Heterozygous RPA2 variant as a novel genetic cause of telomere biology disorders.

Premature telomere shortening or telomere instability is associated with a group of rare and heterogeneous diseases collectively known as telomere biology disorders (TBDs). Here we identified two unrelated individuals with clinical manifestations of TBDs and short telomeres associated with the identical monoallelic variant c.767A>G; Y256C in RPA2 Although the replication protein A2 (RPA2) mutant did not affect ssDNA binding and G-quadruplex-unfolding properties of RPA, the mutation reduced the affinity of RPA2 with the ubiquitin ligase RFWD3 and reduced RPA ubiquitination. Using engineered knock-in cell lines, we found an accumulation of RPA at telomeres that did not trigger ATR activation but caused short and dysfunctional telomeres. Finally, both patients acquired, in a subset of blood cells, somatic genetic rescue events in either POT1 genes or TERT promoters known to counteract the accelerated telomere shortening. Collectively, our study indicates that variants in RPA2 represent a novel genetic cause of TBDs. Our results further support the fundamental role of the RPA complex in regulating telomere length and stability in humans.

Congenital microcoria deletion in mouse links Sox21 dysregulation to disease and suggests a role for TGFB2 in glaucoma and myopia.

Congenital microcoria (MCOR) is a rare hereditary developmental defect of the iris dilator muscle frequently associated with high axial myopia and high intraocular pressure (IOP) glaucoma. The condition is caused by submicroscopic rearrangements of chromosome 13q32.1. However, the mechanisms underlying the failure of iris development and the origin of associated features remain elusive. Here, we present a 3D architecture model of the 13q32.1 region, demonstrating that MCOR-related deletions consistently disrupt the boundary between two topologically associating domains (TADs). Deleting the critical MCOR-causing region in mice reveals ectopic Sox21 expression precisely aligning with Dct, each located in one of the two neighbor TADs. This observation is consistent with the TADs' boundary alteration and adoption of Dct regulatory elements by the Sox21 promoter. Additionally, we identify Tgfb2 as a target gene of SOX21 and show TGFΒ2 accumulation in the aqueous humor of an MCOR-affected subject. Accumulation of TGFB2 is recognized for its role in glaucoma and potential impact on axial myopia. Our results highlight the importance of SOX21-TGFB2 signaling in iris development and control of eye growth and IOP. Insights from MCOR studies may provide therapeutic avenues for this condition but also for glaucoma and high myopia conditions, affecting millions of people.

Cluster B personality disorders and psychotropic medications: a focused analysis of trends and patterns across sex and age groups.

PURPOSE: This study investigated sex and age differences in patterns of psychotropic medication use before and after the initial diagnosis of Cluster B personality disorders (PDs) and analyzed trends over time. METHODS: Analyzing data from the Quebec Integrated Chronic Disease Surveillance System for individuals newly diagnosed with Cluster B PD (≥ 14 years) between 2002 and 2018 and under the provincial public drug plan, we calculated yearly and monthly proportions of individuals exposed to psychotropic medications during the year before and after their diagnosis by sex and age. Robust Poisson regression models assessed the association between sex and exposure to psychotropic medications after the diagnosis of Cluster B PD. RESULTS: Among 87,778 individuals with a first Cluster B PD diagnosis (mean age: 44.5 years; 57.5% women), the proportion of users increased post-diagnosis. Notably, after diagnosis, females were more likely to receive psychiatric medications (between 78.9% and 83.7% during the study period vs. 72.8% and 76.8%). Males were less likely than females to receive antidepressants (adjusted prevalence ratio (aPR): 0.83; 99% confidence interval (CI): 0.82-0.85) and anxiolytics (aPR: 0.86; 99%CI: 0.84-0.88), whereas they had higher exposure to antipsychotics (aPR: 1.04; 99%CI: 1.02-1.06) and ADHD medications (aPR: 1.14; 99%CI: 1.07-1.2). Age-specific trends showed increased ADHD medication use among younger patients (14-24 years), and anxiolytic use predominated in those aged ≥ 65 years. CONCLUSIONS: Psychotropic medication use was high among Cluster B PD patients, with differences in medication classes according to age and sex. The marked sex and age differences in psychotropic medication use among Cluster B PD patients underscore the need for a sex-sensitive and age-specific approach in psychiatric care.

Understanding drug exceptional access programs (DEAPs) in Canada, and their associated social and political issues.

Drug exceptional access programs (DEAPs) exist across Canada to address gaps in access to pharmaceuticals. These programs circumvent standard procedures, raising epistemic, economic, social and political issues. This commentary provides insights into these issues by revealing the context and procedures on which these programs depend.

Vaccine promotion strategies in community pharmacy addressing vulnerable populations: a scoping review.

CONTEXT: Social determinants of health are drivers of vaccine inequity and lead to higher risks of complications from infectious diseases in under vaccinated communities. In many countries, pharmacists have gained the rights to prescribe and administer vaccines, which contributes to improving vaccination rates. However, little is known on how they define and target vulnerable communities. OBJECTIVE: The purpose of this study is to describe how vulnerable communities are targeted in community pharmacies. METHODS: We performed a systematic search of the Embase and MEDLINE database in August 2021 inspired by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocols (PRISMA ScR). Articles in English, French or Spanish addressing any vaccine in a community pharmacy context and that target a population defined as vulnerable were screened for inclusion. RESULTS: A total of 1039 articles were identified through the initial search, and 63 articles met the inclusion criteria. Most of the literature originated from North America (n = 54, 86%) and addressed influenza (n = 29, 46%), pneumococcal (n = 14, 22%), herpes zoster (n = 14, 22%) or human papilloma virus vaccination (n = 14, 22%). Lifecycle vulnerabilities (n = 48, 76%) such as age and pregnancy were most often used to target vulnerable patients followed by clinical factors (n = 18, 29%), socio-economical determinants (n = 16, 25%) and geographical vulnerabilities (n = 7, 11%). The most frequently listed strategy was providing a strong recommendation for vaccination, promotional posters in pharmacy, distributing leaflet/bag stuffers and providing staff training. A total of 24 barriers and 25 facilitators were identified. The main barriers associated to each vulnerable category were associated to effective promotional strategies to overcome them. CONCLUSION: Pharmacists prioritize lifecycle and clinical vulnerability at the expense of narrowing down the definition of vulnerability. Some vulnerable groups are also under targeted in pharmacies. A wide variety of promotional strategies are available to pharmacies to overcome the specific barriers experienced by various groups.

Rab44 regulates murine mast cell-driven anaphylaxis through kinesin-1-dependent secretory granule translocation.

BACKGROUND: Mast cells (MCs) are key effectors of the allergic response. Following the cross-linking of IgE receptors (FcεRIs), they release crucial inflammatory mediators through degranulation. Although degranulation depends critically on secretory granule (SG) trafficking toward the plasma membrane, the molecular machinery underlying this transport has not been fully characterized. OBJECTIVES: This study analyzed the function of Rab44, a large, atypical Rab guanosine triphosphatase highly expressed in MC, in the MC degranulation process. METHODS: Murine knockout (KO) mouse models (KORab44 and DKOKif5b/Rab44) were used to perform passive cutaneous anaphylaxis experiments and analyze granule translocation in bone marrow-derived MCs during degranulation. RESULTS: This study demonstrate that mice lacking Rab44 (KORab44) in their bone marrow-derived MCs are impaired in their ability to translocate and degranulate SGs at the plasma membrane on FcεRI stimulation. Accordingly, KORab44 mice were less sensitive to IgE-mediated passive cutaneous anaphylaxis in vivo. A lack of Rab44 did not impair early FcεRI-stimulated signaling pathways, microtubule reorganization, lipid mediator release, or cytokine secretion. Mechanistically, Rab44 appears to interact with and function as part of the previously described kinesin-1-dependent transport pathway. CONCLUSIONS: These results highlight a novel role of Rab44 as a regulator of SG transport during degranulation and anaphylaxis acting through the kinesin-1-dependent microtubule transport machinery. Rab44 can thus be considered a potential target for modulating MC degranulation and inhibiting IgE-mediated allergic reactions.

Structuring and organizing interprofessional healthcare in partnership with patients with diabetes: the INterprofessional Management and Education in Diabetes care (INMED) pathway.

Type 2 diabetes is a complex chronic disease that requires ongoing monitoring by an interprofessional team to prevent complications. The INMED (INterprofessional Management and Education in Diabetes) care pathway was developed by our team to optimize primary care services for these patients and their families. The objective of this study is to describe the preliminary results of its adoption and implementation. The INMED care pathway is organized into four axes: (a) continuing professional education, (b) self-management support, (c) case management, and (d) ongoing evaluation of the quality of diabetes care and services. A multiple-case study is underway to document its effects on practice change using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. Preliminary results on the adoption and implementation revealed some strengths: (a) regular patient follow-up by the case manager, (b) scheduling of physician appointments when required, and (c) regular screening for risk factors. Barriers were also identified: (a) lack of clear understanding of the case manager role, (b) lack of referrals to team members, and (c) lack of use of the motivational interview approach. The INMED care pathway is being adopted by primary care teams but challenges need to be overcome to improve its reach and effectiveness.

Chest X-ray Analysis With Deep Learning-Based Software as a Triage Test for Pulmonary Tuberculosis: An Individual Patient Data Meta-Analysis of Diagnostic Accuracy.

BACKGROUND: Automated radiologic analysis using computer-aided detection software (CAD) could facilitate chest X-ray (CXR) use in tuberculosis diagnosis. There is little to no evidence on the accuracy of commercially available deep learning-based CAD in different populations, including patients with smear-negative tuberculosis and people living with human immunodeficiency virus (HIV, PLWH). METHODS: We collected CXRs and individual patient data (IPD) from studies evaluating CAD in patients self-referring for tuberculosis symptoms with culture or nucleic acid amplification testing as the reference. We reanalyzed CXRs with three CAD programs (CAD4TB version (v) 6, Lunit v3.1.0.0, and qXR v2). We estimated sensitivity and specificity within each study and pooled using IPD meta-analysis. We used multivariable meta-regression to identify characteristics modifying accuracy. RESULTS: We included CXRs and IPD of 3727/3967 participants from 4/7 eligible studies. 17% (621/3727) were PLWH. 17% (645/3727) had microbiologically confirmed tuberculosis. Despite using the same threshold score for classifying CXR in every study, sensitivity and specificity varied from study to study. The software had similar unadjusted accuracy (at 90% pooled sensitivity, pooled specificities were: CAD4TBv6, 56.9% [95% confidence interval {CI}: 51.7-61.9]; Lunit, 54.1% [95% CI: 44.6-63.3]; qXRv2, 60.5% [95% CI: 51.7-68.6]). Adjusted absolute differences in pooled sensitivity between PLWH and HIV-uninfected participants were: CAD4TBv6, -13.4% [-21.1, -6.9]; Lunit, +2.2% [-3.6, +6.3]; qXRv2: -13.4% [-21.5, -6.6]; between smear-negative and smear-positive tuberculosis was: were CAD4TBv6, -12.3% [-19.5, -6.1]; Lunit, -17.2% [-24.6, -10.5]; qXRv2, -16.6% [-24.4, -9.9]. Accuracy was similar to human readers. CONCLUSIONS: For CAD CXR analysis to be implemented as a high-sensitivity tuberculosis rule-out test, users will need threshold scores identified from their own patient populations and stratified by HIV and smear status.

Traduction et validation du questionnaire de dépistage Borderline Personality Questionnaire.

OBJECTIF: Disposer d'outils de dépistage valides pour évaluer le trouble de la personnalité limite est essentiel en pratique clinique et en recherche. Parmi les outils existants, le questionnaire sur la personnalité limite (BPQ) présente plusieurs qualités. Cependant, il n'existe pas de version française et il n'a pas été validé avec des adultes dans un échantillon clinique. Les objectifs de cette étude étaient : 1) traduire le BPQ en français; 2) mesurer la validité convergente, prédictive et discriminante, la cohérence interne et la fidélité test-retest. MÉTHODE: Les recommandations de Streiner, Norman et Cairney (2014) sur la traduction d'évaluations ont été suivies. Quarante adultes référés à un programme spécialisé en troubles de la personnalité ont participé à l'étude. Pour évaluer la validité du BPQ français, le questionnaire SCID-II (entrevue et auto-évaluation) fut administré et le diagnostic psychiatrique fut établi par un psychiatre à l'insu. RÉSULTATS: Aucune modification majeure n'a été apportée au BPQ français. Les analyses ont montré une cohérence interne élevée (α = 0,84), une bonne fidélité test-retest (r = 0,77), une discrimination significative avec le trouble de la personnalité schizotypique (r = -0,31; p < 0,05), une convergence significative avec le SCID-II (r = 0,72) et une validité prédictive significative du diagnostic psychiatrique (p < 0,01). CONCLUSIONS: La version française du BPQ présente des qualités psychométriques prometteuses à un usage auprès des personnes ayant un trouble de la personnalité limite.

Under consent: participation of people with HIV in an Ebola vaccine trial in Canada.

BACKGROUND: Little is known about volunteers from Northern research settings who participate in vaccine trials of highly infectious diseases with no approved treatments. This article explores the motivations of HIV immunocompromised study participants in Canada who volunteered in a Phase II clinical trial that evaluated the safety and immunogenicity of an Ebola vaccine candidate. METHODS: Observation at the clinical study site and semi-structured interviews employing situational and discursive analysis were conducted with clinical trial participants and staff over one year. Interviews were recorded, transcribed and analysed using critical qualitative interpretivist thematic analytical techniques. Patterns were identified, clustered and sorted to generate distinct and comprehensive themes. We then reassembled events and contexts from the study participants' stories to develop two ideal portraits based on "composite characters" based on study participants features. These provide ethnographically rich details of participants' meaningful social worlds while protecting individual identities. RESULTS: Ten of the 14 clinical trial participants, and 3 study staff were interviewed. Participant demographics and socio-economic profiles expressed limited contextual diversity. Half were men who have sex with men, half were former injection drug users experiencing homelessness, one was female, none were racialized minorities and there were no people from HIV endemic countries. Fully 90% had previous involvement in other clinical studies. Their stories point to particular socio-economic situations that motivated their participation as clinical labor through trial participation. CONCLUSIONS: Our findings support Fisher's argument of "structural coercion" in clinical trial recruitment of vulnerable individuals experiencing precarious living conditions. Clinical trials should provide more detail of the structural socio-economic conditions and healthcare needs which lie "under consent" of study participants. Going well beyond an overly convenient narrative of altruism, ethical deliberation frameworks need to sufficiently address the structural conditions of clinical trials. We offer concrete possibilities for this and acknowledge that further research and clinical data should be made available underlying study participant contexts with regards to recruitment and participation in resource poor settings, in both the South and the North.

Learning from public health and hospital resilience to the SARS-CoV-2 pandemic: protocol for a multiple case study (Brazil, Canada, China, France, Japan, and Mali).

BACKGROUND: All prevention efforts currently being implemented for COVID-19 are aimed at reducing the burden on strained health systems and human resources. There has been little research conducted to understand how SARS-CoV-2 has affected health care systems and professionals in terms of their work. Finding effective ways to share the knowledge and insight between countries, including lessons learned, is paramount to the international containment and management of the COVID-19 pandemic. The aim of this project is to compare the pandemic response to COVID-19 in Brazil, Canada, China, France, Japan, and Mali. This comparison will be used to identify strengths and weaknesses in the response, including challenges for health professionals and health systems. METHODS: We will use a multiple case study approach with multiple levels of nested analysis. We have chosen these countries as they represent different continents and different stages of the pandemic. We will focus on several major hospitals and two public health interventions (contact tracing and testing). It will employ a multidisciplinary research approach that will use qualitative data through observations, document analysis, and interviews, as well as quantitative data based on disease surveillance data and other publicly available data. Given that the methodological approaches of the project will be largely qualitative, the ethical risks are minimal. For the quantitative component, the data being used will be made publicly available. DISCUSSION: We will deliver lessons learned based on a rigorous process and on strong evidence to enable operational-level insight for national and international stakeholders.

Mutations in GREB1L Cause Bilateral Kidney Agenesis in Humans and Mice.

Congenital anomalies of the kidney and urinary tract (CAKUT) constitute a major cause of chronic kidney disease in children and 20% of prenatally detected anomalies. CAKUT encompass a spectrum of developmental kidney defects, including renal agenesis, hypoplasia, and cystic and non-cystic dysplasia. More than 50 genes have been reported as mutated in CAKUT-affected case subjects. However, the pathophysiological mechanisms leading to bilateral kidney agenesis (BKA) remain largely elusive. Whole-exome or targeted exome sequencing of 183 unrelated familial and/or severe CAKUT-affected case subjects, including 54 fetuses with BKA, led to the identification of 16 heterozygous variants in GREB1L (growth regulation by estrogen in breast cancer 1-like), a gene reported as a target of retinoic acid signaling. Four loss-of-function and 12 damaging missense variants, 14 being absent from GnomAD, were identified. Twelve of them were present in familial or simplex BKA-affected case subjects. Female BKA-affected fetuses also displayed uterus agenesis. We demonstrated a significant association between GREB1L variants and BKA. By in situ hybridization, we showed expression of Greb1l in the nephrogenic zone in developing mouse kidney. We generated a Greb1l knock-out mouse model by CRISPR-Cas9. Analysis at E13.5 revealed lack of kidneys and genital tract anomalies in male and female Greb1l-/- embryos and a slight decrease in ureteric bud branching in Greb1l+/- embryos. We showed that Greb1l invalidation in mIMCD3 cells affected tubulomorphogenesis in 3D-collagen culture, a phenotype rescued by expression of the wild-type human protein. This demonstrates that GREB1L plays a major role in early metanephros and genital development in mice and humans.

Pharmaceutical practices before and throughout the opioid crisis: A scoping review.

METHODS: Opioid misuse has reached epidemic status in many countries. This crisis-recognized since 2014-questions the practices of prescribing and dispensing. Did this public health issue change pharmaceutical practices? This literature review presents pharmaceutical practices regarding treatment of noncancer pain. We will assess whether these practices changed after the declaration of the crisis. We will also present barriers and facilitators to their implementation in real life to understand the distance between them and current practices. A scoping review of the literature was conducted on PubMed, Medline, and Embase for references dealing with pharmaceutical practices regarding noncancer pain management, in French and English, from 2000 to 2018. RESULTS: The search yielded 250 results, with 25 studies surviving the exclusion process. Twenty studies took place in the United States, the country most affected by the crisis. Interventions took place as interprofessional collaboration (n = 14), patient counseling (6), or a combination of these (5). Although the nature of the interventions remained constant through the crisis, the number of publications greatly increased over time. The studies demonstrated pharmacists' upstream contributions regarding pain management and opioid use. Several large-scale implementation issues, including knowledge gaps and communication barriers, have been reported in these studies and in others that gathered opinions and perspectives of prescribers, pharmacists, and patients. CONCLUSION: Our review showed that the opioid crisis did not modify the nature of pharmaceutical practices regarding pain treatment and opioid management, but the number of studies reporting these practices greatly increased since its onset. Barriers to implementing the best practices to reduce opioid harm have been identified to explain slow integration in daily practice. Adjustments to teaching and practice methods such as a reviewed pain treatment curriculum, standardized tools, and decision-making algorithms could prove beneficial.

Prevalence, Mortality, and Health Care Use among Patients with Cluster B Personality Disorders Clinically Diagnosed in Quebec: A Provincial Cohort Study, 2001-2012.

BACKGROUND: Cluster B personality disorders (PDs) are prevalent mental health conditions in the general population (1%-6% depending on the subtype and study). Affected patients are known to be heavier users of both mental and medical health care systems than patients with other clinical conditions such as depression. METHODS: Several rates were estimated using data from the integrated monitoring system for chronic diseases in the province of Quebec, Canada. It provides a profile of annual and period prevalence rates, mortality rates, and years of lost life as well as health care utilisation rates for Quebec residents. All Quebec residents are covered by a universal publicly managed care health plan. It is estimated that the monitoring system includes 99% of Quebec's 8 million inhabitants. RESULTS: Quebec residents aged 14 years and older were included in the study. The lifetime prevalence of cluster B PDs was 2.6%. The mean years of lost life expectancy were 13 for men and 9 for women compared to the provincial population. The 3 most important causes of death are suicide (20.4%), cardiovascular diseases (19.1%), and cancers (18.6%). In 2011 to 2012, 78% had consulted a general practitioner and 62% a psychiatrist, 44% were admitted to an emergency department, and 22% were hospitalised. CONCLUSIONS: Considering mortality, cluster B personality disorder is a severe condition, is highly prevalent in the population, and is associated with heavy health care services utilisation, especially in emergency settings.

Measurement, "scriptural economies," and social justice: governing HIV/AIDS treatments by numbers in a fragile state, the Central African Republic (CAR).

Fragile states have been raising increasing concern among donors since the mid-2000s. The policies of the Global Fund to fight HIV/AIDS, Malaria, and Tuberculosis (GF) have not excluded fragile states, and this source has provided financing for these countries according to standardized procedures. They represent interesting cases for exploring the meaning and role of measurement in a globalized context. Measurement in the field of HIV/AIDS and its treatment has given rise to a private outsourcing of expertise and auditing, thereby creating a new form of value based on the social process of registration and the creation of realities produced by the intervention itself. These "scriptural economies" must be questioned in terms of the production of knowledge, but also in terms of social justice. Governing HIV/AIDS treatments by numbers in a fragile state is explored in this article through the experience of the Central African Republic (CAR) in terms of epidemiology and access to antiretroviral drugs. The unexpected effects of performance-based programs in this context underline the need for global health governance to be re-embedded into a social justice framework.

Recovery, as Experienced by Women with Borderline Personality Disorder.

Studies examining recovery through the service users' perspectives have mainly included persons with schizophrenia or bipolar disorder. Giving voice to those with borderline personality disorder (BPD) would enrich our understanding of recovery, as their specific experiences may bring new dimensions, obstacles and facilitators. The objective of this study was to qualitatively capture the experience of recovery in women with BPD. Participants were women between 18 and 65 years old who had a diagnosis of BPD and completed at least 2 years in a program for persons with BPD. During the first meeting, they produced a picture collage, followed by an interview on their experience of recovery. The second meeting was a phone interview to discuss new thoughts. In addition, their medical records were reviewed. A thematic analysis of the interviews was conducted and organized with the Person-Environment-Occupation model. Although recovery was not the best term to name their experience, they all talked about a process towards stability and wellbeing (n = 12). Dimensions of recovery included, for example, letting go of the past (person), being involved in meaningful activities (occupation) and having healthy relationships (environment). Facilitators included social support and participation in a specialized therapy program. The main obstacle was unstable family relationships. The findings from this study showed similar dimensions to previous recovery studies, new perspectives on certain dimensions, as well as new ones. They also reinforced the importance to incorporate intervention outcomes that target the person with BPD, their social environment and meaningful occupations.

Use of a "baby bottle" to allow a "better-than-nothing" death in older adults infected by COVID-19 in Quebec retirement homes - A case study.

The COVID-19 pandemic has brought to the forefront profound questions surrounding dying and the concept of a "good death". This qualitative case study, conducted in a health center in Quebec, Canada, severely affected by outbreaks during the pandemic's first wave, explores end-of-life care for older adults in retirement homes. Through thirty interviews with healthcare practitioners, researchers, and managers, we investigate the critical role of a pharmacological device referred to as the "baby bottle" in providing end-of-life care to older adults infected with COVID-19 in their homes. Drawing upon the boundary object framework, we examine the ambiguities surrounding the use of this device and explores its agency. In this unprecedented context, we argue that the device facilitated a form of death that could be described as "better than nothing", embodying practitioners' efforts to provide some dignity to the dying person, by minimally controlling the distress and ensuring a connection between the dying person and the care team. Additionally, it served as a means of coping with the pandemic's intolerable aspects, such as the exclusion of frail older adults for the supposed common good. This study raises questions about the legitimacy and normalization of such compensatory measure within under-resourced healthcare systems for older people experiencing a loss of autonomy.

Tweaking algorithms. Technopolitical issues associated with artificial intelligence based tuberculosis detection in global health.

Computer-aided detection algorithms based on artificial intelligence are increasingly being tested and used as a means for detecting tuberculosis in countries where the epidemic is still present. Computer-aided detection tools are often presented as a global solution that can be deployed in all the geographical areas concerned by tuberculosis, but at the same time, they need to be adjusted and calibrated according to local populations' characteristics. The aim of this article is to analyze the tensions between the standardization of computer-aided detection algorithms and their local adaptation and the political issues associated with these tensions. We undertook a qualitative analysis of practices associated with tuberculosis detection algorithms in different contexts, contrasting the perspectives of various stakeholders. Algorithms embed the promise of standardization through automation and the bypassing of variable human expertise such as that of radiologists, they are nonetheless objects of local practices that we have characterized as "tweaking." This work of tweaking reveals how the technology is situated but also the many concerns of the users and workers (insertion in care, control over infrastructure, and political ownership). This should be better considered to truly make computer-aided detection innovative tools for tuberculosis management in global health.

AI for Detection of Tuberculosis: Implications for Global Health.

Tuberculosis, which primarily affects developing countries, remains a significant global health concern. Since the 2010s, the role of chest radiography has expanded in tuberculosis triage and screening beyond its traditional complementary role in the diagnosis of tuberculosis. Computer-aided diagnosis (CAD) systems for tuberculosis detection on chest radiographs have recently made substantial progress in diagnostic performance, thanks to deep learning technologies. The current performance of CAD systems for tuberculosis has approximated that of human experts, presenting a potential solution to the shortage of human readers to interpret chest radiographs in low- or middle-income, high-tuberculosis-burden countries. This article provides a critical appraisal of developmental process reporting in extant CAD software for tuberculosis, based on the Checklist for Artificial Intelligence in Medical Imaging. It also explores several considerations to scale up CAD solutions, encompassing manufacturer-independent CAD validation, economic and political aspects, and ethical concerns, as well as the potential for broadening radiography-based diagnosis to other nontuberculosis diseases. Collectively, CAD for tuberculosis will emerge as a representative deep learning application, catalyzing advances in global health and health equity. Keywords: Computer-aided Diagnosis (CAD), Conventional Radiography, Thorax, Lung, Machine Learning Supplemental material is available for this article. © RSNA, 2024.