Bridging distances and saving costs: insights from a pilot project of telerheumatology in a rural area of Pakistan.

Enhancing access to healthcare remains a formidable challenge in rural regions of low- and lower-middle-income countries. Amid evolving healthcare challenges, telerheumatology provides opportunities to bridge gaps and expand access to rheumatology care, particularly in remote areas. We describe a pilot telerheumatology program and its cost-, time-, and travel-saving potential in a remote rural setting in northern Pakistan. The telerheumatology program commenced at the Pakistan Institute of Medical Sciences Islamabad, providing services through video consultations to a basic health unit in the Gilgit-Baltistan region. Patients visiting from the Gilgit-Baltistan region willing to participate were recruited in the program. Demographics and logistical metrics were recorded in a dedicated registry. A total of 533 consultations were carried out from April 2022 to April 2023. The majority of the patients were female (318/533, 59.7%). The median age of patients was 50 ± 15.7 years. The average wait time for consultation was 20 ± 13 min. The average travel time to reach telecentre was 59 ± 53 min. The average travel cost to reach telecentre was 379 ± 780 PKR (1.85 ± 3.81 USD). The average duration of consultation was 15 ± 5 min. The most common diagnosis for consultation was knee osteoarthritis (237, 44.5%), chronic low back pain (118, 22.1%), and rheumatoid arthritis (42, 7.9%). On average, patients saved 787 ± 29 km of distance, 15 ± 1 h of traveling, and 6702 ± 535 PKR (33 ± 3 USD) that would have been required to travel to our tertiary care hospital. Telerheumatology substantially reduced travel time, distance, and cost for patients. It has the potential to deliver outpatient rheumatology consultation in an economically efficient manner, effectively breaking geographical barriers and expanding access to essential services for patients in remote areas.

Referrals for rheumatologic evaluation following a positive antinuclear antibody test result. A cross-sectional single center Brazilian study.

BACKGROUND: In general, patients are referred for rheumatological evaluation due to isolated laboratory abnormalities, especially antinuclear antibody (ANA) positivity, with the risk of more severe patients remaining on the waiting list for longer than desired. The aim of this study was to analyze the demographic, clinical, and laboratory information of patients referred to a specialized rheumatological care unit because of positive antinuclear antibody. METHODS: This is a retrospective study of 99 out of 1670 patients seen by the same rheumatologist between 01/01/2011 and 01/01/2019. Patients whose referrals were exclusively due to the ANA test result and the specialist's final diagnosis being "abnormal finding of serum immunological test" (ICD-10 R769) were included. Sociodemographic, clinical, and laboratory information were extracted from the consulting rheumatologist's chart. Descriptive statistics were used for data analysis. RESULTS: A total of 99 patients were included, most of whom were female (84.8%) with a median age of 49 years. At the moment of specialist's appointment, 97 patients (97.9%) repeated the ANA test, and 77 patients remained positive. Of these, only 35 (35.35%) were in a high titer range (greater than or equal to 1:320). Complete blood count for cytopenia's investigation was not performed in a high percentage of patients (22.2%), as well as urinalysis (31.3%). In addition, more than 70% of patients score 0 to 1 classification criteria for Systemic Lupus Erythematosus, according to SLE - ACR 1987 (American College of Rheumatology) and SLICC 2012 (Systemic Lupus International Collaborating Clinics). CONCLUSIONS: Most patients are still referred for specialized evaluation due to the misinterpretation of laboratory tests that were inappropriately requested in patients without clinical evidence of autoimmune rheumatic disease.

Use of Mendelian randomization to assess the causal status of modifiable exposures for rheumatic diseases.

The explosion in Mendelian randomization (MR) publications is hard to ignore and shows no signs of slowing. Clinician readers, who may not be familiar with jargon-ridden methods, are expected to discern the good from the many low-quality studies that make overconfident claims of causality or stretch the plausibility of what MR can investigate. We aim to equip readers with foundational concepts, contextualized using examples in rheumatology, to appraise the many MR papers that are or will appear in their journals. We highlight the importance of assessing whether exposures are under plausibly specific genetic influence, whether the hypothesized causal pathways make biological sense, and whether results stand up to replication and use of control outcomes. Quality of research can vary substantially using MR as with any design, and all methods have inherent limitations. MR studies have provided and can still contribute valuable insights in the context of evidence triangulation.

Rapidly progressing pediatric Lupus with Diffuse Alveolar Hemorrhage and CNS involvement.

Key Clinical Message: Systemic Lupus Erythematosus (SLE) can have an insidious onset and a fatal prognosis in children. Patients presenting without typical signs of SLE should undergo further evaluation if they are not responding to the initial diagnosis and treatment. This is especially true for patients with rapidly progressing symptoms and deterioration in spite of treatment. Abstract: Pediatric Systemic Lupus Erythematosus is a chronic autoimmune disorder with various organ involvement pulmonary involvement in the course of this disorder is a rare yet potentially life-threatening complication. In this case report we highlight the findings of a 16-year-old girl acutely and initially presenting with cough and fever, eventually complicating to diffuse alveolar hemorrhage and gradual loss of consciousness. Although the patient was started on immunosuppressive treatment after the diagnosis of lupus, based on renal and hematological impairment, was made and initially responded, she eventually deteriorated.

Autoimmunity to stromal-derived autoantigens in rheumatoid ectopic germinal centers exacerbates arthritis and affects clinical response.

Ectopic lymphoid structures (ELSs) in the rheumatoid synovial joints sustain autoreactivity against locally expressed autoantigens. We recently identified recombinant monoclonal antibodies (RA-rmAbs) derived from single, locally differentiated rheumatoid arthritis (RA) synovial B cells, which specifically recognize fibroblast-like synoviocytes (FLSs). Here, we aimed to identify the specificity of FLS-derived autoantigens fueling local autoimmunity and the functional role of anti-FLS antibodies in promoting chronic inflammation. A subset of anti-FLS RA-rmAbs reacting with a 60 kDa band from FLS extracts demonstrated specificity for HSP60 and partial cross-reactivity to other stromal autoantigens (i.e., calreticulin/vimentin) but not to citrullinated fibrinogen. Anti-FLS RA-rmAbs, but not anti-neutrophil extracellular traps rmAbs, exhibited pathogenic properties in a mouse model of collagen-induced arthritis. In patients, anti-HSP60 antibodies were preferentially detected in RA versus osteoarthritis (OA) synovial fluid. Synovial HSPD1 and CALR gene expression analyzed using bulk RNA-Seq and GeoMx-DSP closely correlated with the lympho-myeloid RA pathotype, and HSP60 protein expression was predominantly observed around ELS. Moreover, we observed a significant reduction in synovial HSP60 gene expression followed B cell depletion with rituximab that was strongly associated with the treatment response. Overall, we report that synovial stromal-derived autoantigens are targeted by pathogenic autoantibodies and are associated with specific RA pathotypes, with potential value for patient stratification and as predictors of the response to B cell-depleting therapies.

The cultural differences in transition assessment: Evaluation of TRANSITION-Q and STARx scales on Turkish rheumatic patients.

Objectives: This study aimed to assess the readiness of our patient population for the transfer to adult care and the applicability of the TRANSITION-Q and STARx scales to the Turkish adolescent patient population. Patients and methods: A total of 153 patients (92 males, 61 females; mean age: 15.5±1.9 years; range, 12 to 18 years) were included in the study between September 15, 2021, and December 15, 2021. The patients were divided into two groups according to age groups: 12 to 15 years old and 16 to 18 years old. The patients were also divided into four groups according to their diagnosis: connective tissue diseases, juvenile idiopathic arthritis, vasculitis, and autoinflammatory diseases. The TRANSITION-Q and STARx scales were administered face-to-face by a nurse and a doctor. The transition readiness of the patients was evaluated according to their scores. Results: Sixty-nine (45%) patients were in the 12 to 15 age group, and 84 (55%) were in the 16 to 18 age group. Eight-four (54.9%) patients had juvenile idiopathic arthritis, 47 (30.7%) patients had an autoinflammatory disease, 14 (9.2%) patients had vasculitis, and eight (5.2%) patients had a connective tissue disease. There was no significant difference in the scale scores according to disease groups and sexes in both scales. Considering the age of the patients, the mean scores of the patients in the 16 to 18 age group were found to be significantly higher compared to the 12 to 15 age group for both the TRANSITION-Q (74.3±13.3 vs. 65.4±9.6, p<0.001) and STARx scales (51.8±8.1 vs. 44.8±9.1, p<0.001). Cronbach's alpha score was 0.71 for the STARx scale and 0.79 for the TRANSITION-Q scale. Conclusion: TRANSITION-Q and STARx scales could guide the Turkish patient population in determining the pretransition needs of patients in planning individualized transition processes.

Siglec-1, an easy and contributory inflammation marker in rheumatology.

Objectives: Inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are poorly informative about interferon (IFN)-related disorders. In these conditions, the measure of the interferon score (IS), obtained by measuring the expression of IFN-stimulated genes, has been proposed. Flow cytometry-based assays measuring sialic-acid-binding Ig-like lectin 1 (Siglec-1) expression could be a more practical tool for evaluating IFN-inflammation. The study compared Siglec-1 measures with IS and other inflammatory indexes. We compared Siglec-1 measures with IS and other inflammatory indexes in real-world paediatric rheumatology experience. Methods: We recruited patients with immuno-rheumatological conditions, acute infectious illness and patients undergoing orthopaedic surgery as controls. Siglec-1 expression was measured in all samples, and IS, ESR and CRP were also recorded if available. Results: Overall, 98 subjects were enrolled in the study, with a total of 104 measures of Siglec-1. Compared with IS, Siglec-1 expression showed good accuracy (86.0%), specificity (72.7%) and sensitivity (85.7%). The measure of the percentage of Siglec-1-positive cells performed best at low levels of IFN-inflammation, while the measure of mean fluorescence intensity performed best at higher levels. Ex vivo studies on IFN-stimulated monocytes confirmed this behaviour. There was no link between Siglec-1 expression and either ESR or CRP, and positive Siglec-1 results were found even when ESR and CRP were normal. A high Siglec-1 expression was also recorded in subjects with acute infections. Conclusion: Siglec-1 measurement by flow cytometry is an easy tool to detect IFN-related inflammation, even in subjects with normal results of common inflammation indexes.

Unusual manifestations of Takayasu arteritis: A diagnostic challenge.

Key Clinical Message: Timely recognition of atypical Takayasu arteritis is crucial. Unusual presentations, such as pericardial effusion, can complicate diagnosis. CT angiogram aids in precise diagnosis, guiding targeted immunosuppressive therapy. Multidisciplinary collaboration is vital for comprehensive management, improving patient outcomes in this challenging condition. Abstract: This case study highlights the diagnostic challenges posed by atypical presentations of Takayasu arteritis (TA), focusing on a 42-year-old male presenting with pericardial effusion. Despite inconclusive initial investigations, a CT angiogram revealed large vessel vasculitis, confirming TA. Management with immunosuppressive therapy led to clinical improvement. This case emphasize the importance of recognizing unusual manifestations of TA for timely diagnosis and appropriate treatment, emphasizing the role of multidisciplinary collaboration in optimizing patient outcomes.

Comparative analysis of centrally mediated and inflammatory pain experiences amongst patients diagnosed with rheumatoid arthritis: A multimethods study.

BACKGROUND: The identification of pain originating from distinct biological processes may lead to individualised pain treatment. In this study, we aimed to explore the pain experiences of patients with rheumatoid arthritis (RA), differentiating between those predominantly exhibiting features of peripheral inflammatory versus centrally mediated pain. METHODS: Through a multimethods approach we (i) quantitatively analysed the differences in pain descriptors between patients diagnosed with RA experiencing peripheral inflammatory and centrally mediated pain, utilising the Short Form-McGill Pain Questionnaire which includes the pain visual analogue scale (VAS) and (ii) qualitatively explored their subjective pain experiences grounded in the biopsychosocial model, commonly applied in chronic pain. RESULTS: Participants with centrally mediated pain reported higher pain scores on the VAS, used a wider range of pain descriptors, and a higher proportion selected each descriptor compared to those with inflammatory pain (p < .001). The qualitative analysis revealed the centrally mediated pain group's experiences were overwhelming and relentless, struggling to precisely articulate the nature of their pain. In contrast, individuals with inflammatory pain expressed their pain in more tangible terms and shared their adaptive and coping strategies. Importantly, both groups revealed the substantial psychological, functional and social impacts of their pain, highlighting the often 'invisible' and misunderstood nature of their symptoms. CONCLUSION: This study has gained a deeper insight into the pain experiences of patients living with RA, particularly in differentiating between centrally mediated and inflammatory types of pain, potentially facilitating a more individualised approach to pain treatment. PATIENT CONTRIBUTION: Patients actively participated in the study conception and design. This engagement includes collaboration with key stakeholders, such as members of the National Rheumatoid Arthritis Society and Patient Research Partners (PRPs), who provided continuous feedback and guidance throughout the research process. Specifically, the qualitative element was coproduced with two PRPs, who were involved in co-leading the focus groups and data analysis.

Seronegative Granulomatosis With Polyangiitis With Isolated Lung Lesions: A Case Report.

Granulomatosis with polyangiitis (GPA), previously referred to as Wegener's granulomatosis, is an uncommon form of necrotizing vasculitis that predominantly targets small and medium-sized blood vessels as a result of granulomatous inflammation. Granulomatosis with polyangiitis is defined by the existence of necrotizing granulomas in the upper respiratory tract, along with renal involvement, which includes necrotizing glomerulonephritis with extra capillary crescents. From a diagnostic perspective, there is a high correlation between GPA and proteinase-3 anti-neutrophil cytoplasmic antibody (PR3-ANCA) because of the release of inflammatory cytokines, reactive oxygen species (ROS), and lytic enzymes. While ANCA-positive serology is commonly used as the diagnostic criteria, we present a seronegative GPA case with isolated lung lesions. A 54-year-old woman was referred for an assessment of hemoptysis and alterations in her chest radiograph. The patient's laboratory results showed a positive QuantiFERON test but negative results for ANCA and antinuclear antibodies (ANA) tests. A chest CT scan showed the presence of several pulmonary nodules in both lungs, with some cavitation. A CT-guided biopsy was conducted on a nodule located in the lower lobe of the right lung. The results showed that the nodule had non-neoplastic chronic inflammation and an area of geographic necrosis. A second robotic-assisted left upper and lower lobe wedge resection was done, which showed white to tan granular lesions with necrotizing granulomatous inflammation and lymph nodes with anthracosis and a lot of histiocytes, which is typical of GPA. The patient received a six-month course of intravenous rituximab treatment.

Two challenging cases of anti-MDA-5 dermatomyositis with rapidly progressive interstitial lung disease.

Anti-MDA-5 dermatomyositis (DM) is a subtype of idiopathic inflammatory myopathy, commonly presenting as clinically amyopathic dermatomyositis. It is associated with rapidly progressive interstitial lung disease and a poor prognosis. Here, we present two cases of anti-MDA-5 DM and discuss the challenges associated with timely diagnosis, and the importance of early and aggressive treatment.

Neonatal lupus with complete heart block and long term follow up.

We present the case of a 27-year-old pregnant woman, newly diagnosed with Systemic Lupus Erythematosus (SLE) during pregnancy. The patient delivered a newborn at 38 weeks gestation, who, on the first day of life, manifested complete heart block. This case underscores the clinical challenges associated with neonatal lupus, emphasizing the need for collaborative, multidisciplinary management.

Management and prevention strategies for osteoarthritis in tactical athletes.

Osteoarthritis (OA) affects over 600 million worldwide, is one of the leading causes of disability and has a significant burden of morbidity. There are multiple modifiable and non-modifiable risk factors, with professional and tactical athletes at higher risk than other occupational groups. Without specific anti-OA pharmacological agents, clinicians may feel helpless. However, primary, secondary and tertiary preventative strategies can slow or prevent OA development or progression. There are many modifiable risk factors which, if targeted, can contribute to an improvement in the experience of people living with OA. Radiological features of OA may signify the presence of 'the disease'; however, the pain and symptoms experienced may be more accurately described as 'the illness'. Targeting both, using a combination of the medical and biopsychosocial models of care, will improve the overall experience.This paper outlines some easily adoptable general and specific strategies to help manage this common and disabling condition, focused on improving joint healthspan, not just joint lifespan. They include education and communication, empowering individuals to confidently self-manage their condition with access to healthcare resources when required. A holistic package, including support for sleep, diet and weight loss, physical activity and specific home-based exercise routines, with appropriate analgesia when needed, can all improve OA illness and potentially slow OA disease development or progression. Clinicians should feel confident that there are many opportunities to intervene and mitigate the risk factors of OA, using various preventative strategies, especially in a young, physically active population with functional occupational or recreational demands.

Chronic Pain for Rheumatological Disorders: Pathophysiology, Therapeutics and Evidence.

Pain is the leading reason people seek orthopedic and rheumatological care. By definition, most pain can be classified as nociceptive, or pain resulting from non-neural tissue injury or potential injury, with between 15% and 50% of individuals suffering from concomitant neuropathic pain or the newest category of pain, nociplastic pain, defined as "pain arising from altered nociception despite no clear evidence of actual or threatened tissue damage, or of a disease or lesion affecting the somatosensory system.‿ Pain classification is important because it affects treatment decisions at all levels of care. Although several instruments can assist with classifying treatment, physician designation is the reference standard. The appropriate treatment of pain should ideally involve multidisciplinary care including physical therapy, psychotherapy and integrative therapies when appropriate, and pharmacotherapy with non-steroidal anti-inflammatory drugs for acute, mechanical pain, membrane stabilizers for neuropathic and nociplastic pain, and serotonin-norepinephrine reuptake inhibitors and tricyclic antidepressants for all types of pain. For non-surgical interventions, there is evidence to support a small effect for epidural steroid injections for an intermediate-term duration, and conflicting evidence for radiofrequency ablation to provide at least 6 months of benefit for facet joint pain, knee osteoarthritis, and sacroiliac joint pain. Since pain and disability represent the top reason for elective surgery, it should be reserved for patients who fail conservative interventions. Risk factors for procedural failure are the same as risk factors for conservative treatment failure and include greater disease burden, psychopathology, opioid use, central sensitization and multiple co-morbid pain conditions, poorly controlled preoperative and postoperative pain, and secondary gain.

Dermatological Manifestation of SLE Patients, Living in Aseer Region.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease that affects both men and women differently and has a variety of multisystemic symptoms. One of the diseases most often affected target organs is the skin. Different ethnic and racial groupings may display variations in disease incidence, clinical heterogeneity, and severity depending on environmental, cultural, or genetic factors. This study is conducted to determine the prevalence of SLE's cutaneous symptoms and their relationship to organ involvement. Materials and Methods: Data were gathered for this study from the patient chart, the study design was the retrospective chart review after the consent of the patients and obtaining an ethical approval, The study was carried out in Aseer Central Hospital, Abha Saudi Arabia. Results: Out of a total of 100 patients 92% were females while 8% were males. The mean (SD) of the age of the respondent was 38.3 (8.5). 89.2 of the respondents had skin manifestations. Conclusion: A thorough understanding of SLE skin lesions will aid in the accurate identification of the condition and in the effective therapy of lupus patients. In order to more accurately diagnose cutaneous lesions in SLE patients, we need more dermatology and rheumatology clinics that combine expertise together.

Prevalence and Characteristics of Adults with Difficult-to-Treat Rheumatoid Arthritis in a Large Patient Registry.

OBJECTIVES: An estimated 5-20% of patients with rheumatoid arthritis (RA) fail multiple treatments and are considered "difficult-to-treat" (D2T), posing a substantial clinical challenge for rheumatologists. A European Alliance of Associations for Rheumatology (EULAR) task force proposed a definition of D2T-RA in 2021. We applied EULAR's D2T definition in a cohort of patients with established RA to assess prevalence and we compared clinical characteristics of participants with D2T-RA with matched comparisons. METHODS: Data from the longitudinal Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS) registry was used. Participants were classified as D2T if they met EULAR's definition. A comparison group of non-D2T RA patients were matched 2:1 to every D2T patient, and differences in characteristics were evaluated in descriptive analyses. Prevalence rates of D2T were estimated using Poisson regression. RESULTS: We estimated the prevalence of D2T-RA to be 14.4 (95% CI: 12.8-16.3 per 100 persons) among 1,581 participants with RA, and 22.3 (95% CI: 19.9-25.0 per 100 persons) among 1,021 who were biologic/targeted synthetic DMARD experienced. We observed several differences in demographics, comorbidities, and RA disease activity between D2T-RA and non-D2T RA comparisons. Varying EULAR sub-criteria among all participants in BRASS resulted in a range of D2T-RA prevalence rates, from 0.6-17.5 per 100 persons. CONCLUSION: EULAR's proposed definition of D2T-RA identifies patients with RA who have not achieved treatment targets. Future research should explore heterogeneity in these patients and evaluate outcomes to inform the design of future studies aimed at developing more effective RA management protocols.

Evidence for the use of cannabis-based medicines in osteoarthritis: a scoping review.

The purpose of this study was to conduct a scoping review to describe the evidence on the efficacy and safety of using cannabis-based medicines for osteoarthritis. The review was conducted following the framework proposed by Arksey and O'Malley and reported following PRISMA extension for scoping reviews guidelines. We conducted a comprehensive search across various databases including MEDLINE, Embase, Cochrane Library, CINAHL, Scopus, and Proquest, spanning from inception of each database to March 2023. We retrieved 2533 citations, and after deduplication, title and abstract screening, and full-text screening, 10 articles were included for analysis. These studies were composed of randomized-controlled trials (n = 4/10), cross-sectional surveys (n = 3/10), case studies (n = 2/10), and a cohort study (n = 1/10). Evidence for using cannabis-based medicines was mixed, with just 60% (n = 6/10) of included studies reporting statistically significant improvements in pain. Studies with larger samples sizes and longer durations of exposure did not find significant benefits for pain. The few adverse effects reported were generally mild and affected a minority of participants. Several studies also discovered that cannabis-based medicines were associated with a reduction in opioid use. Currently available data on the use of cannabis-based medicines in osteoarthritis is insufficient to make recommendations. Future research should address concerns regarding small sample sizes and short treatment durations to provide a more robust evidence base. Key Points • Current evidence remains mixed; studies that found a positive benefit with using cannabis-based medicines had limitations with small sample sizes and short durations of exposure • The use of cannabis-based medicines in osteoarthritis appears to be generally well tolerated, adverse effects are mild and experienced by a minority of participants • Cannabis-based medicines may decrease the use of opioids in patients with osteoarthritis • Future research should address the gaps in long-term efficacy and safety data.

Posterior Scleritis: A Case Report and Literature Review of the Management of the Condition.

Posterior scleritis is a rare inflammatory eye condition affecting the posterior segments of the sclera and is more prevalent in females. Its clinical presentation, often nonspecific, includes ocular pain, headache, and vision loss. Misdiagnosis is common due to a lack of specific symptoms posing a potential threat to vision. The etiology is often tied to rheumatic diseases, such as rheumatoid arthritis (RA), systemic erythematous lupus (SLE), and anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis. Posterior scleritis poses diagnostic challenges, mimicking many other ocular conditions, hence necessitating a thorough clinical eye exam. Laboratory studies, including inflammatory markers and markers of rheumatic diseases, may identify underlying systemic diseases. Imaging, including B-scan ultrasound and magnetic resonance imaging (MRI), aids in accurate diagnosis. Treatment involves non-steroidal anti-inflammatory drugs (NSAID), as well as topical corticosteroids for mild disease and systemic corticosteroids for severe disease. Biologic therapy has become increasingly significant for refractory cases. A multidisciplinary approach involving ophthalmology and rheumatology is crucial in the management of this potential sight-threatening disease. This case report highlights a 46-year-old woman with a history of RA-associated posterior scleritis.

Pediatric rheumatology education: the virtual frontier a review.

BACKGROUND: Many children with rheumatic and musculoskeletal diseases are unrecognized. Identifying these children requires health care provider awareness, knowledge, and skills to recognize disease features and how (and when) to refer to specialist care. The aim of this paper is to highlight the need for better access to health care, review the essential role that education and virtual care play to address unmet need in low resource areas and especially to expand workforce capacity. Using collaborative partnerships, virtual platforms, and innovative assessment methods, musculoskeletal care and education can be delivered to reach a greater audience than ever before. Increased awareness through multiple initiatives and readily available resources are imperative to improve global rheumatology care. CONCLUSION: The needs of children with rheumatic diseases and musculoskeletal conditions are vastly underserved around the world resulting in preventable morbidity and mortality. Expanded implementation of virtual education and e-health care platforms provides an opportunity to increase access to care for children globally.