Global HIV prevention, care and treatment services for children: a cross-sectional survey from the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium.

OBJECTIVES: To assess access children with HIV have to comprehensive HIV care services, to longitudinally evaluate the implementation and scale-up of services, and to use site services and clinical cohort data to explore whether access to these services influences retention in care. METHODS: A cross-sectional standardised survey was completed in 2014-2015 by sites providing paediatric HIV care across regions of the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium. We developed a comprehensiveness score based on the WHO's nine categories of essential services to categorise sites as 'low' (0-5), 'medium', (6-7) or 'high' (8-9). When available, comprehensiveness scores were compared with scores from a 2009 survey. We used patient-level data with site services to investigate the relationship between the comprehensiveness of services and retention. RESULTS: Survey data from 174 IeDEA sites in 32 countries were analysed. Of the WHO essential services, sites were most likely to offer antiretroviral therapy (ART) provision and counselling (n=173; 99%), co-trimoxazole prophylaxis (168; 97%), prevention of perinatal transmission services (167; 96%), outreach for patient engagement and follow-up (166; 95%), CD4 cell count testing (126; 88%), tuberculosis screening (151; 87%) and select immunisation services (126; 72%). Sites were less likely to offer nutrition/food support (97; 56%), viral load testing (99; 69%) and HIV counselling and testing (69; 40%). 10% of sites rated 'low', 59% 'medium' and 31% 'high' in the comprehensiveness score. The mean comprehensiveness of services score increased significantly from 5.6 in 2009 to 7.3 in 2014 (p<0.001; n=30). Patient-level analysis of lost to follow-up after ART initiation estimated the hazard was highest in sites rated 'low' and lowest in sites rated 'high'. CONCLUSION: This global assessment suggests the potential care impact of scaling-up and sustaining comprehensive paediatric HIV services. Meeting recommendations for comprehensive HIV services should remain a global priority.

An empirically validated framework for measuring patient's acceptability of health care in Multi-Island Micro States.

Measuring health-care acceptability presents conceptual and contextual challenges, particularly in data-poor Multi-Island Micro States (MIMSs). Thus, there has been limited evidence on the acceptability of health care in MIMS and scarce use of acceptability metrics in policy design and health system evaluation. In the present study, we developed and empirically validated a theoretical framework for measuring users' acceptability of health care in a MIMS in the Caribbean. Using a minimum-data approach, we used a synoptic review of health-care literature and consultations with experts and health system stakeholders to define, scope and select constructs for the theoretical framework of health-care acceptability. Empirical validation of the modelled framework was performed using data collected from household expenditure and health-care utilization surveys in Carriacou and Petite Martinique (n = 226), island dependents of Grenada in the Caribbean. Data were used to create health utilization profiles and analyse measurement scales of the health-care acceptability framework using non-linear partial least square structural equation modelling. The modelled framework included 17 items integrating economic and psychosocial concepts, with 1 dependent construct (utilization) and 3 independent constructs (users' perception, experience and knowledge of health facility). Model analysis and validation indicated that the framework was significant, explaining 19% of the variation in health-care acceptability. Users' experience construct was influenced by perception and knowledge of health facility and was the only construct with a significant negative relationship with acceptability. Health-care acceptability declined with increased waiting and travel times and unsuitable opening hours. We conclude that acceptability comprises a complex multidimensional concept, which is highly dependent on various interacting variables and contextual characteristics of the health system. Therefore, policies and actions to improve acceptability should be context specific and focused on evaluating factors infringing health-care acceptability. Routine acceptability and/or satisfaction studies represent baseline evidence towards understanding and integrating acceptability in health-care assessment.

Longitudinal impacts of the COVID-19 pandemic on adolescents living with HIV in New York City.

Adolescents living with HIV (ALWH) are particularly susceptible to disruptions in care, which may lead to poor HIV-related health outcomes. Here, we report the results of a longitudinal phone-based study investigating impacts of the COVID-19 pandemic on ALWH in New York City. Participants (N = 10, mean age 21.2 years, 50% female) demonstrated substantial COVID-19 knowledge and identified Instagram as their primary source of COVID-19 information. Nearly all participants reported loss of income, and 50% reported experiencing food insecurity as a result of the pandemic. These findings highlight existing vulnerabilities among ALWH that may threaten the continuum of care.

Multi-media teacher training and HIV-related stigma among primary and secondary school teachers in Western Kenya.

ABSTRACTHIV stigma is associated with delayed HIV disclosure and worse clinical outcomes for adolescents living with HIV (ALWH). Teachers critically influence school environments, but are understudied in terms of HIV stigma. We implemented a school-level, cluster-randomized trial to assess the impact of a one-day multi-media training on the knowledge, attitudes and beliefs (K/A/B) of school teachers in western Kenya. Teachers' K/A/B were evaluated at baseline and six months. Additionally, we assessed stigma with ALWH enrolled in the included schools to explore the impact of the training. Teachers (N = 311) and ALWH (N = 19) were enrolled from 10 primary and 10 secondary schools. The intervention and control groups did not significantly differ in overall stigma score (mean 1.83 vs. 1.84; adjusted difference, 0.18 [95% CI, -0.082 to 0.045]) at six months; however, we found a trend towards improvement in overall stigma score and a significant difference in the community discrimination sub-scale among secondary school teachers (mean 3.02 vs. 3.19; adjusted difference, -0.166 [95% CI, -0.310 to -0.022]). ALWH reported few experiences of discrimination, but emphasized keeping their HIV status secret (84%). The teacher-training reduced secondary school teacher perceptions of community-level stigma, but did not impact individual attitudes or beliefs..

A Systematic Review of Digital Interventions to Improve ART Adherence among Youth Living with HIV in sub-Saharan Africa.

An estimated 3.4 million youth aged 15-24 years live with human immunodeficiency virus (HIV), a majority of whom reside in sub-Saharan Africa (SSA). Youth living with HIV (YLHIV) generally maintain lower levels of antiretroviral therapy (ART) adherence compared to other age groups, which has negative impacts on long-term clinical outcomes. Given expanding mobile phone and Internet usage among youth in SSA, and a need for strategies to increase ART adherence, this review systematically assessed whether digital interventions could be used to improve YLHIV ART adherence in SSA. PRISMA 2020 guidelines were followed, and PubMed and Scopus databases were searched using terms to reflect the population of interest and different digital intervention strategies to improve ART adherence. Experimental or quasi-experimental studies in SSA evaluating the quantitative effect of digital interventions on YLHIV ART adherence were included. 3849 articles and abstracts, and 122 full texts were screened by two researchers (KG and RM). A third researcher (AC) resolved conflicts. Data were extracted from six eligible articles published between 2017 and 2021. Interventions from included studies lasted 13-96 weeks and took place in Kenya, Nigeria, Uganda, and Zimbabwe. Two of the six studies found significant intervention-related improvements in viral suppression. Of these two studies, one used short message service (SMS) for appointment and daily adherence reminders, and the other combined weekly SMS reminders with phone calls, support groups, home visits, and clinic-based counseling. The four remaining studies, using SMS and Internet-based interventions, did not find any significant adherence-related improvements. This review provides mixed evidence for using digital interventions to improve ART adherence among YLHIV in SSA. Given the relative novelty of using digital interventions in this context, further research is required to evaluate their effectiveness in improving youth ART adherence.

Factors associated with COVID-19 vaccine receipt at two integrated healthcare systems in New York City: a cross-sectional study of healthcare workers.

OBJECTIVES: To examine the factors associated with COVID-19 vaccine receipt among healthcare workers and the role of vaccine confidence in decisions to vaccinate, and to better understand concerns related to COVID-19 vaccination. DESIGN: Cross-sectional anonymous survey among front-line, support service and administrative healthcare workers. SETTING: Two large integrated healthcare systems (one private and one public) in New York City during the initial roll-out of the COVID-19 vaccine. PARTICIPANTS: 1933 healthcare workers, including nurses, physicians, allied health professionals, environmental services staff, researchers and administrative staff. PRIMARY OUTCOME MEASURES: The primary outcome was COVID-19 vaccine receipt during the initial roll-out of the vaccine among healthcare workers. RESULTS: Among 1933 healthcare workers who had been offered the vaccine, 81% had received the vaccine at the time of the survey. Receipt was lower among black (58%; OR: 0.14, 95% CI 0.1 to 0.2) compared with white (91%) healthcare workers, and higher among non-Hispanic (84%) compared with Hispanic (69%; OR: 2.37, 95% CI 1.8 to 3.1) healthcare workers. Among healthcare workers with concerns about COVID-19 vaccine safety, 65% received the vaccine. Among healthcare workers who agreed with the statement that the vaccine is important to protect family members, 86% were vaccinated. Of those who disagreed, 25% received the vaccine (p<0.001). In a multivariable analysis, concern about being experimented on (OR: 0.44, 95% CI 0.31 to 0.6), concern about COVID-19 vaccine safety (OR: 0.39, 95% CI 0.28 to 0.55), lack of influenza vaccine receipt (OR: 0.28, 95% CI 0.18 to 0.44), disagreeing that COVID-19 vaccination is important to protect others (OR: 0.37, 95% CI 0.27 to 0.52) and black race (OR: 0.38, 95% CI 0.24 to 0.59) were independently associated with COVID-19 vaccine non-receipt. Over 70% of all healthcare workers responded that they had been approached for vaccine advice multiple times by family, community members and patients. CONCLUSIONS: Our data demonstrated high overall receipt among healthcare workers. Even among healthcare workers with concerns about COVID-19 vaccine safety, side effects or being experimented on, over 50% received the vaccine. Attitudes around the importance of COVID-19 vaccination to protect others played a large role in healthcare workers' decisions to vaccinate. We observed striking inequities in COVID-19 vaccine receipt, particularly affecting black and Hispanic workers. Further research is urgently needed to address issues related to vaccine equity and uptake in the context of systemic racism and barriers to care. This is particularly important given the influence healthcare workers have in vaccine decision-making conversations in their communities.

Evaluating the performance of GIS methodologies for quantifying spatial accessibility to healthcare in Multi-Island Micro States (MIMS).

There has been limited information on spatial accessibility to healthcare in Multi-island Micro States (MIMS). This is partly due to the application of methodologies that do not sufficiently consider the dynamic or unique characteristics of MIMS. The objective of the paper is to evaluate the performance of different Geographic Information Systems (GIS) methodologies for quantifying spatial accessibility to public healthcare in Multi-island States (MIMS). Spatial accessibility was measured using three GIS-based methodologies: Temporally Available Two-Step Floating Catchment Area (TA2SFCA) and traditional models [Two-Step Floating Catchment Area (2SFCA) and the Gravity Model]. Unlike the Gravity Model and the 2SFCA which only used population and health facilities locations along with travel times to quantify spatial accessibility, the TA2SFCA also included information on the hours of operations and health schedules in its assessment. These additional variables were used to develop the time windows to assess differences in capacity among available service sites. TA2SFCA results showed that spatial accessibility was linked to a 'traveling doctor' dynamic with access to healthcare services reflecting changes in the supply of services. As such, the Gravity Model and 2SFCA which did not account for this peculiarity were inadequate for measuring spatial accessibility in MIMS. The TA2SFCA addressed both the temporal and spatial aspects of health which were most reflective of the health system of these islands. Given the spatial-temporal dynamics, improving accessibility to healthcare requires periodic assessments and reassessments of health service delivery since this is affected by operating times and changes in capacity. Furthermore, there is the need for more research to develop methodologies that are more reflective or sensitive to MIMS dynamics.

A systematic review of interventions to reduce HIV-related stigma among primary and secondary school teachers.

HIV/AIDS-related stigma (HIV stigma) affects every aspect of adolescents' HIV management. Adolescents living with HIV (ALWH) are particularly vulnerable in schools where they have described experiencing HIV stigma. Teachers play a significant role in their students' lives. Stigmatizing attitudes or behaviors by teachers not only impact ALWH directly, but may influence the attitudes and behaviors of their peers. There is a dearth of literature exploring interventions to address HIV stigma in school-based settings. The objective of this review is to examine interventions to reduce HIV stigma among teachers globally. To conduct this systematic review, we used the PRISMA guidelines. Two articles met the inclusion criteria. Both eligible studies aimed to reduce HIV stigma among teachers or teachers in training through teacher training interventions in sub-Saharan Africa. The interventions included an interactive CD-ROM, a 2-day workshop, and peer facilitated workshops. Both studies demonstrated a significant decrease in HIV stigma in at least one study measure. Findings from this review are inconclusive. There is evidence to suggest that interventions can successfully decrease HIV stigma among teachers, but it is very limited. More research is needed in order to develop, implement, and evaluate stigma reducing interventions in the classroom.

Social Stigma Related to COVID-19 Disease Described by Primary and Secondary School Teachers and Adolescents Living With HIV in Western Kenya.

Introduction: Understanding community members' knowledge, attitudes, and beliefs about the novel SARS-CoV-2 virus and the prevalence of associated stigma are critical steps for increasing accurate public health knowledge, encouraging uptake of preventative or mitigating health behaviors, and ultimately bringing the COVID-19 pandemic under control. Methods: We conducted a one-time, phone-based assessment to assess the presence of perceived COVID-19 community stigma reported by Kenyan primary and secondary school teachers, as well as adolescents living with HIV. Participants were previously enrolled in an ongoing, cluster-randomized trial to evaluate the impact of multi-media teacher training on teachers' negative attitudes and beliefs around HIV. The SAFI Stigma Questionnaire, a validated tool to assess HIV-related stigma in this setting, was adapted to ask questions regarding the stigma and discrimination experienced or perceived during the COVID-19 pandemic. Results: We enrolled 330 participants in this study, including 311 primary and secondary teachers (56% female, average age 36 years) and 19 adolescents living with HIV (57.89% female, average age 16.37 years). None of the adolescent participants reported witnessing or experiencing discrimination related to COVID-19, nor did they report losing financial and/or social support. In contrast, the teacher participants reported prominent social stigma experiences of various levels and related to COVID-19. Teachers in the intervention group, who had completed the multi-media training on HIV-related stigma, were significantly less likely to think that the community viewed COVID-19 as a dirty or shameful disease, and less likely to feel it was important to keep their COVID-19 infection a secret, compared to the teacher control group. Conclusion: These findings suggest that COVID-19-related stigma may be prevalent in western Kenya and that interventions to reduce community-level stigma for HIV may also have a protective impact on other stigmatized infectious diseases such as COVID-19.

HIV-Related Knowledge, Attitudes, Behaviors and Experiences of Kenyan Adolescents Living with HIV Revealed in WhatsApp Group Chats.

INTRODUCTION: Mobile technologies represent a scalable platform for delivering knowledge and interventions targeting adolescents living with HIV (ALWH) in low and middle income countries. Data from mobile interventions can be used to assess the contextual understanding and experiences of ALWH. METHODS: We examined HIV-related knowledge, attitudes, beliefs, behaviors, and experiences of Kenyan ALWH revealed in the contextual data from enrollment in a WhatsApp® group chat intervention. RESULTS: Thirty ALWH (17 female, mean age 15.4) on ART, engaged in HIV care and aware of their status, were enrolled. Qualitative analysis of WhatsApp® chat discussions identified a gap in HIV knowledge, high medication-taking literacy, need for mental health support and significant barriers to adherence. Participants discussed challenges with HIV stigma and medication-taking in the school setting. CONCLUSION: These discussions demonstrate a need for education on HIV topics, mental health support for ALWH, and interventions for stigma mitigation in the school setting.

A double-blind, randomized controlled trial to explore oral tranexamic acid as adjunct for the treatment for postpartum hemorrhage.

BACKGROUND: Oral tranexamic acid (TXA), if effective in reducing blood loss after delivery for women experiencing primary PPH, could be administered where parenteral administration is not feasible. This trial assessed the efficacy, safety, and acceptability of oral TXA when used as an adjunct to sublingual misoprostol to treat postpartum hemorrhage (PPH) following vaginal delivery. METHODS: From October 2016 to January 2018, women presenting at four hospitals in Senegal and Vietnam for vaginal delivery were screened for enrollment in the trial. Women diagnosed with postpartum hemorrhage (defined as blood loss ≥700 ml) were randomized to receive either oral TXA (1950 mg) or placebo in addition to 800 mcg sublingual misoprostol. Postpartum blood loss was measured using a calibrated drape. Blood loss for all PPH cases was recorded for 2 h after administration of the drugs. The primary outcome measure was the proportion of women with bleeding controlled with the trial regimen without recourse to further treatment. Secondary outcomes including the rate of severe PPH, mean/median blood loss, use of additional uterotonics and/or interventions side effects, and acceptability were also recorded. RESULTS: Of the 258 women who received treatment for PPH, 128 received placebo and misoprostol and 130 received TXA and misoprostol. The proportion of women who had active bleeding controlled with trial drugs alone and no additional interventions was similar in both groups: 77(60.2%) placebo; 74 (56.9%) TXA, p = 0.59). Use of other interventions to control bleeding, including uterotonics, did not differ significantly between groups. Median blood loss at PPH diagnosis was 700 ml in both groups. Uterine atony alone or in addition to another cause contributed to over 90% of PPH cases reported (92.2% placebo vs. 91.5% TXA), other causes included perineal and cervical lacerations and retained placenta. Reports of side effects and acceptability were similar in the two groups. CONCLUSION: Adjunct use of oral TXA with misoprostol to treat PPH resulted in similar clinical and acceptability outcomes when compared to treatment with misoprostol alone. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov, number NCT02805426. Registered on 3 September 2016.

High fever after sublingual administration of misoprostol for treatment of post-partum haemorrhage: a hospital-based, prospective observational study in Argentina.

OBJECTIVE: To characterise the occurrence of fever (≥38.0°C) after treatment for post-partum haemorrhage (PPH) with sublingual misoprostol 800 mcg in Latin America, where elevated rates of misoprostol's thermoregulatory effects and recipients' increased susceptibility to high fever have been documented. METHODS: A prospective observational study in hospitals in Argentina enrolled consenting women with atonic PPH after vaginal delivery, eligible to receive misoprostol. Corporal temperature was assessed at 30, 60, 90 and 120 min post-treatment; other effects were recorded. The incidence of high fever ≥ 40.0°C (primary outcome) was compared to the rate observed previously in Ecuador. Logistic regressions were performed to identify clinical and population-based predictors of misoprostol-induced fever. RESULTS: Transient shivering and fever were experienced by 75.5% (37/49) of treated participants and described as acceptable by three-quarters of women interviewed (35/47). The high fever rate was 12.2% (6/49), [95% Confidence Interval (CI) 4.6, 24.8], compared to Ecuador's rate following misoprostol treatment (35.6% (58/163) [95% CI 28.3, 43.5], P = 0.002). Significant predictors of misoprostol-induced fever (model dependent) were as follows: pre-delivery haemoglobin < 11.0g/dl, rapid placental expulsion, and higher age of the woman. No serious outcomes were reported prior to discharge. CONCLUSIONS: Misoprostol to treat PPH in Argentina resulted in a significantly lower rate of high fever than in Ecuador, although both are notably higher than rates seen elsewhere. A greater understanding of misoprostol's side effects and factors involved in their occurrence, including genetics, will help alleviate concerns. The onset of shivering may be the simplest way to know if fever can also be expected.

OBJECTIF: Caractériser la survenue de fièvre (≥ 38,0°C) après traitement d'une hémorragie post-partum (HPP) avec du misoprostol sublingual à 800 mcg en Amérique latine, où des taux élevés d'effets thermorégulateurs du misoprostol et une sensibilité accrue des receveurs à une forte fièvre ont été documentés. MÉTHODES: Une étude observationnelle prospective dans des hôpitaux en Argentine a recruté des femmes consentantes atteintes d'HPP atonique après un accouchement vaginal éligibles pour recevoir du misoprostol. La température corporelle a été évaluée 30, 60, 90 et 120 minutes après le traitement; d'autres effets ont été enregistrés. L'incidence d'une fièvre élevée ≥40,0°C (critère principal) a été comparée au taux observé précédemment en Equateur. Des régressions logistiques ont été effectuées pour identifier les prédicteurs cliniques et ceux basés sur la population de la fièvre induite par le misoprostol . RÉSULTATS: Des frissons transitoires et de la fièvre ont été ressentis par 75% (37/49) des participantes traitées et décrits comme acceptables par les trois quarts des femmes interrogées (35/47). Le taux de fièvre élevé était de 12% (6/49), [intervalle de confiance (IC) à 95%: 4,6, 24,8] contre 35,6% en Equateur après traitement au misoprostol (58/163) [IC95%: 28,3, 43,5], p = 0,002). Les prédicteurs significatifs de la fièvre induite par le misoprostol (selon le modèle) étaient: hémoglobine avant l'accouchement <11,0 g/dL, expulsion placentaire rapide et âge plus élevé de la femme. Aucun résultat sévère n'a été signalé avant le sortie d'hôpital. CONCLUSIONS: Le misoprostol pour traiter l'HPP en Argentine a entraîné un taux de fièvre élevée significativement plus bas qu'en Equateur, bien que les taux dans les deux pays soient notablement plus élevés que les taux observés ailleurs. Une meilleure compréhension des effets secondaires du misoprostol et des facteurs impliqués dans leur apparition, y compris la génétique, aidera à atténuer les inquiétudes. L'apparition de frissons peut être le moyen le plus simple de savoir si l'on peut également s'attendre à de la fièvre.

Does route matter? Impact of route of oxytocin administration on postpartum bleeding: A double-blind, randomized controlled trial.

OBJECTIVE: We assessed the impact of intravenous (IV) infusion versus intramuscular (IM) oxytocin on postpartum blood loss and rates of postpartum hemorrhage (PPH) when administered during the third stage of labor. While oxytocin is recommended for prevention of PPH, few double-blind studies have compared outcomes by routes of administration. METHODS: A double-blind, placebo-controlled randomized trial was conducted at a hospital in Argentina. Participants were assigned to receive 10 IU oxytocin via IV infusion or IM injection and a matching saline ampoule for the other route after vaginal birth. Blood loss was measured using a calibrated receptacle for a 1-hour minimum. Shock index (SI) was also calculated, based on vital signs measurements, and additional interventions were recorded. Primary outcomes included: the frequency of blood loss ≥500ml and mean blood loss. RESULTS: 239 (IV infusion) and 241 (IM) women were enrolled with comparable baseline characteristics. Mean blood loss was 43ml less in the IV infusion group (p = 0.161). Rates of blood loss ≥500ml were similar (IV infusion = 21%; IM = 24%, p = 0.362). Women in the IV infusion group received significantly fewer additional uterotonics (5%), than women in the IM group (12%, p = 0.007). Women with PPH in the IM group experienced a larger increase in SI after delivery, which may have influenced recourse to additional interventions. CONCLUSIONS: The route of oxytocin administration for PPH prevention did not significantly impact measured blood loss after vaginal birth. However, differences were observed in recourse to additional uterotonics, favoring IV infusion over IM. In settings where IV lines are routinely placed, oxytocin infusion may be preferable to IM injection.

Austerity, and funding cuts: Implications for sustainability of the response to the Caribbean HIV/AIDS epidemic.

The Caribbean, accessed significant external funding over the first three decades of the epidemic, which provided local authorities the opportunity to defer their responsibility in leading or matching the support provided from the external agencies. The reduction in external support has placed increased pressure on the response to the epidemic, with some countries more likely to be affected than others. This paper undertakes a review of the expenditure and funding landscape for HIV programs in the Caribbean. The findings confirm that despite the dwindling number of funding sources, some countries continue to display a significant degree of dependency on external funding sources. It is noteworthy that Treatment and Care accounted for the largest share of HIV expenditure in those countries, which displayed the highest degree of dependency on external funding. While, HIV spending was a relatively small percentage of both total health expenditure and gross domestic product, expenditure levels were noticeably higher in Haiti. These averages however conceal significant differences across countries, which should inform the magnitude and direction of any spending expansion by these countries if they are to achieve financial sustainability. Some recommendations are provided on the way forward to facilitate building a sustainable response to the epidemic.

Early abortion with buccal versus sublingual misoprostol alone: a multicenter, randomized trial.

OBJECTIVE: To compare efficacy, safety/side effects and acceptability of buccal versus sublingual administration of a misoprostol-only regimen commonly used for early medical abortion. STUDY DESIGN: We conducted a randomized trial at six clinics in two Latin American countries. We randomized women seeking early abortion to buccal or sublingual administration of three doses of misoprostol 800 mcg repeated every 3 h. At initial follow-up (7-14 days after misoprostol), we offered women without a complete abortion aspiration or additional misoprostol plus waiting 7 more days. The primary outcome was continuing pregnancy at initial follow-up. Secondary outcomes included continuing pregnancy at final follow-up, incomplete abortion, successful abortion, side effects, acceptability and complications. We analyzed all outcomes as intention to treat. RESULTS: We enrolled 401 women and randomized 202 into the buccal arm and 199 into the sublingual arm. Continuing pregnancy at initial follow-up occurred in 11/201 (5.5%) and 2/189 (1.1%) women, respectively (p=.02). Additional misoprostol at follow-up increased success, defined as complete abortion, from 170/201 (84.6%) to 184/199 (92.5%) in the buccal arm and 165/189 (87.3%) to 177/189 (93.7%) in the sublingual arm. We found no differences by gestational age. Women reported similar acceptability and side effects across groups except for chills and fever, which women using sublingual misoprostol reported more frequently (p<.05). CONCLUSIONS: Sublingual administration was superior to buccal administration in reducing continuing pregnancy risk after a three-dose regimen of 800 mcg misoprostol. Complete abortion rates were comparable across groups, and in both cases, additional misoprostol at follow-up increased success. IMPLICATIONS: If the primary goal is to avoid continuing pregnancy, sublingual administration of misoprostol 800 mcg every 3 h for three doses should be recommended. If chills or fever are a concern and the primary goal is to avoid surgery, buccal administration may be preferable. For either route, additional misoprostol can be given for incomplete abortion or continuing pregnancy.

Simultaneous Administration Compared With a 24-Hour Mifepristone-Misoprostol Interval in Second-Trimester Abortion: A Randomized Controlled Trial.

OBJECTIVE: To compare outcomes with simultaneous administration of mifepristone and misoprostol with a regimen in which the drugs are administered at a 24-hour interval for second-trimester abortion. METHODS: In this placebo-controlled, double-blind trial, participants were randomized to receive mifepristone either 24 hours before or at the same time as misoprostol. Participants were hospitalized to receive 400 micrograms buccal misoprostol at 3-hour intervals up to 48 hours or until uterine expulsion. The primary outcome was the proportion of women who experienced uterine expulsion within 24 hours after the first misoprostol dose and this required 504 women to examine our hypothesis that this rate would be 85% in the 24-hour interval arm compared with 70% in the simultaneous arm. Secondary outcomes included total abortion time from mifepristone and misoprostol. RESULTS: From February 2013 to April 2014, 509 women were enrolled. Women in the 24-hour interval arm were more likely to abort within 24 hours (94.4% compared with 85.0%, relative risk 1.11, 95% confidence interval [CI] 1.05-1.18). At 48 hours, the rate was similar in the two arms (96.8% [24-hour interval] and 95.7% [simultaneous], relative risk 1.01, 95% CI 0.97-1.04). Median misoprostol dosing time was shorter in the 24-hour interval arm (7.7 compared with 13 hours; P<.001) and consistent with the median misoprostol doses required (three compared with five; P<.001). Median time from mifepristone to uterine expulsion was longer in the 24-hour interval arm (32.3 compared with 13 hours; P<.001). Both regimens had high acceptability rates and reported similar side effects and pain scores. CONCLUSION: Administering mifepristone and misoprostol simultaneously results in lower expulsion rates within 24 hours of taking misoprostol, longer median misoprostol treatment times, and requires more misoprostol doses. At 48 hours, both regimens work equally well. Simultaneous dosing results in less total time from the first clinical contact to complete abortion. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01768299.

Randomized trial assessing home use of two pregnancy tests for determining early medical abortion outcomes at 3, 7 and 14days after mifepristone.

OBJECTIVE: To evaluate the accuracy, feasibility and acceptability of two urine pregnancy tests in assessing abortion outcomes at three time points after mifepristone administration. STUDY DESIGN: This randomized trial enrolled women seeking early medical abortion at two hospitals in Vietnam. Investigators randomly allocated participants to at-home administration of a multilevel urine pregnancy test (MLPT) or a high sensitivity urine pregnancy test (HSPT) to assess their abortion outcomes. A baseline test was administered on the same day as mifepristone. Participants performed and interpreted results of pregnancy tests taken 3, 7 and 14days after mifepristone. Ultrasound exam determined continuing pregnancy. RESULTS: Six hundred women enrolled, and 300 received each test. A percentage of 97.4 (584) had follow-up, of whom 13 women had continuing pregnancies. The specificity of MLPT at detecting absence of continuing pregnancy was 63.9%, 90.4% and 97.1% at study day 3, 7 and 14. The specificity of HSPT was 6.0%, 19.8% and 62.2%, respectively. The positive predictive value (PPV) of MLPT at detecting continuing pregnancy was 6.4% at day 3 and rose to 46.7% at day 14. In contrast, the PPV for HSPT was 2.2% at day 3 and rose to 6.5% at day 14. At all three time points, the sensitivity and negative predictive values for both tests were 100.0%. Most women found their assigned tests easy to use and would prefer future home follow-up with a pregnancy test. CONCLUSIONS: The MLPT enables women to assess their abortion outcomes more reliably than with HSPT. With MLPT, women can know their outcomes as early as 3 days after mifepristone. IMPLICATIONS: Medical abortion service delivery with an MLPT to obtain a baseline (preabortion) human chorionic gonadotropin (hCG) estimate and a second follow-up MLPT 1 to 2 weeks later can establish whether there has been a drop in hCG, signifying absence of a continuing pregnancy. Used this way, MLPTs can enable women to assess their abortion status outside of a clinic setting and without serum hCG testing and/or ultrasound.

Additional evidence for the involvement of the basal ganglia in formalin-induced nociception: the role of the nucleus accumbens.

Identification of the brain areas that contribute to pain is an essential undertaking towards understanding persistent pain. Areas of the basal ganglia have been proposed to play important roles in nociception as previous studies have determined the involvement of the substantia nigra pars compacta and the dorsolateral striatum in pain. The purpose of the present study was therefore to expand upon these findings by determining the involvement of other areas of the basal ganglia such as the nucleus accumbens shell and core in formalin-induced nociception. It was found that injection of a local anaesthetic (bupivacaine) into the nucleus accumbens shell had no effect on formalin-induced nociception. However, injection into the nucleus accumbens core enhanced formalin-induced nociception. These results implicate the nucleus accumbens in the processing of pain and provide additional evidence for the involvement of the basal ganglia and possibly dopamine in pain.