Tisagenlecleucel, a chimeric antigen receptor (CAR) T-cell product targeting CD19 is approved for relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, the impact of pretreatment variables, such as CD19 expression level, on leukemic blasts, the presence of CD19^– subpopulations, and especially prior CD19-targeted therapy, on the response to CAR T-cell therapy has not been determined. We analyzed 166 patients treated with CAR T-cell therapy at our institution. Eleven patients did not achieve a minimal residual disease (MRD)^– deep remission, whereas 67 patients had a recurrence after achieving a MRD^– deep remission: 28 patients with CD19⁺ leukemia and 39 patients with CD19^– leukemia. Return of CD19⁺ leukemia was associated with loss of CAR T-cell function, whereas CD19^– leukemia was associated with continued CAR T-cell function. There were no significant differences in efficacy of CAR T cells in CD19-dim B-ALL, compared with CD19-normal or -bright B-ALL. Consistent with this, CAR T cells recognized and lysed cells with very low levels of CD19 expression in vitro. The presence of dim CD19 or rare CD19^– events by flow cytometry did not predict nonresponse or recurrence after CAR T-cell therapy. However, prior therapy with the CD19-directed, bispecific T-cell engager blinatumomab was associated with a significantly higher rate of failure to achieve MRD^– remission or subsequent loss of remission with antigen escape. Finally, immunophenotypic heterogeneity and lineage plasticity were independent of underlying clonotype and cytogenetic abnormalities.

The ‘continuum of care’ is proposed as a key framework for the delivery of maternal, neonatal and child health services. This study examined the extent of dropout as well as factors associated with retention across the MNCH continuum from antenatal care (ANC), through skilled birth attendance (SBA), to postnatal care (PNC). We analyzed data from 1931 women who delivered in the preceding 2–14 months, from a two-stage cluster sampling household survey in four districts of Tanzania’s Morogoro region. The survey was conducted in 2011 as a part of a baseline for an independent evaluation of a maternal health program. Using the Anderson model of health care seeking, we fitted logistic models for three transition stages in the continuum. Only 10% of women received the ‘recommended’ care package (4+ ANC visits, SBA, and 1+ PNC visit), while 1% reported not having care at any stage. Receipt of four ANC visits was positively associated with women being older in age (age 20–34 years—OR: 1.77, 95%CI: 1.22–2.56; age 35–49 years—2.03, 1.29–3.2), and knowledge of danger signs (1.75, 1.39 –2.1). A pro-rich bias was observed in facility-based deliveries (proxy for SBA), with women from the fourth (1.66, 1.12–2.47) and highest quintiles of household wealth (3.4, 2.04–5.66) and the top tertile of communities by wealth (2.9, 1.14–7.4). Higher rates of facility deliveries were also reported with antenatal complications (1.37, 1.05–1.79), and 4+ ANC visits (1.55, 1.14–2.09). Returning for PNC was highest among the wealthiest communities (2.25, 1.21–4.44); catchment areas of a new PNC program (1.89, 1.03–3.45); knowledge of danger signs (1.78, 1.13–2.83); community health worker counselling (4.22, 1.97–9.05); complicated delivery (3.25, 1.84–5.73); and previous health provider counselling on family planning (2.39, 1.71–3.35). Dropout from maternal care continuum is high, especially for the poorest, in rural Tanzania. Interactions with formal health system and perceived need for future services appear to be important factors for retention.

Postnatal care (PNC) for the mother and infant is a neglected area, even for women who give birth in a health facility. Currently, there is very little evidence on the determinants of use of postnatal care from health facilities in Tanzania. This study examined the role of individual and community-level variables on the use of postnatal health services, defined as a check up from a heath facility within 42 days of delivery, using multilevel logistic regression analysis. We analyzed data of 1931 women, who had delivered in the preceding 2–14 months, from a two-stage household survey in 4 rural districts of Morogoro region, Tanzania. Individual level explanatory variables included i) Socio-demographic factors: age, birth order, education, and wealth, ii) Factors related to pregnancy: frequency of antenatal visits, history of complications, mode of delivery, place of delivery care, and counseling received. Community level variables included community levels of family planning, health service utilization, trust, poverty and education, and distance to health facility. Less than one in four women in Morogoro reported having visited a health facility for postnatal care. Individual-level attributes positively associated with postnatal care use were women’s education of primary level or higher [Odds Ratio (OR) 1.37, 95 % Confidence Interval (CI) 1.04–1.81], having had a caesarean section or forceps delivery (2.95, 1.8–4.81), and being counseled by a community health worker to go for postnatal care at a health facility (2.3, 1.36–3.89). Other positive associations included those recommended HIV testing for baby (1.94, 1.19–3.15), and whose partners tested for HIV (1.41, 1.07–1.86). High community levels of postpartum family planning usage (2.48, 1.15–5.37) and high level of trust in health system (1.77, 1.12–2.79) were two significant community-level predictors. Lower postnatal care use was associated with having delivered at a hospital (0.5, 0.33–0.76), health center (0.57, 0.38–0.85), or dispensary (0.48, 0.33–0.69), and having had severe swelling of face and legs during pregnancy (0.65, 0.43–0.97). In the context of low postnatal care use in a rural setting, programs should direct efforts towards reaching women who do not avail themselves of postnatal care as identified in our study.

Despite the growing use of technology in the health sector, little evidence is available on the technological performance of mobile health programs nor on the willingness of target users to utilize these technologies as intended (behavioral performance). In this case study of the Mobile Technology for Health (MOTECH) program in Ghana, we assess the platform’s effectiveness in delivering messages, along with user response across sites in five districts from 2011 to 2014. MOTECH is comprised of “Client Data Application" (CDA) which allows providers to digitize and track service delivery information for women and infants and “Mobile Midwife” (MM) which sends automated educational voice messages to the mobile phones of pregnant and postpartum women. Using a naturalist study design, we draw upon system generated data to evaluate message delivery, client engagement, and provider responsiveness to MOTECH over time and by level of facility. A total of 7,370 women were enrolled in MM during pregnancy and 14,867 women were enrolled postpa1rtum. While providers were able to register and upload patient-level health information using CDA, the majority of these uploads occurred in Community-based facilities versus Health Centers. For MM, 25% or less of expected messages were received by pregnant women, despite the majority (>77%) owning a private mobile phone. While over 80% of messages received by pregnant women were listened to, postpartum rates of listening declined over time. Only 25% of pregnant women received and listened to at least 1 first trimester message. By 6–12 months postpartum, less than 6% of enrolled women were exposed to at least one message. Caution should be exercised in assuming that digital health programs perform as intended. Evaluations should measure the technological, behavioral, health systems, and/or community factors which may lead to breaks in the impact pathway and influence findings on effectiveness. The MOTECH platform’s technological limitations in ‘pushing’ out voice messages highlights the need for more timely use of data to mitigate delivery challenges and improve exposure to health information. Alternative message delivery channels (USSD or SMS) could improve the platform’s ability to deliver messages but may not be appropriate for illiterate users. Not applicable.

Background: Digital technologies may improve sexual and reproductive health (SRH) across diverse settings. Chatbots are computer programs designed to simulate human conversation, and there is a growing interest in the potential for chatbots to provide responsive and accurate information, counseling, linkages to products and services, or a companion on an SRH journey. Objective: This review aimed to identify assumptions about the value of chatbots for SRH and collate the evidence to support them. Methods: We used a realist approach that starts with an initial program theory and generates causal explanations in the form of context, mechanism, and outcome configurations to test and develop that theory. We generated our program theory, drawing on the expertise of the research team, and then searched the literature to add depth and develop this theory with evidence. Results: The evidence supports our program theory, which suggests that chatbots are a promising intervention for SRH information and service delivery. This is because chatbots offer anonymous and nonjudgmental interactions that encourage disclosure of personal information, provide complex information in a responsive and conversational tone that increases understanding, link to SRH conversations within web-based and offline social networks, provide immediate support or service provision 24/7 by automating some tasks, and provide the potential to develop long-term relationships with users who return over time. However, chatbots may be less valuable where people find any conversation about SRH (even with a chatbot) stigmatizing, for those who lack confidential access to digital devices, where conversations do not feel natural, and where chatbots are developed as stand-alone interventions without reference to service contexts. Conclusions: Chatbots in SRH could be developed further to automate simple tasks and support service delivery. They should prioritize achieving an authentic conversational tone, which could be developed to facilitate content sharing in social networks, should support long-term relationship building with their users, and should be integrated into wider service networks.

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: Mobile technologies are emerging as tools to enhance health service delivery systems and empower clients to improve maternal, newborn and child health. Limited evidence exists on the value for money of mobile health programs in low and middle income countries. Objective: This study aims to forecast the incremental cost effectiveness of the Mobile Technology for Community Health (MOTECH) initiative at scale across 170 districts in Ghana. Methods: MOTECH’s “Client Data Application" allows frontline health workers to digitize service delivery information and track care for patients. MOTECH’s other main component, the “Mobile Midwife”, sends automated educational voice messages to mobile phones of pregnant and postpartum women. We measured program costs and consequences of scaling up MOTECH over a 10-year analytic time horizon. Economic costs were estimated from informant interviews and financial records. Health effects were modeled using the Lives Saved Tool with data from an independent evaluation of changes in key services coverage observed in Gomoa West. Incremental cost effectiveness ratios are presented overall and for each year of implementation. Uncertainty analyses assessed the robustness of results to changes in key parameters. Results: MOTECH was scaled in clusters over a 3-year period to reach 170 (78%) of Ghana’s 216 districts. Sustaining the program would cost $17,618 on average annually per district. Over 10-years, MOTECH could potentially save an estimated 59,906 lives at total cost of $32 million. The incremental cost per DALY averted ranged from $174 in year 1 to $6.54 in the 10th year of implementation, and $20.94 (95% CI: $20.34-$21.55) over 10 years. Uncertainty analyses suggest that the ICER is most sensitive to changes in health effects, followed by personnel time. Probabilistic sensitivity analyses suggest that MOTECH has a 100% probability of being cost effective above a willingness to pay threshold of USD $50. Conclusions: This is the first study to estimate the value for money of a supply- and demand-side mobile health initiative. The adoption of MOTECH to improve MNCH service delivery and uptake represents good value for money in Ghana and should be considered for expansion. Integration with other mobile health solutions, including eTracker, may provide opportunities to continue or combine beneficial components of MOTECH to achieve greater impact for health. Clinical Trial: Not applicable