Increasing access to thrombolysis and thrombectomy through improved pathway organisation remains a health service challenge that requires contextualisation to the geographic, demographic and resourcing status of any regional stroke service. Pre-hospital delays or delays during inter-hospital transfers can result in patients being outside the window for one or both interventions. Pre-hospital triage using technology-enabled interdisciplinary communication networks may facilitate rapid individualized care decisions, permitting streamlined care pathways to hospital sites most appropriate to their clinical presentation and history in the first instance. Understanding the experience of those involved in efforts to improve or reorganise care may help to explain the impact observed.1. To review the impact of pre-hospital telemedicine enabled workflow intervention strategies on patient outcomes and on service process metrics in hyper-acute stroke care2. To examine how the experience of those involved in providing or receiving such interventions might identify key characteristics of effective interventionsQuantitative, qualitative and primary mixed methods studies will be included. Quantitative studies will assess effectiveness of telemedicine-enabled interventions that facilitate pre-hospital acute stroke triage. Intervention effects on functional outcomes of patients, on intervention rates and on key time metrics in hyperacute stroke care will be assessed. Qualitative studies will explore the experiences of people involved in or impacted by these interventions.A convergent segregated mixed methods systematic review will synthesise and integrate primary qualitative, quantitative and mixed methods studies using the Joanna Briggs Institute methodology. Database searches will include OVID (MEDLINE), EMBASE, The Cochrane Library, CINAHL and Web of Science. Critical appraisal will include the Mixed Methods Assessment Tool. Results of quantitative studies and findings of qualitative studies will be integrated and configured to explore and contextualize each single method synthesis.This protocol has been submitted for registration with PROSPERO. Parallel improvements in telecommunications infrastructure and reliability, with increasing evidence for highly effective interventions for hyperacute stroke care, have led clinicians and researchers to consider information and communications technology (ICT) based approaches to address treatment delays in the provision of acute stroke care. Telemedicine is defined by the World Health Organisation as “the provision of healthcare services at a distance with communication conducted between healthcare providers seeking clinical guidance and support from other healthcare providers (provider-to-provider telemedicine); or conducted between remote healthcare users seeking health services and healthcare providers (client-to-provider telemedicine)”. Applying ICT solutions to health system challenges offers potential ways to maximise access to limited human and infrastructure resources. Telemedicine has been shown to reduce death and dependency when applied to stroke unit care. Understanding the role of telemedicine systems in acute stroke care is a research priority outlined in The Stroke Action Plan for Europe 2018–2030 (SAP-E). However, while ICT solutions can act as a platform to enable improved human performance they do not replace it. Telemedicine solutions hinge on human factors to maximise their effectiveness including buy-in for piloting and implementation.Intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT) are time-dependent revascularisation treatments used in the very early (<24 hours since symptom onset) phase of acute stroke that can result in significantly improved patient outcomes, with greatest effect achieved the earlier they are delivered“human behavior and organizational inertia, infrastructure and resource constraints, and the messiness of proving the effectiveness of “moving targets” under conditions that investigators cannot fully control”. This review will address these challenges by using a mixed methods approach to understanding the experiential aspects involved in effective telemedicine interventions used in the hyperacute stroke care context.To understand the challenges of systems change we can learn from translational research which acknowledges that human behaviour takes place in complex social situations and that knowledge and intention do not necessarily result in predictable, expected or presumed behaviour. Woolf described how Type 2 translational research is concerned with. This review seeks to synthesise the existing evidence from both quantitative and qualitative research paradigms to identify effective telecommunications strategies for patient triage in the pre-hospital phase of acute stroke, and to identify and understand key characteristics of effective strategies through the experiences of participants.Quantitative studies such as randomized control trials give us reliable evidence of effect but do not explain context – the why, the where and for whom an intervention is effective. Qualitative research can offer insights into how those involved in or affected by an intervention or system change experience or perceive it, including potentially unintended or unforeseen impacts or consequences. Mixed methods review approaches have been used to better understand the impact of interventions aimed at improving outcomes in chronic disease managementTo summarise and synthesise existing qualitative and quantitative evidence of the impact of telemedicine on key patient and service level outcomes in acute stroke, when used to facilitate patient triage in the pre-hospital setting, and to understand how human factors impact on these complex health system interventions in the acute stroke pathway.Quantitative: What is the impact of pre-hospital telemedicine enabled triage on functional outcomes of patients experiencing acute stroke, and on key time metrics reflective of quality in hyperacute stroke care?Qualitative: How do the experiences and perspectives of end users of telemedicine-based interventions help explain the effectiveness, acceptability and feasibility of such interventions?.A convergent segregated mixed method systematic review (MMSR) will be conducted in line with the Joanna Briggs Institute (JBI) methodology. The protocol has been submitted for prospective registration on the international database for systematic reviews, PROSPERO. This protocol establishes a priori the authors’ intentions for this MMSR.This protocol has been guided using the PRISMA-P checklist.The writing and reporting of the review will be guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 statement and the Enhancing Transparency in Reporting the Synthesis of Qualitative research (ENTREQ) guidelinesThis mixed method systematic review (MMSR) will include quantitative, qualitative and mixed method studies.Study design: This mixed method systematic review will assess telemedicine enabled communication strategies or networks that facilitate and support pre-hospital decision making on the most appropriate patient disposition or routing (primary stroke centre or comprehensive stroke centre) of patients experiencing acute stroke when compared to usual care. Usual care is defined as undifferentiated transportation of patients to their local hospital.Primary quantitative studies will include randomised controlled trials (RCTs), non-randomised controlled trails (NRCTs), controlled before-after studies (CBA) and interrupted time series and repeated measures studies (ITS). We will also include retrospective or prospective observational cohort studies.Qualitative studies will include any primary research study that uses recognised methodologies for data collection and analysis. Data collection techniques may include interviews, focus group discussions or surveys, while standard accepted qualitative analysis and synthesis methods such as narrative, thematic or framework approaches may be included. Feasibility studies or process evaluations that include formal qualitative methodology for data collection and analysis will also be included.Primary mixed methods studies which permit disaggregation and analysis of quantitative and qualitative data separately will be included. If the quantitative or qualitative component of any primary mixed methods study does not meet the pre-established criteria above then only the study component  meeting the criteria will be included with the second study component data excluded at the full text screening step.Using the following population, intervention, comparison and outcome (PICO) elements for quantitative studies or quantitative components of mixed methods studies we will identify studies meeting our inclusion criteria:Population: The target study population will be adults ≥ 18yrs with suspected acute stroke <24hrs since symptom onset, unknown time of symptom onset or wake-up stroke (WUS). .Intervention: The quantitative component of this review will consider studies that examine the use of telemedicine-enabled interventions for patient triage in the pre-hospital setting of acute stroke care. Such interventions should aim to facilitate rapid communication, decision making and triage of patients to the most appropriate destination stroke centre (PSC or CSC) potentially bypassing the geographically nearest hospital, in order to take a person directly to a stroke centre deemed most suitable to their clinical presentation.Telemedicine in this context may comprise: telephone communications between the pre-hospital and hospital setting that also include a formal objective clinical assessment tool; televisual or tele-audio-visual communications including smartphone applications or other remote Wi-Fi-enabled communication links to hardware on board an ambulance to the hospital-based team; Mobile Stroke Units (MSU). . Included studies may focus on IVT, EVT or both. Any transportation mode will be considered. Pilot studies that meet the inclusion criteria will be included. This review is focused on pre-hospital tele-triage and so will not include studies that use telemedicine to facilitate remote hospital-based clinical assessment (hub-and-spoke models) or to facilitate inter-hospital transfer decisions between a PSC and CSC (drip-and-ship models).It is acknowledged that some studies will include results for all patients evaluated by a triage intervention while other studies will report results only of patients receiving treatment for acute ischaemic stroke , some of whom will include stroke mimics. If a study does not report its rate of treatment of mimics, authors will be contacted for more specific treatment metrics related to mimics. If additional information on the treatment rate of mimics is not available this will be highlighted and the study excluded where deemed appropriate.Comparison: The quantitative component of the review will consider studies that compare the intervention to the immediate transportation of a patient with stroke or stroke-like symptoms to the nearest hospital without pre-hospital differentiation or triage . Historical controls will be accepted. A control group must be present for any quantitative study to be included.Outcomes: The quantitative component of this review will consider studies that include the following outcome measures: the primary patient-centred outcome will be assessment of functional ability at 90 days using the Modified Rankin Scale (mRS). Safety will be assessed using the 90-day mortality rate.Secondary quantitative outcomes will be considered at a health service level, where available, to include the key time metrics, proportions of people receiving IVT and additional clinical impacts. The following outcomes will be considered: symptom onset to hospital (door) time; onset to decision time thrombolysis (IVT); onset to decision time endovascular thrombectomy (EVT); onset to treatment time (“onset to needle” for (IVT) and “onset to puncture” for (EVT)); alarm to treatment times; door to first imaging time; overall rates of interventions (IVT and EVT); rates of interventions <60 minutes from symptom onset; time to first contact with CSC; NIHSS at 24 hours; rate of symptomatic intracranial haemorrhage at <1 week; proportion of stroke mimics treated with IVT; hospital length of stay; ambulance usage time. Additionally, depression, cognition and quality of life at 90 days will be assessed where recorded.Using the following Population, Phenomenon, Context (PICo) for qualitative studies, or the qualitative components of mixed methods studies, we will identify studies meeting the following inclusion criteria:Population: Any adult ≥18 years involved in the provision or receipt of an intervention as described above. This may include patients, family members or healthcare staff.Phenomenon of Interest: The qualitative component of this review will consider studies that investigate the experiences, perspectives and perceptions of those involved in providing or receiving a telemedicine-based intervention.Context: The setting of the qualitative studies will primarily be in the pre-hospital phase of the acute stroke pathway may cross both primary and secondary care.We will exclude studies involving children or young people ≤17yr. Studies that involve inter-hospital transfers without pre-hospital triage or studies that used patient simulations will be excluded. Studies that use ICT for pre-notification of ambulance arrival purposes only will not be sufficient for inclusion. We will exclude systematic reviews or any trial without a control.Search strategy: A systematic search of electronic databases MEDLINE (Ovid), EMBASE, The Cochrane Library, CINAHL and Web of Science, will be undertaken using a search strategy based on the key concepts under review developed in collaboration with a data information specialist(PM). A preliminary scoping search identified qualitative and quantitative studies of interest in the area. An expanded search using relevant terms including stroke, telemedicine, pre-hospital and triage will be incorporated into medical subject headings, and key words will be searched and combined systematically in an iterative approach to maximise information retrieval. No language or date limits will be applied. A sample search strategy for MEDLINE (Ovid) is provided inStudy selection: Two researchers (DMcC and SL) will independently screen by title and abstract against the documented eligibility criteria using Covidence software. A solution to any disagreements will initially be through conferral and discussion between the two reviewers. Unresolved disagreements will be discussed with the project supervisors (DW and AH) in order to reach consensus.Included studies will be retrieved in full text and will again be screened independently by the two reviewers. Disagreement on inclusion of any study at this stage will be resolved by discussion, or again with the project supervisors, if necessary to gain consensus. Reasons will be recorded for studies excluded at full-text stage. A PRISMA flow diagram will record all steps for accuracy and transparency.Data management: A record will be maintained of all final database searches. References will be managed using EndNote20.1. Screening software will permit efficient screening of titles and abstracts, and of full texts, independently by both reviewers. Review Manager (RevMan) version 5.4 will be used for meta-analysis and qualitative synthesis if results permit through its open-access link to GRADE-Pro software.Data extraction: A data collection form will be designed to ensure that complete and consistent data extraction from quantitative, qualitative and mixed methods studies is achieved. Collected data will include year of publication, study design, study setting, population or perspective, participant numbers and demographics, intervention, control or comparator, primary outcome, secondary outcomes, measures of intervention effect and findings or themes.Reviewers will be trained on the utilization of the data collection form and it will be piloted prior to use to ensure utility and consistent use by reviewers. Data extraction will be undertaken independently by the same reviewers involved in screening. Disagreement on inclusion of any data will be resolved by discussion as described for screening steps. Efforts will be made to find missing data including by contacting study authors.Assessment of methodological quality: The Mixed Methods Appraisal Tool (MMAT) will used at study level to assess methodological quality of empirical quantitative , qualitative and mixed methods studies, using five domains for each design assessed. Judgements of quality will be by two reviewers undertaking independent appraisals. Sensitivity analyses will be undertaken where possible and appropriate, excluding any studies of low methodological quality if they exert any undue influence on estimates. Unpublished data will be included in this review if it made available by authors. Should none be made available, this limitation will be acknowledged when interpreting any funnel plot assessing potential publication bias.The TIDIER (Template for Intervention Description and Replication) checklist will be used as a guide to reporting of details of included interventions.Overall assessment of certainty: An assessment of the overall certainty in the accumulated evidence will be made using the GRADE and Grade-CerQual tools for quantitative and qualitative studies respectively that permits an evidence to decision framework. GRADE narrative statements will further clarify the authors’ confidence in the evidence extracted in the review.Data synthesis and integration: The convergent segregated mixed methods approach to this systematic review involves separate but parallel synthesis of quantitative results and qualitative findings. Data will not be transformed from quantitative to qualitative or vice versa and a clear distinction will be maintained between quantitative results (including the quantitative results of MM studies) and qualitative results  until the integration step. Synthesis of each single method type will be complete before moving to integration. Quantitative results will be synthesised using meta-analysis. Subgroup analyses will be undertaken where appropriate for example where geographic location of studies varies, or study methodology may be significant to the quality of any primary analysis. Synthesis of qualitative findings will categorise themes extracted from primary studies based on the research question and will be described in narrative and schematic form. NVIVO  software will assist inductive thematic synthesis.Integration will follow a parallel results-based approach and will be configured via juxtaposition of synthesized quantitative results and synthesized qualitative findings framed around the JBI methodology. This approach will permit formal consideration of how or if the findings of one single method complements the other or can otherwise explore, contextualise or explain findings in the other results set.Statistics: Statistical analysis will be undertaken using Stata (StataCorp) software with meta-analysis of primary and secondary quantitative outcomes, and subgroup analysis by intervention type, if data permits. Heterogeneity in the study methodologies is likely and so a random effects statistical model will be used for analysis. Statistical heterogeneity across study results will be estimated using theI2 statistic and Chi2 test. If meta-analysis is not possible, a narrative meta-synthesis will proceed.PPI: The members of a Public and Patient Involvement (PPI) panel with experience in stroke will be involved in an advisory role.Acute stroke care requires early patient assessment and care decisions within narrow time windows. People present with heterogeneous symptoms at variable time points from symptom onset. Telemedicine may offer the potential for early differentiation of a patient’s acute care needs through high quality consistent and responsive communication channels established between EMS and designated acute hospital sites. Mobile Stroke Units with on board imaging and point of care blood testing can facilitate rapid treatment but their cost can be prohibitive in many jurisdictions. Telephone, audio-visual and televisual communication methods aim to improve time to decision-making and time to treatment and may be more appropriate in resource poor or geographically remote settings. Formal and reliable communications strategies have the potential to account for deficiencies in local availability of expert opinion and decision-making, local health area resourcing or performance, and local geographic challenges such as distance from PSC or CSC or even prevailing travel conditions. This review will summarise and synthesise the evidence for a range of telecommunication-enabled interventions for triage in the pre-hospital acute care pathway that aim to improve patient outcomes, treatment rates and quality-associated time metrics through integrated care delivery networks. Additionally, the review will consider the context of effectiveness so that we might understand not only what is effective but also how those that experience or implement an intervention can impact or explain its effectiveness, feasibility and generalisability. While this review focuses on the use of telemedicine as a means of process improvement in acute stroke care provision, the results of this review will be interpreted in the context of recent broader emphasis on improving knowledge of and accessibility to IVT, EVT and stroke unit care which could contribute a confounding bias to the results. We aim that this review will help to inform the future research agenda in this field. We had a good look at the revisions and comments by the authors. We are happy to recommend “Approved” status. We thank for the authors for addressing our comments.Is the study design appropriate for the research question?YesIs the rationale for, and objectives of, the study clearly described?YesAre sufficient details of the methods provided to allow replication by others?PartlyAre the datasets clearly presented in a useable and accessible format?Not applicableReviewer Expertise:Stroke and stroke telemedicineWe confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. This comprehensive protocol, delineating the objectives, methodology, and anticipated outcomes in a significant and relevant field. Its integration of quantitative and ancillary qualitative analyses provides insightful exploration of the pre-hospital triage processes facilitated by telemedicine in acute stroke care. The methodological approach is robust, encompassing a thorough search strategy - including commitment to translating non-English articles - data extraction, and data synthesis procedures. The systematic review design exhibits considerable rigor, utilising recognised tools for evidence quality assessment. The points raised below are minor suggestions to an overall excellent protocol paper. The protocol refers to mobile stroke units within the context of stroke triage. Could there be a clearer distinction whether this review primarily focuses on telemedicine triage services, as implied in the title, or does it also extend to more interventional services? There is a broad spectrum of stroke telemedicine models ranging from paramedic-accessible triage hotlines to a live video link from a mobile stroke unit with a scanner onboard, connecting a stroke specialist who can directly assess patients, with the advantage of immediate imaging. Will models relying solely on telephone communication be classified as "telemedicine" within the context of this review? Furthermore, some services allow for remote treatment options such as regional thrombolysis, often referred to as the "drip and ship" model, or mobile stroke unit models. It would be beneficial to clarify these aspects for more comprehensive understanding. Pre-hospital triage is highly influenced by the use of large vessel occlusion scales. The final article would benefit from a discussion of these with consideration of how these impact the stroke telemedicine process. The protocol does not address how it will consider geographical variations in the availability and recognition of telemedicine. Such variations could influence the results, given that different regions may have distinct infrastructures, resources, and policy regulations, which could significantly affect the use and effectiveness of telemedicine for stroke triage. Consider, for instance, the implementation of perfusion imaging, extended thrombolysis criteria, endovascular clot retrieval availability, and ambulance service efficiency. These factors may cause substantial inter-regional variability in several key metrics. We concur that evaluating long-term functional outcomes is pivotal in assessing the effectiveness of these services. We observe that many studies on stroke telemedicine and mobile stroke units focus on process measures such as time to thrombolysis or time to clot retrieval. While these studies report encouraging results, there are fewer studies directly examining long-term disability outcomes, with some presenting mixed results. Your inclusion of 90-day mRS scores and other secondary outcomes should help elucidate these benefits. You state that secondary quantitative outcomes will encompass “onset to decision time thrombolysis” and “onset to decision time endovascular thrombectomy”. Do you mean the time difference between symptom onset and the decision to administer thrombolysis or thrombectomy? As this terminology does not appear to be universally documented, it may benefit from a clearer definition in the final article. The time when the decision for treatment or transfer is made is different from when the treatment or transfer happen. Door to needle time (door to treatment administration time), Door-in-door-out time (in cases where a primary stroke centre transfer out a patient with large vessel occlusion for consideration of thrombectomy), and Door to puncture time are the metrics most commonly recorded. Of course one should be able to replace “door” with “symptoms onset” time, the latter is fairly consistently reported as well. It is also stated in the “intervention” section of the quantitative inclusion criteria that “diagnosis of stroke at discharge must be confirmed”. Does this mean that all included patients must have reported evidence of stroke identified on imaging? We anticipate that many of the stroke telemedicine papers will report metrics such as door to needle time without necessarily definitively excluding patients with stroke mimics from these metrics. It would be worth mentioning how this challenge will be dealt with. It's worth acknowledging the significant global advancements in acute stroke medicine concerning training, infrastructure, and process implementation, all of which contribute to enhancing the speed and precision of acute stroke assessment and management. These developments, often introduced in conjunction with telemedicine services, could confound the impact of stroke telemedicine triage services in some study designs. A description of how this confounding bias will be mitigated could be beneficial. You've noted that funnel plots will be used to evaluate potential publication bias. In light of this, do you have plans to incorporate unpublished data into this review? We recognise that acquiring such data may pose challenges. In the data extraction section, you might want to correct the typographical error where the "s" in "study design" is mistakenly bolded. Despite the need for these clarifications, this paper presents a thorough systematic review protocol that would be a useful addition to the field.Is the study design appropriate for the research question?YesIs the rationale for, and objectives of, the study clearly described?YesAre sufficient details of the methods provided to allow replication by others?PartlyAre the datasets clearly presented in a useable and accessible format?Not applicableReviewer Expertise:Stroke and stroke telemedicineWe confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however we have significant reservations, as outlined above. Dear Dr. Choi and Dr. Callaly, So many thanks to you both for taking the time to read and critically appraise the protocol for my mixed methods systematic review. Your comments and suggestions are both interesting and important and will strengthen the quality of the review. I have re-drafted my protocol to incorporate your feedback which should be available on the HRB site shortly I believe. The following are some points of note: In the “intervention” section of the inclusion criteria I have been more specific on the nature of the telemedicine-based triage that I am reviewing. It was not clear that the telephone triage should also have an objective clinical assessment tool to guide the consultation between the pre-hospital EMS crews and the hospital team. I will include a discussion of triage tools and their utility in the review. Additionally I agree that MSUs can be considered an intervention tool. I feel their role is also field-based triage of those who may benefit from EVT by potentially, depending on the time of onset if known, permitting rapid triage to a CSC rather than PSC. I have clarified also that I am interested only in pre-hospital triage and not in the hospital-based hub-and-spoke telemedicine model or the drip-and-ship model. Where geographic or inter-regional variation exists between studies I will undertake subgroup analysis to assess the impact of these differences. It became clear that my intention to only include confirmed stroke would outrule a number of useful and innovative studies that were interested in improving the pre-hospital pathway and in turn improving onset- to-door or door-to CT-times and so included all screened or evaluated patients. You intuitively predicted this and I appreciate this helpful point. I agree that onset-to-treatment decision time is not universally documented. It is a variable collected in the Irish National Audit of Stroke and is helpful in identifying transportation delays between a patient being accepted by a CSC and actually arriving for care, whether that be due to geography, ambulance availability, crew availability, prevailing weather or road conditions. I had thought that perhaps others would have incorporated this metric into their studies. I wish to include it as a noteworthy  variable. I have acknowledged in the protocol discussion that improvements across the spectrum of stroke care is having a “raising all boats” effect in stroke and I will discuss this within the body of the review in order to contextualise findings and identify potential confounding effects. I have fixed the typo mistakenly bolded. I will publish unpublished data if it is made available to me. Again, it really is with thanks that I respond to your very detailed and thoughtful review of my protocol. I know that time demands are high and every increasing so your time on this is immensely helpful and appreciated. Deirdre The authors have provided a thorough and comprehensive protocol for a mixed methods systematic review and potential meta-analysis of the impact of telemedicine for pre-hospital triage in acute stroke. This is a timely and important topic where a literature synthesis - especially one considering qualitative aspects - is lacking.  The study protocol is clear and would allow for easy replication. Appropriate statistical considerations for the quantitative analysis have been taken. I have only two suggestions:  1) For the qualitative analysis I'd ask the authors to clarify if themes will be inductively or deductively determined.  2) While it is stated that studies of low methodological quality will be noted but not excluded, I recommend performing sensitivity analyses excluding any studies of low methodological quality to ascertain if they exert any undue influence on estimates.  I look forward to the results of this mixed methods systematic review and meta-analysis.Is the study design appropriate for the research question?YesIs the rationale for, and objectives of, the study clearly described?YesAre sufficient details of the methods provided to allow replication by others?YesAre the datasets clearly presented in a useable and accessible format?Not applicableReviewer Expertise:Stroke epidemiology and biostatisticsI confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.


Maternal mental health (MMH) problems, such as perinatal depression, maternal anxiety, suicide ideation and puerperal psychosis among others, have a significant impact on maternal morbidity and mortality, as well as the health and development of children. One in every four pregnant women and one in every five postpartum women in low-income countries, suffer from maternal mental health (MMH) problems. Despite this, MMH screening, diagnosis, and reporting remain scanty in Uganda. Consequently, this study aimed to investigate the knowledge, practices, and impediments that maternity care workers face when screening and managing women with maternal mental health disorders in health facilities in south-western Uganda.In-depth interviews were conducted with 22 health-care professionals who work in maternity care departments in primary and tertiary healthcare facilities in southwestern Uganda to investigate their medical knowledge, clinical practices, and challenges related to the screening and management of maternal mental health problems. Using qualitative content analysis, distinct categories and subcategories were found.Medical staff especially midwives lacked specialized training in screening and managing women with maternal mental health problems They screened and managed MMH problems solely based on history and physical examination, and they referred nearly every mother displaying signs of mental illness because they felt ill-prepared to handle them. On the other hand, medical staff with some level of specialized training in mental health particularly staff working in mental health units, were more likely to use a mental health screening tool in addition to history and physical examination; and to treat any women exhibiting signs and symptoms of maternal mental problems without referring them. Lack of in-service training on maternal mental health, poorly coordinated referral systems, reluctance of mentally ill to visit medical facilities, scarcity of mental health specialists, and shortage of relevant medications were identified as the major challenges. Age, experience level, or gender had no effect on screening or management practices.The results suggest that specialized training in mental health, and particularly maternal mental health, is essential for the effective screening and management of maternal mental health conditions in South Western Uganda. Maternal mental health (MMH) illnesses during pregnancy and puerperium are major contributors to maternal morbidity and mortality, and have negative effects on the health and development of children –3. MMH iIn low- and middle-income countries (LMICs), including Uganda, one in four pregnant women and one in five postpartum women experience MMH problems respectively , indicatThis was a cross-sectional qualitative study.The study was conducted at health centre (HC) III, IV and referral health facilities in two districts, that is Mbarara and Kabale, located in southwestern Uganda. The selected health facilities had maternity care facilities with antenatal and postnatal services. Southwestern Uganda is made up of 16 districts . The twoIn Uganda, provision of mental health services starts at health center III (HC III), that is a sub-county level, with subsequent referrals to health center IV (HC IV) at the county level, district hospitals, regional referral hospitals, and finally to the only national psychiatry referral hospital called Butabika Hospital, , 25. FroRespondents to the study included specialized mental health workers  as well as non-specialized health professionals (midwives and nurses) who were directly involved in the screening and management of maternal mental disorders within the participating health care facilities, regardless of sexual orientation, age, or level of experience. Purposive sampling was used to ensure representation from the various categories of health professionals at the selected healthcare facilities in order to get insight into how various categories of health care professionals screened for and handled maternal mental health problems. A maximum of two health workers working in the maternal environment  were purposively selected at each health facility (HC III and IV). Only individuals with at least two years of experience caring for pregnant or postpartum women or working as maternity unit managers (in-charges) knowledgeable with the clinical and administrative environments of the relevant health care facility were chosen. In addition to maternity care workers, specialized staff from the mental health department were included at the referral hospitals if they had a history of handling a woman with perinatal mental health difficulties. This purposive selection was bench marked on prior research  to captuThe study included only specialized mental health workers  and non-specialized health professionals (midwives and nurses) who were directly involved in the screening and management of maternal mental disorders within the participating health care facilities and who consented to participate, regardless of sexual orientation, age, or level of experience.The study excluded all specialized mental health workers and non-specialized health professionals who were not directly involved in the screening and management of maternal mental disorders, did not consent to participate, or were absent at the time of data collection within the participating health care facilities.We collected data through in-depth face-to-face interviews using open-ended questions designed in accordance to the study objectives. We developed the in-depth interview guide Table  based onThe first author and trained research assistants conducted in-depth interviews between July and November 2022. There were two research teams each with two members. Each interview lasted approximately 30 to 45 min. All interviews were conducted in English, Uganda’s official national language. With the permission of each respondent, each interview was audio recorded and accompanied by field notes. Each study team interviewed a maximum of three respondents per day. One team member conducted the interview, while the other made notes and recorded the conversation with an audio recorder. With each subsequent interview, the team members reversed roles. We recruited respondents until saturation, or when no new information was gained from additional interviews . SaturatThe data collection research assistants  were chosen based on previous experience in qualitative research as well as their baseline knowledge regarding mental health in their prior training and practice. The research assistants were trained for two days by the first author and an experienced mental health researcher on study objectives, informed consent, and data collection procedures, and then they participated in a hands-on pilot study, which increased their confidence in collecting data. Interview guides were field tested on three participants at a Health Centre III facility for practicality and intelligibility; however the results from the field test were not included in the final analysis. At the end of each day of data collecting, feedback meetings were held to review the data collecting process, discuss issues encountered, and plan for the next set of interviews. This ensured quality data and completeness. Completeness mainly centered on obtaining full information per question not necessarily the entire interview since participants were free to withdraw from the interview at any time. This was intended to obtain clarifications in time and in context before research assistants could forget and to perfect subsequent interviews. In order to guarantee that interviews were carried out correctly and in line with the study objectives, an experienced qualitative researcher provided oversight during the feedback process and did attend some of the interviews.Trustworthiness including; credibility, transferability, dependability and conformability was ensured , 29.This was ensured by selecting only those respondents who met the inclusion criteria, and by strictly adhering to the in-depth interview guide. Furthermore, the research team ensured that the respondents correctly understood the questions and the research being conducted. We ensured that the respondents understood the study through respondent checks, and during the interviews, respondents were checked for understanding by rephrasing and summarizing the questions. We also carried out peer debriefing by reviewing the interview transcripts with the research team.A purposive sample was used to enable researchers to maximize the range of information by consciously choosing respondents from different health facility levels and locations.The researchers ensured detailed description of data collection methods to enable reproducibility. A consultant psychiatric clinician and researcher provided over sight by cross checking the data collected by the research teams to ensure that the information given by the respondents was accurately captured. The details of the interviews were recorded using a recorder, documented and verified.Confirmability was ensured by coding the information provided by the respondents and by ensuring that the interpretations of the data was not influenced by the researcher’s imagination . The leaBefore proceeding to the next set of interviews, data was transcribed verbatim and cleaned. Data was transcribed in English because the respondents were all educated, that is, professional health workers, and so data was collected in English. The first author then checked the accuracy of the information against the audio recordings.The data analysis was done using Creswell’s six-step model  which inThe research team read and re-read the transcripts to become familiar with the data and ensure representativeness . Each meA total of 22 respondents were interviewed. Demographic characteristics are shown in Table From the analysis, hybrid coding (both deductive and inductive) was employed as initially, codes were developed based on literature review but additional categories and subcategories were included during analysis to capture the depth of the data. Three main categories are presented: (1) training and knowledge regarding maternal mental health; (2) screening and management of maternal mental health; and (3) Challenges in providing maternal mental health. Based on the common patterns that emerged from the aggregated data, additional subcategories were identified under the main categories namely: Training in MMH, Knowledge of MMH conditions, Confidence to screen and manage MMH problems, screening practices, management practices, challenges and recommendations.Apart from pre-service (in-school) training in general mental health, the vast majority of respondents claimed they had never taken any formal training on maternal mental health, and yet they indicated a desire to do so in order to provide better services.Maternal mental health is something new and no health worker has formal training. If the training is available, we will be happy to participate and offer services because we are handling [women] as a whole. Mental health [training] was done in school as overall but not specific to maternal mental health. I have general knowledge on mental health”. .“I have had training in epilepsy management but not specifically in pregnancy during work (in-service). [Otherwise] I [last] had training in school generally. .When such opportunities come to train in mental health, they give chance to nurses but not us the midwives. So, we have never had any training, not even CME in mental health issues of mothers. .Respondents who said they had ever received in-service mental health training said the focus was never on maternal mental health. Moreover, they stated that, when the opportunity arises, maternity care providers are not typically invited to such mental health trainings.I can identify some of the signs and symptoms [of MMH illness] and refer but I have no knowledge to manage the [women]. .There is no standard tool but in clerking this patient I am able to tell that the patient is mentally unwell. The majority of respondents who worked in maternity units admitted to lacking the knowledge required to identify and treat pregnant women with mental illnesses. Some stated that they were able to detect symptoms of mental illness during pregnancy and after delivery, but they lacked the information or instructions needed to treat such women.I am somehow confident (to screen) of course not 100% but at least 70%. This is because of the tool, PHQ-9; I usually refer to during assessment. I can recognize signs and symptoms at least. I am somehow confident just that I lack the proper guidelines. .There were mixed responses when asked how confident they felt about screening and managing mothers with signs of maternal mental illness. In general, respondents with specialized mental health training reported higher levels of confidence than those without specialized mental health training. The majority of the latter expressed skepticism because they lacked knowledge of MMH as a discipline.“We have general form or questionnaires [Antenatal cards] that assess the mother’s health and history of mental health in her family. No guidelines for assessment of maternal mental health.” .“What appears on the antenatal care is the aspect of IPV [intimate partner violence] screening but from there the psychosocial assessment helps to bring out mental problems if present, but there is no specific screening tool to for depression or anxiety, though many mothers go without our notice.” .When asked how they conducted screening and which screening tools they used to assess women with MMH illnesses, the majority of non-specialized respondents stated that they had no specific tools to assess and manage MMH illnesses aside from the standard clinical assessment methods of history and physical examination.start at OPD [out patient department] with health education, we have a clinic every Tuesday where we sit with the patients and clerk them and see where the problem is. We have [use] DSM-V.” .“We “When the midwives call us to review, we use the [mini] mental status exam and history to see if the mother has a problem… you can surely tell if the mother has psychosis or depression.’’ .Those with specialized mental health training identified a number of tools for screening suspected patients for MMH disorders. Individuals and healthcare facilities used different tools, but the most notable were the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), Mini Mental State Exam (MMSE) and Patient Health Questionnaire—9 (PHQ-9) screening tools.The primary management strategy used by non-specialized respondents was to refer women with MMH illnesses to mental health specialists working at the same hospital  or at a different higher level care facility with specialized mental health care .“We screen them [mothers with signs of MMH illnesses] using general assessment and refer them [to psychiatrists] for management.” .“…. But they may need more time to open up’’… Usually we refer them [to] the psychiatric team to help.” .The fact that screening and managing those mothers takes so much time is one of the factors cited for why non-specialist care providers refer mothers with MMH problems. Others cited a lack of knowledge of MMH.When screening and managing women with MMH conditions, respondents mentioned a number of difficulties they encounter. These include;In most cases, the patients and their families are responsible for arranging their own transportation to the referral facility. As a result, a significant portion of referred mothers never receive the necessary medical care because they are unable to travel due to financial constraints.“……. a major challenge is the referral system in place. In case we get a [woman] with a mental challenge and needs referral, the referral system is poor, not in place, so the patient ends up going to higher.”  facility on their own. Facility also has no transport (ambulance) so patients use private means” .Another barrier mentioned was the community practice of hiding women who exhibit signs of mental illness. Respondents stated that this practice is most likely motivated by stigma and negative cultural perceptions of mental illness. The communities are not well sensitized about mental health. Because of the community negativity about mental health, many women are denied the opportunity to receive appropriate medical treatment, exacerbating their suffering.“Most mothers with maternal mental health problems are hidden by their families in the communities and do not come for treatment and it’s challenging to find them in community.” .“………….. and communities are not sensitized on mental health.” .Respondents cited lack of mental health care specialists and drugs for the most common MMH disorders as among the challenges they faced. Because there are few psychiatric nurses, clinical officers, and doctors, consultation by non-specialized care providers is difficult. The number of patients is far too great in comparison to the number of available mental health specialists. The shortage of specialists is exacerbated by a lack of mental health specific medications in the majority of health care facilities that participated in the study. According to the respondents, maternity units are not supplied with antipsychotics because it is assumed that they only handle obstetric and gynecological conditions.“We don’t have psychiatric personnel so whenever we detect someone with mental health problems; we consult the ones in regional referral  which is hard. If we could get our own psychiatry personnel, it would be better. Also, there are no drugs for managing such conditions.” Most people running maternity department are enrolled midwives who have minimum capacity [training and knowledge] in managing these mothers.A knowledge gap among non-specialist health care providers regarding MMH was also recognized among the key obstacles to provision of MMH services by respondents. The low level of training in mental health for the staff within the maternity care settings especially midwives who primarily receive, assess and manage pregnant and post-delivery mothers especially at lower-level facilities was a key challenge. Many midwives acknowledge a general lack of knowledge and hence confidence to manage MMH illnesses.“….there should be deliberate effort that all health care providers are reminded that these conditions exist in our community and be equipped enough so that they are able to identify these conditions early enough. Avail a clear appointment and follow-up of these patients like [is the case] with HIV.” .Respondents made a number of suggestions when asked to offer possible solutions to the challenges faced in providing MMH services. One of the major recommendations was that MMH be given the same level of attention as other chronic conditions such as Human Immune Virus (HIV) in terms of raising awareness among health workers and the general public, as well as creating special clinic days with well-developed patient follow-up systems.“More trainings to the midwives to have the capacity to screen these mothers and also push for drugs used in treat of MMH problems.” .“I would love that as the midwives are employed, they should get refresher courses on maternal mental health.” .Respondents also suggested providing pre-service (in school) and in-service maternal mental health training to midwives and other medical staff working in maternity units, in order for them to effectively recognize and treat women with MMH conditions without relying heavily on mental health specialists.“We should have easy to use screening tools and this aspect integrated in the package offered to all pregnant mothers and post-delivery. …even where to document is very important for follow up.” .Further recommendations from the respondents included the requirement for MMH screening tools to be developed and validated that are user-friendly for non-mental health professionals. The instrument needs to be incorporated into the postpartum and antepartum screening tools that are used regularly for women. This will make it possible to quickly identify women who are suffering from MMH conditions and provide them with the appropriate medical care.“Government should also facilitate [healthcare] facilities with medication for MMH and resources, strengthen home visits and community outreaches to sensitize people” .Finally, in order to increase communities’ receptivity to MMH services on a cultural level, many respondents favored strategies by the government and relevant stakeholders to develop community outreach programs that involve communities in MMH awareness campaigns. They also advocated for properly stocking medical facilities with the right medications to treat MMH illnesses.This qualitative study investigated health care workers’ medical knowledge, clinical practices, and challenges in screening and managing maternal mental health services in southwestern Uganda. Respondents identified medical history, physical examination, and the use of tools such as the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), Mini Mental State Exam (MMSE), and Patient Health Questionnaire—9 (PHQ-9) as the basis for assessing women with MMH problems. Screening and management of MMH conditions differed significantly between specialized mental health workers and other healthcare workers. Respondents with specialized mental health training were more likely to use standardized assessment tools or neuropsychological tests such as the MMSE, DSM-V, and PHQ-9. The provision of MMH services was hampered by disorganized referral systems, social norms that mothers showing signs of mental illness should be hidden, a lack of specialized mental health workers, a lack of medications tailored to MMH illnesses, and a knowledge gap among non-specialized healthcare professionals. Respondents noted that MMH screening and management services would be facilitated by community outreach programs to raise MMH awareness; in-service and in-school MMH training for all health workers, the development of screening tools that are user-friendly for non-specialized health workers, and an adequate supply of MMH-specific drugs in maternity units.Our findings on health workers’ medical knowledge in relation to MMH reflected previous research claiming that specialized mental health workers who are relatively more knowledgeable in screening and managing MMH illnesses than their non-specialized counterparts are also very scarce , 32. TheIn our study, only healthcare professionals who had received specialized training in mental health felt confident to screen and manage MMH conditions using a patient’s medical history and psychometric tests like the MMSE, DSM-V, and PHQ-9, whereas nearly all non-specialized care providers referred all women displaying signs of mental illness. The results of our study were supported by those of previous African studies , 28, 31 According to our study, one of the main challenges to MMH care services is the practice of women with MMH problems not seeking mental health care. This finding was consistent with the findings of numerous previous studies , 43, 44.Individual interviews and qualitative content analysis were used in the design of this qualitative study. Since the scope of individual interviews is limited, it is challenging to make meaningful statistical inferences and extrapolate the results to other contexts. To get a deep understanding of experiences and beliefs connected to a phenomenon, however, individual interviews and qualitative content analysis are most effective , 53. As Our study revealed patient, social, and health worker-related barriers to MMH service provision, warranting intervention and policy approaches that effect change at multiple levels, namely, increasing health worker knowledge of MMH, improving closer cooperation and integration of MMH services with general mental health care provision, and increasing MMH awareness in communities. More research is required to examine the impact of health workers’ attitudes, cultural beliefs, and social support networks on MMH care services.


With assumption of the upright posture, gravitational pooling of blood and plasma extravasation in the lower body challenges the cardiovascular system. In healthy persons, activation of compensatory autonomic reflexes maintains blood pressure while standing. Failure of these compensatory mechanisms results in orthostatic hypotension, which is not only one of the most disabling symptoms in patients with autonomic failure, but is now recognized as an independent risk factor for cardiovascular morbidity and mortality . At the In this issue of Clinical Autonomic Research, Palatini et al. present data on the prevalence of orthostatic hypertension in 1245 younger-to-middle aged persons who had participated in the Hypertension and Ambulatory Recording Venetia Study (HARVEST) . Study pThis carefully conducted study highlights the challenges in diagnosing orthostatic hypertension. The prevalence of orthostatic hypertension as per the consensus definition , 5 was 0The study by Palatini et al.  reveals A separate question is whether the presence of orthostatic hypertension should influence the selection of antihypertensive treatment. The few mechanistic studies suggest age-related differences; an increase in sympathetic responses has been proposed as the mechanism for orthostatic hypertension in the young and increase vascular stiffness in older patients , 9. MorePalatini et al. propose that the threshold for diagnosing orthostatic hypertension in younger persons may have to be revisited. Indeed, lesser increases in blood pressure with standing predict cardiovascular risk in younger-to-middle aged people , 11. We We welcome the contribution by Palatini et al., which highlights the importance of recognizing orthostatic hypertension, and emphasizes the need for further research in this area. For example, mechanisms contributing to sympathetically mediated increases in blood pressure with standing deserve to be studied in more detail. Orthostatic hypertension has also been described in younger individuals suffering from other “hyperadrenergic” conditions such as postural tachycardia syndrome, which are arguably unrelated to hypertension. The clinical implication for autonomic specialists is that orthostatic testing is useful in detecting orthostatic hypotension and orthostatic hypertension, which both indicate altered autonomic cardiovascular control. However, even smaller changes in blood pressure may have prognostic implications.


Despite progress in providing antiretroviral therapy to pregnant women living with HIV, a substantial number of vertical transmissions continue to occur. Novel approaches leveraging modern potent, safe, and well-tolerated antiretroviral drugs are urgently needed. Postnatal prophylaxis continues to play an essential role in efforts to eliminate new pediatric HIV infections and maximize HIV-free survival.New approaches to postnatal prophylaxis using currently available modern oral antiretroviral drugs could surmount many current barriers.Long-acting agents and delivery platforms currently in development for treating people living with HIV have great potential as postnatal prophylaxis for infants.Studies of novel postnatal prophylactic agents are possible and imperative in the near future and must be prioritized early in the antiretroviral drug development pipeline.Close collaboration between researchers, community representatives, industry, regulators, and policymakers will be the critical ingredient to ensure HIV-free survival for all infants with HIV exposure. With new advances in antiretroviral drugs for HIV prevention and treatment, as well as increasing coverage globally, the landscape around vertical transmission of HIV is rapidly changing. It is estimated that 82% of pregnant women globally received antiretroviral therapy (ART) in 2021.Postnatal prophylaxis—the provision of antiretroviral drugs to HIV-exposed infants—remains a key tool to reduce vertical transmission. In the absence of effective maternal ART, postnatal prophylaxis has been demonstrated effective in the prevention of vertical transmission around the time of delivery and during breastfeeding. Current World Health Organization (WHO) guidelines for postnatal prophylaxis are designed primarily to reduce the risk of transmission around the time of delivery, with regimens that are risk-stratified depending on maternal treatment status, timing of ART initiation, and virological suppression .4Infants born to women who start ART late in pregnancy or at the time of delivery are at high risk of HIV acquisition. For these high-risk situations, the WHO guidelines recommend giving postnatal prophylaxis to the infant for 12 weeks .5These guidelines have been adopted widely, with countries customizing to their contexts. But their effective implementation has been limited for several reasons. Risk stratification, which identifies infants requiring more complex postnatal prophylactic regimens at birth, can be difficult to implement, especially in resource-limited settings with limited access to viral load monitoring. Furthermore, there are challenges to administering antiretroviral drugs to newborns. Those currently in use, nevirapine and zidovudine, require daily or twice daily oral administration and are delivered as syrups dispensed in bulky bottles with the potential for unintentional disclosure of the maternal HIV status. Because these drugs are no longer considered optimal for treating HIV infection, the decreasing global market for them has led to challenges in supply security. Finally, postnatal prophylaxis is not currently routinely recommended by the WHO for infants aged older than 12 weeks. This leaves breastfeeding infants vulnerable to transmission if their mothers experience viremia secondary to lapses in adherence or treatment failure or if there are drug stock-outs. Some countries have adapted the guidelines to include prophylaxis during breastfeeding.To further reduce the risk of HIV acquisition during breastfeeding, there is a need for more effective approaches to infant prophylaxis that are easier to implement, safe when used for prolonged durations, take advantage of modern drugs, and capitalize on novel delivery platforms. In 2021, the WHO and the International Maternal Pediatric Adolescent AIDS Clinical Trials Network convened a workshop to accelerate the research and development of new agents and new approaches to postnatal prophylaxis. The second meeting of the series was held June 8–10, 2021. In this article, we present the data reviewed and the ideas generated by workshop participants to identify potential innovative strategies for postnatal prophylaxis to prevent HIV vertical transmission.More effective approaches to postnatal HIV prophylaxis are needed that are easier to implement, safe for prolonged use, take advantage of modern drugs, and capitalize on novel delivery platforms.–––,The first evidence that antiretroviral drugs reduced the risk of vertical transmission—and one of the earliest success stories in the HIV epidemic response—came from the Pediatric AIDS Clinical Trials Group 076 study.,Many currently approved antiretroviral drugs like dolutegravir used in the treatment of children with HIV have untested potential as potent agents for postnatal prophylaxis. A new generation of long-acting antiretroviral drugs, such as injectable cabotegravir, has been approved by the U.S. Food and Drug Administration for treatment and prophylaxis for adolescents and adults. Recent studies suggest that combinations of broadly neutralizing antibodies could potentially be effective for prophylaxis in adults. But the pharmacokinetics of all of these products must be established in neonates and infants before they can be trialed for efficacy. Drug development and dose-finding for neonates is particularly challenging not only because of difficulties in performing clinical research in this vulnerable population but also because of highly variable pharmacokinetics during the first months of life. Additionally, the necessity for multiple blood draws, safety procedures, and frequent study visits soon after birth can be a burden for families. Drug dosing for children older than 2 years can be relatively accurately estimated by extrapolating adult doses using allometric scaling according to body weight, which empirically describes the nonlinear relationship between drug elimination and body size. However, this is not applicable for neonates as the rapid maturation of the physiological processes underlying drug absorption, distribution, metabolism, and excretion immediately after birth must also be considered. Rapid increases in antiretroviral drug metabolism and/or elimination can occur during the first few weeks of life, necessitating very low doses at birth followed by frequent dose increases during the first weeks of life.Drug development and dose-finding for neonates is particularly challenging because of difficulties in performing clinical research in this population and highly variable pharmacokinetics during the first months of life.,Studies of neonatal “washout” are an efficient way to gain insight into the neonatal metabolism of drugs before formal neonatal pharmacokinetic dosing trials. Washout studies assess a drug taken by the mother that crosses the placenta; through repeated infant blood sampling after birth, this washout data can help provide an estimate of drug clearance over the first days and weeks of life. For newer antiretroviral drugs, drug exposure targets for postnatal prophylaxis are similar to those for treatment.,–Within the context of HIV prevention in adults, the ideal product profile for an agent includes efficacy, safety, high partitioning into genital tissue compartments, prolonged activity with convenient dosing, high barrier to resistance, unique resistance profile , no significant drug-drug interactions with commonly coadministered medications, and low cost.,While current approaches to prophylaxis against HIV infection in adults and children are based primarily on small-molecule drugs, it is important to remember that antibodies can provide powerful protection against viral infections. The gold standard for both prevention of vertical transmission and the generation of life-long immunity is the hepatitis B prevention program, which is highly effective when implemented during prenatal, delivery, and neonatal care visits. This maternal-infant targeted program employs both risk-based and universal prevention strategies: (1) passive immunization with hyperimmune globulin at delivery in infants of mothers with evidence of active hepatitis B infection; (2) antiviral treatment of mothers with high viral replication; and (3) universal active immunization at delivery and throughout infancy that can generate life-long protective immunity.The addition of passive immunization of the infant with a combination of broadly neutralizing antibodies at birth to maternal and infant antiretroviral drugs is an attractive option particularly in high-risk situations.One of the central challenges in designing new approaches to postnatal prophylaxis is how to accommodate infants at different levels of risk during each period of exposure—in utero, intrapartum, and during breastfeeding. Traditionally, guidelines have recommended different regimens for the immediate postnatal period based on maternal risk factors (documented viremia and/or the recent start of ART). Furthermore, there is little evidence and hence limited guidance to address new or escalating risk if a mother becomes viremic during breastfeeding. A “1 regimen for all” approach would be ideal to overcome the challenges of implementing a risk-stratified approach to postnatal prophylaxis, depending on the feasibility and safety of the regimen. One strategy would be to use potent 3-drug antiretroviral regimens that could serve dual roles as “presumptive treatment” for infants with in-utero HIV infection while providing a high level of protection for those at high risk of intrapartum/early postnatal acquisition. However, using 3-drug antiretroviral regimens as prophylaxis for infants at low risk would be resource intensive and places those infants at potential additional risk of toxicity. It is possible that some agents in the pipeline, such as broadly neutralizing antibodies, could be both highly potent and safe enough to be used as routine postnatal prophylaxis for all infants at birth and throughout breastfeeding, independent of the risk of HIV acquisition. Arguments in favor of and against maintaining risk-based approaches to postnatal prophylaxis are summarized in A “1 regimen for all” approach would be ideal to overcome the challenges of implementing a risk-stratified approach to postnatal prophylaxis but would depend on the feasibility and safety of the regimen.,,There are also many questions about the added value of providing prophylaxis to infants during breastfeeding. While current WHO guidelines recommend breastfeeding without any prophylaxis, after completion of the perinatal regimen, if a mother is on ART and virally suppressed, sustaining complete adherence throughout breastfeeding can be difficult, and episodes of viremia are not uncommon.There are several antiretroviral drugs currently available for the treatment of infants with HIV and others in the pipeline that hold potential for postnatal prophylaxis.–,Dolutegravir is a highly potent antiretroviral drug that may play an important role in postnatal prevention.Nevirapine, lamivudine, and zidovudine will likely remain the best current options for premature neonates until pharmacokinetics and safety of newer drugs are defined for that population.In the development pipeline for treating HIV, there are several long-acting agents and formulations that are very appealing as prophylaxis for infants. Agents that are injectable, either as intramuscular  or subcutaneous  formulations, could surmount challenges of adherence that arise from administering daily oral medications to infants. However, it is likely that dosing intervals obtained in adults will be difficult to achieve in the neonatal period, given the changes in clearance and growth that occur over the first weeks and months of life. Given their distinct clearance mechanisms and safety, broadly neutralizing antibodies could be ideal and potentially cost effective if effective combination regimens were to be identified that could be used universally or in high-risk settings.Until all the “leaks” in coverage and treatment failures among mothers with HIV are addressed, postnatal prophylaxis will continue to play an essential role in global efforts to eliminate new pediatric HIV infections and maximize HIV-free survival. Several postnatal prophylaxis strategies have the potential to provide more effective and feasible options for infants and their mothers. In the short term, evaluating universal and risk-stratified approaches that combine legacy and novel antiretroviral drugs that are also used for treatment and passive immunization approaches appears to be the most feasible and expeditious route to advance beyond legacy postnatal prophylaxis regimens. These new strategies will require rapid investigation of the most appropriate dosing in preterm and term neonates with pharmacokinetic modeling and studies. In the long term, pipeline products that allow for less frequent administration open the door to a more integrated approach where a single well-tolerated and effective strategy could be administered across the risk spectrum perinatally and postnatally. These options will require building on the evidence generated in the adult population, defining clearly preferred product characteristics, and actively investigating novel molecules in neonates and infants.