/1000 GP registered population, this rose to 2.5/1000 registered patients by the second year of the service. The majority (> 80%) did not require a traditional outpatient appointment, but could be managed with written advice for the referring clinician. The wait for specialist advice fell from 64 to 6 days. General practitioners (GPs) had positive views of the service, valuing the rapid response to clinical questions and improved access for patients unable to travel to clinic. They also reported improved confidence in managing CKD, and high levels of patient satisfaction. Nephrologists valued seeing the entire primary care record but reported concerns about the volume of referrals and changes to working practices., Conclusions: 'Virtual' specialist services using shared access to the complete primary care EHR are feasible and can expand capacity to deliver timely advice. To use both specialist and generalist expertise efficiently these services require support from community interventions which engage primary care clinicians in a data driven programme of service improvement.

Endothelial dysfunction and vitamin D deficiency are prevalent in patients with cardiovascular disease (CVD) and chronic kidney disease (CKD). Both are risk factors for cardiovascular events in patients with CKD. No studies have investigated the effect of nutritional forms of vitamin D on endothelial function in earlier stages of CKD, when vascular endothelium may be more amenable to this therapy. We studied the effect of ergocalciferol in a pre-clinical model of mild uraemia. Male Wistar rats underwent either a 5/6th nephrectomy or sham surgery. Four weeks after the final stage of the surgery, these two groups were randomly allocated to placebo or an oral dose of 1000 iu of ergocalcfierol at day 7 and 2 pre sacrifice. Vascular responses to acetylcholine, Spermine NONOate and phenylephrine were determined in aortic rings. Blood pressure, calcium, phosphate and parathyroid hormone were measured in all groups. Ergocalciferol significantly improved the endothelium-dependent responses to acetylcholine and overcame the blunting of the contractile response to phenylephrine seen in uraemic animals. Ergocalciferol improved the contractile response to potassium chloride in uraemic, but not sham animals. All effects occurred independently of changes to calcium, phosphate, parathyroid hormone and systolic blood pressure. There were no differences in endothelium-independent relaxation to Spermine NONOate. In summary, in a model of mild uraemia, ergocalciferol improved vasodilator and vasoconstrictor tone independently of blood pressure and bone mineral parameters suggesting a direct effect of ergocalciferol on the endothelium., (© 2019 The Author(s).)

Background: Cervical cancer is a major cause of morbidity and mortality among women yet access to treatment and care remains a huge challenge in Zimbabwe. The objective of this study was to investigate health system constraints affecting engagement into treatment and care by women with cervical cancer in Harare, Zimbabwe., Methods: A sequential explanatory mixed methods design was used for this study. Phase 1 comprised of two surveys namely: patient and health worker surveys with sample sizes of 134 and 78 participants respectively. Validated structured questionnaires programmed in Android tablet with SurveytoGo software were used for data collection during the surveys. Univariate analyses were conducted using STATA® version 14 to generate descriptive statistics. In phase 2, 16 in-depth interviews, 20 key informant interviews and 6 focus groups were conducted to explain survey results. Participants were purposively selected and sample sizes were informed by saturation principle. Participants in phase 1 and 2 were different. English transcripts were manually coded line by line in Dedoose software using the thematic codes that had been established from the survey data. The final codes were used to support and explain the survey data at the interpretation stages., Results: Health system constraints identified in surveys were: limited or lack of training for health workers, weakness of surveillance system for cervical cancer, limited access to treatment and care, inadequate health workers, reliance of patients on out-of-pocket funding for treatment services, lack of back-up for major equipment. Qualitative inquiry revealed the following barriers to treatment and care: high costs of treatment and care, lack of knowledge about cervical cancer and bad attitudes of health workers, few screening and treating centres located mostly in urban areas, lack of clear referral system resulting in bureaucratic processes, and limited screening and treating capacities in health facilities due to lack of resources., Conclusion: The results of this study show that health system and its organization present barriers to access of cervical cancer treatment and care among women. Strong political will, mobilization of resources both domestically and from partners in addition to sound policies are imperative to address key health system challenges.

Objective: To determine the performance of molecular screening strategies for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in comparison with cytology screening in women living with HIV., Design: Post-hoc analysis using data from a South African study cohort., Methods: Cytology and human papillomavirus (HPV)-based strategies were evaluated, including single test and FAM19A4/miR124-2 methylation triage strategies. Participants underwent cytology screening and a colposcopy-directed biopsy. Valid results on cytology, HPV status, 16/18 genotyping and histology were available for 318 women. Detection of HPV and FAM19A4/miR124-2 hypermethylation was performed on DNA from cervical scrapes. Histological diagnosis of CIN3+ was used as outcome., Results: Cytology provided highest specificity (91.6%), but lowest sensitivity (59.3%), whereas a single HPV test provided highest sensitivity (83.1%), but lowest specificity (66.4%). Combining cytology with methylation did not improve the performance compared with cytology alone: a slight increase in sensitivity was seen, at the cost of a decrease in specificity. Triage of high-risk HPV positive women with methylation increased specificity (76.1%) compared with a single HPV or cytology test, while maintaining acceptable sensitivity (72.9%). Similar performance was observed for HPV16/18 with methylation triage (sensitivity 79.7%, specificity 74.8%). The number of women needed to refer to detect one CIN3+ ranged from 1.5 (cytology) to 2.6 (single HPV test)., Conclusion: Molecular screening strategies using HPV, with or without HPV16/18 genotyping, and FAM19A4/miR124-2 methylation have higher sensitivity with an acceptable loss in specificity compared with current cytology screening and are efficient for the detection of CIN3+ in South African women living with HIV.

Cytology remains the mainstay of cervical cancer screening in South Africa (SA), however false negative rates are 25-50%. In contrast, human papillomavirus (HPV) screening techniques have higher sensitivity for cervical cancer precursors. The cobas® 4800 HPV test detects pooled high-risk HPV types and individual genotypes HPV 16 and 18. Using a mathematical budget impact model, the study objective was to evaluate the clinical and budget impact of replacing primary liquid-based cytology (LBC) with primary HPV-based screening strategies. In SA, current LBC screening practice recommends one test every ten years, followed by large loop excision of the transformation zone (LLETZ) if indicated. HPV testing can be performed from an LBC sample, where no additional consultations nor samples are required. In the budget impact model, LBC screening for 2 cycles (one test every ten years) was compared to cobas® 4800 HPV test for 2 cycles (one test every 5 years). The model inputs were gathered from literature and primary data sources. Indicative prices for LBC and cobas® 4800 HPV test were R189 and R457, respectively. Model results indicate that best outcomes for detection of disease were seen using cobas® 4800 HPV test. Forty-eight percent of cervical cancer cases were detected compared to 28% using LBC, and 50% of cervical intraepithelial neoplasia (CIN) 2 and CIN3 cases, compared to 25% with LBC. The budget impact analysis predicted that the cost per detected case of CIN2 or higher would be R 56,835 and R46,980 for the cobas® 4800 HPV and LBC scenarios, respectively. This equates to an incremental cost per detected case of CIN2 or higher of R9 855. From this model we conclude that a primary HPV screening strategy will have a significant clinical impact on disease burden in South Africa., Competing Interests: The authors’ affiliation with TCD Outcomes Research does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Cervical cancer treatment and care services have remained largely centralized in Zimbabwe thereby entrenching inequities to access amongst patients. The objective of this study was to investigate the determinants of access to treatment and care among women with cervical cancer in Harare, Zimbabwe., Methods: A sequential explanatory mixed methods design was used. In phase 1, three surveys (namely community, patient and health worker) were conducted with sample sizes of 143, 134 and 78 participants respectively. Validated structured questionnaires programmed in Android tablet with SurveytoGo software were used for data collection during the surveys. Univariate, bivariate and multivariate logistic regression analyzes were conducted using STATA® version 14 to generate descriptive statistics and identify determinants of access to cervical cancer treatment and care. In phase 2, 16 in-depth interviews, 20 key informant interviews and 6 focus groups were conducted to explain quantitative data. Participants were purposively selected and saturation principle was used to guide sample sizes. Manually generated thematic codes were processed in Dedoose software to produce final outputs for qualitative study., Results: Knowledge of causes (p = 0.046), perceptions of adequacy of specialists (p < 0.001), locus of control (p = 0.009), service satisfaction (p = 0.022) and walking as a means of reaching nearest health facilities (p < 0.001) were associated with treatment or perceptions of access by healthy women. Perceptions of access to treatment amongst health workers were associated with their basic training institution (p = 0.046), health service quality perceptions (p = 0.035) and electricity supply status in their respective health facilities (p = 0.036).Qualitative findings revealed health system, societal and individual factors as barriers to accessing treatment and palliative care., Conclusions: There are numerous prevailing multi-dimensional barriers to accessing cervical cancer treatment and palliative care in a low -income setting. The findings of this study revealed that heath system and societal factors were more important than individual level factors. Multi-sectoral approaches are recommended to address all the multifaceted barriers in order to improve cervical cancer treatment and palliative care access for better outcomes in resource-limited contexts.

Background: Cervical cancer is the most common cancer and a major cause of morbidity and mortality among women in Zimbabwe yet it is preventable, early detectable and highly curable. The objective of this study was to investigate knowledge, attitudes, beliefs and practices towards cervical cancer, its prevention and treatment in Harare, Zimbabwe., Methods: Sequential explanatory mixed methods approach consisting of analytical cross sectional survey and a qualitative inquiry was used. Study population consisted of women with cervical cancer, health workers and other stakeholders who are involved in cancer control programmes. Patient survey data were collected using validated structured questionnaire in Surveytogo software in an android tablet. Qualitative study used key informant interviews to understand survey findings better. Data analyses for the survey involved univariate and multivariate analyses using STATA version 14. For qualitative study, themes in transcripts were coded and analyzed using Dedoose software to generate evidence for the study., Results: Participants reported different levels of knowledge of causes (23%), risk factors (71%), prevention (72%), screening (73%) and treatment (80%) of cervical cancer. Knowledge of causes of cervical cancer were negatively associated with: being aged 45 or more years (OR = 0.02; p = 0.004), having no household income (OR = 0.02;p = 0.007), household income

Background: The UK national chronic kidney disease (CKD) audit in primary care shows diagnostic coding in the electronic health record for CKD averages 70%, with wide practice variation. Coding is associated with improvements to risk factor management; CKD cases coded in primary care have lower rates of unplanned hospital admission., Aim: To increase diagnostic coding of CKD (stages 3-5) and primary care management, including blood pressure to target and prescription of statins to reduce cardiovascular disease risk., Design and Setting: Controlled, cross-sectional study in four East London clinical commissioning groups (CCGs)., Method: Interventions to improve coding formed part of a larger system change to the delivery of renal services in both primary and secondary care in East London. Quarterly anonymised data on CKD coding, blood pressure values, and statin prescriptions were extracted from practice computer systems for 1-year pre- and post-initiation of the intervention., Results: Three intervention CCGs showed significant coding improvement over a 1 year period following the intervention (regression for post-intervention trend P <0.001). The CCG with highest coding rates increased from 76-90% of CKD cases coded; the lowest coding CCG increased from 52-81%. The comparison CCG showed no change in coding rates. Combined data from all practices in the intervention CCGs showed a significant increase in the proportion of cases with blood pressure achieving target levels (difference in proportion P <0.001) over the 2-year study period. Differences in statin prescribing were not significant., Conclusion: Clinically important improvements to coding and management of CKD in primary care can be achieved by quality improvement interventions that use shared data to track and monitor change supported by practice-based facilitation. Alignment of clinical and CCG priorities and the provision of clinical targets, financial incentives, and educational resource were additional important elements of the intervention., (© British Journal of General Practice 2019.)

Objectives: To assess the survival of patients who have received an operation for recurrent cervical and endometrial cancer and to determine prognostic variables for improved oncologic outcome., Methods: A retrospective multicenter analysis of the medical records of 518 patients with cervical (N = 288) or endometrial cancer (N = 230) who underwent surgery for disease recurrence and who had completed at least 1 year of follow-up., Results: The median survival reached 57 months for patients with cervical cancer and 113 months for patients with endometrial cancer after surgical treatment of recurrence (p = 0.036). Histological sub-type had a significant impact on overall survival, with the best outcome in endometrial endometrioid cancer (121 months), followed by cervical squamous cell carcinoma, cervical adenocarcinoma, or other types of endometrial cancer (81 vs 35 vs 35 months; p <0.001). The site of recurrence did not significantly influence survival in cervical or in endometrial cancer. Cancer stage at first diagnosis, tumor grade, lymph node status at recurrence, progression-free interval after first diagnosis, and free resection margins were associated with improved overall survival on univariate analysis. On multivariate analysis, the stage at first diagnosis and resection margins were significant independent predictive parameters of an improved oncologic outcome., Conclusion: Long-term survival can be achieved via secondary cytoreductive surgery in selected patients with recurrent cervical and endometrial cancer. An excellent outcome is possible even if the recurrence site is located in the lymph nodes. The possibility of achieving complete resection should be the main criterion for patient selection., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cervical cancer is the most commonly diagnosed cancer among women in Zimbabwe; however; access to screening and treatment services remain challenged. The objective of this study was to investigate socio-demographic inequities in cervical cancer screening and utilization of treatment among women in Harare, Zimbabwe., Methods: Two cross sectional surveys were conducted in Harare with a total sample of 277 women aged at least 25 years. In the community survey, stratified random sampling was conducted to select 143 healthy women in Glen View, Cranborne, Highlands and Hopely communities of Harare to present high, medium, low density suburbs and rural areas respectively. In the patient survey, 134 histologically confirmed cervical cancer patients were also randomly selected at Harare hospital, Parirenyatwa Hospital and Island Hospice during their routine visits or while in hospital admission. All consenting participants were interviewed using a validated structured questionnaire programmed in Surveytogo software in an android tablet. Data was analyzed using STATA version 14 to yield descriptive statistics, bivariate and multivariate logistic regression outcomes for the study., Results: Women who reported ever screening for cervical cancer were only 29%. Cervical cancer screening was less likely in women affiliated to major religions (p < 0.05) and those who never visited health facilities or doctors or visited once in previous 6 months (p < 0.05). Ninety-two (69%) of selected patients were on treatment. Women with cervical cancer affiliated to protestant churches were 68 times [95% CI: 1.22 to 381] more likely to utilize treatment and care services compared to those in other religions (p = 0.040). Province of residence, education, occupation, marital status, income (personal and household), wealth, medical aid status, having a regular doctor, frequency of visiting health facilities, sources of cervical cancer information and knowledge of treatability of cervical cancer were not associated with cervical cancer screening and treatment respectively., Conclusion: This study revealed few variations in the participation of women in cervical cancer screening and treatment explained only by religious affiliations and usage of health facilities. Strengthening of health education in communities including churches and universal healthcare coverage are recommended strategies to improve uptake of screening and treatment of cervical cancer.

Introduction: The epidemiology of acute kidney injury (AKI) in children in sub-Sahara Africa (SSA) is poorly described. The aim of this study was to establish the incidence, etiology, and outcomes of community-acquired AKI in pediatric admissions in Southern Malawi., Methods: We conducted a prospective observational study of pediatric admissions to a tertiary hospital in Blantyre between 5 February and 30 April 2016. Children were screened for kidney disease on admission with measurement of serum creatinine and assessment of urine output. The clinical presentation, etiology, and management of children with AKI were documented., Results: A total of 412 patients (median age 4 years, 52.6% male, and 7.5% human immunodeficiency virus [HIV] infected) were included in the study. Forty-five patients (10.9%) had AKI (Kidney Disease: Improving Global Outcomes [KDIGO] criteria), which was stage 3 in 16 (35.6%) patients. Sepsis and hypoperfusion, most commonly due to malaria ( n = 19; 42.2%), were the causes of AKI in 38 cases (84.4%). Three patients (6.7%) underwent peritoneal dialysis (PD) for AKI: 2 of them recovered kidney function, and the other one died. In-hospital mortality was 20.5% in AKI and 2.9% if no kidney disease was present ( p < 0.0001). Seventeen (47.2%) patients with kidney disease had persistent kidney injury on hospital discharge., Conclusion: Acute kidney injury occurs in 10.9% of pediatric admissions in Malawi and is primarily due to infections, particularly malaria. Acute kidney injury results in significantly increased in-hospital mortality. Urgent interventions are required to eliminate preventable causes of death in this region., (Copyright © 2018 International Society for Peritoneal Dialysis.)

Data on human papillomavirus (HPV) type-specific cervical cancer risk in women living with human immunodeficiency virus (WLHIV) are needed to understand HPV⁻HIV interaction and to inform prevention programs for this population. We assessed high-risk HPV type-specific prevalence in cervical samples from 463 WLHIV from South Africa with different underlying, histologically confirmed stages of cervical disease. Secondly, we investigated DNA hypermethylation of host cell genes ASCL1 , LHX8 , and ST6GALNAC5 , as markers of advanced cervical disease, in relation to type-specific HPV infection. Overall, HPV prevalence was 56% and positivity increased with severity of cervical disease: from 28.0% in cervical intraepithelial neoplasia (CIN) grade 1 or less (≤CIN1) to 100% in invasive cervical cancer (ICC). HPV16 was the most prevalent type, accounting for 9.9% of HPV-positive ≤CIN1, 14.3% of CIN2, 31.7% of CIN3, and 45.5% of ICC. HPV16 was significantly more associated with ICC and CIN3 than with ≤CIN1 (adjusted for age, OR MH 7.36 (95% CI 2.33⁻23.21) and 4.37 (95% CI 1.81⁻10.58), respectively), as opposed to non-16 high-risk HPV types. Methylation levels of ASCL1 , LHX8 , and ST6GALNAC5 in cervical scrapes of women with CIN3 or worse (CIN3+) associated with HPV16 were significantly higher compared with methylation levels in cervical scrapes of women with CIN3+ associated with non-16 high-risk HPV types ( p -values 0.017, 0.019, and 0.026, respectively). When CIN3 and ICC were analysed separately, the same trend was observed, but the differences were not significant. Our results confirm the key role that HPV16 plays in uterine cervix carcinogenesis, and suggest that the evaluation of host cell gene methylation levels may monitor the progression of cervical neoplasms also in WLHIV.

Introduction: To evaluate the performance of hypermethylation analysis of ASCL1, LHX8 and ST6GALNAC5 in physician-taken cervical scrapes for detection of cervical cancer and cervical intraepithelial neoplasia (CIN) grade 3 in women living with HIV (WLHIV) in South Africa., Methods: Samples from a prospective observational cohort study were used for these analyses. Two cohorts were included: a cohort of WLHIV who were invited for cervical screening (n = 321) and a gynaecologic outpatient cohort of women referred for evaluation of abnormal cytology or biopsy proven cervical cancer (n = 108, 60% HIV seropositive). Cervical scrapes collected from all subjects were analysed for hypermethylation of ASCL1, LHX8 and ST6GALNAC5 by multiplex quantitative methylation specific PCR (qMSP). Histology endpoints were available for all study subjects., Results: Hypermethylation levels of ASCL1, LHX8 and ST6GALNAC5 increased with severity of cervical disease. The performance for detection of CIN3 or worse (CIN3 + ) as assessed by the area under the receiver operating characteristic (ROC) curves (AUC) was good for ASCL1 and LHX8 (AUC 0.79 and 0.81 respectively), and moderate for ST6GALNAC5 (AUC 0.71). At a threshold corresponding to 75% specificity, CIN3 + sensitivity was 72.1% for ASCL1 and 73.8% for LHX8 and all samples from women with cervical cancer scored positive for these two markers., Conclusions: Hypermethylation analysis of ASCL1 or LHX8 in cervical scrape material of WLHIV detects all cervical carcinomas with an acceptable sensitivity and good specificity for CIN3 + , warranting further exploration of these methylation markers as a stand-alone test for cervical screening in low-resource settings., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.)

Background: Low 25-hydroxyvitamin D levels are associated with an increased risk of cardiovascular events, but the effect of vitamin D supplementation on markers of vascular function associated with major adverse cardiovascular events is unclear., Methods and Results: We conducted a systematic review and individual participant meta-analysis to examine the effect of vitamin D supplementation on flow-mediated dilatation of the brachial artery, pulse wave velocity, augmentation index, central blood pressure, microvascular function, and reactive hyperemia index. MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.gov were searched until the end of 2016 without language restrictions. Placebo-controlled randomized trials of at least 4 weeks duration were included. Individual participant data were sought from investigators on included trials. Trial-level meta-analysis was performed using random-effects models; individual participant meta-analyses used a 2-stage analytic strategy, examining effects in prespecified subgroups. 31 trials (2751 participants) were included; 29 trials (2641 participants) contributed data to trial-level meta-analysis, and 24 trials (2051 participants) contributed to individual-participant analyses. Vitamin D3 daily dose equivalents ranged from 900 to 5000 IU; duration was 4 weeks to 12 months. Trial-level meta-analysis showed no significant effect of supplementation on macrovascular measures (flow-mediated dilatation, 0.37% [95% confidence interval, -0.23 to 0.97]; carotid-femoral pulse wave velocity, 0.00 m/s [95% confidence interval, -0.36 to 0.37]); similar results were obtained from individual participant data. Microvascular function showed a modest improvement in trial-level data only. No consistent benefit was observed in subgroup analyses or between different vitamin D analogues., Conclusions: Vitamin D supplementation had no significant effect on most markers of vascular function in this analysis., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: In endemic areas, lymphangiectasia is the fundamental alteration to live Wuchereria bancrofti adult worms which, in adult males, are usually found in the lymphatic vessels of the spermatic cord; accordingly, hydrocele/filaricele is the most common clinical manifestation of bancroftian filariasis. The pathogenic role of the lymphatic endothelial cells (LECs) and the status of mesothelial cells (MCs) samples of the parietal layer (PL) of the tunica vaginalis testis were examined., Methods: The PL of thirty-two patients, excised for different reasons, was examined by histology and immunohistochemistry using the D2-40 monoclonal antibody for identification of LECs and CK-7 antibody for recognition of mesothelial cells (MCs)., Results: The most important findings were (a) marked lymphangiectasia, especially in hydroceles with minor evolution time; (b) the first report of lymphatic stomata and submesothelial lacunae in filarial acute hydrocele; (c) the likely participation of LECs in filarial granuloma; (d) the potential phenotypic transition of LECs into myofibroblasts in severe chylocele; and (e) mesothelial reactive hyperplasia, a hallmark of filaricele, varying in intensity from mild to severe, sometimes mimicking a mesothelial neoplasia., Conclusion: The data suggest that LECs have an active role in the pathogenesis of bancroftian hydrocele and, possibly, in other clinical forms of lymphatic filariasis.

Objective: To determine ethnic differences in the progression of chronic kidney disease (CKD) and risk of end-stage renal failure (ESRF) and death in adults with type 2 diabetes mellitus (T2DM), and to identify predictors of rapid renal decline., Design: Observational community-based cohort study undertaken from 2006 to 2016 with nested case-control study., Setting: 135 inner London primary care practices contributing to the east London Database., Participants: General practice-registered adults aged 25-85 years with established T2DM and CKD at baseline., Outcomes: The annual rate of renal decline was compared between white, south Asian and black groups, and stratified by proteinuria and raised blood pressure (BP) at baseline. Predictors of rapid renal decline were identified in a nested case-control study. Cox proportional hazards regression was used to determine ethnic differences in the risk of ESRF and death., Results: Age-sex adjusted annual decline was greatest in the Bangladeshi population. There was stepwise increase in the rate of decline when stratifying the cohort by baseline proteinuria and BP control, with south Asian groups being most sensitive to the combined effect of proteinuria and raised BP after accounting for key confounders.The odds of rapid renal decline were increased for individuals of Bangladeshi, African and Caribbean ethnicity, those with hypertension, proteinuria, cardiovascular disease and with increasing duration of diabetes. Rapid progression was more frequent in younger age groups. Risk of developing ESRF was highest in the black group compared with the white group (HR 1.88, 95% CI 1.11 to 3.19). Risk of death from any cause was 29% lower in the south Asian group compared with the white group (HR 0.71, 95% CI 0.56 to 0.91)., Conclusions: Proteinuria and hypertension trigger accelerated estimated glomerular filtration rate decline differentially by ethnicity. Active monitoring of younger adults, who have greater odds of rapid progression and the most to gain from interventions, is essential., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Obstetric-related acute kidney injury (AKI) is thought to be a key contributor to the overall burden of AKI in low resource settings, causing significant and preventable morbidity and mortality. However, epidemiological data to corroborate these hypotheses is sparse. This prospective observational study aims to determine the incidence, aetiology and maternal-fetal outcomes of obstetric-related AKI in Malawi., Methods: Women greater than 20 weeks gestation or less than 6 weeks postpartum admitted to obstetric wards at a tertiary hospital in Blantyre, Malawi, and at high-risk of AKI were recruited between 21st September and 11th December 2015. All participants had serum creatinine tested at enrolment; those with creatinine above normal range (> 82 μmol/L) underwent serial measurement, investigations to determine cause of kidney injury, and were managed by obstetric and nephrology teams. AKI was diagnosed and staged by Kidney Disease Improving Global Outcomes (KDIGO) criteria. Primary outcomes were the incidence proportion and aetiology of AKI. Secondary outcomes were in-hospital maternal mortality, need for dialysis, renal recovery and length of stay; in-hospital perinatal mortality, gestational age at delivery, birthweight and Apgar score., Results: 354 patients were identified at risk of AKI from the approximate 2300 deliveries that occurred during the study period. Three hundred twenty-two were enrolled and 26 (8.1%) had AKI (median age 27 years; HIV 3.9%). The most common primary causes of AKI were preeclampsia/eclampsia (n = 19, 73.1%), antepartum haemorrhage (n = 3, 11.5%), and sepsis (n = 3, 11.5%). There was an association between preeclampsia spectrum and AKI (12.2% AKI incidence in preeclampsia spectrum vs. 4.3% in other patients, p = 0.015). No women with AKI died or required dialysis and complete renal recovery occurred in 22 (84.6%) cases. The perinatal mortality rate across all high-risk admissions was 13.8%. AKI did not impact on maternal or fetal outcomes., Conclusions: The incidence of AKI in high-risk obstetric admissions in Malawi is 8.1% and preeclampsia was the commonest cause. With tertiary nephrology and obstetric care the majority of AKI resolved with no effect on maternal-fetal outcomes. Maternal-fetal outcomes in Sub-Saharan Africa may be improved with earlier detection of hypertensive disease in pregnancy.

HIV-related immunodeficiency has complex effects on female genital HPV, which include increased risks of infection, multiple types, persistence, reactivation and the risk to develop pre-invasive and invasive disease. Reconstitution of immunity with anti-viral drugs improves cellular immunity, but the risk of HPV-related malignancy remains higher than background incidences and presents at younger ages. Early initiation of antiretroviral therapy (ART) allows improved retention of immune memory through existing antibodies and T-cell clones and improves long-term outcomes. Suggestions of a higher risk to contract HIV if there is existing genital HPV infection are supported and explained by pathophysiological cervical changes, including inflammation. HIV-HPV interactions should influence public health decisions towards prioritising large-scale prepubertal HPV-vaccine roll-out, secondary cervical cancer prevention and early detection programmes for HIV-infected women and early initiation of ART. This chapter will also focus on special considerations for the management of women with co-infection with these two viruses and genital HPV-related diseases., (Copyright © 2017. Published by Elsevier Ltd.)