The Monarch Initiative in 2024: an analytic platform integrating phenotypes, genes and diseases across species.

Bridging the gap between genetic variations, environmental determinants, and phenotypic outcomes is critical for supporting clinical diagnosis and understanding mechanisms of diseases. It requires integrating open data at a global scale. The Monarch Initiative advances these goals by developing open ontologies, semantic data models, and knowledge graphs for translational research. The Monarch App is an integrated platform combining data about genes, phenotypes, and diseases across species. Monarch's APIs enable access to carefully curated datasets and advanced analysis tools that support the understanding and diagnosis of disease for diverse applications such as variant prioritization, deep phenotyping, and patient profile-matching. We have migrated our system into a scalable, cloud-based infrastructure; simplified Monarch's data ingestion and knowledge graph integration systems; enhanced data mapping and integration standards; and developed a new user interface with novel search and graph navigation features. Furthermore, we advanced Monarch's analytic tools by developing a customized plugin for OpenAI's ChatGPT to increase the reliability of its responses about phenotypic data, allowing us to interrogate the knowledge in the Monarch graph using state-of-the-art Large Language Models. The resources of the Monarch Initiative can be found at monarchinitiative.org and its corresponding code repository at github.com/monarch-initiative/monarch-app.

SSRI use during acute COVID-19 and risk of long COVID among patients with depression.

BACKGROUND: Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is a poorly understood condition with symptoms across a range of biological domains that often have debilitating consequences. Some have recently suggested that lingering SARS-CoV-2 virus particles in the gut may impede serotonin production and that low serotonin may drive many Long COVID symptoms across a range of biological systems. Therefore, selective serotonin reuptake inhibitors (SSRIs), which increase synaptic serotonin availability, may be used to prevent or treat Long COVID. SSRIs are commonly prescribed for depression, therefore restricting a study sample to only include patients with depression can reduce the concern of confounding by indication. METHODS: In an observational sample of electronic health records from patients in the National COVID Cohort Collaborative (N3C) with a COVID-19 diagnosis between September 1, 2021, and December 1, 2022, and a comorbid depressive disorder, the leading indication for SSRI use, we evaluated the relationship between SSRI use during acute COVID-19 and subsequent 12-month risk of Long COVID (defined by ICD-10 code U09.9). We defined SSRI use as a prescription for SSRI medication beginning at least 30 days before acute COVID-19 and not ending before SARS-CoV-2 infection. To minimize bias, we estimated relationships using nonparametric targeted maximum likelihood estimation to aggressively adjust for high-dimensional covariates. RESULTS: We analyzed a sample (n = 302,626) of patients with a diagnosis of a depressive condition before COVID-19 diagnosis, where 100,803 (33%) were using an SSRI. We found that SSRI users had a significantly lower risk of Long COVID compared to nonusers (adjusted causal relative risk 0.92, 95% CI (0.86, 0.99)) and we found a similar relationship comparing new SSRI users (first SSRI prescription 1 to 4 months before acute COVID-19 with no prior history of SSRI use) to nonusers (adjusted causal relative risk 0.89, 95% CI (0.80, 0.98)). CONCLUSIONS: These findings suggest that SSRI use during acute COVID-19 may be protective against Long COVID, supporting the hypothesis that serotonin may be a key mechanistic biomarker of Long COVID.

The Intersections of COVID-19, HIV, and Race/Ethnicity: Machine Learning Methods to Identify and Model Risk Factors for Severe COVID-19 in a Large U.S. National Dataset.

We investigate risk factors for severe COVID-19 in persons living with HIV (PWH), including among racialized PWH, using the U.S. population-sampled National COVID Cohort Collaborative (N3C) data released from January 1, 2020 to October 10, 2022. We defined severe COVID-19 as hospitalized with invasive mechanical ventilation, extracorporeal membrane oxygenation, discharge to hospice or death. We used machine learning methods to identify highly ranked, uncorrelated factors predicting severe COVID-19, and used multivariable logistic regression models to assess the associations of these variables with severe COVID-19 in several models, including race-stratified models. There were 3 241 627 individuals with incident COVID-19 cases and 81 549 (2.5%) with severe COVID-19, of which 17 445 incident COVID-19 and 1 020 (5.8%) severe cases were among PWH. The top highly ranked factors of severe COVID-19 were age, congestive heart failure (CHF), dementia, renal disease, sodium concentration, smoking status, and sex. Among PWH, age and sodium concentration were important predictors of COVID-19 severity, and the effect of sodium concentration was more pronounced in Hispanics (aOR 4.11 compared to aOR range: 1.47-1.88 for Black, White, and Other non-Hispanics). Dementia, CHF, and renal disease was associated with higher odds of severe COVID-19 among Black, Hispanic, and Other non-Hispanics PWH, respectively. Our findings suggest that the impact of factors, especially clinical comorbidities, predictive of severe COVID-19 among PWH varies by racialized groups, highlighting a need to account for race and comorbidity burden when assessing the risk of PWH developing severe COVID-19.

Associations of County-Level Social Determinants of Health with COVID-19 Related Hospitalization Among People with HIV: A Retrospective Analysis of the U.S. National COVID Cohort Collaborative (N3C).

Individually, the COVID-19 and HIV pandemics have differentially impacted minoritized groups due to the role of social determinants of health (SDoH) in the U.S. Little is known how the collision of these two pandemics may have exacerbated adverse health outcomes. We evaluated county-level SDoH and associations with hospitalization after a COVID-19 diagnosis among people with (PWH) and without HIV (PWOH) by racial/ethnic groups. We used the U.S. National COVID Cohort Collaborative (January 2020-November 2023), a nationally-sampled electronic health record repository, to identify adults who were diagnosed with COVID-19 with HIV (n = 22,491) and without HIV (n = 2,220,660). We aggregated SDoH measures at the county-level and categorized racial/ethnic groups as Non-Hispanic (NH) White, NH-Black, Hispanic/Latinx, NH-Asian and Pacific Islander (AAPI), and NH-American Indian or Alaskan Native (AIAN). To estimate associations of county-level SDoH with hospitalization after a COVID-19 diagnosis, we used multilevel, multivariable logistic regressions, calculating adjusted relative risks (aRR) with 95% confidence intervals (95% CI). COVID-19 related hospitalization occurred among 11% of PWH and 7% of PWOH, with the highest proportion among NH-Black PWH (15%). In evaluating county-level SDoH among PWH, we found higher average household size was associated with lower risk of COVID-19 related hospitalization across racial/ethnic groups. Higher mean commute time (aRR: 1.76; 95% CI 1.10-2.62) and higher proportion of adults without health insurance (aRR: 1.40; 95% CI 1.04-1.84) was associated with a higher risk of COVID-19 hospitalization among NH-Black PWH, however, NH-Black PWOH did not demonstrate these associations. Differences by race and ethnicity exist in associations of adverse county-level SDoH with COVID-19 outcomes among people with and without HIV in the U.S.

Determination of Child Waist Circumference Cut Points for Metabolic Risk Based on Acanthosis Nigricans, the Children's Healthy Living Program.

INTRODUCTION: Waist circumference is a common anthropometric measure for predicting abdominal obesity and insulin resistance. We developed optimal waist circumference cut points for children aged 2 to 8 years in the US-Affiliated Pacific (USAP) region based on the relationship of waist circumference and acanthosis nigricans in this population. METHODS: We conducted a cross-sectional analysis from the Children's Healthy Living Program's 2012-2013 data on 4,023 children. We used receiver-operating characteristic analysis to determine the sensitivity and specificity for acanthosis nigricans across waist circumference, by sex and age. We determined optimal waist circumference cutoff points corresponding to Youden index (J), (equal to [sensitivity + specificity] - 1), with acanthosis nigricans. We compared these cut points with the 90th percentile. RESULTS: The 90th-percentile cut points for boys aged 2 to 5 years (58.15 cm) and 6 to 8 years (71.63 cm) were slightly higher than for girls in both age groups (aged 2-5 y, 57.97 cm; 6-8 y: 70.37 cm). The optimal cut points (corresponding to the highest sensitivity and specificity) were as follows: for boys aged 2 to 5 years, 90th percentile (58.25 cm; sensitivity, 48.0%; specificity, 91.5%); for boys aged 6 to 8 years, 78th percentile (63.59 cm; sensitivity, 86.8%; specificity, 82.8%); for girls aged 2 to 5 years, 62nd percentile (53.27 cm; sensitivity, 71.4%; specificity, 63.1%), and for girls aged 6 to 8 years, 80th percentile (63.63 cm; sensitivity, 55.4%; specificity, 82.9%). CONCLUSION: Among USAP children, waist circumference was a reasonable predictor for acanthosis nigricans. Further analysis is warranted to examine causes of acanthosis nigricans at lower-than-expected waist circumference percentiles. The cut points can be used for early detection of metabolic risk.

Paradoxical association between atrial fibrillation/flutter and high cholesterol over age 75 years: The Kuakini Honolulu Heart Program and Honolulu-Asia Aging Study.

INTRODUCTION: Several studies have indicated high cholesterol is paradoxically associated with low prevalence of atrial fibrillation/flutter (AF). However, the etiology is uncertain. One potential explanation might be the confounding effect of age exemplifying prevalence-incidence (Neyman's) bias. However, this bias has not often been discussed in depth in the literature. Therefore, we conducted a cross-sectional analysis to test the hypothesis that there is a paradoxical association between lipid profile and AF prevalence. METHODS: This is a cross-sectional study design, using data from the Kuakini Honolulu Heart Program. Participants were 3741 Japanese-American men between 71 and 93 years old living in Hawaii. Serum total cholesterol (TC) level was measured and categorized into quartiles. AF was diagnosed by 12­lead Electrocardiogram. We categorized age into quartiles (71-74, 75-77, 78-80 and 81+ years). RESULTS: We observed opposite associations between AF and TC among different age groups. For participants age ≥75, higher TC levels were paradoxically associated with lower prevalence of AF after multivariable adjustment, i.e. the odds ratios of AF comparing the highest TC quartile with the lowest TC quartile for age 75-77, 78-80 and 81+ years were 0.17 (95% confidence interval [CI], 0.06-0.52), 0.28 (95% CI, 0.07-1.09) and 0.14 (95% CI, 0.03-0.62), respectively. Conversely, for those who were 71-74 years old, the odds ratio of AF was 2.09 (95% CI, 0.76-5.75) between the highest and the lowest TC quartiles. CONCLUSIONS: There is a paradoxical association of TC with AF in Japanese-American men age ≥75, but not <75 years. The paradox might be explained by Neyman's bias.

Extrapolating Beyond the Data in a Systematic Review of Spinal Manipulation for Nonmusculoskeletal Disorders: A Fall From the Summit.

OBJECTIVE: The purpose of this article is to discuss a literature review-a recent systematic review of nonmusculoskeletal disorders-that demonstrates the potential for faulty conclusions and misguided policy implications, and to offer an alternate interpretation of the data using present models and criteria. METHODS: We participated in a chiropractic meeting (Global Summit) that aimed to perform a systematic review of the literature on the efficacy and effectiveness of mobilization or spinal manipulative therapy (SMT) for the primary, secondary, and tertiary prevention and treatment of nonmusculoskeletal disorders. After considering an early draft of the resulting manuscript, we identified points of concern and therefore declined authorship. The present article was developed to describe those concerns about the review and its conclusions. RESULTS: Three main concerns were identified: the inherent limitations of a systematic review of 6 articles on the topic of SMT for nonmusculoskeletal disorders, the lack of biological plausibility of collapsing 5 different disorders into a single category, and considerations for best practices when using evidence in policy-making. We propose that the following conclusion is more consistent with a review of the 6 articles. The small cadre of high- or moderate-quality randomized controlled trials reviewed in this study found either no or equivocal effects from SMT as a stand-alone treatment for infantile colic, childhood asthma, hypertension, primary dysmenorrhea, or migraine, and found no or low-quality evidence available to support other nonmusculoskeletal conditions. Therefore, further research is needed to determine if SMT may have an effect in these and other nonmusculoskeletal conditions. Until the results of such research are available, the benefits of SMT for specific or general nonmusculoskeletal disorders should not be promoted as having strong supportive evidence. Further, a lack of evidence cannot be interpreted as counterevidence, nor used as evidence of falsification or verification. CONCLUSION: Based on the available evidence, some statements generated from the Summit were extrapolated beyond the data, have the potential to misrepresent the literature, and should be used with caution. Given that none of the trials included in the literature review were definitively negative, the current evidence suggests that more research on nonmusculoskeletal conditions is warranted before any definitive conclusions can be made. Governments, insurers, payers, regulators, educators, and clinicians should avoid using systematic reviews in decisions where the research is insufficient to determine the clinical appropriateness of specific care.

Long-Term Medicare Costs Associated With Opioid Analgesic Therapy vs Spinal Manipulative Therapy for Chronic Low Back Pain in a Cohort of Older Adults.

OBJECTIVES: The purpose of this study was to compare Medicare healthcare expenditures for patients who received long-term treatment of chronic low back pain (cLBP) with either opioid analgesic therapy (OAT) or spinal manipulative therapy (SMT). METHODS: We conducted a retrospective observational study using a cohort design for analysis of Medicare claims data. The study population included Medicare beneficiaries enrolled under Medicare Parts A, B, and D from 2012 through 2016. We assembled cohorts of patients who received long-term management of cLBP with OAT or SMT (such as delivered by chiropractic or osteopathic practitioners) and evaluated the comparative effect of OAT vs SMT upon expenditures, using multivariable regression to control for beneficiary characteristics and measures of health status, and propensity score weighting and binning to account for selection bias. RESULTS: The study sample totaled 28,160 participants, of whom 77% initiated long-term care of cLBP with OAT, and 23% initiated care with SMT. For care of low back pain specifically, average long-term costs for patients who initiated care with OAT were 58% lower than those who initiated care with SMT. However, overall long-term healthcare expenditures under Medicare were 1.87 times higher for patients who initiated care via OAT compared with those initiated care with SMT (95% CI 1.65-2.11; P < .0001). CONCLUSIONS: Adults aged 65 to 84 who initiated long-term treatment for cLBP via OAT incurred lower long-term costs for low back pain but higher long-term total healthcare costs under Medicare compared with patients who initiated long-term treatment with SMT.

Spinal Manipulation vs Prescription Drug Therapy for Chronic Low Back Pain: Beliefs, Satisfaction With Care, and Qualify of Life Among Older Medicare Beneficiaries.

OBJECTIVE: The objective of this study was to compare patients' perspectives on the use of spinal manipulative therapy (SMT) compared to prescription drug therapy (PDT) with regard to health-related quality of life (HRQoL), patient beliefs, and satisfaction with treatment. METHODS: Four cohorts of Medicare beneficiaries were assembled according to previous treatment received as evidenced in claims data: SMT, PDT, and 2 crossover cohorts (where participants experienced both types of treatments). A total of 195 Medicare beneficiaries responded to the survey. Outcome measures used were a 0-to-10 numeric rating scale to measure satisfaction, the Low Back Pain Treatment Beliefs Questionnaire to measure patient beliefs, and the 12-item Short Form Health Survey to measure HRQoL. RESULTS: Recipients of SMT were more likely to be very satisfied with their care (84%) than recipients of PDT (50%; P = .002). The SMT cohort self-reported significantly higher HRQoL compared to the PDT cohort; mean differences in physical and mental health scores on the 12-item Short Form Health Survey were 12.85 and 9.92, respectively. The SMT cohort had a lower degree of concern regarding chiropractic care for their back pain compared to the PDT cohort's reported concern about PDT (P = .03). CONCLUSION: Among older Medicare beneficiaries with chronic low back pain, long-term recipients of SMT had higher self-reported rates of HRQoL and greater satisfaction with their modality of care than long-term recipients of PDT. Participants who had longer-term management of care were more likely to have positive attitudes and beliefs toward the mode of care they received.

Predictors of visit frequency for patients using ongoing chiropractic care for chronic low back and chronic neck pain; analysis of observational data.

BACKGROUND: Chronic spinal pain is prevalent, expensive and long-lasting. Several provider-based nonpharmacologic therapies have now been recommended for chronic low-back pain (CLBP) and chronic neck pain (CNP). However, healthcare and coverage policies provide little guidance or evidence regarding the long-term use of this care. To provide one glimpse into the long-term use of nonpharmacologic provider-based care, this study examines the predictors of visit frequency in a large sample of patients with CLBP and CNP using ongoing chiropractic care. METHODS: Observational data were collected from a large national sample of chiropractic patients in the US with non-specific CLBP and CNP. Visit frequency was defined as average number of chiropractic visits per month over the 3-month study period. Potential baseline predictor variables were entered into two sets of multi-level models according to a defined causal theory-in this case, Anderson's Behavioral Model of Health Services Use. RESULTS: Our sample included 852 patients with CLBP and 705 with CNP. Visit frequency varied significantly by chiropractor/clinic, so our models controlled for this clustering. Patients with either condition used an average of 2.3 visits per month. In the final models visit frequency increased (0.44 visits per month, p = .008) for those with CLBP and some coverage for chiropractic, but coverage had little effect on visits for patients with CNP. Patients with worse function or just starting care also had more visits and those near to ending care had fewer visits. However, visit frequency was also determined by the chiropractor/clinic where treatment was received. Chiropractors who reported seeing more patients per day also had patients with higher visit frequency, and the patients of chiropractors with 20 to 30 years of experience had fewer visits per month. In addition, after controlling for both patient and chiropractor characteristics, the state in which care was received made a difference, likely through state-level policies and regulations. CONCLUSIONS: Chiropractic patients with CLBP and CNP use a range of visit frequencies for their ongoing care. The predictors of these frequencies could be useful for understanding and developing policies for ongoing provider-based care.

Association between central sleep apnea and atrial fibrillation/flutter in Japanese-American men: The Kuakini Honolulu Heart Program (HHP) and Honolulu-Asia Aging Study (HAAS).

INTRODUCTION: While several studies have indicated that central sleep apnea (CSA) is associated with atrial fibrillation and atrial flutter (AF) in older populations, few studies have focused on older Asian populations. METHODS: We conducted a cross- sectional analysis using data from the 1999-2000, 7th exam cycle of the Kuakini Honolulu-Asia Aging Study. Participants were 718 Japanese-American men between 79 and 97 years old, who had overnight polysomnography. Obstructive Apnea-Hypopnea Index (OAHI) was the measure of the number of obstructive apneas and hypopneas with >4% oxygen desaturation. Additionally, the Central Apnea Index (CAI) was the measure of the number of central apneas. Obstructive sleep apnea (OSA) was categorized as none (OAHI <5), mild (OAHI 5-14), moderate (OAHI 15-29) and severe (OAHI ≥30). CSA was defined by CAI of 5 or more. Cheyne-Stokes Breathing (CSB) was defined as a minimum consecutive 5-minute period of a crescendo-decrescendo respiratory pattern associated with CSA. RESULTS: AF prevalence was 5.5% (39 of 709). The prevalence proportions of severe OSA, CSA, and CSB were 20.2% (143 of 709), 6.4% (43 of 673) and 3.2% (22 of 673), respectively. In multivariable-adjusted logistic regression models, CSA and CSB were significantly associated with AF prevalence: odds ratio (OR) 5.15, 95% confidential interval (CI), 2.21-12.52 and OR 6.26, 95% CI, 2.05-19.14, respectively. However, OSA was not significantly associated with AF prevalence. CONCLUSION: AF prevalence is associated with CSA and CSB but not OSA in older Japanese-American men. This information could help target AF prevention strategies in this population.

Clinical Scenarios for Which Spinal Mobilization and Manipulation Are Considered by an Expert Panel to be Inappropriate (and Appropriate) for Patients With Chronic Low Back Pain.

BACKGROUND: Spinal mobilization and manipulation are 2 therapies found to be generally safe and effective for chronic low back pain (CLBP). However, the question remains whether they are appropriate for all CLBP patients. RESEARCH DESIGN: An expert panel used a well-validated approach, including an evidence synthesis and clinical acumen, to develop and then rate the appropriateness of the use of spinal mobilization and manipulation across an exhaustive list of clinical scenarios which could present for CLBP. Decision tree analysis (DTA) was used to identify the key patient characteristics that affected the ratings. RESULTS: Nine hundred clinical scenarios were defined and then rated by a 9-member expert panel as to the appropriateness of spinal mobilization and manipulation. Across clinical scenarios more were rated appropriate than inappropriate. However, the number patients presenting with each scenario is not yet known. Nevertheless, DTA indicates that all clinical scenarios that included major neurological findings, and some others involving imaging findings of central herniated nucleus pulposus, spinal stenosis, or free fragments, were rated as inappropriate for both spinal mobilization and manipulation. DTA also identified the absence of these imaging findings and no previous laminectomy as the most important patient characteristics in predicting ratings of appropriate. CONCLUSIONS: A well-validated expert panel-based approach was used to develop and then rate the appropriateness of the use of spinal mobilization and manipulation across the clinical scenarios which could present for CLBP. Information on the clinical scenarios for which these therapies are inappropriate should be added to clinical guidelines for CLBP.

The impact of patient preferences and costs on the appropriateness of spinal manipulation and mobilization for chronic low back pain and chronic neck pain.

BACKGROUND: Although the delivery of appropriate healthcare is an important goal, the definition of what constitutes appropriate care is not always agreed upon. The RAND/UCLA Appropriateness Method is one of the most well-known and used approaches to define care appropriateness from the clinical perspective-i.e., that the expected effectiveness of a treatment exceeds its expected risks. However, patient preferences (the patient perspective) and costs (the healthcare system perspective) are also important determinants of appropriateness and should be considered. METHODS: We examined the impact of including information on patient preferences and cost on expert panel ratings of clinical appropriateness for spinal mobilization and manipulation for chronic low back pain and chronic neck pain. RESULTS: The majority of panelists thought patient preferences were important to consider in determining appropriateness and that their inclusion could change ratings, and half thought the same about cost. However, few actually changed their appropriateness ratings based on the information presented on patient preferences regarding the use of these therapies and their costs. This could be because the panel received information on average patient preferences for spinal mobilization and manipulation whereas some panelists commented that appropriateness should be determined based on the preferences of individual patients. Also, because these therapies are not expensive, their ratings may not be cost sensitive. The panelists also generally agreed that preferences and costs would only impact their ratings if the therapies were considered clinically appropriate. CONCLUSIONS: This study found that the information presented on patient preferences and costs for spinal mobilization and manipulation had little impact on the rated appropriateness of these therapies for chronic low back pain and chronic neck pain. Although it was generally agreed that patient preferences and costs were important to the appropriateness of M/M for CLBP and CNP, it seems that what would be most important were the preferences of the individual patient, not patients in general, and large cost differentials.

Yoga for Quality of Life in Individuals With Chronic Disease: A Systematic Review.

BACKGROUND: Chronic diseases, including heart disease, stroke, cancer, and chronic pulmonary disease are the leading causes of death and disability worldwide. Compounding symptoms and loss of function, people living with chronic disease often experience reduced quality of life (QoL). Various physical and mental practices have been shown to relieve stress and improve QoL. Yoga is a physical and mental practice that may be a viable approach for improving QoL in people with chronic disease. OBJECTIVE: The objective of this study was to examine and summarize the evidence for the effectiveness of yoga on QoL in patients with chronic disease. DESIGN: The study design was a a systematic review with qualitative synthesis. METHODS: We included randomized controlled trials that evaluated the effect of yoga on QoL or health-related QoL (HRQoL) for individuals with chronic disease. We included only studies that used at least 1 previously validated measure of QoL or HRQoL and specified a minimum duration of follow-up of at least 1 wk. INTERVENTIONS: We included both movement-based and breath-based yoga practices. Studies that included yoga as part of a larger intervention program (eg, mindfulness-based stress reduction training) or studies that did not provide findings specific to yoga were excluded. PRIMARY OUTCOME MEASURES: The primary outcome analyzed was improvement in QoL as measured by a validated QoL or HRQoL scale. RESULTS: Among the 1488 studies that were identified on initial search, 7 articles met all inclusion criteria. Five studies reported a statistically significant advantage over usual care alone for improvement of QoL in patients with chronic disease, but the clinical significance of the differences was clear in only 1 trial. We found considerable heterogeneity among the included studies and study quality was generally low. CONCLUSIONS: More high-quality research is needed to determine the value of yoga as an adjunctive approach to improving QoL in patients with chronic disease.

Advanced Prescription of Emergency Contraceptive Pills Among Adolescents and Young Adults.

OBJECTIVE: To examine healthcare providers' adherence to professional recommendations for advanced prescription of emergency contraceptive pills (ECPs). METHODS: We conducted a retrospective chart review of 432 visits by 282 unique nonpregnant women 14 to 25 years of age seen at an obstetrics and gynecology teaching clinic to determine the percentage of visits during which advanced prescriptions of ECPs were provided when indicated. A logistic regression model, which accounted for nonindependent observations through generalized estimating equations, was used to identify factors associated with the provision of ECP advanced prescriptions. RESULTS: Approximately one-fifth of eligible visits (19.9%) and eligible patients (19.1%) had documentation of an ECP advanced prescription when indicated. Healthcare providers in this clinical setting were more likely to prescribe ECPs to adolescents and women whose primary contraceptive methods were associated with higher failure rates in typical use, such as condoms. Compared with women aged 20 to 25 years, the adjusted odds ratio of receiving an advanced prescription for ECPs was 5.94 (95% confidence interval [CI] 2.85-12.41) for adolescents. Compared with users of depot medroxyprogesterone acetate, the adjusted odds ratio was 4.25 (95% CI 1.62-11.15) for condom users, and 3.90 (95% CI 1.54-9.86) for users of other short-term hormonal contraceptives. CONCLUSIONS: Despite clear professional recommendations for ECP advanced prescriptions for all women at risk for unintended pregnancy, a substantial gap exists between this standard of care and routine clinical service provision in an obstetrics and gynecology teaching clinic.

An Exploratory Analysis of Gender as a Potential Modifier of Treatment Effect Among Patients in a Randomized Controlled Trial of Integrative Acupuncture and Spinal Manipulation for Low Back Pain.

OBJECTIVE: To identify the potential association of self-reported gender on pain and disability among patients in a randomized controlled trial of integrative acupuncture and spinal manipulation therapy (SMT) for low back pain (LBP). METHODS: In the original study, 100 participants with LBP were randomized to receive acupuncture, SMT, or both combined. Eighty completed treatment and were followed for 60 days. Primary outcome measures were the Roland-Morris Disability Questionnaire and numeric pain scales. This study was a secondary analysis and used regression models to estimate and test for gender-specific differences in outcomes from baseline through end of treatment. RESULTS: Women assigned to acupuncture averaged a 3.8-point reduction in highest LBP vs 2.0 points for SMT, whereas men assigned to SMT averaged a 3.5-point reduction vs 1.8 points for acupuncture (P for interaction = .04). There was a trend toward the same for disability (P for interaction = .12). For women, acupuncture alone led to better outcomes without SMT, and for men, SMT alone led to better outcomes without acupuncture. Women who received acupuncture were more likely to experience 50% or greater reductions in disability and pain, whereas men who received SMT were more likely to experience 50% or greater reductions in disability and pain. CONCLUSION: An association was found between self-reported gender and response to LBP treatment. Women demonstrated a greater reduction in pain and disability with acupuncture and men with SMT. Future clinical trials should consider sex as a potential determinant of treatment outcomes for LBP.

Researching the Appropriateness of Care in the Complementary and Integrative Health Professions Part 5: Using Patient Records: Selection, Protection, and Abstraction.

OBJECTIVES: The purpose of this paper is to describe the 4-step process (consent, selection, protection, and abstraction) of acquiring a large sample of chiropractic patient records from multiple practices and subsequent data abstraction. METHODS: From April 2017 to December 2017, RAND acquired patient records from 99 chiropractic practices across the United States. The records included patients enrolled in a survey e-study (prospective sample) and a random sample of all clinic patients (retrospective sample) with chronic back or neck pain. Clinic staff were trained to collect the sample, scan, and transfer the records. We designed an online data collection tool for abstraction. Protocols were instituted to protect patient confidentiality. Doctors of chiropractic were selected and trained as abstractors, and a system was established to monitor data collection. RESULTS: In compliance with data protection protocols, 3603 patient records were scanned, including 1475 in the prospective sample and 2128 in the random sample. A total of 1716 patients (prospective sample) consented to having their records scanned, but only 1475 could be retrieved. Of records scanned, 19% were unusable owing to illegibility, no care during the period of interest, or poor scanning. The abstractor interrater reliability for appropriateness of care decisions was fair to moderate (κ .38-.48). CONCLUSION: The acquisition, handling, and abstraction of a large sample of chiropractic records was a complex task with challenges that necessitated adapting planned approaches. Of the records abstracted, many revealed incomplete provider documentation regarding the details of and rationale for care. Better documentation and more standardized record keeping would facilitate future research using patient records.

The Global Spine Care Initiative: a summary of the global burden of low back and neck pain studies.

PURPOSE: This article summarizes relevant findings related to low back and neck pain from the Global Burden of Disease (GBD) reports for the purpose of informing the Global Spine Care Initiative. METHODS: We reviewed and summarized back and neck pain burden data from two studies that were published in Lancet in 2016, namely: "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015" and "Global, regional, and national disability-adjusted life years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015." RESULTS: In 2015, low back and neck pain were ranked the fourth leading cause of disability-adjusted life years (DALYs) globally just after ischemic heart disease, cerebrovascular disease, and lower respiratory infection {low back and neck pain DALYs [thousands]: 94 941.5 [95% uncertainty interval (UI) 67 745.5-128 118.6]}. In 2015, over half a billion people worldwide had low back pain and more than a third of a billion had neck pain of more than 3 months duration. Low back and neck pain are the leading causes of years lived with disability in most countries and age groups. CONCLUSION: Low back and neck pain prevalence and disability have increased markedly over the past 25 years and will likely increase further with population aging. Spinal disorders should be prioritized for research funding given the huge and growing global burden. These slides can be retrieved under Electronic Supplementary Material.

The Global Spine Care Initiative: a systematic review of individual and community-based burden of spinal disorders in rural populations in low- and middle-income communities.

PURPOSE: The purpose of this review was to synthesize literature on the burden of spinal disorders in rural communities to inform the Global Spine Care Initiative care pathway and model of care for their application in medically underserved areas and low- and middle-income countries. METHODS: A systematic review was conducted. Inclusion criteria included all age groups with nonspecific low back pain, neck pain, and associated disorders, nonspecific thoracic spinal pain, musculoskeletal chest pain, radiculopathy, or spinal stenosis. Study designs included observational study design (case-control, cross-sectional, cohort, ecologic, qualitative) or review or meta-analysis. After study selection, studies with low or moderate risk of bias were qualitatively synthesized. RESULTS: Of 1150 potentially relevant articles, 43 were eligible and included in the review. All 10 low and 18 moderate risk of bias studies were cross-sectional, 14 of which included rural residents only. All studies included estimates of low back pain prevalence, one included neck pain and one reported estimates for spinal disorders other than back or neck pain. The prevalence of low back pain appears greater among females and in those with less education, psychological factors (stress, anxiety, depression), and alcohol consumers. The literature is inconsistent as to whether back pain is more common in rural or urban areas. High risk of bias in many studies, lack of data on disability and other burden measures and few studies on conditions other than back and neck pain preclude a more comprehensive assessment of the individual and community-based burden of spinal disorders in less-developed communities. CONCLUSION: We identified few high-quality studies that may inform patients, providers, policymakers, and other stakeholders about spinal disorders and their burden on individuals and communities in most rural places of the developing world. These findings should be a call to action to devote resources for high-quality research to fill these knowledge gaps in medically underserved areas and low and middle-income countries. These slides can be retrieved under Electronic Supplementary Material.

The Global Spine Care Initiative: applying evidence-based guidelines on the non-invasive management of back and neck pain to low- and middle-income communities.

PURPOSE: The purpose of this review was to develop recommendations for the management of spinal disorders in low-income communities, with a focus on non-invasive pharmacological and non-pharmacological therapies for non-specific low back and neck pain. METHODS: We synthesized two evidence-based clinical practice guidelines for the management of low back and neck pain. Our recommendations considered benefits, harms, quality of evidence, and costs, with attention to feasibility in medically underserved areas and low- and middle-income countries. RESULTS: Clinicians should provide education and reassurance, advise patients to remain active, and provide information about self-care options. For acute low back and neck pain without serious pathology, primary conservative treatment options are exercise, manual therapy, superficial heat, and nonsteroidal anti-inflammatory drugs (NSAIDs). For patients with chronic low back and neck pain without serious pathology, primary treatment options are exercise, yoga, cognitive behavioral therapies, acupuncture, biofeedback, progressive relaxation, massage, manual therapy, interdisciplinary rehabilitation, NSAIDs, acetaminophen, and antidepressants. For patients with spinal pain with radiculopathy, clinicians may consider exercise, spinal manipulation, or NSAIDs; use of other interventions requires extrapolation from evidence regarding effectiveness for non-radicular spinal pain. Clinicians should not offer treatments that are not effective, including benzodiazepines, botulinum toxin injection, systemic corticosteroids, cervical collar, electrical muscle stimulation, short-wave diathermy, transcutaneous electrical nerve stimulation, and traction. CONCLUSION: Guidelines developed for high-income settings were adapted to inform a care pathway and model of care for medically underserved areas and low- and middle-income countries by considering factors such as costs and feasibility, in addition to benefits, harms, and the quality of underlying evidence. The selection of recommended conservative treatments must be finalized through discussion with the involved community and based on a biopsychosocial approach. Decision determinants for selecting recommended treatments include costs, availability of interventions, and cultural and patient preferences. These slides can be retrieved under Electronic Supplementary Material.