An integrated isothermal nucleic acid amplification test to detect HPV16 and HPV18 DNA in resource-limited settings.

High-risk human papillomavirus (HPV) DNA testing is widely acknowledged as the most sensitive cervical cancer screening method but has limited availability in resource-limited settings, where the burden of cervical cancer is highest. Recently, HPV DNA tests have been developed for use in resource-limited settings, but they remain too costly for widespread use and require instruments that are often limited to centralized laboratories. To help meet the global need for low-cost cervical cancer screening, we developed a prototype, sample-to-answer, point-of-care test for HPV16 and HPV18 DNA. Our test relies on isothermal DNA amplification and lateral flow detection, two technologies that reduce the need for complex instrumentation. We integrated all test components into a low-cost, manufacturable platform, and performance of the integrated test was evaluated with synthetic samples, provider-collected clinical samples in a high-resource setting in the United States, and self-collected clinical samples in a low-resource setting in Mozambique. We demonstrated a clinically relevant limit of detection of 1000 HPV16 or HPV18 DNA copies per test. The test requires six user steps, yields results in 45 min, and can be performed using a benchtop instrument and minicentrifuge by minimally trained personnel. The projected per-test cost is <$5, and the projected instrumentation cost is <$1000. These results show the feasibility of a sample-to-answer, point-of-care HPV DNA test. With the inclusion of other HPV types, this test has the potential to fill a critical gap for decentralized and globally accessible cervical cancer screening.

A low-cost, paper-based hybrid capture assay to detect high-risk HPV DNA for cervical cancer screening in low-resource settings.

Cervical cancer is a leading cause of cancer death for women in low-resource settings. The World Health Organization recommends that cervical cancer screening programs incorporate HPV DNA testing, but available tests are expensive, require laboratory infrastructure, and cannot be performed at the point-of-care. We developed a two-dimensional paper network (2DPN), hybrid-capture, signal amplification assay and a point-of-care sample preparation protocol to detect high-risk HPV DNA from exfoliated cervical cells within an hour. The test does not require expensive equipment and has an estimated cost of <$3 per test without the need for batching. We evaluated performance of the paper HPV DNA assay with short synthetic and genomic HPV DNA targets, HPV positive and negative cellular samples, and two sets of clinical samples. The first set of clinical samples consisted of 16 biobanked, provider-collected cervical samples from a study in El Salvador previously tested with careHPV and subsequently tested in a controlled laboratory environment. The paper HPV DNA test correctly identified eight of eight HPV-negative clinical samples and seven of eight HPV-positive clinical samples. We then performed a field evaluation of the paper HPV DNA test in a hospital laboratory in Mozambique. Cellular controls generated expected results throughout field testing with fully lyophilized sample preparation and 2DPN reagents. When evaluated with 16 residual self-collected cervicovaginal samples previously tested by the GeneXpert HPV assay ("Xpert"), the accuracy of the HPV DNA paper test in the field was reduced compared to testing in the controlled laboratory environment, with positive results obtained for all eight HPV-positive samples as well as seven of eight HPV-negative samples. Further evaluation showed reduction in performance was likely due in part to increased concentration of exfoliated cells in the self-collected clinical samples from Mozambique compared with provider-collected samples from El Salvador. Finally, a formal usability assessment was conducted with users in El Salvador and Mozambique; the assay was rated as acceptable to perform after minimal training. With additional optimization for higher cell concentrations and inclusion of an internal cellular control, the paper HPV DNA assay offers promise as a low-cost, point-of-care cervical cancer screening test in low-resource settings.

Multicenter Study of Utility and Acceptability of Depression and Anxiety Screening in Adolescents and Young Adults With Childhood-Onset Systemic Lupus.

OBJECTIVE: To determine the utility and acceptability for depression and anxiety screening of adolescents and young adults (AYA) with childhood-onset systemic lupus erythematosus (cSLE) in the pediatric rheumatology setting. METHODS: AYA with cSLE, ages 12-21 years, from 8 collaborating sites, were consecutively screened for depression and anxiety with the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder 7-item scale (GAD-7). Demographic and disease characteristics were collected, as well as patient-reported outcome measures using the Patient Reported Outcomes Measurement Information System (PROMIS) pediatric profile-25. Acceptability of screening was assessed with postscreening surveys completed by AYA and parents. Chi-square and Wilcoxon rank sum tests examined the relationship between patient characteristics and history of previous screening. Spearman correlations examined relationships between screening scores, PROMIS domains, and other disease factors. RESULTS: Among 106 AYA screened, 64 (60%) had been previously screened, 25 (24%) by general pediatricians. Thirty-two (30%) AYA screened positive, including 24% for depression, 17% for anxiety, and 14% for suicidal ideation. Depression and anxiety symptom severity were highly correlated with increased PROMIS domain scores for fatigue and pain interference and moderately correlated with increased pain severity, decreased mobility, and decreased peer relationships. Eighty-six percent of AYA and 95% of parents expressed comfort with screening in the pediatric rheumatology setting. CONCLUSION: Depression, anxiety, and suicidal ideation are common among AYA with cSLE, and symptoms are correlated with important patient-reported outcomes. Mental health screening in the pediatric rheumatology setting was highly acceptable among AYA with cSLE and their parents.

Impact of diabetes status and related factors on COVID-19-associated hospitalization: A nationwide retrospective cohort study of 116,370 adults with SARS-CoV-2 infection.

AIMS: We examined diabetes status (no diabetes; type 1 diabetes [T1D]; type 2 diabetes [T2D]) and other demographic and clinical factors as correlates of coronavirus disease 2019 (COVID-19)-related hospitalization. Further, we evaluated predictors of COVID-19-related hospitalization in T1D and T2D. METHODS: We analyzed electronic health record data from the de-identified COVID-19 database (December 2019 through mid-September 2020; 87 US health systems). Logistic mixed models were used to examine predictors of hospitalization at index encounters associated with confirmed SARS-CoV-2 infection. RESULTS: In 116,370 adults (>=18 years old) with COVID-19 (93,098 no diabetes; 802 T1D; 22,470 T2D), factors that independently increased risk for hospitalization included diabetes, male sex, public health insurance, decreased body mass index (BMI; <25.0-29.9 kg/m2), increased BMI (>25.0-29.9 kg/m2), vitamin D deficiency/insufficiency, and Elixhauser comorbidity score. After further adjustment for concurrent hyperglycemia and acidosis in those with diabetes, hospitalization risk was substantially higher in T1D than T2D and in those with low vitamin D and elevated hemoglobin A1c (HbA1c). CONCLUSIONS: The higher hospitalization risk in T1D versus T2D warrants further investigation. Modifiable risk factors such as vitamin D deficiency/insufficiency, BMI, and elevated HbA1c may serve as prognostic indicators for COVID-19-related hospitalization in adults with diabetes.

Sample-to-answer, extraction-free, real-time RT-LAMP test for SARS-CoV-2 in nasopharyngeal, nasal, and saliva samples: Implications and use for surveillance testing.

The global COVID-19 pandemic has highlighted the need for rapid, accurate and accessible nucleic acid tests to enable timely identification of infected individuals. We optimized a sample-to-answer nucleic acid test for SARS-CoV-2 that provides results in <1 hour using inexpensive and readily available reagents. The test workflow includes a simple lysis and viral inactivation protocol followed by direct isothermal amplification of viral RNA using RT-LAMP. The assay was validated using two different instruments, a portable isothermal fluorimeter and a standard thermocycler. Results of the RT-LAMP assay were compared to traditional RT-qPCR for nasopharyngeal swabs, nasal swabs, and saliva collected from a cohort of patients hospitalized due to COVID-19. For all three sample types, positive agreement with RT-LAMP performed using the isothermal fluorimeter was 100% for samples with Ct <30 and 69-91% for samples with Ct <40. Following validation, the test was successfully scaled to test the saliva of up to 400 asymptomatic individuals per day as part of the campus surveillance program at Rice University. Successful development, validation, and scaling of this sample-to-answer, extraction-free real-time RT-LAMP test for SARS-CoV-2 adds a highly adaptable tool to efforts to control the COVID-19 pandemic, and can inform test development strategies for future infectious disease threats.

Hands-On Training Courses for Cervical Cancer Screening, Diagnosis, and Treatment Procedures in Low- and Middle-Income Countries.

In 2018, there were approximately 570,000 new cases of cervical cancer worldwide. More than 85% of cases occurred in low- and middle-income countries (LMICs), primarily because of poor access to screening and a limited number of medical providers trained to diagnose and treat cervical precancerous lesions. Our objective was to provide locally arranged, hands-on training courses for medical providers in LMICs to learn to perform cervical cancer screening, diagnosis, and treatment procedures. The courses included didactic lectures and hands-on training stations using low-cost simulation models developed by bioengineers and students at Rice University in Houston, TX, United States, and the Malawi Polytechnic in Blantyre, Malawi. The hands-on training stations included visual inspection with acetic acid (VIA), colposcopy, cervical biopsy, endocervical curettage, loop electrosurgical excision procedure (LEEP), and thermal ablation. Provider pre- and postcourse confidence levels in performing the procedures were evaluated. From February 2017 to January 2020, we arranged 15 hands-on training courses in seven cities across six countries (El Salvador, Mozambique, Trinidad and Tobago, Lesotho, Malawi, and Nepal). Overall, there were 506 participants. The average number of participants per course was 38 (range 19-92). The participants included doctors, nurses, and midwives. The course duration varied from 1 to 3 days. Increased confidence in performing VIA, colposcopy and cervical biopsy, ablation, and LEEP was reported by 69%, 71%, 61%, and 76% of participants, respectively. Our findings suggest that locally arranged, hands-on cervical cancer prevention training courses in LMICs can improve provider confidence in performing cervical cancer screening, diagnosis, and treatment procedures. These courses are part of a larger strategy to build local capacity for delivering and improving cervical cancer prevention services in LMICs.

Prenatal acetaminophen use in women with autoimmune disorders and adverse pregnancy and birth outcomes.

OBJECTIVES: Most women may have temporary pain for which they use analgesics, but those with autoimmune disorders have chronic pain that may be exacerbated for some during pregnancy. This study aimed to determine whether prenatal acetaminophen use was associated with an increased risk of adverse pregnancy and birth outcomes in women with autoimmune disorders. METHODS: Participants were enrolled between 2004 and 2018 in the MotherToBaby cohort study and limited to women with an autoimmune disorder (n = 1821). Self-reported acetaminophen use was characterized over gestation for indication, timing of use and duration. Cumulative acetaminophen use through 20 and 32 weeks was categorized into quintiles, with no acetaminophen use as the reference category. The association between acetaminophen quintile and preeclampsia or pregnancy-induced hypertension, small for gestational age and preterm birth was examined using adjusted multiple log-linear regression. RESULTS: Overall, 74% of women reported acetaminophen use during pregnancy. The most often reported indication for using acetaminophen was headache/migraines, followed by pain and injury. Risk of preeclampsia was 1.62 (95% CI: 1.10, 2.40) times greater for those in the fifth quintile of cumulative acetaminophen use through 20 weeks compared with those with no acetaminophen use. There were no associations with lower use quintiles, nor for the other outcomes. CONCLUSION: The highest quintile of cumulative acetaminophen was associated with a modestly increased risk for preeclampsia. Some women with autoimmune conditions have pain throughout pregnancy; clinicians and patients should discuss approaches to best avoid high levels of acetaminophen in their pain management strategies.

Knowledge about juvenile idiopathic arthritis-associated uveitis: more frequent reminders are associated with higher patient and family uveitis knowledge.

BACKGROUND: Chronic anterior uveitis is a sight-threatening complication of juvenile idiopathic arthritis (JIA) and a primary contributor to long-term morbidity in people with JIA. Levels of knowledge about uveitis among JIA patients and their parents are unknown. A survey of JIA patients and parents was conducted to assess knowledge about uveitis complications and recommended screening. METHODS: A survey was developed consisting of six demographic questions, six arthritis/uveitis history questions, and nine uveitis knowledge questions. The survey was administered to JIA patients age 14 and older and parents of patients with JIA at three pediatric rheumatology practices and online through the Patients, Advocates, and Rheumatology Teams Network for Research and Service (PARTNERS) network. ANOVA, chi-square and Fisher's exact tests were used to look for relationships between survey questions and demographic variables. RESULTS: Thirty-three patients and 111 parents completed the survey. Overall, 17.4% reported a history of uveitis, and 89.6% had heard of uveitis. The mean composite knowledge score was 6.46 ± 2.6 out of 9. Patients and parents with a history of uveitis had higher composite knowledge scores than their counterparts without a uveitis history (p = 0.01 and p < 0.01, respectively). Parents whose rheumatologist reminded them about eye exams at every visit had higher knowledge of the risk of blindness (p = 0.04), the risk for uveitis when arthritis is controlled (p = 0.02), the need for ongoing eye exams when off of medications (p = 0.01), and had a higher overall score (p = 0.02) than those who were reminded at some visits or not at all. CONCLUSIONS: JIA patients and parents report variable levels of knowledge regarding uveitis complications and recommended screening. Frequent discussion between the rheumatology provider and family about uveitis screening is associated with higher uveitis knowledge. Incorporating detailed and frequent education about uveitis into rheumatology clinic appointments may improve early uveitis detection and visual outcomes.

Improving Performance of a SARS-CoV-2 RT-LAMP Assay for Use With a Portable Isothermal Fluorimeter: Towards a Point-of-Care Molecular Testing Strategy.

Frequent and accessible testing is a critical tool to contain the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To develop low-cost rapid tests, many researchers have used reverse transcription loop-mediated isothermal amplification (RT-LAMP) with fluorescent readout. Fluorescent LAMP-based assays can be performed using cost-effective, portable, isothermal instruments that are simpler to use and more rugged than polymerase chain reaction (PCR) instruments. However, false-positive results due to nonspecific priming and amplification have been reported for a number of LAMP-based assays. In this report, we implemented a RT-LAMP assay for SARS-CoV-2 on a portable isothermal fluorimeter and a traditional thermocycler; nonspecific amplification was not observed using the thermocycler but did occur frequently with the isothermal fluorimeter. We explored 4 strategies to optimize the SARS-CoV-2 RT-LAMP assay for use with an isothermal fluorimeter and found that overlaying the reaction with mineral oil and including the enzyme Tte UvrD helicase in the reaction eliminated the problem. We anticipate these results and strategies will be relevant for use with a wide range of portable isothermal instruments.

Down Syndrome-Associated Arthritis Cohort in the New Childhood Arthritis and Rheumatology Research Alliance Registry: Clinical Characteristics, Treatment, and Outcomes.

OBJECTIVE: Down syndrome-associated arthritis (DA) is underrecognized, and current therapies used for juvenile idiopathic arthritis (JIA) appear to be poorly tolerated and less effective in patients with DA. The objective of this study was to characterize clinical manifestations and therapeutic preferences in DA compared to JIA, using the new Childhood Arthritis and Rheumatology Research Alliance (nCARRA) registry. METHODS: In a case-control study, between July 2015 and March 2019, patients with a diagnosis of JIA and Down syndrome (DS) were identified and matched by age, sex, and JIA subtype to patients who have JIA without DS. Collected data included demographic characteristics, disease characteristics, laboratory results, treatment exposure, and outcome measures. RESULTS: A total of 36 children with DA and 165 with JIA were identified. Most patients presented with polyarticular rheumatoid factor-negative disease. At entry into the nCARRA registry, there were minimal differences between the groups, and at the last visit there were significant differences (P < 0.05) for multiple outcome measures. Patients with DA and those with JIA had similar therapeutic exposure to disease-modifying antirheumatic drugs (DMARDs) and biologics, but those with DA had more DMARD-related adverse events (93% versus 25%) and biologic therapy ineffectiveness (60% versus 17%). CONCLUSION: There was little difference between patients with DA and those with JIA at baseline, and similar therapy was implemented for those in the nCARRA registry; however, at the last visit, the patients with DA had greater disease burden. Additionally, there were more DMARD-related adverse events and biologic ineffectiveness for those patients with DA. More research is needed to determine differences in pathophysiology and optimal therapeutic approaches.

Cervical cancer prevention in El Salvador: A prospective evaluation of screening and triage strategies incorporating high-resolution microendoscopy to detect cervical precancer.

Cervical cancer remains a leading cause of cancer death for women in low- and middle-income countries. The goal of our study was to evaluate screening and triage strategies, including high-resolution microendoscopy (HRME), to detect cervical abnormalities concerning for precancer at the point of care. Women (n = 1824) were enrolled at the Instituto de Cáncer de El Salvador. All underwent screening by both human papillomavirus (HPV) testing using careHPV and visual inspection with acetic acid (VIA). Screen-positives, along with 10% of screen-negatives, were invited to return for a follow-up examination that included triage with VIA, colposcopy and HRME imaging. Biopsies were taken of any abnormalities identified. If no abnormalities were identified, then the worst scoring site by HRME was biopsied. The sensitivities of HPV testing and VIA to screen for cervical intraepithelial neoplasia Grade 2 or more severe diagnoses (CIN2+) were 82.1% and 75% (P = .77), while the specificities were 90.4% and 80.9% (P < .001), respectively. The sensitivities of VIA, colposcopy and HRME as triage tests for CIN2+ were 82.1%, 82.1% and 71.4%, respectively (P ≥ .38). HRME had a significantly higher specificity (66.7%) than VIA (51.9%) (P < .001) and colposcopy (53.3%) (P < .001). When evaluating different theoretical screening and triage strategies, screening with HPV testing followed by triage with HRME would result in more women receiving appropriate care (97%) compared to screening with VIA (75%) or HPV alone (90%). Our findings demonstrate that screening with HPV is superior to VIA, and that triage with HRME imaging increases the specificity of detecting CIN2+ at the point of care in a low-resource setting.

Assessment and treatment of Down syndrome-associated arthritis: a survey of pediatric rheumatologists.

BACKGROUND: Inflammatory arthritis in children with Down syndrome (DS) was first described in 1984 and is now termed Down syndrome-associated arthritis (DA). Studies have shown that DA is under-recognized with a 19-month average delay in diagnosis. Additionally, most patients present with polyarticular, rheumatoid factor (RF) and anti-nuclear antibody (ANA) negative disease. Current therapies for juvenile idiopathic arthritis (JIA) have been used, but appear to be poorly tolerated, more toxic and less effective in patients with DA. There is currently no standardized approach to the assessment or management of DA. The objective of this study was to describe provider perspectives toward diagnostic and treatment approach of DA, to provide baseline information upon which to design future studies. METHODS: An electronic survey, organized into sections regarding individual practices of assessment and treatment approach of DA, was sent to the Pediatric Rheumatology electronic list-serv. Survey responses were voluntary and results were analyzed by descriptive statistics. RESULTS: Of 90 survey responses received, 89 were included in the analysis (one was a duplicate response). The respondents were mostly pediatric rheumatologist (94%), with greater than 10 years of experience (55%). The majority (64%) currently see 1-3 patients with DA. Most view DA as the same disease as JIA (73%), and the majority (63%) use a combination of history, exam and imaging to diagnose DA. The most ordered diagnostic tests are CBC (97%) and ESR (96%). The most used treatments include NSAIDs (94%) and methotrexate (91%) followed by anti-TNF agents (90%). Methotrexate is most administered by subcutaneous route (84%) at a dose of 15 mg/m2 (56%). Oral corticosteroids were only used in 19% of the patients with DA. CONCLUSION: This is the first study to evaluate provider perspectives towards the diagnostic and treatment approach of DA. Most pediatric rheumatologists feel that DA and JIA are synonymous, and similar approaches to diagnosis are employed, utilizing history, physical exam, laboratory tests, and imaging modalities. DA is treated similarly to JIA with initiation of NSAIDs, disease-modifying anti-rheumatic drugs and biologic therapy. More research is needed to determine optimal screening and therapeutic approach specific to DA.

Development of Low-Cost Point-of-Care Technologies for Cervical Cancer Prevention Based on a Single-Board Computer.

Cervical cancer disproportionally affects women in low- and middle-income countries, in part due to the difficulty of implementing existing cervical cancer screening and diagnostic technologies in low-resource settings. Single-board computers offer a low-cost alternative to provide computational support for automated point-of-care technologies. Here we demonstrate two new devices for cervical cancer prevention that use a single-board computer: 1) a low-cost imaging system for real-time detection of cervical precancer and 2) a low-cost reader for real-time interpretation of lateral flow-based molecular tests to detect cervical cancer biomarkers. Using a Raspberry Pi computer to provide real-time image collection and processing, we developed: 1) a low-cost, portable high-resolution microendoscope system (PiHRME); and 2) a low-cost automatic lateral flow test reader (PiReader). The PiHRME acquired high-resolution ([Formula: see text]) images of the cervix at half the cost of existing high-resolution microendoscope systems; image analysis algorithms based on convolutional neural networks were implemented to provide real-time image interpretation. The PiReader acquired and analyzed images of a point-of-care human papillomavirus (HPV) serology test with the same contrast and accuracy as a standard flatbed high-resolution scanner coupled to a laptop computer, for less than one-fifth of the cost. Raspberry Pi single-board computers provide a low-cost means to implement point-of-care tools with automatic image analysis. This work demonstrates the promise of single-board computers to develop and translate low-cost, point-of-care technologies for use in low-resource settings.

Birth Outcomes and Disease Activity During Pregnancy in a Prospective Cohort of Women With Psoriatic Arthritis and Ankylosing Spondylitis.

OBJECTIVE: To add to data on adverse birth outcomes accounting for disease activity in women with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). METHODS: Data were analyzed from women enrolled in the Organization of Teratology Information Specialists Autoimmune Disease Project from 2004 to 2018. Disease activity was measured according to the Health Assessment Questionnaire (HAQ) or Routine Assessment of Patient Index Data 3 (RAPID3) scores. Poisson regression was used to estimate adjusted risk ratios (ARRs) with 95% confidence intervals (95% CIs) for selected adverse pregnancy outcomes. RESULTS: Compared to healthy controls (n = 717), women with PsA (n = 117) were at increased risk for moderate preterm delivery (32-36 weeks' gestation) (ARR 1.81, 95% CI 1.01-3.26), oligohydramnios (ARR 3.79, 95% CI 1.34-10.74), and cesarean delivery (ARR 1.63, 95% CI 1.26-2.12). Women with AS (n = 129) had an increased risk of delivering infants requiring intensive care (ARR 1.67, 95% CI 1.05-2.67). A high HAQ score at 32 weeks was associated with preterm delivery in women with PsA (ARR 3.82, 95% CI 1.51-9.67). In women with AS, a high RAPID3 score was associated with cesarean delivery (ARR 5.82, 95% 1.06-31.78), and second trimester glucocorticoid use was associated with preterm delivery (ARR 4.41, 95% CI 1.57-12.41). CONCLUSION: Women with PsA and AS have increased risk for selected adverse pregnancy outcomes. Active disease and use of glucocorticoids may increase the risk for some adverse pregnancy outcomes in women with these conditions.

Association of SLCO1B1 *14 Allele with Poor Response to Methotrexate in Juvenile Idiopathic Arthritis Patients.

OBJECTIVE: Variants in the SLCO1B1 gene, encoding a hepatic methotrexate (MTX) transporter, affect clearance of high-dose MTX. We tested whether in the *14 and *15 alleles of SLCO1B1 influenced the response to low-dose MTX in juvenile idiopathic arthritis (JIA) patients. METHODS: The study included 310 JIA patients genotyped for three single nucleotide polymorphisms (SNPs) in SLCO1B1 (rs4149056, rs2306283, and rs11045819). A patient's SLCO1B1 diplotype was determined by combining the SNPs into the *1a, *1b, *4, *5, *14, and *15 alleles. Number of active joints at follow-up (visit closest to 6 months of treatment and prior to starting a tumor necrosis factor inhibitor) was used as the dependent variable in a negative binomial regression model that included active joint count at baseline as a covariate. RESULTS: The SLCO1B1*14 allele was associated with less response to MTX (P = 0.024) and the *15 allele was not associated with response to MTX (P = 0.392). CONCLUSION: SLCO1B1 alleles may be associated with poor response to MTX in JIA patients. The *14 allele has been associated with fast clearance (low exposure) after high-dose MTX in patients with leukemia. Thus, the SLCO1B1 gene may be informative for precision dosing of MTX in JIA patients. Patients carrying the *14 allele may require a higher dose than noncarriers to achieve a similar response to MTX.

Advances in technologies for cervical cancer detection in low-resource settings.

Introduction: Cervical cancer mortality rates remain high in low- and middle-income countries (LMICs) and other medically underserved areas due to challenges with implementation and sustainability of routine screening, accurate diagnosis, and early treatment of preinvasive lesions. Areas covered: In this review, we first discuss the standard of care for cervical cancer screening and diagnosis in high- and low-resource settings, biomarkers that correlate to cervical precancer and cancer, and needs for new tests. We review technologies for screening and diagnosis with a focus on tests that are already in use in LMICs or have the potential to be adapted for use in LMICs. Finally, we provide perspectives on the next five years of technology development for improved cervical cancer screening and diagnosis in LMICs. Expert opinion: Innovation toward improved molecular and imaging tests is needed to enable effective, affordable see-and-treat approaches to detect and treat cervical precancer in a single visit. Current molecular tests remain too complex and/or costly for widespread use. Especially with imaging tests, decision support may improve performance of new technologies.

Factors Associated With Preterm Delivery Among Women With Rheumatoid Arthritis and Women With Juvenile Idiopathic Arthritis.

OBJECTIVE: Pregnant women with inflammatory arthritis may be at increased risk for preterm delivery (PTD), yet it is unclear what drives this risk. This aim of this prospective cohort study of pregnant women with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), or healthier comparison women was to analyze the independent effects of maternal disease activity, medication use, and comorbid pregnancy conditions on PTD risk. METHODS: Women were enrolled before 19 weeks completed gestation as part of the Organization of Teratology Information Specialists (OTIS) Autoimmune Disease in Pregnancy Project. Data on pregnancy events, medications, disease activity, and outcomes were obtained by maternal report and validated by medical records. Poisson regression with robust standard errors estimated risk ratios (RR), multivariable adjusted risk ratios (ARRs), and 95% confidence intervals (95% CIs). RESULTS: A total of 657 women with RA, 170 with JIA, and 564 comparison women without autoimmune disease who delivered live born infants, from 2004 to 2017 were included for analysis. Both the RA and JIA groups had an increased risk of PTD versus the comparison group (RR 2.09 [95% CI 1.50-2.91] and RR 1.81 [95% CI 1.14-2.89], respectively). Active RA at enrollment (ARR 1.58 [95% CI 1.10-2.27]) and any time during pregnancy (ARR 1.52 [95% CI 1.06-2.18]) was associated with PTD. Corticosteroid use in every trimester was associated with an approximate 2- to 5-fold increased risk for PTD for both arthritis groups, independent of disease activity. CONCLUSION: Women with RA and women with JIA are at increased risk for PTD. Maternal disease activity and corticosteroid use may contribute to some of this excess risk.