Strategies for primary HPV test-based cervical cancer screening programme in resource-limited settings in India: Results from a quasi-experimental pragmatic implementation trial.

BACKGROUND: In order for low and middle income countries (LMIC) to transition to Human Papilloma Virus (HPV) test based cervical cancer screening, a greater understanding of how to implement these evidence based interventions (EBI) among vulnerable populations is needed. This paper documents outcomes of an implementation research on HPV screening among women from tribal, rural, urban slum settings in India. METHODS: A mixed-method, pragmatic, quasi-experimental trial design was used. HPV screening on self-collected cervical samples was offered to women aged 30-60 years. Implementation strategies were 1) Assessment of contextual factors using both qualitative and quantitative methods like key informant interviews (KII), focus group discussions (FGDs), pre-post population sample surveys, capacity assessment of participating departments 2) enhancing provider capacity through training workshops, access to HPV testing facility, colposcopy, thermal ablation/cryotherapy at the primary health care centers 3) community engagement, counselling for self-sampling and triage process by frontline health care workers (HCWs). Outcomes were assessed using the RE-AIM (Reach, Effectiveness, adoption, implementation, maintenance) framework. RESULTS: Screening rate in 8 months' of study was 31.0%, 26.7%, 32.9%, prevalence of oncogenic HPV was 12.1%, 3.1%, 5.5%, compliance to triage was 53.6%, 45.5%, 84.6% in tribal, urban slum, rural sites respectively. Pre-cancer among triage compliant HPV positive women was 13.6% in tribal, 4% in rural and 0% among urban slum women. Unique challenges faced in the tribal setting led to programme adaptations like increasing honoraria of community health workers for late-evening work and recalling HPV positive women for colposcopy by nurses, thermal ablation by gynaecologist at the outreach camp site. CONCLUSIONS: Self-collection of samples combined with HCW led community engagement activities, flexible triage processes and strengthening of health system showed an acceptable screening rate and better compliance to triage, highlighting the importance of identifying the barriers and developing strategies suitable for the setting. TRIAL REGISTRATION: CTRI/2021/09/036130.

Protocol for the formative phase of a trial (SHE-CAN) to test co-designed implementation strategies for HPV-based cervical screening among vulnerable women in two diverse settings in India.

BACKGROUND: In view of the WHO's call for the elimination of cervical cancer as a public health problem, and current low screening coverage, Indian policy makers need evidence on how to effectively implement cervical screening programmes, ensuring equity in access. Our study will follow the INSPIRE implementation framework to co-design and test HPV-based screening approaches in two states of India with different health system organisation, based on understanding the status of screening as currently implemented, readiness and challenges to transition to HPV-based screening, and preferences of key stakeholders. Here, we describe our protocol for the formative phase of the study (SHE-CAN). METHODS: The study population includes women from vulnerable populations, defined as residents of tribal areas, rural villages, and urban slums, in the states of Mizoram and Tamil Nadu. The baseline assessment will use mixed methods research, with desktop reviews, qualitative studies, and surveys. A capacity assessment survey of screening and treatment facilities will be done, followed by interviews with healthcare providers, programme managers, and community health workers. Interviews will be conducted with previously screened women and focus group discussions with under and never-screened women and community members. Stakeholder workshops will be held in each state to co-design the approaches to delivering HPV-based screening among 30-49-year-old women. DISCUSSION: The quality and outcomes of existing screening services, readiness to transition to HPV-based screening, challenges in providing and participating in the cervical cancer care continuum, and acceptability of screening and treatment approaches will be examined. The knowledge gained about the current system, as well as recognition of actions to be taken, will inform a stakeholder workshop to co-design and evaluate implementation approaches for HPV-based screening through a cluster randomised implementation trial.

Impact of maternal iron deficiency anemia on fetal iron status and placental iron transporters in human pregnancy.

Iron deficiency anemia is associated with maternal morbidity and poor pregnancy outcomes. Heme and non-heme iron transport proteins expressed in the placenta help in adequate iron supply from anemic mother to fetus. Here we examined the expression of placental iron trafficking molecules and their association with maternal and neonatal iron status in pregnant women with iron deficiency anemia (IDA). Pregnant women who received prenatal care at Christian Medical College, Vellore, India for childbirth were recruited. Pregnant women who were 18-35 years old with gestational age (GA) of ≥36 weeks were eligible to participate in the study. In a prospective cohort of pregnant women, 22 % were iron deficiency anemia and 42 % were iron replete. Samples were collected (Maternal blood, placental tissue, and cord blood) from pregnant women with a gestational age of ≥38 weeks at the time of delivery. The mean gestational age at the first visit and delivery was 12.8 ± 2.72 weeks and 39 ± 1.65 weeks, respectively. Hemoglobin (9.3 ± 0.9 g/dl) and ferritin (15.4(0.8-28.3) ng/ml) levels at delivery were significantly decreased in IDA as compared to controls. The fetal hemoglobin and ferritin levels were in the normal range in both groups. There was no correlation between maternal and cord blood hepcidin with fetal iron status in IDA. We further analyzed the expression of iron transport genes in the placenta of controls and the IDA group. Under maternal iron insufficiency, the expression of placental iron transporters DMT1, FPN1, and GDF15 was upregulated at the protein level. In IDA, placental GDF15 and ferroportin protein had an association with fetal iron status. These findings confirm that placental iron traffickers respond to maternal iron deficiency by increasing their expression and allowing sufficient iron to pass to the fetus.

Induction of labor using Foley catheter with weight attached versus without weight attached: A randomized control trial.

OBJECTIVE: To assess the effectiveness in preventing cesarean section for failed induction by using Foley catheter for cervical ripening in comparison to Foley catheter with a weight attached to it. METHODS: A randomized control trial conducted between November 2018 and July 2020, which looked at induction of labor with 30-ml Foley catheter in one arm and the Foley placed with a 500 ml weight attached to it in the other arm. Primary outcome was the cesarean section rate. RESULTS: We randomized 399 women. Modes of delivery were similar in both groups. Numbers undergoing cesarean section for failed induction were higher in the group that underwent induction with Foley with weight but this was not statistically significant (45.7% vs 26.5%, P = 0.1). There was a shorter time to expulsion of the Foley with weight attached (mean ± standard deviation: 2.6 ± 3.3 h vs 10.9 ± 3.2 h, P < 0.001) but this did not translate into a difference in time to active labor or time to delivery. CONCLUSION: Placing a weight at the end of the Foley catheter for induction of labor does not affect the time to delivery or the rate of cesarean deliveries, although there is faster expulsion of the Foley. CLINICAL TRIAL REGISTRATION NO: CTRI/2018/10/016154.

Feasibility, uptake and real-life challenges of a rural cervical and breast cancer screening program in Vellore, Tamil Nadu, South India.

BACKGROUND: Early detection of breast and cervical cancer by organized screening has been found to reduce mortality rates in trials, but documentation of programme results and challenges is rarely done from non-trial settings. This study reports results of a population-based cancer control programme in a rural block in Vellore, Tamil Nadu, population size (116,085), targeting a population of 18,490 women aged 25-60 years, between November 2014 and March 2018. METHODS: Village-based health education sessions were conducted by social workers, using trained volunteers and health workers to motivate eligible women. Screening was done at a secondary level hospital, by trained general physicians using visual inspection with acetic acid and clinical breast examination, followed by colposcopy, radiological imaging (breast) and biopsy as required. RESULTS: A total of 8 volunteers and 17 health workers motivated women for 93 health education and screening sessions, in 46 out of 82 villages. While 1,890/18,490 (10.2 per cent) were screened for breast cancer, 1,783 (9.6 per cent) were screened for cervical cancer, with a yield of 3.4/1,000 for cervical pre-cancer/cancer. The main challenges were creating time for screening activities in a busy secondary hospital and difficulty in ensuring treatment completion of screen-detected cases. CONCLUSIONS: Population-based cancer screening programs can be offered by secondary hospitals that also run primary care services, to increase screening rates. Clear referral systems need to be established, bearing in mind that social factors, especially poor family support, may pose a threat to treatment, in spite of easy availability of cure.

Outcomes of carcinosarcoma in a tertiary care institution in India.

BACKGROUND: Carcinosarcoma is a rare malignancy, and reports are often mixed along with other sarcomas. The literature on uterine carcinosarcoma per se is sparse. AIMS: This study aims to evaluate the demography, survival, and optimal treatment strategy of uterine carcinosarcoma. SETTINGS AND DESIGN: A tertiary care center in India. The study design was descriptive with survival analysis. MATERIALS AND METHODS: The medical records of all 18 patients admitted with uterine carcinosarcoma between January 2011 and December 2015 were reviewed. Baseline characteristics and outcomes were studied. Survival analysis was done using the Kaplan-Meier method and compared between treatment groups using the Log-rank test. RESULTS: The total number of uterine malignancies operated in our center over this time period was 311 of which 18 were carcinosarcomas (5.7%). Median age of presentation was 61 years (36-77 years). Most women (94%) were postmenopausal and 67% of them presented with postmenopausal bleeding. Over half of the patients (56%) presented late (Stage III or IV). Only 11 (61%) had adjuvant treatment and 7 patients had expired at the time of follow-up. The median survival was 284 days (95% confidence interval 107-461). Patients who received adjuvant therapy did better compared to those who did not (P = 0.036). CONCLUSIONS: Carcinosarcomas are aggressive tumors of postmenopausal women who present with bleeding or discharge per vaginum. In spite of adequate surgical staging followed by adjuvant therapy, survival remains poor. Improvements in early detection and optimal therapy need to be made.

3D Decellularized Native Extracellular Matrix Scaffold for In Vitro Culture Expansion of Human Wharton's Jelly-Derived Mesenchymal Stem Cells (hWJ MSCs).

Mesenchymal stem cells (MSCs) are derived from Wharton's jelly tissue of the human umbilical cord. Given appropriate culture conditions, these cells can self-renew and differentiate into multiple cell types across the lineages. Among the properties exhibited by these cells, immunomodulation through secretion of trophic factors has been widely exploited in a broad spectrum of preclinical/clinical regenerative applications. Moreover, the extracellular matrix is found to play a major role apart from niche cells in determining stem cell fate including that of MSCs. Therefore, the currently employed technique of two-dimensional culture expansion can alter the inherent properties of naïve MSCs originally residing within the three-dimensional space. This limitation can be overcome to some extent by using native extracellular matrix scaffold culture system which mimics the in situ microenvironment. In this chapter, we have elucidated the protocol for the preparation of a native extracellular matrix scaffold by decellularization of the MSC sheet and thereof culture expansion and characterization of human Wharton's jelly-derived MSCs.

Prevalence of Congenital Anomalies in a Secondary Care Hospital in South India: A Cross-Sectional Study.

OBJECTIVE: To study the prevalence and types of congenital anomalies that present at birth in a secondary-level hospital in South India and its contribution to perinatal mortality. MATERIALS AND METHODS: A total of 36,074 births over 10 years, from 2003 to 2013, were studied for the prevalence of gross congenital malformations at birth. It was a descriptive, cross-sectional study using data from the birth register and available medical records. RESULTS: The incidence of birth defects was 12.5 per 1000 live births, with musculoskeletal disorders being the commonest, followed by craniovertebral anomalies. The prevalence of anomalies over the past 10 years has not shown any significant change (p= 0.555). DISCUSSION: The high prevalence of neural tube defects indicates the need for periconceptional folic acid supplementation and early detection of anomalies, which would help in timely management. Detection of musculoskeletal anomalies would help in counseling patients antenatally.