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.

Brief Report: Robo1 Regulates the Migration of Human Subventricular Zone Neural Progenitor Cells During Development.

Human neural progenitor cell (NPC) migration within the subventricular zone (SVZ) of the lateral ganglionic eminence is an active process throughout early brain development. The migration of human NPCs from the SVZ to the olfactory bulb during fetal stages resembles what occurs in adult rodents. As the human brain develops during infancy, this migratory stream is drastically reduced in cell number and becomes barely evident in adults. The mechanisms regulating human NPC migration are unknown. The Slit-Robo signaling pathway has been defined as a chemorepulsive cue involved in axon guidance and neuroblast migration in rodents. Slit and Robo proteins expressed in the rodent brain help guide neuroblast migration from the SVZ through the rostral migratory stream to the olfactory bulb. Here, we present the first study on the role that Slit and Robo proteins play in human-derived fetal neural progenitor cell migration (hfNPC). We describe that Robo1 and Robo2 isoforms are expressed in the human fetal SVZ. Furthermore, we demonstrate that Slit2 is able to induce a chemorepellent effect on the migration of hfNPCs derived from the human fetal SVZ. In addition, when Robo1 expression is inhibited, hfNPCs are unable to migrate to the olfactory bulb of mice when injected in the anterior SVZ. Our findings indicate that the migration of human NPCs from the SVZ is partially regulated by the Slit-Robo axis. This pathway could be regulated to direct the migration of NPCs in human endogenous neural cell therapy. Stem Cells 2017;35:1860-1865.

Development and evaluation of measures to assess self-determination in peripartum contraceptive decision-making.

OBJECTIVES: We aimed to adapt and validate person-centered measures to evaluate various contributors to self-determination in perinatal contraceptive decision-making. STUDY DESIGN: We developed and administered four scales adapted from existing measures in the context of Self-Determination Theory: the Treatment Self-Regulation Questionnaire (TSRQ), Perceived Competence Scale, modified Health Care Climate Questionnaire, and Important Other Climate Questionnaire. The TSRQ consists of three subscales: autonomous motivation, controlled motivation, and amotivation. We recruited a nonprobability convenience sample of 300 hospitalized postpartum patients in Baltimore, MD, between 2015 and 2016 and administered surveys in English and Spanish. We validated the scales with Cronbach's alpha coefficients, confirmatory factor analysis, and invariance analysis. We examined construct validity by testing correlations between the scales and other person-centered measures, such as satisfaction with counseling. RESULTS: Cronbach's alpha was >0.8 except for the amotivation subscale. Confirmatory factor analysis was adequate for all scales. Autonomous motivation correlated positively and significantly with perceived competence, health care provider autonomy support, important other autonomy support, and other measures of patient satisfaction. CONCLUSIONS: We found the four scales to be internally consistent and valid except for the amotivation subscale. We recommend using the autonomous motivation subscale in place of the full TSRQ. The autonomous motivation subscale, Perceived Competence Scale, modified Health Care Climate Questionnaire, and Important Other Climate Questionnaire showed adequate internal consistency, construct validity, and adherence to the expected conceptual structure of the scales. IMPLICATIONS: Autonomous decision-making is central to ethics and quality of care, especially for contraceptive methods that require a provider for initiation or discontinuation and at more vulnerable times, such as postpartum and postabortion. These scales may help tailor person-centered and autonomy-supportive interventions and programs to improve contraceptive counseling and care delivery.

Oral sedation for pain with cervical dilator placement: a randomized controlled trial.

OBJECTIVE: Assess oral sedation versus placebo for pain control with cervical dilator placement. STUDY DESIGN: We randomized participants presenting for dilation and evacuation to lorazepam 1 mg/oxycodone 5 mg or placebo 45 min before cervical dilator placement. Our primary outcome was median visual analog scale (VAS) pain score after dilator placement using a 100-mm VAS. We used our outcome data to calculate median pain score changes from baseline to better reflect pain score differences between study groups. Planned sample size was 30 participants per group, for a total of 60. RESULTS: We randomized 27 participants; 9 received sedation and 11 placebo. Median pain score increase from baseline to last dilator placement was 20 [interquartile range (IQR) 8-29] and 31 (IQR 15-81) in the oral sedation and placebo groups, p = .16. CONCLUSION: We were unable to enroll our desired sample size, and our sample is underpowered to make any conclusions. Our results suggest that oral sedation may provide some benefit for pain relief with dilator insertion and indicate that further research might be worthwhile especially in settings that do not routinely provide these analgesics. IMPLICATIONS: We had difficulty with study recruitment because many patients desired oral sedation for pain management for cervical dilator placement and declined randomization. Randomized trials of pain management with a placebo arm may find recruitment challenging especially if default clinical care already includes a pain management option that patients would have to opt out of.

Women with sickle cell disease report low knowledge and use of long acting reversible contraception.

BACKGROUND: High rates of unplanned pregnancy and low rates of contraception use are reported among women with sickle cell disease (SCD). Pregnancy in women with SCD is high risk and unintended pregnancies limit opportunities to provide indicated preconception care and counseling. Contraceptive use in women with SCD is complicated by a lack of disease-specific data about treatment risks and benefits. The purpose of this study was to describe, for the first time in the U.S. context, contraceptive use, knowledge and preferences in adult cohort of women with SCD. MATERIALS AND METHODS: A single-center survey study of women with SCD of reproductive age from our Center's adult and pediatric sickle cell centers. RESULTS: Seventy-eight women ages 28-65 years (median 33.5 years, IQR 16) completed surveys. Seventy-three percent of respondents had an average of 2.5 pregnancies (S.D. 1.22) and of these, 58% reported being pregnant when they did not want to be pregnant at least once. The most common forms of contraception used were condoms (87%), birth control pills (46%), medroxyprogesterone (44%) and withdrawal (44%). Twenty-two percent of subjects reported using a long-acting reversible form of contraception and 21% reported a tubal ligation or partner vasectomy. Respondents demonstrated low knowledge of the efficacy of contraceptive options and over-estimated the risk of pregnancy with the IUD, implant. Contraceptive priorities included pregnancy prevention, decreasing HIV transmission and effects on SCD symptoms. CONCLUSIONS: Women with SCD have high rates of unintended pregnancy, low knowledge of contraceptive efficacy and low use of long-acting reversible contraception.

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.