Provision of DMPA-SC for self-administration in different practice settings during the COVID-19 pandemic: Data from providers across the United States.

OBJECTIVES: Depot medroxyprogesterone acetate-subcutaneous (DMPA-SC) can be prescribed through telemedicine and self-administered, but data about availability, particularly during the COVID-19 pandemic, are limited. This study assessed changes in the availability of DMPA-SC for self-administration during the pandemic. STUDY DESIGN: This study used survey data from a convenience sample of US providers engaged in contraceptive care and participating in a Continuing Medical Education-accredited contraceptive training (April 2020-April 2022; n = 849). Providers were recruited from across 503 clinics, including primary care and family planning clinics, public health departments, college and school-based health centers, independent abortion care clinics, and outpatient clinics in hospital settings. Measures included the availability of DMPA-SC for self-administration before and during the pandemic and the use of telemedicine. We used Poisson regression models and cluster-robust errors by clinic, adjusting for region, time of survey, and clinic size, to assess clinic availability of DMPA-SC for self-administration by practice setting. RESULTS: Compared to the prepandemic period (4%), the availability of DMPA-SC for self-administration increased significantly during the pandemic (14%) (adjusted prevalence ratios [aPR] 3.43, 95% CI [2.43-4.85]). During the pandemic, independent abortion clinics were more likely to offer DMPA-SC for self-administration compared to primary care clinics (aPR 2.44, 95% CI [1.10-5.41]). Clinics receiving Title X funds were also more likely to provide DMPA-SC for self-administration during the pandemic compared to other clinics (aPR 2.32, 95% CI [1.57-3.43]), and more likely to offer DMPA-SC for self-administration through telemedicine (aPR 2.35, 95% CI [1.52-3.63]). Compared to the early pandemic period (April-September 2022), telemedicine access to DMPA-SC for self-administration was highest during the later pandemic time period (October 2021-April 2022) (aPR 2.10, 95% CI [1.06-4.17]). CONCLUSIONS: The availability of DMPA-SC for self-administration significantly increased during the pandemic with differences by practice setting and Title X funding. However, overall method availability remains persistently low. IMPLICATIONS: Despite increased availability of DMPA-SC for self-administration among US contraceptive providers during the COVID-19 pandemic, there remains a need to train providers, educate patients, and remove barriers to ensure broader availability of this method across different practice settings.

"She should support me, she's my doctor:" Patient perceptions of agency in contraceptive decision-making in the clinical encounter in Northern California.

INTRODUCTION: Agency in contraceptive decision-making is an essential aspect of reproductive autonomy. We conducted qualitative research to investigate what agency means to patients seeking contraceptive care to inform the development of a validated measure of this construct. METHODOLOGY: We held four focus group discussions and seven interviews with sexually-active individuals assigned female at birth, ages 16-29 years, recruited from reproductive health clinics in Northern California. We explored experiences in contraceptive decision-making during the clinic visit. We coded data in ATLAS.ti and by hand, compared codes across three coders, and used thematic analysis to identify salient themes. RESULTS: The sample mean age was 21 years, with 17% of participants identifying as Asian, 23% as Black, 27% as Latinx, 17% as Multiracial/other, and 27% as white. Overall, participants reported active and engaged decision-making in their recent contraceptive visit but noted experiences that had undermined their agency in the past. They described how non-judgmental care allowed them to communicate openly, affirming their ability to make their own decisions. However, several mentioned how unexpected contraceptive side effects after the visit had reduced their sense of agency over their decision in retrospect. Several participants, including those who identified as Black, Latinx, and/or Asian, described prior experiences where pressure to use a contraceptive method had undermined their agency and where they had switched providers to regain agency over their contraceptive decisions. DISCUSSION: Most participants were aware of their agency during contraceptive visits and how it varied in different experiences with providers and the healthcare system. Patient perspectives can help to inform measurement development and ultimately the delivery of care that supports contraceptive agency.

Telehealth for Contraceptive Services During the COVID-19 Pandemic: Provider Perspectives.

BACKGROUND: Telehealth use rapidly increased during the COVID-19 pandemic, including for contraceptive care (e.g., counseling and method provision). This study explored providers' experiences with contraceptive care via telehealth. METHODS: We conducted a survey with open-ended responses among contraceptive providers across the United States. The study population included physicians, nurse practitioners, health educators, and other health professionals (n = 546). Data were collected from April 10, 2020, to January 29, 2021. We conducted qualitative content analysis of the open-ended responses. RESULTS: Providers highlighted the benefits of telehealth, including continuing access to contraceptive services and accommodating patients who faced challenges attending in-person contraceptive visits. Providers at school-based health centers reported telehealth allowed them to reach young people while schools were closed. However, many providers noted a lack of patient awareness about the availability of telehealth services and disparities in access to technology. Providers felt there was less personal connection in virtual contraceptive counseling, noted challenges with confidentiality, and expressed concern about the inability to provide the full range of contraceptive methods through telehealth alone. CONCLUSIONS: The pandemic significantly impacted contraceptive health care delivery. Telehealth has sustained access to contraception in important ways, but has been accompanied by various challenges, including technological access and confidentiality. As hybrid models of care evolve, it is important to assess how telehealth can play a role in providing contraceptive care while addressing its barriers.

Concerns About the Cost of Contraception Among Young Women Attending Community College.

INTRODUCTION: Contraceptive use is lower among students attending community college than 4-year college students, which may be due to financial barriers to accessing contraceptives. This study examined insurance coverage, access to free or low-cost birth control, and concerns about contraceptive costs among women in community college. METHODS: We analyzed data from a study conducted at five community colleges in California and Oregon, which have expanded Medicaid coverage of family planning services for low-income individuals. Participants were students aged 18-25 years who self-identified as female, had vaginal sex, and were not pregnant or trying to become pregnant (N = 389). Multivariate analyses were conducted to examine concerns about the cost of contraception among these young women and how cost concerns varied by insurance coverage and access to free or low-cost birth control. RESULTS: Nearly one-half of participants (49%) were concerned about the cost of contraception. In multivariate models, privately insured women had lower odds of being concerned about the cost of birth control than the uninsured (adjusted odds ratio, 0.42; 95% confidence interval, 0.22-0.83), yet women with public insurance had cost concerns similar to those of women without insurance. Women who reported they knew where to get free or low-cost birth control had lower odds of reporting cost concerns (adjusted odds ratio, 0.42; 95% confidence interval, 0.24-0.75), as did the few women enrolled in a state family planning program (adjusted odds ratio, 0.56; 95% confidence interval, 0.32-1.00). CONCLUSIONS: Even in states with publicly funded services for young people, concerns about the affordability of contraception were common among women, particularly the uninsured or publicly insured. Addressing students' cost concerns is an important aspect of ensuring access to contraception during their pursuit of higher education.

Implementation science: Scaling a training intervention to include IUDs and implants in contraceptive services in primary care.

Building capacity for contraceptive services in primary care settings, including for intrauterine devices (IUDs) and implants, can help to broaden contraceptive access across the US. Following a randomized trial in family planning clinics, we brought a provider training intervention to other clinical settings including primary care in all regions. This implementation science study evaluates a national scale-up of a contraceptive training intervention to varied practice settings from 2013 to 2019 among 3216 clinic staff serving an estimated 1.6 million annual contraceptive patients. We measured providers' knowledge and clinical practice changes regarding IUDs and implants using survey data. We estimated the overall intervention effect, and its relative effectiveness in primary care settings, with generalized estimating equations for clustered data. Patient-centered counseling improved, along with comfort with method provision and removal. Provider knowledge increased (p < 0.001), as did evidence-based counseling for IUDs (aOR 3.3 95% CI 2.8-3.9) and implants (aOR 3.5, 95% CI 3.0-4.1), and clinician competency in copper and levonorgestrel IUDs (aORs 1.8-2.6 95% CIs 1.5-3.2) and implants (aOR 2.4 95% CI 2.0-2.9). While proficiency was lower initially in primary care, gains were significant and at times greater than in Planned Parenthood health clinics. This intervention was effectively scaled, including in primary care settings with limited prior experience with these methods. Recent changes to Title X family planning funding rules exclude several large family planning providers, shifting greater responsibility to primary care and other settings. Scaling effective contraceptive interventions is one way to ensure capacity to offer patients full contraceptive services.

Pharmacy access to medical abortion from trained providers and post-abortion contraception in Nepal.

OBJECTIVE: To examine whether auxiliary nurse-midwife provision of medical abortion in pharmacies was associated with reduced post-abortion contraceptive use in Nepal. METHODS: The present prospective observational study compared contraceptive use among women aged 16-45 years and up to 63 days of pregnancy, who presented at one of six privately-owned pharmacies or six public health facilities in the Chitwan and Jhapa districts of Nepal for medical abortion between October 16, 2014, and September 1, 2015. Participants obtained medical abortions per Nepali protocol and completed a follow-up visit and interview at 14-21 days. Effective contraceptive use was compared between abortion care settings using multivariable mixed effects logistic regression. RESULTS: Of 605 participants, 600 completed follow-up at 14-21 days; 474 (79.0%) were using a contraceptive method, most commonly pills (180 [30.0%]) and injectables (175 [29.2%]), followed by condoms (82 [13.7%]), long-acting reversible methods (33 [5.5%]), and sterilization (4 [0.7%]). Receipt of care from a private pharmacy was not associated with a difference in the use of hormonal or long-acting methods (adjusted odd ratio 0.89, 95% confidence interval 0.60-1.33). CONCLUSION: Medical abortion provision from pharmacies by qualified providers can provide women with necessary induced-abortion care while not compromising longer-term pregnancy prevention.

Gestational dating using last menstrual period and bimanual exam for medication abortion in pharmacies and health centers in Nepal.

OBJECTIVE: To evaluate whether conducting a bimanual examination prior to medication abortion (MAB) provision results in meaningful changes in gestational age (GA) assessment after patient-reported last menstrual period (LMP) in Nepal. STUDY DESIGN: Women ages 16-45 (n=660) seeking MAB at twelve participating pharmacies and government health facilities, between October 2014 and September 2015, self-reported LMP. Trained auxiliary nurse midwives assessed GA using a bimanual exam after recording LMP. We compared GA assessments as measured via patient-reported LMP alone versus via LMP plus bimanual exam. RESULTS: Overall, 660 women (326 at pharmacies, 334 at health facilities) presented for MAB, and 95% were able to provide an LMP. Overall agreement between LMP alone and LMP with bimanual exam was 99.3%. If LMP alone had been used without bimanual exam, fewer than one in 200 women would have been given MAB beyond the legal gestational limit. Among the three women who were ≤63 days by LMP but >63 days by bimanual exam, only one would have received MAB beyond 70 days gestation. Fewer than one in 600 women would not have received MAB care when eligible by adding a bimanual exam. CONCLUSION: There was high agreement between LMP alone and LMP plus bimanual exam. Routine bimanual exam may not be essential for safe and effective MAB care for women who are able to report an LMP. Removing the bimanual exam requirement could decrease barriers to provision outside of currently approved clinical settings and allow for expanded abortion access through provision by providers without bimanual exam training or facilities. IMPLICATIONS: Routine bimanual exams may not be essential for safe medication abortion provision by trained clinicians in pharmacies and health facilities in low resource settings like Nepal.

Human peptidergic nociceptive sensory neurons generated from human epidermal neural crest stem cells (hEPI-NCSC).

Here we provide new technology for generating human peptidergic nociceptive sensory neurons in a straightforward and efficient way. The cellular source, human epidermal neural crest stem cells (hEPI-NCSC), consists of multipotent somatic stem cells that reside in the bulge of hair follicles. hEPI-NCSC and primary sensory neurons have a common origin, the embryonic neural crest. For directed differentiation, hEPI-NCSC were exposed to pertinent growth factors and small molecules in order to modulate master signalling networks involved in differentiation of neural crest cells into postmitotic peptidergic sensory neurons during embryonic development. The neuronal populations were homogenous in regard to antibody marker expression. Cells were immunoreactive for essential master regulatory genes, including NGN1/2, SOX10, and BRN3a among others, and for the pain-mediating genes substance P (SP), calcitonin gene related protein (CGRP) and the TRPV1 channel. Approximately 30% of total cells responded to capsaicin, indicating that they expressed an active TRPV1 channel. In summary, hEPI-NCSC are a biologically relevant and easily available source of somatic stem cells for generating human peptidergic nociceptive neurons without the need for genetic manipulation and cell purification. As no analgesics exist that specifically target TRPV1, a ready supply of high-quality human peptidergic nociceptive sensory neurons could open the way for new approaches, in a biologically relevant cellular context, to drug discovery and patient-specific disease modelling that is aimed at pain control, and as such is highly desirable.

Effectiveness and safety of early medication abortion provided in pharmacies by auxiliary nurse-midwives: A non-inferiority study in Nepal.

BACKGROUND: Expanding access to medication abortion through pharmacies is a promising avenue to reach women with safe and convenient care, yet no pharmacy provision interventions have been evaluated. This observational non-inferiority study investigated the effectiveness and safety of mifepristone-misoprostol medication abortion provided at pharmacies, compared to government-certified public health facilities, by trained auxiliary nurse-midwives in Nepal. METHODS: Auxiliary nurse-midwives were trained to provide medication abortion through twelve pharmacies and public facilities as part of a demonstration project in two districts. Eligible women were ≤63 days pregnant, aged 16-45, and had no medical contraindications. Between 2014-2015, participants (n = 605) obtained 200 mg mifepristone orally and 800 µg misoprostol sublingually or intravaginally 24 hours later, and followed-up 14-21 days later. The primary outcome was complete abortion without manual vacuum aspiration; the secondary outcome was complication requiring treatment. We assessed risk differences by facility type with multivariable logistic mixed-effects regression. RESULTS: Over 99% of enrolled women completed follow-up (n = 600). Complete abortions occurred in 588 (98·0%) cases, with ten incomplete abortions and two continuing pregnancies. 293/297 (98·7%) pharmacy participants and 295/303 (97·4%) public facility participants had complete abortions, with an adjusted risk difference falling within the pre-specified 5 percentage-point non-inferiority margin (1·5% [-0·8%, 3·8%]). No serious adverse events occurred. Five (1.7%) pharmacy and two (0.7%) public facility participants experienced a complication warranting treatment (aRD, 0.8% [-1.0%-2.7%]). CONCLUSIONS: Early mifepristone-misoprostol abortion was as effective and safe when provided by trained auxiliary nurse-midwives at pharmacies as at government-certified health facilities. Findings support policy expanding provision through registered pharmacies by trained auxiliary nurse-midwives to improve access to safe care.

Pharmacy Provision of Medication Abortion in Nepal: Pharmacy Owner and Worker Perspectives.

CONTEXT: Medication abortion has the potential to transform the provision of safe abortion care in low- and middle-income countries, and can be provided with minimal clinical skills and equipment. In Nepal, first-trimester abortion using mifepristone and misoprostol is legally available at government-certified health facilities, but little is known about pharmacy workers' perspectives regarding pharmacy-based provision. METHODS: In-depth interviews were conducted in 2015 with 19 pharmacy owners and auxiliary nurse-midwives in two districts of Nepal to examine respondents' views on medication abortion and on potential legal provision of medication abortion from pharmacies. Two coders independently reviewed interview transcripts, and coded and analyzed them using a thematic approach. RESULTS: Participants were confident that they could provide safe medication abortion and felt that they filled an important niche by providing affordable, convenient and confidential services to women in their communities. They saw benefits of integrating pharmacies into legal abortion networks in Nepal, such as improved access to medication abortion and greater privacy. Participants also felt that the quality of the care they provided could be improved through ongoing training of pharmacy-based providers and formal incorporation of such providers into existing networks of abortion provision to streamline referrals. CONCLUSIONS: Integration of pharmacies into the legal abortion provision system could aid in regulation and training. Consideration of pharmacy workers' perspectives can help to ensure the sustainability and success of safe abortion programs.

RESUMEN Contexto: El aborto con medicamentos tiene el potencial de transformar la provisión de servicios de aborto seguro en países de bajos y medianos ingresos y puede proporcionarse con un mínimo de habilidades y equipos clínicos. En Nepal, el aborto en el primer trimestre con mifepristona y misoprostol está legalmente disponible en centros de salud certificados por el gobierno, pero se sabe poco sobre las perspectivas de los trabajadores farmacéuticos con respecto a la provisión en farmacias. Métodos: En 2015, se condujeron entrevistas en profundidad con 19 dueños de farmacias y enfermeras auxiliares-parteras en dos distritos de Nepal para examinar las opiniones de las personas entrevistadas sobre el aborto con medicamentos y sobre la potencial provisión legal de medicamentos para el aborto en farmacias. Dos codificadores revisaron independientemente las transcripciones y las codificaron y analizaron usando un enfoque temático. Resultados: Los participantes expresaron su confianza en su capacidad para proporcionar un aborto seguro con medicamentos y consideraron que llenaban un nicho importante al proporcionar servicios asequibles, convenientes y confidenciales a las mujeres en sus comunidades. Vieron los beneficios de integrar a las farmacias en redes de aborto legal en Nepal, como un mejor acceso al aborto con medicamentos y una mayor privacidad. Los participantes también consideraron que la calidad de atención que brindaban podría mejorarse a través de la capacitación continua de proveedores farmacéuticos y la incorporación formal de dichos proveedores a las redes existentes de provisión de servicios de aborto para simplificar las referencias. Conclusiones: La integración de las farmacias en el sistema legal de provisión de abortos podría ayudar en la regulación y la capacitación. Tomar en cuenta las perspectivas de los trabajadores farmacéuticos puede ayudar a asegurar la sostenibilidad y el éxito de los programas de aborto seguro.

RÉSUMÉ Contexte: L'avortement médicamenteux a le potentiel de transformer la prestation des soins d'avortement sans risques dans les pays à revenu faible et intermédiaire. Il ne requiert du reste qu'un minimum de compétences cliniques et d'équipement. Au Népal, l'avortement provoqué au premier trimestre par la prise de mifépristone et de misoprostol est légalement accessible dans les structures de santé agréées par l'État. Le point de vue des employés de pharmacie concernant la prestation en pharmacie n'est cependant guère documenté. Méthodes: Des entretiens en profondeur ont été menés en 2015 avec 19 propriétaires de pharmacie et sages-femmes auxiliaires dans deux districts du Népal, afin d'examiner l'opinion des répondants sur l'avortement médicamenteux et sur la possibilité de la prestation légale de l'avortement médicamenteux en pharmacie. Deux codeurs ont examiné indépendamment la transcription de ces entretiens, assurant leur codage et leur analyse selon une approche thématique. Résultats: Les participants étaient sûrs de pouvoir offrir l'avortement médicamenteux sans risques et estimaient combler un créneau important de services abordables, pratiques et confidentiels aux femmes de leurs communautés. Ils percevaient les avantages de l'intégration des pharmacies dans les réseaux de l'avortement légal au Népal, comme l'amélioration de l'accès à l'avortement médicamenteux et une plus grande protection de la vie privée. Les participants estimaient aussi que la qualité de leurs soins pourrait être améliorée par une formation permanente des prestataires rattachés aux pharmacies et par l'insertion formelle de ces prestataires dans les réseaux existants de prestation de l'avortement, pour simplifier les orientations et renvois. Conclusions: L'intégration des pharmacies au système de prestation de l'avortement légal pourrait faciliter la réglementation et la formation. La prise en compte du point de vue des employés de pharmacie peut être propice à la durabilité et au succès des programmes d'avortement sans risques.

The impact of an IUD and implant intervention on dual method use among young women: Results from a cluster randomized trial.

Long-acting reversible contraceptives (LARCs) are highly effective at preventing pregnancy but do not protect against sexually transmitted infection (STI). Recent efforts to improve access to intrauterine devices (IUDs) and implants have raised concerns about STI prevention and reduced condom use, particularly among teenagers and young women. We evaluated whether a provider-targeted intervention to increase LARC access negatively impacted dual method use and STI incidence among an at-risk patient population. We conducted a cluster randomized trial in 40 reproductive health centers across the United States from May 2011 to May 2013. After training providers at 20 intervention sites, we recruited 1500 sexually-active women aged 18-25years who did not desire pregnancy and followed them for one year. We assessed intervention effects on dual method use, condom use and STI incidence, modeling dual method use with generalized estimating equations and STI incidence with Cox proportional hazard regression models, accounting for clustering. We found no differences between intervention and control groups in dual method use (14.3% vs. 14.4%, aOR 1.03, 95% CI 0.74-1.44) or condom use (30% vs. 31%, aOR 1.03, 95% CI 0.79-1.35) at last sex at one year. STI incidence was 16.5 per 100 person-years and did not differ between intervention and control groups (aHR 1.20, 95% CI 0.88-1.64). A provider training intervention to increase LARC access neither compromised condom use nor increased STI incidence among young women. Dual method use was very low overall, highlighting the need to bolster STI prevention efforts among adolescents and young women.

Public Funding for Contraception, Provider Training, and Use of Highly Effective Contraceptives: A Cluster Randomized Trial.

OBJECTIVES: We determined whether public funding for contraception was associated with long-acting reversible contraceptive (LARC) use when providers received training on these methods. METHODS: We evaluated the impact of a clinic training intervention and public funding on LARC use in a cluster randomized trial at 40 randomly assigned clinics across the United States (2011-2013). Twenty intervention clinics received a 4-hour training. Women aged 18 to 25 were enrolled and followed for 1 year (n = 1500: 802 intervention, 698 control). We estimated the effects of the intervention and funding sources on LARC initiation with Cox proportional hazards models with shared frailty. RESULTS: Women at intervention sites had higher LARC initiation than those at control (22 vs 18 per 100 person-years; adjusted hazard ratio [AHR] = 1.43; 95% confidence interval [CI] = 1.04, 1.98). Participants receiving care at clinics with Medicaid family planning expansion programs had almost twice the initiation rate as those at clinics without (25 vs 13 per 100 person-years; AHR = 2.26; 95% CI = 1.59, 3.19). LARC initiation also increased among participants with public (AHR = 1.56; 95% CI = 1.09, 2.22) but not private health insurance. CONCLUSIONS: Public funding and provider training substantially improve LARC access.

Service provider perspectives on post-abortion contraception in Nepal.

The government of Nepal has articulated a commitment to the provision of post-abortion contraception since the implementation of a legal safe abortion policy in 2004. Despite this, gaps in services remain. This study examined the perspectives of abortion service providers and administrators regarding strengths and shortcomings of post-abortion contraceptive service provision. In-depth interviews were conducted with 24 abortion providers and administrators at four major health facilities that provide legal abortion in Nepal. Facility factors perceived to impact post-abortion contraceptive services included on-site availability of contraceptive supplies, dedicated and well-trained staff and adequate infrastructure. Cultural norms emerged as influencing contraceptive demand by patients, including method use being unacceptable for women whose husbands migrate and limited decision-making power among women. Service providers described their personal views on appropriate childbearing and the use of specific contraceptive methods that influenced counselling. Findings suggest that improvements to a facility's infrastructure and training to address provider biases and misinformation may improve post-abortion family planning uptake. Adapting services to be sensitive to cultural expectations and norms may help address some barriers to contraceptive use. More research is needed to determine how to best meet the contraceptive needs of women who have infrequent sexual activity or who may face stigma for using family planning, including adolescents, unmarried women and women whose husbands migrate.

Human epidermal neural crest stem cells as a source of Schwann cells.

We show that highly pure populations of human Schwann cells can be derived rapidly and in a straightforward way, without the need for genetic manipulation, from human epidermal neural crest stem cells [hEPI-NCSC(s)] present in the bulge of hair follicles. These human Schwann cells promise to be a useful tool for cell-based therapies, disease modelling and drug discovery. Schwann cells are glia that support axons of peripheral nerves and are direct descendants of the embryonic neural crest. Peripheral nerves are damaged in various conditions, including through trauma or tumour-related surgery, and Schwann cells are required for their repair and regeneration. Schwann cells also promise to be useful for treating spinal cord injuries. Ex vivo expansion of hEPI-NCSC isolated from hair bulge explants, manipulating the WNT, sonic hedgehog and TGFß signalling pathways, and exposure of the cells to pertinent growth factors led to the expression of the Schwann cell markers SOX10, KROX20 (EGR2), p75NTR (NGFR), MBP and S100B by day 4 in virtually all cells, and maturation was completed by 2 weeks of differentiation. Gene expression profiling demonstrated expression of transcripts for neurotrophic and angiogenic factors, as well as JUN, all of which are essential for nerve regeneration. Co-culture of hEPI-NCSC-derived human Schwann cells with rodent dorsal root ganglia showed interaction of the Schwann cells with axons, providing evidence of Schwann cell functionality. We conclude that hEPI-NCSCs are a biologically relevant source for generating large and highly pure populations of human Schwann cells.

Feasibility Study of Canine Epidermal Neural Crest Stem Cell Transplantation in the Spinal Cords of Dogs.

UNLABELLED: This pilot feasibility study aimed to determine the outcome of canine epidermal neural crest stem cell (cEPI-NCSC) grafts in the normal spinal cords of healthy bred-for-research dogs. This included developing novel protocols for (a) the ex vivo expansion of cEPI-NCSCs, (b) the delivery of cEPI-NCSCs into the spinal cord, and (c) the labeling of the cells and subsequent tracing of the graft in the live animal by magnetic resonance imaging. A total of four million cEPI-NCSCs were injected into the spinal cord divided in two locations. Differences in locomotion at baseline and post-treatment were evaluated by gait analysis and compared with neurological outcome and behavioral exams. Histopathological analyses of the spinal cords and cEPI-NCSC grafts were performed at 3 weeks post-transplantation. Neurological and gait parameters were minimally affected by the stem cell injection. cEPI-NCSCs survived in the canine spinal cord for the entire period of investigation and did not migrate or proliferate. Subsets of cEPI-NCSCs expressed the neural crest stem cell marker Sox10. There was no detectable expression of markers for glial cells or neurons. The tissue reaction to the cell graft was predominantly vascular in addition to a degree of reactive astrogliosis and microglial activation. In the present study, we demonstrated that cEPI-NCSC grafts survive in the spinal cords of healthy dogs without major adverse effects. They persist locally in the normal spinal cord, may promote angiogenesis and tissue remodeling, and elicit a tissue response that may be beneficial in patients with spinal cord injury. SIGNIFICANCE: It has been established that mouse and human epidermal neural crest stem cells are somatic multipotent stem cells with proved innovative potential in a mouse model of spinal cord injury (SCI) offering promise of a valid treatment for SCI. Traumatic SCI is a common neurological problem in dogs with marked similarities, clinically and pathologically, to the syndrome in people. For this reason, dogs provide a readily accessible, clinically realistic, spontaneous model for evaluation of epidermal neural crest stem cells therapeutic intervention. The results of this study are expected to give the baseline data for a future clinical trial in dogs with traumatic SCI.

Contraceptive discontinuation and pregnancy postabortion in Nepal: a longitudinal cohort study.

OBJECTIVE: To examine postabortion contraceptive discontinuation and pregnancy in Nepal, where abortion was decriminalized in 2002. STUDY DESIGN: We conducted an observational cohort study of 654 women obtaining abortions from four public and nongovernmental facilities in 2011. Patients completed questionnaires at their abortion visit and 6 and 12 months later. We used Cox proportional hazards models to assess contraceptive discontinuation and pregnancy by method initiated postabortion and other sociodemographic and reproductive factors. RESULTS: Among the 78% (508/654) of women who initiated a modern contraceptive method within 3 months postabortion, the 1-year contraceptive discontinuation rate was 62 per 100 person-years. Discontinuation was far lower among the 5% of women using long-acting reversible methods (21/100 person-years) than among those using condoms (74/100 person-years), pills (61/100 person-years) and the injectable [64/100 person-years; adjusted hazard ratio (aHR)=0.32 (0.15-0.68)]. Unmarried women and those not living with their husband experienced higher contraceptive discontinuation [aHR=2.16 (1.47-3.17)]. The 1-year pregnancy rate for all women was 9/100 person-years. Pregnancy was highest among those who initiated no modern method postabortion (13/100 person-years) and condoms (12/100 person-years), and pregnancy was lowest among users of long-acting reversible methods (3/100 person-years). The poorest women were at increased pregnancy risk [aHR=2.31 (1.32-4.10)]. CONCLUSION: Women using intrauterine devices and implants experienced greatly reduced contraceptive discontinuation and pregnancy within a year postabortion, although initiation of these long-acting methods was low. Increased availability of long-acting methods in Nepal and similar settings may help to prevent unwanted pregnancy and attendant maternal mortality and morbidities. IMPLICATIONS: Initiation of modern contraception was high postabortion; however, 1-year discontinuation was high for the condom, pill and injectable, the methods most commonly used. Rates for intrauterine devices and implants were low. Results support efforts to facilitate patient knowledge and access to the full range of contraceptives, including long-acting reversible methods.

Stem cells in canine spinal cord injury--promise for regenerative therapy in a large animal model of human disease.

The use of cell transplantation for spinal cord injury is a rapidly evolving field in regenerative medicine. Numerous animal models are currently being used. However, translation to human patients is still a challenging step. Dogs are of increasing importance as a translational model for human disease since there is a greater awareness of the need to increase the quality of preclinical data. The use of dogs ultimately brings benefit to both human and veterinary medicine. In this review we analyze experimental and clinical studies using cell transplantation for canine spinal cord injury. Overall, in experimental studies, transplantation groups showed improvement over control groups. Improvements were measured at the functional, electrophysiological, histological, RNA and protein levels. Most clinical studies support beneficial effects of cell transplantation despite the fact that methodological limitations preclude definitive conclusions. However, the mechanisms of action and underlying the behavior of transplanted cells in the injured spinal cord remain unclear. Overall, we conclude here that stem cell interventions are a promising avenue for the treatment of spinal cord injury. Canines are a promising model that may help bridge the gap between translational research and human clinical trials.

Human epidermal neural crest stem cells as candidates for cell-based therapies, disease modeling, and drug discovery.

In this review article I explore the suitability of human epidermal neural crest stem cells (hEPI-NCSC) for translational medicine. hEPI-NCSC are multipotent somatic stem cells that are derived from the embryonic neural crest. hEPI-NCSC are located in the bulge of hair follicles where they persist postnatally and into adulthood. Because of their location in the hairy skin and their migratory behavior, hEPI-NCSC can be easily isolated as a highly pure population of stem cells without the need for purification. Furthermore they can be expanded ex vivo into millions of stem cells, they do not form tumors in vivo, and they can undergo directed differentiation into crest and noncrest-derived cell types of clinical relevance. Taken together, these characteristics make hEPI-NCSC attractive candidates for cell-based therapies, drug discovery, and disease modeling.

Postabortion contraception a decade after legalization of abortion in Nepal.

OBJECTIVE: To assess the contraceptive information received and methods chosen, received, and used among women having abortions one decade after legalization of abortion in Nepal. METHODS: We examined postabortion contraception with questionnaires at baseline and six months among women obtaining legal abortions (n=838) at four facilities in 2011. Multivariate regression analysis was used to measure factors associated with method information, choice, receipt, and use. RESULTS: One-third of participants received no information on effective methods, and 56% left facilities without a method. The majority of women who chose to use injectables and pills were able to do so (88% and 75%, respectively). However, only 44% of women choosing long-acting reversible contraceptives and 5% choosing sterilization had initiated use of the method by six months. Levels of contraceptive use after medical abortion were on par with those after aspiration abortion. Nulliparous women were far less likely than parous women to receive information and use methods. Women living without husbands or partners were also less likely to receive information and supplies, or to use methods. CONCLUSION: Improvements in postabortion counseling and provision are needed. Ensuring that women choosing long-acting and permanent contraceptive methods are able to obtain either them or interim methods is essential.

Differentiation of human epidermal neural crest stem cells (hEPI-NCSC) into virtually homogenous populations of dopaminergic neurons.

Here we provide a protocol for the directed differentiation of hEPI-NCSC into midbrain dopaminergic neurons, which degenerate in Parkinson's disease. hEPI-NCSC are neural crest-derived multipotent stem cells that persist into adulthood in the bulge of hair follicles. The experimental design is distinctly different from conventional protocols for embryonic stem cells and induced pluripotent stem (iPS) cells. It includes pre-differentiation of the multipotent hEPI-NCSC into neural stem cell-like cells, followed by ventralizing, patterning, continued exposure to the TGFß receptor inhibitor, SB431542, and at later stages of differentiation the presence of the WNT inhibitor, IWP-4. All cells expressed A9 midbrain dopaminergic neuron progenitor markers with gene expression levels comparable to those in normal human substantia nigra. The current study shows for the first time that virtually homogeneous populations of dopaminergic neurons can be derived ex vivo from somatic stem cells without the need for purification, with useful timeliness and high efficacy. This novel development is an important first step towards the establishment of fully functional dopaminergic neurons from an ontologically relevant stem cell type, hEPI-NCSC.