Phase I of the DiaVACCS screening trial: Study design, methods, population demographics and baseline results.

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.

Do virtual renal clinics improve access to kidney care? A preliminary impact evaluation of a virtual clinic in East London.

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.

Health system constraints affecting treatment and care among women with cervical cancer in Harare, Zimbabwe.

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.

Cervical cancer knowledge, attitudes, beliefs and practices of women aged at least 25 years in Harare, Zimbabwe.

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

Determinants of access and utilization of cervical cancer treatment and palliative care services in Harare, Zimbabwe.

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.

Sociodemographic inequities in cervical cancer screening, treatment and care amongst women aged at least 25 years: evidence from surveys in Harare, Zimbabwe.

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.

Deficiencies in education and experience in the management of acute kidney injury among Malawian healthcare workers.

BACKGROUND: Acute kidney injury (AKI) is a common but under-recognised disease process, which carries a high risk of mortality or chronic complications, such as chronic kidney disease and other organ dysfunction. Management of AKI, however, is suboptimal, both in developed settings and in Malawi. This is partly because of deficiencies in AKI education and training. AIM: To establish current levels of AKI education in a range of healthcare workers in Malawi. METHODS: An AKI symposium was held in Blantyre in March 2015. Delegates were asked to complete a survey at the start of the symposium to assess their clinical experience and education in the management of AKI. RESULTS: From 100 delegates, 89 nurses, clinical officers, and physicians, originating from 11 different districts, responded to the survey. Twenty-two percent of healthcare workers (including 28% of district workers of the various cadres and 31% of nurses) had never received teaching on any aspect of renal disease, and 50% (including 63% of district workers and 61% of nurses) had never received teaching specifically on AKI. Forty-four percent did not feel confident managing AKI, and 98% wanted more support managing patients with renal disease. Thirty-four percent (including 55% of district workers) were unaware that haemodialysis was available at Queen Elizabeth Central Hospital (QECH) for the treatment of AKI and 53% (74% of district workers) were unaware that peritoneal dialysis was available for the treatment of AKI in children. Only 33% had ever referred a patient with AKI to QECH. CONCLUSIONS: There are deficiencies in education about, and clinical experience in, the management of AKI among Malawian healthcare workers, in addition to limited awareness of the renal service available at QECH. Urgent action is required to address these issues in order to prevent morbidity and mortality from AKI in Malawi.

Transplanting the elderly: Balancing aging with histocompatibility.

Across the world, the proportions of senior citizens (i.e. those ≥65years) increase rapidly and are predicted to constitute over 25% of the general population by 2050. In 2012 already 48% of the population with end stage renal disease (ESRD) was aged 65years or older. Transplantation is considered the preferred treatment option for ESRD offering survival advantage over long-term dialysis in the majority of patients. Indeed, acceptable outcomes have been documented for selected patients over the age of 70years or even cases over 80years. The reality of organ scarcity and prolonged waiting times for a deceased donor kidney transplantation, however, indicate that at best 50% of the selected elderly may have realistic expectations to receive a timely transplant offer. By choice or medical selection, access to transplantation also decreases with increasing age. In order to expedite the chance for elderly to receive a kidney transplant dedicated allocation systems have been developed. These allocation systems, like the Eurotransplant Senior Program (ESP), support preferential local allocation of kidneys from older donors to older patients in order to match recipient and graft life while disregarding histocompatibility for HLA antigens. The consequence has been more acute rejection episodes and an increase in immunosuppressive load. In the elderly, the most common cause of graft loss is death with functioning graft and death from infectious diseases is one of the dominant causes. The Eurotransplant Senior DR-compatible Program (ESDP) was designed to further improve the perspective of successful transplantation in the elderly in terms of life and quality of life by re-introducing matching criteria for HLA-DR in the old-for-old algorithm.

The Vaccine and Cervical Cancer Screen project 2 (VACCS 2): Linking cervical cancer screening to a two-dose HPV vaccination schedule in the South-West District of Tshwane, Gauteng, South Africa.

BACKGROUND: Cervical cancer is a preventable disease with a high prevalence in South Africa (SA), where screening is opportunistic. Primary prevention is now possible through HPV vaccination. In VACCS 1 the feasibility of linking cervical cancer with HPV vaccination was demonstrated. OBJECTIVES: To investigate the feasibility of linking HPV self-testing with a two-dose HPV vaccination schedule and to compare results with VACCS 1. METHODS: The project was conducted in five schools in the South-West District of Tshwane, Gauteng, SA. Leaflet information on cervical cancer and screening was provided, with requests for consent and assent for a two-dose HPV vaccination of schoolgirls. Female caregivers were invited to take part in HPV self-screening. RESULTS: Of 965 girls invited for vaccination, 519 (53.7%) had full consent and 518 (99.8%) received at least one vaccine dose. The invited uptake rate was 53.7% and 495 girls received both doses, giving a completion rate of 95.4% v. 82.6% in VACCS 1. Of 1 135 self-screen kits handed out, 560 (49.3%) were not returned. The mean age (standard deviation) of the 160 women who participated in self-screening was 38.7 (7.7) years. HPV testing was negative in 116 women (72.5%), 15 women (9.4%) tested positive for HPV 16 and/or 18, and 27 (16.9%) were positive for non-16/18 oncogenic HPV. CONCLUSION: Data from the VACCS projects suggest that school-based vaccine programmes can be successfully implemented. A two-dose schedule allowed for higher completion rates. Linking self-collected HPV screening to HPV vaccination is feasible, is a promising and viable screening strategy, and reached the appropriate age group for screening.

The vaccine and cervical cancer screen (VACCS) project: acceptance of human papillomavirus vaccination in a school-based programme in two provinces of South Africa.

BACKGROUND: The incidence of cervical cancer in South Africa (SA) remains high, and the current screening programme has had limited success. New approaches to prevention and screening tactics are needed. OBJECTIVES: To investigate acceptance of school-based human papillomavirus (HPV) vaccination, as well as the information provided, methods of obtaining consent and assent, and completion rates achieved. METHODS: Information on cervical cancer and HPV vaccination was provided to 19 primary schools in Western Cape and Gauteng provinces participating in the study. Girls with parental consent and child assent were vaccinated during school hours at their schools. RESULTS: A total of 3 465 girls were invited to receive HPV vaccine, of whom 2 046 provided written parental consent as well as child assent. At least one dose of vaccine was delivered to 2 030 girls (99.2% of the consented cohort), while a total of 1 782 girls received all three doses. Sufficient vaccination was achieved in 91.6% of the vaccinated cohort. Of all invited girls, 56.9% in Gauteng and 50.7% in the Western Cape were sufficiently vaccinated. CONCLUSION: This implementation project demonstrated that HPV vaccination is practical and safe in SA schools. Political and community acceptance was good, and positive attitudes towards vaccination were encountered. During the study, which mimicked a governmental vaccine roll-out programme, high completion rates were achieved in spite of several challenges encountered.

Age-specific prevalence of cervical human papillomavirus infection and cytological abnormalities in women in Gauteng Province, South Africa.

BACKGROUND: Women accessing the public health system in Gauteng province, South Africa are largely unscreened for cervical cancer and have a high background prevalence of human immunodeficiency virus (HIV) infection. OBJECTIVES: This cross-sectional study describes the age-specific prevalence of human papillomavirus (HPV) infection and cytological abnormalities among this urban and peri-urban population. METHOD: Over the period March 2009 - September 2011, 1 524 women attending public sector primary healthcare clinics were invited to participate in a cervical cancer screening study. All participants were screened with conventional cytology and HPV testing undertaken using the HPV linear array genotyping kit (Roche Molecular Systems). RESULTS: Of 1 472 women with valid cytology results, abnormalities were detected in 17.3% (n = 255), of which 9.1% (n = 134) were high-grade squamous intraepithelial lesions, and 0.5% (n = 8) suggestive of squamous carcinoma. Of the 1,445 women with complete data, the overall and high-risk HPV DNA prevalences were 74.6% (n = 1 078) and 54.3% (n = 784), respectively. HPV type 16 and/or 18 were detected in 19.5% (n = 282) of women. Age-specific prevalence of HPV showed a plateau-shaped curve. CONCLUSIONS: The prevalences of HPV infection and abnormal cytology were much higher than previously reported in general populations in South Africa and elsewhere. Higher age-specific prevalence and similar plateau-like age-specific epidemiological curves have previously only been described in studies among HIV-positive women. These findings have implications for planning and development of cervical screening programmes in developing countries with largely unscreened populations with a high background prevalence of HIV.

Progression of chronic kidney disease in a multi-ethnic community cohort of patients with diabetes mellitus.

AIMS: Ethnicity is a risk factor for the prevalence of severe chronic kidney disease among patients with diabetes. We studied the effect of ethnicity on progression of chronic kidney disease in people with diabetes managed in community settings. METHODS: A 5-year retrospective, community-based cohort study of 3855 people with diabetes mellitus of white, black or South Asian ethnicity with an estimated glomerular filtration rate of < 60 ml min⁻¹ 1.73 m⁻² was undertaken. From 135 general practices in east London, all cases with at least 3 years clinical data were included. Using repeated-measures analysis, the annual decline in estimated glomerular filtration rate was calculated. Comparisons between the rate of decline in the three main ethnic groups, with and without proteinuria at baseline, were made. RESULTS: The annual adjusted decline in estimated glomerular filtration rate for this cohort was 0.85 ml min⁻¹ 1.73 m⁻². The rate of chronic kidney disease progression was significantly greater in South Asian groups (-1.01 ml min⁻¹ 1.73 m⁻²) compared with white groups (-0.70 ml min⁻¹ 1.73 m⁻²) (P = 0.001). For those with proteinuria at baseline, the annual decline was greater at 2.05 ml min⁻¹ 1.73 m⁻², with both South Asian and black groups having a significantly faster rate of decline than white groups. CONCLUSIONS: For patients with diabetes and chronic kidney disease managed in primary care, the annual decline of renal function is less than previously thought and approximates the age-related annual decline of 1 ml min⁻¹ 1.73 m⁻². Patients with proteinuria and those of South Asian and Black ethnicity need additional monitoring as they are at greater risk of rapid chronic kidney disease progression.

Cancer prevalence in 129 breast-ovarian cancer families tested for BRCA1 and BRCA2 mutations.

BACKGROUND: Women who carry germline mutations in the breast-ovarian cancer susceptibility genes, BRCA1 and BRCA2, are at very high risk of developing breast and/or ovarian cancer. Both genes are tumour suppressor genes that protect all cells from deregulation, and there are reports of their involvement in other cancers that vary and seem to depend on the population investigated. It is therefore important to investigate the other associated cancers in different populations to assist with risk assessments. OBJECTIVES: To assess the cancer risk profile in BRCA-mutation-positive and negative South African breast-ovarian cancer families, mainly of Caucasian origin. DESIGN: Descriptive study in which the prevalence of all cancers in the pedigrees of BRCA1- and BRCA2-mutation-positive groups and a group of families without mutations in either gene were compared with the general population. RESULTS: As expected, female breast and ovarian cancer was significantly increased in all three groups. Furthermore, male breast cancer was significantly elevated in the BRCA2-positive and BRCA-negative groups. Stomach cancer prevalence was significantly elevated in the BRCA2-positive families compared with the general population. CONCLUSIONS: These results can be applied in estimation of cancer risks and may contribute to more comprehensive counselling of mutation-positive Caucasian breast and/or ovarian cancer families.

Ultrastructural analysis of Wuchereria bancrofti (Nematoda: Filarioidea) body wall.

Bancroftian filariasis constitutes the principal mosquito-borne nematode infection of humans and the surface of adult of Wuchereria bancrofti seems to be especially important in the intricate interplay between host and parasite. The study of the parasite's surface structure might help to understand the localization and function of various organelles. W. bancrofti adult worms were recovered from untreated patients during hydrocele repair surgery and studied by transmission electron microscopy. The body wall of adult parasite is composed of cuticle, hypodermis and muscular layer. Cuticle is the external layer and shows transverse cuticular striation. It is composed by an epicuticle, cortical layers, median layer, fibrous layers and basal layer. The epicuticle is the most external cuticular layer and appears as a single laminar electron-dense layer. The cortical external region is more electron-dense and granular in appearance than the inner cortical layer. Electron-dense structures, called bosses are randomly distributed filling the cuticular striation. The median layer is formed by an electron-dense and continuous thick line. The fibrous layer is subdivided in inner and external layers connected by projections. The basal layer includes a large quantity of membranous projections directed toward the hypodermis. The hypodermis is a syncytium where some cellular organelles are observed. The somatic musculature is meromyarian. The muscle fibers consist of contractile and non-contractile regions and the contractile region is composed of myofilaments separated by dense body. This is the first study of W. bancrofti adult worms obtained from untreated patients and studied by transmission electron microscopy.

The effect of ethnicity on the prevalence of diabetes and associated chronic kidney disease.

BACKGROUND: The effect of ethnicity on the prevalence of diabetes mellitus (DM) and associated chronic kidney disease (CKD) is unknown. AIM: To establish the impact of ethnicity on the prevalence and severity of diabetes mellitus and associated CKD. DESIGN: Cross-sectional study of 34 359 adult diabetic patients in three primary care trusts in the UK. METHODS: Read coded data from general practice computers was used to analyse the relationship between ethnicity, DM and CKD. RESULTS: The prevalence of DM was 3.5% for Whites, 11% for South Asians and 8% for Black groups. The prevalence of CKD (stages 3-5) among diabetics was 18%. CKD stage 3 was more prevalent in Whites compared to South Asians--OR 0.79 (95% CI: 0.71-0.87) and Blacks--OR 0.49 (95% CI: 0.43-0.57). Among all CKD patients severity (CKD stages 4, 5) was associated with Black (OR 1.39, 95% CI: 1.06-1.81) and South Asian (OR 1.54, 95% CI: 1.26-1.88) ethnicity compared to Whites. Less than 50% of diabetics with CKD met the target blood pressure (BP) of 130/80 mmHg. The prevalence of a blood pressure > 150/90 mmHg in diabetics with CKD was South Asian 15.6%, White 13.9%, Black 21.8% (P < 0.001). Proteinuria was present in 8.6% of all diabetic patients. However, this increased to 18.6% in patients with CKD, and was more frequent in Black (22.6%) and South Asian (21%) patients compared to White patients (14.1%) (P < 0.001). CONCLUSION: Significant disparities exist between the major ethnic groups in both disease prevalence and management. Future studies examining the management of CKD need to take variation by ethnicity into account.