Outlier analysis for accelerating clinical discovery: An augmented intelligence framework and a systematic review.

Clinical discoveries largely depend on dedicated clinicians and scientists to identify and pursue unique and unusual clinical encounters with patients and communicate these through case reports and case series. This process has remained essentially unchanged throughout the history of modern medicine. However, these traditional methods are inefficient, especially considering the modern-day availability of health-related data and the sophistication of computer processing. Outlier analysis has been used in various fields to uncover unique observations, including fraud detection in finance and quality control in manufacturing. We propose that clinical discovery can be formulated as an outlier problem within an augmented intelligence framework to be implemented on any health-related data. Such an augmented intelligence approach would accelerate the identification and pursuit of clinical discoveries, advancing our medical knowledge and uncovering new therapies and management approaches. We define clinical discoveries as contextual outliers measured through an information-based approach and with a novelty-based root cause. Our augmented intelligence framework has five steps: define a patient population with a desired clinical outcome, build a predictive model, identify outliers through appropriate measures, investigate outliers through domain content experts, and generate scientific hypotheses. Recognizing that the field of obstetrics can particularly benefit from this approach, as it is traditionally neglected in commercial research, we conducted a systematic review to explore how outlier analysis is implemented in obstetric research. We identified two obstetrics-related studies that assessed outliers at an aggregate level for purposes outside of clinical discovery. Our findings indicate that using outlier analysis in clinical research in obstetrics and clinical research, in general, requires further development.

Exploring Care and Recovery for Individuals With Post-traumatic Stress Disorder: A Scoping Review.

Most people experience trauma at some point in their lives. The sources of trauma can include accidents, natural disasters, physical or sexual assault, combat, torture, or the death of a loved one. Experiencing or witnessing any of these, or other terrifying events, may make one susceptible to developing post-traumatic stress disorder (PTSD), a trauma- and stressor-related mental health condition. The common symptoms and consequences of PTSD include intrusive and distressing thoughts, memories, or flashbacks related to the traumatic event; avoidance of situations, people, or activities that remind one of the traumatic event; irritability, sleep difficulties, or hypervigilance; feelings of guilt, shame, or fear; substance use; strains on relationships; and suicidal thoughts and behaviors. These consequences can have devastating effects on the individual and their family members, friends, co-workers, peers, and communities. Effectively treating PTSD, therefore, is critical not only for the individual but also for the well-being of families, communities, and society at large. However, while treatments for PTSD exist, effectively treating patients with PTSD remains elusive. Further, despite the recognition that people's experiences are essential in understanding PTSD and provide valuable insights into what interventions are effective and how they impact recovery, patient perspectives and experiences of care and recovery have not been well-explored. We conducted a scoping review to address the following question: what is known about the experiences and perspectives of care and recovery for individuals with PTSD? We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE), Embase, American Psychological Association's (APA) PsycInfo, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PTSDPubs, and Google Scholar for peer-reviewed and grey literature that used qualitative methods to report on the recovery or care experiences of adults with lived experiences of PTSD. We extracted information about study objectives, study characteristics, and key findings; reported summary statistics; and performed content and thematic analyses. We identified 14 relevant studies that provide insight into the participants' lived experiences and perspectives of PTSD care and recovery. Though limited, the body of literature sheds light on critical themes and processes in the journey of care of PTSD, which we organized into four overarching categories: pre-treatment understanding and experiences of PTSD, the experience of care or treatment, the importance of relationships and social support, and expanding the understandings of recovery. Living with and healing from PTSD are a unique and individualized human experience of developing and redeveloping relationships with oneself, with others, and with society. The recommendations for practice include educating and establishing well-informed support networks for individuals with PTSD, training healthcare practitioners in all aspects of formal and informal PTSD treatment and care needs, ensuring a continuum of care, and understanding the human experience of PTSD.

Seeking support for abortion care from national hotlines in Canada: Caller characteristics and call outcomes, 2019-2021.

OBJECTIVES: Both the National Abortion Federation Canada and Action Canada for Sexual Health and Rights operate national toll-free hotlines that provide information, financial support, and travel assistance to abortion seekers. We aimed to characterize callers to both hotlines before and after the onset of the COVID-19 pandemic. METHODS: Hotline personnel routinely document information about callers and type(s) of assistance needed and received. We received call logs from both organizations for a two-year period (April 1, 2019 through March 31, 2021). We exported these data to Microsoft Excel® and analyzed them using descriptive statistics. We analyzed case notes for content and themes. RESULTS: Over the study period, the two hotlines worked with 270 unique callers. Nearly two-thirds of callers (n = 174) were seeking support to obtain abortion care for pregnancies after 14 weeks gestation, including 69 callers (26%) who were at or beyond 24 weeks gestation. Most callers were seeking support to obtain abortion care outside of their province of residence because services at their gestational age were not available. Caller needs were similar before and after the onset of the pandemic, but fewer traveled to the United States for abortion care in the COVID-19 era. DISCUSSION: Assistance hotlines play an important role in helping some abortion seekers navigate the Canadian health system to obtain needed abortion care. The needs of those seeking care after the 14 weeks gestation points to gaps in current service availability. Identifying ways to expand later abortion care in Canada, particularly after 24 weeks, appears warranted.

Augmented Intelligence for Clinical Discovery in Hypertensive Disorders of Pregnancy Using Outlier Analysis.

Objectives Clinical discoveries are heralded by observing unique and unusual clinical cases. The effort of identifying such cases rests on the shoulders of busy clinicians. We assess the feasibility and applicability of an augmented intelligence framework to accelerate the rate of clinical discovery in preeclampsia and hypertensive disorders of pregnancy-an area that has seen little change in its clinical management. Methods We conducted a retrospective exploratory outlier analysis of participants enrolled in the folic acid clinical trial (FACT, N=2,301) and the Ottawa and Kingston birth cohort (OaK, N=8,085). We applied two outlier analysis methods: extreme misclassification contextual outlier and isolation forest point outlier. The extreme misclassification contextual outlier is based on a random forest predictive model for the outcome of preeclampsia in FACT and hypertensive disorder of pregnancy in OaK. We defined outliers in the extreme misclassification approach as mislabelled observations with a confidence level of more than 90%. Within the isolation forest approach, we defined outliers as observations with an average path length z score less or equal to -3, or more or equal to 3. Content experts reviewed the identified outliers and determined if they represented a potential novelty that could conceivably lead to a clinical discovery. Results In the FACT study, we identified 19 outliers using the isolation forest algorithm and 13 outliers using the random forest extreme misclassification approach. We determined that three (15.8%) and 10 (76.9%) were potential novelties, respectively. Out of 8,085 participants in the OaK study, we identified 172 outliers using the isolation forest algorithm and 98 outliers using the random forest extreme misclassification approach; four (2.3%) and 32 (32.7%), respectively, were potential novelties. Overall, the outlier analysis part of the augmented intelligence framework identified a total of 302 outliers. These were subsequently reviewed by content experts, representing the human part of the augmented intelligence framework. The clinical review determined that 49 of the 302 outliers represented potential novelties.  Conclusions Augmented intelligence using extreme misclassification outlier analysis is a feasible and applicable approach for accelerating the rate of clinical discoveries. The use of an extreme misclassification contextual outlier analysis approach has resulted in a higher proportion of potential novelties than using the more traditional point outlier isolation forest approach. This finding was consistent in both the clinical trial and real-world cohort study data. Using augmented intelligence through outlier analysis has the potential to speed up the process of identifying potential clinical discoveries. This approach can be replicated across clinical disciplines and could exist within electronic medical records systems to automatically identify outliers within clinical notes to clinical experts.

Exploring the feasibility of establishing a core set of sexual, reproductive, maternal, newborn, child, and adolescent health indicators in humanitarian settings: results from a multi-methods assessment in Jordan.

BACKGROUND: Reliable and rigorously collected sexual, reproductive, maternal, newborn, child, and adolescent health (SRMNCAH) data in humanitarian settings is often sparse and variable in quality across different humanitarian settings. To address this gap in data quality, the World Health Organization (WHO) developed a core set of indicators for monitoring and evaluating SRMNCAH services and outcomes in humanitarian settings, and assessed their feasibility in the field in Jordan, in addition to three other countries; with the goal of aggregating information from global consultations and field-level assessments to reach consensus on a set of core SRMNCAH indicators for services and outcome evaluation in humanitarian settings among WHO global partners. METHODS: The feasibility assessment in Jordan focused on the following constructs: relevance/usefulness, feasibility of measurement, systems and resources, and ethical issues. The multi-methods assessment included five components; a desk review, key informant interviews, focus group discussions, facility assessments, and observational sessions. RESULTS: Findings suggest that there is widespread support among regional, national, as well as global stakeholders for developing a core list of SRMNCAH indicators for monitoring and evaluation of services and outcomes in humanitarian settings in Jordan. There are numerous resources and data collection systems that could be leveraged, built upon, and improved to ensure the feasibility of collecting this proposed set of indicators. However, the data collection load requested from donors, the national government, international and UN agencies, coordination/cluster systems must be better harmonized, standardized, and less burdensome. CONCLUSIONS: Despite stakeholder support in developing a core set of indicators, this would only be useful if it has the buy-in from the international community. Greater harmonization and coordination, alongside increased resource allocation, would improve data collection efforts and allow stakeholders to meet indicators' reporting requirements.

Do Case Reports and Case Series Generate Clinical Discoveries About Preeclampsia? A Systematic Review.

Background: Preeclampsia is a leading cause of maternal and perinatal mortality and morbidity. The management of preeclampsia has not changed much in more than two decades, and its aetiology is still not fully understood. Case reports and case series have traditionally been used to communicate new knowledge about existing conditions. Whether this is true for preeclampsia is not known. Objective: To determine whether recent case reports or case series have generated new knowledge and clinical discoveries about preeclampsia. Methods: A detailed search strategy was developed in consultation with a medical librarian. Two bibliographic databases were searched through Ovid: Embase and MEDLINE. We selected case reports or case series published between 2015 and 2020, comprising pregnant persons diagnosed with hypertensive disorders of pregnancy, including preeclampsia. Two reviewers independently screened all publications. One reviewer extracted data from included studies, while another conducted a quality check of extracted data. We developed a codebook to guide our data extraction and outcomes assessment. The quality of each report was determined based on Joanna Briggs Institute (JBI) critical appraisal checklist for case reports and case series. Results: We included 104 case reports and three case series, together comprising 118 pregnancies. A severe presentation or complication of preeclampsia was reported in 81% of pregnancies, and 84% had a positive maternal outcome, free of death or persistent complications. Only 8% of the case reports were deemed to be of high quality, and 53.8% of moderate quality; none of the case series were of high quality. A total of 26 of the 107 publications (24.3%) included a novel clinical discovery as a central theme. Conclusion: Over two-thirds of recent case reports and case series about preeclampsia do not appear to present new knowledge or discoveries about preeclampsia, and most are of low quality.

"I just was really scared, because it's already such an uncertain time": Exploring women's abortion experiences during the COVID-19 pandemic in Canada.

OBJECTIVE: Travel restrictions, physical distancing and quarantine requirements, lockdowns, and stay-at-home orders due to COVID-19 have impacted abortion services across Canada. We aimed to explore the decision-making and care experiences of those who obtained abortion services during the COVID-19 pandemic and understand recent abortion patients' perspectives on demedicalized models of medication abortion service delivery. STUDY DESIGN: We conducted 23 semi-structured, in-depth interviews with women across Canada who obtained abortion care after March 15, 2020. We audio-recorded and transcribed the telephone/Skype/Zoom interviews and managed our data with ATLAS.ti. We analyzed the English-language interviews for content and themes using inductive and deductive techniques. RESULTS: The COVID-19 pandemic, and the associated economic and social support uncertainties, factored into many of our participants' decisions to obtain an abortion. Participants expressed relief and gratitude for being able to secure abortion care during the pandemic. Although women in our study reflected positively on their abortion care experiences, many felt that service delivery changes initiated because of the public health emergency exacerbated pre-COVID-19 barriers to care and contributed to feelings of loneliness and isolation. Our participants expressed considerable enthusiasm for demedicalized models of medication abortion care, including telemedicine services and behind-the-counter availability of mifepristone/misoprostol. CONCLUSIONS: For our participants, abortion care constituted an essential health service. Our findings demonstrate the importance of continuing to provide access to safe, effective, and timely abortion care during public health emergencies. Exploring additional models of demedicalized medication abortion service delivery to address persistent access barriers in Canada is warranted. IMPLICATIONS: Policymakers and clinicians should consider patient experiences as well as clinical evidence when considering regulatory changes to facilitate access to abortion care during public health emergencies. Identifying a multitude of ways to offer a full range of abortion services, including demedicalized models of medication abortion care, has the potential to meet significant needs in the COVID-19 era and beyond. The COVID pandemic highlights the need for demedicalized models, not only for the sake of those seeking abortion care but also to ease the burden on medical professionals during public health emergencies.

Integrating mifepristone into primary care in Canada's capital: A multi-methods exploration of the Medical Abortion Access Project.

OBJECTIVES: Following the 2017 introduction of mifepristone in Canada and both ensuing regulatory changes and increased demand for medication abortion care, Planned Parenthood Ottawa created the Medical Abortion Access Project (MAAP). This study aimed to document outcomes, identify facilitators and barriers, and distill learnings from an initiative that sought to recruit and support primary care clinicians in providing mifepristone/misoprostol in Canada's capital. STUDY DESIGN: We employed a multi-methods evaluation strategy that included reviewing MAAP-related documents, evaluating the project log, and conducting in-depth interviews with clinicians at 5 sites. In the final analytic phase, we integrated the findings from the different evaluation components. RESULTS: From May 2017 through July 2018, the MAAP helped 14 primary care facilities in Ottawa become medication abortion providers; 9 began providing mifepristone/misoprostol to existing patients and 5 began offering mifepristone/misoprostol to the public. The program recruited 4 new pharmacies to stock the combination package and trained 2 sonography clinics in abortion-related protocols. Program participants identified patient demand as a key driver of medication abortion provision but required information and logistical support from the MAAP to operationalize service delivery. New abortion providers reflected positively on the community of practice that the MAAP created, which enabled them to offer and receive technical and emotional support from colleagues across the city. CONCLUSIONS: A number of primary care clinicians in Ottawa were able to successfully integrate medication abortion care into their practices with MAAP support. Future research should explore whether this type of community-based intervention can be replicated in other settings. IMPLICATIONS: Evidence-based regulation of mifepristone by health authorities is a critical step to increasing access to medication abortion care. However, deregulation alone was insufficient to integrate medication abortion services into primary care in Ottawa. Community-based programs like the MAAP can help providers make sense of shifting regulations and practice guidelines, overcome logistical barriers, and ultimately increase access to this medically necessary service. Establishing and facilitating communities of practice is especially important for new primary care providers.

"Who is driving you home today?" Escort policies as a barrier to abortion access.

Post-sedation escort policies are not evidence-based but traditional consensus recommendations made by professional societies. As people travel further for abortion care, escort policies are increasingly difficult to navigate and force people to delay care, compromise privacy, or undergo procedures without sedation. At worst, clinics may turn away people who present without an escort. Recent research shows that patients can be discharged safely after sedation using rideshare or transport services without a known escort. Updating escort policies lowers barriers to abortion and preserves autonomy, comfort, and choice.

Community-based distribution of misoprostol for early abortion: Outcomes from a program in Sindh, Pakistan.

OBJECTIVE: To evaluate the outcomes of a community-based distribution program in which lay providers offer women in Sindh, Pakistan misoprostol for early abortion. STUDY DESIGN: We reviewed monitoring logbooks to examine pregnancy outcomes and analyzed logbook data using descriptive statistics. RESULTS: In late 2019, 120 women obtained abortion care through this program. None of the women (n = 0) were pregnant 4 weeks after initiating the regimen and none (n = 0) experienced complications requiring medical intervention. CONCLUSIONS: Outcomes from this initiative may be valuable for those working to expand access to misoprostol-alone for early abortion in other settings.

Incidents of violence and disruption reported by the National Abortion Federation's Canadian members in 2017.

OBJECTIVE: To explore violence and disruption events reported by Canadian facilities providing abortion care in 2017, when only 3 provinces had passed safe access zone legislation. METHODS: We reviewed self-reported data from 16 of 38 Canadian members of the National Abortion Federation. RESULTS: Twelve facilities in 7 provinces reported 571 instances of picketing (97%), trespassing (1%), threats of harm (0.2%), and harassing calls/mail/emails (2%); 4 facilities reported no incidents. Freestanding clinics reported more picketing than hospital-based facilities. DISCUSSION: Abortion providing facilities in Canada experienced picketing and other kinds of violence and disruption in 2017. These data serve as a baseline for future studies.

"We have to make sure you meet certain criteria": exploring patient experiences of the criminalisation of abortion in Australia.

INTRODUCTION: Nine different sets of laws govern abortion in Australia, and the criteria for an abortion to be considered lawful varies considerably by jurisdiction. We explored how the criminal status of abortion affected patients' experiences in accessing care in a country where abortion services are widely available. METHODS: We conducted qualitative, in-depth interviews with 22 people who had an abortion in Australia since 2009 across a variety of legal contexts. We audio-recorded all interviews and transcribed them in their entirety. We carried out content and thematic analyses of the interviews using deductive and inductive techniques. RESULTS: At the time of their procedures, more than half of our participants (n = 13) obtained their abortion in a state or territory that had criminal sanctions associated with procuring an abortion and required abortion seekers to meet strict legal requirements to access care. In general, participants reported confusion about the legal status of abortion. Participants who had an abortion in criminalised settings described significant negative emotional impacts that were directly linked to the law. They were often required to fit their abortion story into a state-mandated narrative. Further, the criminalisation of abortion meant that some participants felt they could not be honest with clinicians for fear of being denied care. The participants were overwhelmingly in support of decriminalisation of abortion and increased consistency of the legal status of the procedure across Australia. CONCLUSIONS: The criminalisation of abortion in some Australian states negatively impacts patients' emotional wellbeing, undermines the patient-clinician relationship, and perpetuates abortion stigma. In the absence of legislative reform, training for clinicians - including abortion providers and general practitioners - to explain the implications of the legal status to their patients appears warranted. Patient-centred resources, such as a website with state-specific information, could fill an important knowledge gap for the public.

The future of abortion is now: Mifepristone by mail and in-clinic abortion access in the United States.

The COVID-19 pandemic disrupted health care delivery in all aspects of medicine, including abortion care. For 6 months, the mifepristone Risk Evaluation and Mitigation Strategy (REMS) was temporarily blocked, allowing for the remote provision of medication abortion. Remote medication abortion may become a dominant model of care in the future, either through the formal health system or through self-sourced, self-managed abortion. Clinics already face pressure from falling abortion rates and excessive regulation and with a transition to remote abortion, may not be able to sustain services. Although remote medication abortion improves access for many, those who need or want in-clinic care such as people later in pregnancy, people for whom abortion at home is not safe or feasible, or people who are not eligible for medication abortion, will need comprehensive support to access safe and appropriate care. To understand how we may adapt to remote abortion without leaving people behind, we can look outside of the U.S. to become familiar with emerging and alternative models of abortion care.

Patient-Centered Care for Women: Delphi Consensus on Evidence-Derived Recommendations.

OBJECTIVE: Patient-centered care (PCC) could reduce gender inequities in quality of care. Little is known about how to implement patient-centered care for women (PCCW). We aimed to generate consensus recommendations for achieving PCCW. METHODS: We used a 2-round Delphi technique. Panelists included 21 women of varied age, ethnicity, education, and urban/rural residence; and 21 health professionals with PCC or women's health expertise. Panelists rated recommendations, derived from prior research and organized by a 6-domain PCC framework, on a 7-point Likert scale in an online survey. We used summary statistics to report response frequencies and defined consensus as when ≥85% panelists chose 5 to 7. RESULTS: The response rate was 100%. In round 1, women and professionals retained 46 (97.9%) and 42 (89.4%) of 47 initial recommendations, respectively. The round 2 survey included 6 recommendations for women and 5 recommendations for professionals (did not achieve consensus in round 1 or were newly suggested). In round 2, women retained 2 of 6 recommendations and professionals retained 3 of 5 recommendations. Overall, 49 recommendations were generated. Both groups agreed on 44 (94.0%) recommendations (13 retained by 100% of both women and clinicians): fostering patient-physician relationship (n = 11), exchanging information (n = 10), responding to emotions (n = 4), managing uncertainty (n = 5), making decisions (n = 8), and enabling patient self-management (n = 6). CONCLUSION: The recommendations represent the range of PCC domains, are based on evidence from primary research, and reflect high concordance between women and professional panelists. They can inform the development of policies, guidelines, programs, and performance measures that foster PCCW.

"I didn't doubt my choice, but I felt bad": A qualitative exploration of Canadian abortion patients' experiences with protesters.

OBJECTIVES: Although a body of research has focused on violence, disruption, and harassment targeting abortion clinics and clinic staff, little research has explored Canadian abortion patients' experiences with protesters. Through this national qualitative study we aimed to address this gap. METHODS: Between 2012 and 2016, we conducted in-depth interviews with 305 Canadian women who had an abortion in the previous five years. Thirty participants reported encountering protesters when seeking abortion care. We focused on this sub-set of interviews and analyzed these data for content and themes using inductive and deductive techniques. RESULTS: Across the country, participants reported encountering protesters holding signs, chanting slogans, and shouting insults. These interactions were concentrated at clinics in New Brunswick, Newfoundland and Labrador, and Ontario. Although no participants reported that these encounters made them reconsider their decision, they did report that seeing and interacting with protesters was at times unsettling, stigmatizing, and frustrating. Participants who struggled with the decision to have an abortion and those who made the decision in the context of health issues or violence found these encounters especially upsetting. Participants discussed how their interactions with protesters and the additional security measures put in place by clinics contrasted with their experiences accessing other kinds of health care and they wished that the protesters had not been there. CONCLUSIONS: For some Canadian abortion patients, encountering protesters is upsetting and stigmatizing. Exploring ways to minimize interactions between protesters and those seeking abortion care, such as enacting and enforcing safe access zone legislation, appears warranted. IMPLICATIONS: Although several Canadian provinces have enacted safe access zone laws, these do not currently exist across all jurisdictions. In addition to protecting clinics and clinic staff, implementation of these buffer zones have the potential to improve some patients' experiences obtaining a medically necessary and essential service.

Exploring the Availability of Emergency Contraception in New Brunswick Pharmacies: A Mystery-Client Telephone Study.

Although levonorgestrel-only emergency contraceptive pills (LNg-ECPs) have been available over the counter in Canada for more than a decade, barriers to access persist. We aimed to obtain information about the availability and cost of LNg-ECPs in New Brunswick. Using a mystery-client study design, we called all 207 non-specialty pharmacies in the province posing as a 17-year-old woman seeking something to prevent pregnancy after sex. We evaluated the information provided for accuracy and quality. The overwhelming majority of pharmacies (n = 180, 87%) had at least one brand of LNg-ECPs in stock; the price averaged CAD28.69 (USD21.65). Although the majority of pharmacy representatives provided accurate information about LNg-ECPs, a small number made incorrect statements about the timeframe for use, side effects, and mechanism of action. In nine interactions (4%) pharmacy representatives incorrectly indicated that a male partner could not obtain LNg-ECPs; none indicated that parental involvement was required to procure LNg-ECPs. None of the pharmacy representatives referenced any other modality of emergency contraception, including ulipristal acetate. Our findings suggest that LNg-ECPs are widely available and that most pharmacy representatives are providing accurate medical and regulatory information. However, supporting the continuing education of pharmacists and pharmacy staff, particularly around alternative modalities of emergency contraception, appears warranted.