The CryoPop study: Screening for high-grade cervical dysplasia in Karnataka, India.

OBJECTIVE: To describe our experience of screening with visual inspection with acetic acid (VIA) and colposcopy to identify women with high-grade precancerous cervical lesions who were candidates for cryotherapy. Women were screened to determine eligibility for a clinical trial testing the safety and efficacy of a new, simple and inexpensive cryotherapy device (CryoPop®) targeted for use in low and middle-income countries (LMICs). DESIGN: Prospective cohort study. SETTING: Primary and urban health centres in Belagavi, Hubballi and Vijayapur, India. POPULATION: Women in the age-group 30-49 years, premenopausal, with no prior hysterectomy and no known HIV infection were eligible for screening. METHODS: Visual inspection with acetic acid was performed on eligible women following informed consent. VIA-positive women were referred for colposcopy and biopsy. Biopsies were read by two pathologists independently, with a third pathologist acting as tie-breaker if needed. MAIN OUTCOME MEASURES: The primary outcome measures were the number/proportion of women screening positive by VIA and the number/proportion of those women screening VIA-positive found to have high-grade cervical lesions on biopsy (cervical intraepithelial neoplasia 2/3 [CIN 2/3]). Demographic variables were compared between women who screened VIA-positive and those who screened VIA-negative; a separate comparison of demographic and limited reproductive variables was performed between women who had CIN 2/3 on biopsy and those without CIN 2/3 on biopsy. Chi-square or Fisher's exact tests for categorical data and t-tests or analysis of variance for numeric data were used with all tests two-sided and performed at an alpha 0.05 level of statistical significance. RESULTS: A total of 9130 women were screened with VIA between 4 July 2020 and 31 March 2021. The mean age of all women screened was 37 years (standard deviation = 5.6 years) with 6073 of the women (66.5%) in the 30-39 year range. Only 1% of women reported prior cervical cancer screening. A total of 501 women (5.5%) were VIA-positive; of these, 401 women underwent colposcopy. Of those who had colposcopy, 17 (4.2%) had high-grade lesions on biopsy, an additional 164 (40.9%) had low-grade cervical lesions on biopsy or endocervical curettage and one woman (0.2%) was found to have invasive cancer. VIA-positive women were younger and had higher levels of education and income; however, women who were VIA-positive and found to have CIN 2/3 were older, were more likely to be housewives and had higher household income than those without CIN 2/3. CONCLUSION: Despite the COVID-19 pandemic, over 9100 women were screened with VIA for precancerous lesions. However, only 17 (4.2%) were found to have biopsy-proven high-grade cervical lesions, underscoring the subjective performance of VIA as a screening method. Given that this is significantly lower than rates reported in the literature, it is possible that the prevalence of high-grade lesions in this population was impacted by screening a younger and more rural population. This study demonstrates that screening is feasible in an organised fashion and can be scaled up rapidly. However, while inexpensive and allowing for same-day treatment, VIA may be too subjective and have insufficient accuracy clearly to identify lesions requiring treatment, particularly in low-prevalence and low-risk populations, calling into question its overall cost-effectiveness.

Infant feeding for people living with HIV in high resource settings: a multi-disciplinary approach with best practices to maximise risk reduction.

Shared decision making for infant feeding in the context of HIV in high-resourced settings is necessary to acknowledge patient autonomy, meet increasing patient requests and address the changing reality of perinatal HIV care. In low-to middle-income countries (LMIC), where the majority of individuals living with HIV reside, persons with HIV are recommended to breastfeed their infants. In the setting of maternal anti-retroviral therapy (ART) use throughout pregnancy, viral suppression and appropriate neonatal post-exposure prophylaxis (PEP) use, updated information indicates that the risk of HIV transmission through breastmilk may be between 0.3 and 1%. While not endorsing or recommending breastfeeding, the United States' DHHS perinatal guidelines are similarly pivoting, stating that individuals should "receive patient-centred, evidence-based counselling on infant feeding options." Similar statements appear in the British, Canadian, Swiss, European, and Australasian perinatal guidelines. We assembled a multi-disciplinary group at our institution to develop a structured shared decision-making process and protocol for successful implementation of breastfeeding. We recommend early and frequent counselling about infant feeding options, which should include well known benefits of breastfeeding even in the context of HIV and the individual's medical and psychosocial circumstances, with respect and support for patient's autonomy in choosing their infant feeding option.

Women Living with Human Immunodeficiency Virus with Intended and Unintended Pregnancy: Characteristics and Patient Outcomes.

Background: Rates of unintended pregnancy may be higher in women living with human immunodeficiency virus (WLWH) than in the general population, and it is unclear how populations of WLWH with intended and unintended pregnancy differ. We compared baseline characteristics and outcomes between WLWH with intended and unintended pregnancy. Materials and Methods: We conducted a retrospective analysis of WLWH enrolled in a human immunodeficiency virus (HIV) and Pregnancy clinic from 2003 to 2014. Data were analyzed using descriptive statistics, chi-square test, Student's t-test, one-way analysis of variance, and linear and logistic regression analysis. Two-tailed p-value <0.05 was considered significant. The study was approved by the Johns Hopkins University School of Medicine Institutional Review Board. Results: Sixty-nine (27.1%) of 255 women reported an intended pregnancy. Women with intended pregnancy (WWIP) were more likely to be older, White, married, privately insured, and college educated. WWIP were less likely to use tobacco (15.9% vs. 44.2%, p < 0.001), alcohol (2.9% vs. 11.1%, p = 0.041), opiates (0.0% vs. 19.3%, p < 0.001), or cocaine (2.9% vs. 21.0%, p < 0.001) during pregnancy, more likely to disclose their HIV status to the father of the baby by delivery (100.0% vs. 15.8%, p < 0.001), and more likely to receive less effective contraception at delivery (condoms 14.9% vs. 4.8%, p = 0.024; sterilization 11.9% vs. 22.1%, p = 0.028). In multivariate regression analysis, pregnancy intendedness was an important predictor of nondetectable viral load at pregnancy entry but not at delivery. Conclusions: WLWH vary in their baseline characteristics and pregnancy outcomes depending on pregnancy intendedness, highlighting the need to improve pregnancy timing in WLWH and intensify interventions for women with unintended pregnancy.

Markers of intestinal immune activation and inflammation are not associated with preterm birth among women with low level HIV viremia.

BACKGROUND: Maternal markers of intestinal immune activation may be used to predict preterm birth (PTB) in pregnant women living with HIV. METHODS: This study used de-identified samples from the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) Protocol P1025 study. Singleton pregnancies with ≥3 ml plasma available and HIV viral load ≤400 copies/ml within 4 weeks of specimen collection were included. Frequency matching of PTB cases and term birth controls was performed on basis of maternal race, number of available plasma specimens, and timing of plasma sample collection in a 1:1 ratio. Plasma progesterone, 25-hydroxy vitamin D, soluble CD14, intestinal fatty acid binding protein (I-FABP), Lipopolysaccharide (LPS)-binding protein, and inflammatory cytokines (IL-1B, IFN-gamma, IL-6, TNF-alpha) were measured. Generalized mixed linear regression modeling was used to examine the association between PTB and biomarkers, adjusting for covariates and confounders. Data analyses were performed using SAS 9.4 (Cary, NC). RESULTS: We included 104 PTB compared to 104 controls. Third trimester log2 IL-1B was lower among PTB versus term birth controls by univariate analysis (-1.50 ± 2.26 vs. -.24 ± 2.69, p = .01) though this association was no longer significant by regression modeling. In an uncontrolled, exploratory sub-analysis, subjects with prior PTB had increased odds of PTB with higher I-FABP [aOR 2.72, 95% CI 1.18-6.24] and lower IFN-gamma [aOR .23, 95% CI .12-.41] after adjustment for covariates and confounders. CONCLUSIONS: Intestinal immune activation measured by soluble CD14 or intestinal fatty acid binding protein was not associated with preterm birth among pregnant women with low-level HIV viremia.

Case Report: Tubal Atypical Placental Site Nodule.

Placental site nodule (PSN) is a benign proliferation of chorionic-type intermediate trophoblastic cells that forms a tumor-like lesion. Most PSNs are intrauterine, but a few have been reported outside the uterus, including in fallopian tubes. PSN is related to epithelioid trophoblastic tumor (ETT) in that both are composed of chorionic-type intermediate trophoblastic cells, while ETT is hypercellular and contains trophoblastic cells with increased nuclear atypia and a higher Ki-67 proliferation index as compared with PSN. Occasionally, an intermediate stage between a PSN and an ETT is observed, and such a lesion is often recognized as an atypical PSN (aPSN) characterized by trophoblastic cells exhibiting morphologic features in transition from a conventional PSN to an ETT. aPSN has been thought to exhibit benign behavior; however, it has also been reported that up to 15% of aPSN lesions either coexist with, or subsequently develop into, ETT. To the best of our knowledge, there has been no case report of an aPSN in an extrauterine site. Here, we reported a highly unusual case of tubal aPSN, which illustrates several key features associated with PSN and its possible pathogenesis.

Experience and Outcomes of Breastfed Infants of Women Living With HIV in the United States: Findings From a Single-Center Breastfeeding Support Initiative.

We assessed breastfeeding outcomes for a cohort of infants born to women living with HIV (WLHIV) at an urban health care center in the United States. Ten infants were exclusively breastfed for a mean duration of 4.4 (1.0-8.6) months. All had negative HIV RNA PCRs at a median age of 16 months.

Safety and efficacy of the new CryoPop® cryotherapy device for cervical dysplasia in low- and middle-income countries: study protocol for a multicenter open-label non-inferiority clinical trial with historical controls.

BACKGROUND: Cervical cancer is the fourth most common cancer in the world, affecting mainly women residing in low- and middle-income countries. Progression from a pre-invasive phase to that of an invasive phase generally takes years and provides a window of opportunity to screen for and treat precancerous lesions. METHODS: This study is being conducted at four sites in north Karnataka, India. Community sensitization activities have been organized in the study areas to create awareness among stakeholders, including elected representatives, physicians, health care workers, and potential participants. Organized community based as well as hospital-based screening is being conducted using visual inspection with acetic acid (VIA). Screen positive women are referred to respective study hospitals for colposcopy and directed biopsy. Participants with confirmed high-grade cervical dysplasia (high-grade squamous intraepithelial lesions or HSIL) who fit all other eligibility criteria will be recruited to the study and will receive cryotherapy using CryoPop®, an innovative new cryotherapy device. DISCUSSION: There is a need to develop an inexpensive, simple, and effective cryotherapy device for use by frontline health care providers at locations where screening and timely treatment can be given, accelerating access to cervical cancer prevention services and minimizing loss to follow-up of women with precancerous lesions who need treatment. TRIAL REGISTRATION: Clinical Trial Registry - India CTRI/2019/01/017289 ClinicalTrials.Gov number NCT04154644 . Registered on November 6, 2019.

Pregnant Individuals' Views on Fetal Tissue Research in the United States.

OBJECTIVE: Fetal tissue research has driven significant medical advances but remains publicly contentious in the United States. The views of pregnant individuals in the United States regarding the donation of fetal tissue offer an important and previously unexplored perspective on this issue. METHODS: We conducted a secondary analysis of data from two separate, broader qualitative studies. Pregnant and recently pregnant individuals (N=79) from clinical sites at the University of North Carolina at Chapel Hill, Johns Hopkins University, and Massachusetts General Hospital were interviewed individually using a semi-structured guide addressing a range of issues related to infectious disease research and pregnancy, including the acceptability of fetal tissue research. Interviews were transcribed, coded, and analyzed for emergent themes. RESULTS: Among this sample of predominantly Black (61%), reproductive-aged pregnant and recently pregnant participants, the majority (72%) generally supported fetal tissue research. The following three themes were identified: choice, respect, and meaning. Respondents discussed the deeply personal nature of decisions surrounding fetal tissue research, emphasizing the importance of informed consent and respect for the person's emotional state when approaching for consent. The ways in which participants regarded how to respectfully handle fetal tissue also shaped views about the acceptability of donation, both for and against. For many participants, fetal tissue donation to research represented one way of ascribing meaning to pregnancy termination or loss. CONCLUSION: Among this diverse sample of pregnant and recently pregnant individuals, most were supportive of fetal tissue donation for research. A better understanding of pregnant individuals' views on this topic may lead to policies and practices that are congruent with the needs and values of people facing decisions regarding the disposition of fetal remains.

Pregnancy in an Urban Cohort of Adolescents Living with Human Immunodeficiency Virus: Characteristics and Outcomes in Comparison to Adults.

Adolescents (13-24 years of age) account for more than one-fifth of new HIV diagnoses yearly, and the United States has one of the highest rates of adolescent pregnancy among high resource countries. However, there is limited information on the characteristics and outcomes of adolescents living with HIV (ALWHIV) during pregnancy and differences with pregnancy in adults living with HIV. We performed a retrospective cohort study to compare demographic characteristics, HIV viral suppression, and pregnancy outcomes in adolescents (n = 90) as compared with adults (n = 250) in an urban HIV pregnancy clinic from 2003 to 2015. Seventy-one women overall were diagnosed with HIV during pregnancy (adolescents, 25/90; adults, 46/250). One-fifth of adolescents acquired HIV perinatally. Adolescents were more likely than adults to have unintended pregnancy (83.6% vs. 68.7%, p = 0.016) and were less likely to be virally suppressed at delivery (50.0% vs. 69.7% overall, p = 0.001; 48.0% vs. 78.2% in postuniversal antiretroviral therapy era, p = 0.007%). Over one-third of adolescents reported a history of any illicit substance use, and adolescents were more likely than adults to use marijuana during pregnancy (29.2% vs. 16.9%, p = 0.013). Adolescents were less likely to experience preterm labor (11.0% vs. 24.1%, p = 0.012) or preterm premature rupture of membranes (3.7% vs. 16.7%, p = 0.003). There was one case of maternal-fetal transmission, which occurred in an adult pregnancy. Despite the high rate of unintended pregnancy, one-third of adolescents were discharged without an identified contraception plan. We identify several opportunities for intervention to improve reproductive health outcomes in ALWHIV.

Postpartum care content and delivery throughout the African continent: An integrative review.

OBJECTIVE: The objective of this review was to describe and evaluate the content of postpartum care and models of delivery throughout the African continent. DESIGN: Integrative review was used to allow for the combination of studies using diverse research methodologies. DATA SOURCES: A comprehensive search strategy using the phrases 'postpartum period', 'healthcare delivery', and 'Africa,' including all spelling variants and countries within the continent, was used in the following databases: PubMed, Cumulative Index of Nursing and Allied Health Literature Plus, and Embase for studies published through September 2019. REVIEW METHOD: The integrative review process included five stages: problem identification, literature search, data evaluation, data analysis and presentation. Twelve studies from eight African countries were identified in the search and met the inclusion criteria for the review. The Mixed Methods Appraisal Tool was used to evaluate the quality of the studies included in the review. The theoretical framework developed by the World Health Organization Maternal Morbidity Working Group for healthcare interventions to address maternal morbidity was used for data analysis and to synthesize the results for presentation. RESULTS: Definitions of the postpartum period varied among studies with service delivery ranging from six weeks to one year postpartum. There was no standard package of postpartum care across studies. Based on the World Health Organization theoretical framework, five primary topics were covered in postpartum care interventions: preventive care and counseling, health systems innovation, a life course approach, family planning, and health literacy and education. In contrast, five gaps in content of postpartum care services and service delivery included: integration of screening and treatment of noncommunicable diseases with maternal healthcare, intimate partner violence screening, social protection, a rights-based approach, and social vulnerability. No study addressed all aspects of the World Health Organization framework to address maternal morbidity. CONCLUSIONS: The results from this review indicate the need to address gaps in postpartum care services throughout the African continent in order to reduce maternal morbidity. Re- conceptualizing the paradigm of maternal health to take a life course approach and focusing future research on developing and building interventions to target postpartum care and healthcare delivery of postpartum care are necessary and important in efforts to reduce maternal morbidity and improve health outcomes for mother and child.

A Checklist to Assess Childbearing Intentions and Promote Referral to Preconception Care or Contraception: A Multi-Site Study.

INTRODUCTION: This study assesses HIV provider views on the value of a checklist designed to assess patients' preconception care (PCC) needs and guide implementation of PCC. METHODS: Ninety-two HIV providers in seven U.S. cities provided perspectives via an in-depth phone interview regarding a checklist to facilitate communication and referrals for PCC. A sub-sample of 27 providers shared feedback on a checklist designed for this purpose. Interview audio files were transcribed and uploaded to a web-based program supporting coding and analysis of qualitative data. Content analysis was utilized to identify key themes within the larger, a priori themes of interest. Feedback regarding the checklist was analyzed using a grounded theory approach to examine patterns and emergent themes across transcripts. RESULTS: Providers averaged 11.5 years of HIV treatment experience; over 80 percent were physicians (MD) or nurse practitioners (NP) and 76 percent were HIV/infectious disease specialists. The majority of providers were female (70%) and Caucasian (72%). Checklist benefits identified included standardization of care, assisting new/inexperienced providers, educational resource for patients, and aid in normalizing childbearing. Concerns included over-protocolizing care, interfering with patient-provider communication, or requiring providers address non-priority issues during visits. Providers suggested checklists be simple, incorporated into the electronic medical record, and accompanied with appropriate referral systems. DISCUSSION: Findings support a need for a checklist tool to assist in conversations about reproductive intentions/desires. Additional referral or innovative consultative services will be needed as more persons living with HIV/AIDS are engaged on the topic of childbearing.

Acceptability and Barriers to Use of the ASMAN Provider-Facing Electronic Platform for Peripartum Care in Public Facilities in Madhya Pradesh and Rajasthan, India: A Qualitative Study Using the Technology Acceptance Model-3.

The evolving field of mobile health (mHealth) is revolutionizing collection, management, and quality of clinical data in health systems. Particularly in low- and middle-income countries (LMICs), mHealth approaches for clinical decision support and record-keeping offer numerous potential advantages over paper records and in-person training and supervision. We conducted a content analysis of qualitative in-depth interviews using the Technology Acceptance Model 3 (TAM-3) to explore perspectives of providers and health managers in Madhya Pradesh and Rajasthan, India who were using the ASMAN (Alliance for Saving Mothers and Newborns) platform, a package of mHealth technologies to support management during the peripartum period. Respondents uniformly found ASMAN easy to use and felt it improved quality of care, reduced referral rates, ensured timely referral when needed, and aided reporting requirements. The TAM-3 model captured many determinants of reported respondent use behavior, including shifting workflow and job performance. However, some barriers to ASMAN digital platform use were structural and reported more often in facilities where ASMAN use was less consistent; these affect long-term impact, sustainability, and scalability of ASMAN and similar mHealth interventions. The transitioning of the program to the government, ensuring availability of dedicated funds, human resource support, and training and integration with government health information systems will ensure the sustainability of ASMAN.

Performance and acceptability of self-collected human papillomavirus testing among women living with HIV.

OBJECTIVE: To assess the validity, reliability, and acceptability of self-collected human papillomavirus (HPV) tests in women living with HIV (WLHIV) in the United States. METHODS: WLHIV ≥30 years of age underwent self-collected (clinic and home) and clinician-collected HPV tests. Sensitivity and specificity analyses were performed using the clinician-collected HPV tests as the comparator. The unweighted kappa statistic was used to evaluate the validity and reliability of self-collected HPV testing, and the level of agreement between the clinician-collected mRNA test and a DNA test that was used for routine care. A 13-question survey was used to assess acceptability. RESULTS: Among the 70 participants, the median age was 50 years, 75% had an undetectable HIV RNA, and 11% had a CD4 count of <200 cells/µl. Nearly 63% had at least one positive HPV test. The sensitivity and specificity of the self-collected HPV test were 84.6% (95% confidence interval (CI) 65.1-95.6%) and 62.9% (95% CI 44.9-78.5%), respectively (κ=0.5, 95% CI 0.2-0.7). The agreement between the two self-collected tests was good (κ=0.8, 95% CI 0.5-1.0). There was good agreement between clinician-collected mRNA tests and DNA tests (κ=0.8, 95% CI 0.7-1.0). Self-collection was highly acceptable. CONCLUSIONS: Among WLHIV, self-collected HPV tests had good sensitivity and moderate specificity compared to clinician-collected HPV tests. The reliability between self-collected testing locations was good. Self-collected HPV testing had high acceptability.

Special ambulatory gynecologic considerations in the era of coronavirus disease 2019 (COVID-19) and implications for future practice.

The coronavirus disease 2019 pandemic has altered medical practice in unprecedented ways. Although much of the emphasis in obstetrics and gynecology to date has been on the as yet uncertain effects of coronavirus disease 2019 in pregnancy and on changes to surgical management, the pandemic has broad implications for ambulatory gynecologic care. In this article, we review important ambulatory gynecologic topics such as safety and mental health, reproductive life planning, sexually transmitted infections, and routine screening for breast and cervical cancer. For each topic, we review how care may be modified during the pandemic, provide recommendations when possible on how to ensure continued access to comprehensive healthcare at this time, and discuss ways that future practice may change. Social distancing requirements may place patients at higher risk for intimate partner violence and mental health concerns, threaten continued access to contraception and abortion services, affect prepregnancy planning, interrupt routine screening for breast and cervical cancer, increase risk of sexually transmitted infection acquisition and decrease access to treatment, and exacerbate already underlying racial and minority disparities in care and health outcomes. We advocate for increased use of telemedicine services with increased screening for intimate partner violence and depression using validated questionnaires. Appointments for long-acting contraceptive insertions can be prioritized. Easier access to patient-controlled injectable contraception and pharmacist-provided hormonal contraception can be facilitated. Reproductive healthcare access can be ensured through reducing needs for ultrasonography and laboratory testing for certain eligible patients desiring abortion and conducting phone follow-up for medication abortions. Priority for in-person appointments should be given to patients with sexually transmitted infection symptoms, particularly if at risk for complications, while also offering expedited partner therapy. Although routine mammography screening and cervical cancer screening may be safely delayed, we discuss society guideline recommendations for higher-risk populations. There may be an increasing role for patient-collected human papillomavirus self-samples using new cervical cancer screening guidelines that can be expanded considering the pandemic situation. Although the pandemic has strained our healthcare system, it also affords ambulatory clinicians with opportunities to expand care to vulnerable populations in ways that were previously underutilized to improve health equity.

Genetically Related Choriocarcinoma Developing 5 Yr After a Complete Hydatidiform Mole and Simulating a Cornual Ectopic Pregnancy.

Persistent gestational trophoblastic disease can arise from any type of antecedent pregnancy, including molar and tubal pregnancies. While most cases of persistent gestational trophoblastic disease present within the first year following initial diagnosis, recurrence has rarely been reported many years after initial diagnosis. Distinguishing recurrence from a new independent lesion is clinically important. A 25-yr-old woman presented with a mass in the right uterine cornu that was discontiguous with the endometrial cavity and was associated with an elevated serum human chorionic gonadotropin level. She had a history of an invasive complete hydatidiform mole with lung involvement treated with chemotherapy 5 yr prior. Wedge resection of the right cornu was performed due to concern for a cornual ectopic pregnancy. Pathologic evaluation demonstrated a choriocarcinoma. Molecular genotyping confirmed the tumor as recurrent disease genetically related to the prior complete hydatidiform mole. She completed 4 cycles of EMA-CO therapy, and has been disease-free with undetectable serum human chorionic gonadotropin level for 2 yr.