Building Capacity for Pragmatic Trials of Digital Technology in Primary Care.

Frontline primary care teams face important challenges in seeking to transform the quality of care delivered to patients and to reduce clerical burden for clinicians. Digital technologies using artificial intelligence hold substantial promise to aid in this transformation. Both pragmatic clinical trials and implementation science are key tools to successfully introduce, evaluate, and sustain innovations in real-world primary care practices. Previous articles in this thematic series have provided an in-depth overview of pragmatic trials and implementation science. This paper demonstrates and provides a framework for how these concepts, together with digital transformation, can be used to solve many of the challenges facing primary care. This framework is conceived as the collaboration of frontline primary care teams with innovators in academic institutions and industry through pragmatic trials and implementation science.

Treatment of vitamin D deficiency in children.

INTRODUCTION: Vitamin D deficiency affects from 10% to 50% in various pediatric population groups and causes life-threatening hypocalcemia in infants, crippling rickets in infants and children, and increased risk of subsequent adult metabolic and neurologic problems. AREAS COVERED: An English language literature search of PubMed was performed since 1940 as were the authors' personal literature collections. References identified in the reviewed literature are considered. DIAGNOSIS: The diagnosis of vitamin D deficiency is based on serum 25-hydroxyvitamin D levels. Clinical features of rickets include bone deformities and elevated alkaline phosphatase. Most children and adolescents who are biochemically vitamin D deficient do not have specific symptoms or signs of deficiency. PREVENTION: Prevention of vitamin D deficiency is via exposure to sunshine, food and beverage fortification, and dietary supplementation. TREATMENT: Effective treatment of vitamin D deficiency is via oral or injectable administration of vitamin D. Dosing and duration of vitamin D therapy have been described for healthy children and for children with underlying medical conditions, but recommendations vary. EXPERT OPINION: Further investigation is needed to determine long-term non-skeletal effects of childhood vitamin D deficiency, benefits of supplementation in asymptomatic individuals with biochemical vitamin D deficiency, and appropriate screening for vitamin D deficiency in asymptomatic children and adolescents.

Development and Early Experience of a Primary Care Learning Collaborative in a Large Health Care System.

INTRODUCTION: Primary care clinicians are presented with hundreds of new clinical recommendations and guidelines. To consider practice change clinicians must identify relevant information and develop a contextual framework. Too much attention to information irrelevant to one's practice results in wasted resources. Too little results in care gaps. A small group of primary care clinicians in a large health system sought to address the problem of vetting new information and providing peer reviewed context. This was done by engaging colleagues across the system though a primary care learning collaborative. METHODS: The collaborative was a grass roots initiative between community and academic-based clinicians. They invited all the system's primary care clinicians to participate. They selected new recommendations or guidelines and used surveys as the principal communication instrument. Surveys shared practice experience and also invited members to give narrative feedback regarding their acceptance of variation in care relate to the topic. A description of the collaborative along with its development, processes, and evolution are discussed. Process changes to address needs during the COVID-19 pandemic including expanded information sharing was necessary. RESULTS: Collaborative membership reached across 5 states and included family medicine, internal medicine, and pediatrics. Members found involvement with the collaborative useful. Less variation in care was thought important for public health crises: the COVID pandemic and opioid epidemic. Greater practice variation was thought acceptable for adherence to multispecialty guidelines, such as diabetes, lipid management, and adult ADHD care. Process changes during the pandemic resulted in more communications between members to avoid practice gaps. CONCLUSION: An internet-based learning collaborative in a health system had good engagement from its members. Using novel methods, it was able to provide members with feedback related to the importance of new practice recommendations as perceived by their peers. Greater standardization was thought necessary when adopting measures to address public health crisis, and less necessary when addressing multispecialty guidelines. By employing a learning collaborative, this group was able to keep members interested and engaged. During the first year of the COVID pandemic the collaborative also served as a vehicle to share timely information.

The effect of primary care clinician type and care team characteristics on health care costs.

OBJECTIVE: To evaluate health care costs as a function of assigned primary care clinician type and care team characteristics. METHODS: Administrative data were collected for 68 family medicine clinicians (40 physicians and 28 nurse practitioners [NPs]/physician assistant [PAs]), on 11 care teams (variable MD, NP and PA on teams), caring for 77,141 patients. We performed a generalized linear mixed multivariable regression model of standardized per member per month (PMPM) median cost as the outcome, with four practice sites included as random effects. RESULTS: In bivariate analysis, cost was higher in physicians than NP/PAs, in more complex patients, and associated with emergency department (ED) visit rate. On multivariate analysis, patient complexity, ED visit rate and higher patient experience ratings were independently associated with greater PMPM cost. More time in practice was associated with lower PMPM cost. In the adjusted multivariate model, physicians had 8.3% lower median PMPM costs than NP/PAs (p = 0.046). CONCLUSIONS: The primary drivers of greater PMPM cost were patient complexity, ED visits and patient satisfaction.

One year of COVID: primary care learning experiences in a health system.

Context: Patients and communities consider their primary care clinicians (PCC's) to be their most trusted source of information. During the first 12 months of the COVID pandemic, initially reliable, accurate information was scare, evolving, and at times conflicting. From testing, public health prevention, treatment, and vaccinations clinicians had to learn, apply, and convey this information honestly and openly. Objective: This was a survey of a health system's PCC's after the first year of the pandemic. The objective was to determine the clinical, educational, and advisory roles performed by PCC's and the sources of from which PCC's obtained the information necessary to fulfill these roles. Study Design: An intranet survey was sent to members of the system's primary care learning collaborative. Questions were multiple answer with options for open-ended answers. Setting: Large health system. Population: Learning collaborative membership consisting of physicians, nurse practitioners (NP), and physician assistants (PA). Instrument: Brief intranet survey. Outcome measures: Identify clinical and educational roles for PCC. Results: 192 surveys were sent; 109 responses; 72% physicians, 28% NP/PA. 25 unique clinical roles were identified. Most common: discuss vaccine (94%), work excuse/return to work (88%), outpatient care (87%), virtual assessment for COVID (74%). 14 unique educational or advisory roles were identified; the most common being teaching residents (45%) or students (42%), lecture/discussion on COVID (20%) or vaccines (22%) or advising community groups (18%). Sources of information related to COVID were diverse. When asked to identify the three most relied on sources, system (internal COVID website or disseminated by system) (83%), colleagues (34%), and consultants (33%), were the most common source. CME was the least relied upon (7%). Frequently the system utilized information from CDC, state/local health department information along with national organizations. Conclusions: During the pandemic, primary care clinicians provided a broad array of clinical services, and are a source of information for colleagues, patients, and communities. They rely on a broad array of sources for reliable information, mostly relationship-based, not formal CME. The trusted relationships primary care clinicians have with others throughout their communities was essential in promulgating accurate reliable information during the first year of the pandemic.

Assessing Biomarkers of Breast Cancer Risk in Underserved Women in a Midwestern County.

OBJECTIVE: The primary aim of this study was to evaluate the feasibility of collecting risk factor information and accessing digitized mammographic data in a medically marginalized population. A secondary aim was to examine the association between vitamin D status and mammographic density. METHODS: Breast-screening examinations were provided for age-appropriate patients, and a referral for no-cost screening mammography was offered. Study participants were asked to undergo 25-hydroxyvitamin D testing at mammography and 1-year follow-up. RESULTS: Of 62 women approached, 35 (56%) consented to participate. Of 32 participants who had baseline mammography, the median mammographic density measured by VolparaDensity (Volpara Solutions Limited) was 5.7%. After 1 year, 9 women obtained follow-up mammograms, with a median density of 5.7%. Vitamin D status was measured for 31 participants at baseline and 13 participants in the following year. Insufficient vitamin D status (<30 ng/mL) was noted in 77% at each time point. Mammographic density was not significantly correlated with vitamin D status (P = .06). CONCLUSIONS: On the basis of this small pilot study, vitamin D insufficiency is common in this study population. Owing to the small sample size, an association between vitamin D insufficiency and breast density was not clear. Additional unexpected findings included substantial barriers in initial access to care and longitudinal follow-up in this population. Further study of these issues is needed.

Artificial intelligence-enabled electrocardiograms for identification of patients with low ejection fraction: a pragmatic, randomized clinical trial.

We have conducted a pragmatic clinical trial aimed to assess whether an electrocardiogram (ECG)-based, artificial intelligence (AI)-powered clinical decision support tool enables early diagnosis of low ejection fraction (EF), a condition that is underdiagnosed but treatable. In this trial ( NCT04000087 ), 120 primary care teams from 45 clinics or hospitals were cluster-randomized to either the intervention arm (access to AI results; 181 clinicians) or the control arm (usual care; 177 clinicians). ECGs were obtained as part of routine care from a total of 22,641 adults (N = 11,573 intervention; N = 11,068 control) without prior heart failure. The primary outcome was a new diagnosis of low EF (≤50%) within 90 days of the ECG. The trial met the prespecified primary endpoint, demonstrating that the intervention increased the diagnosis of low EF in the overall cohort (1.6% in the control arm versus 2.1% in the intervention arm, odds ratio (OR) 1.32 (1.01-1.61), P = 0.007) and among those who were identified as having a high likelihood of low EF (that is, positive AI-ECG, 6% of the overall cohort) (14.5% in the control arm versus 19.5% in the intervention arm, OR 1.43 (1.08-1.91), P = 0.01). In the overall cohort, echocardiogram utilization was similar between the two arms (18.2% control versus 19.2% intervention, P = 0.17); for patients with positive AI-ECGs, more echocardiograms were obtained in the intervention compared to the control arm (38.1% control versus 49.6% intervention, P < 0.001). These results indicate that use of an AI algorithm based on ECGs can enable the early diagnosis of low EF in patients in the setting of routine primary care.

A Proposed Opioid Tapering Tool.

INTRODUCTION: Previous studies suggest a lack of confidence among primary care providers in managing patients on chronic opioid therapy (COT) for chronic non-cancer related pain (CNCP). The US Department of Health and Human Services (HHS) recently introduced guidelines on opioid tapering. In light of these recommendations, our group developed an opioid tapering software to assist healthcare providers in managing patients on COT. METHODS: The initial iteration of our software utilizes RedCap for the application programming interface (API). This tool is designed to reduce a patient's prescribed chronic opioids by 5-10% every month, or 5 morphine milligram equivalents per day (MME), whichever is the greatest, in line with HHS guidelines. Users can also adjust the rate of taper. DISCUSSION: Our group plans to use this software in an upcoming pilot study to taper patients on COT for CNCP. We are exploring the possibility of transitioning our software into other available APIs with the goal of integrating this software into major electronic health record systems. Our group envisions that our software will provide an additional tool within a patient-centered, multi-modal framework in managing patients on COT for CNCP.

Thiamin deficiency in low- and middle-income countries: Disorders, prevalences, previous interventions and current recommendations.

BACKGROUND: Thiamin deficiency is a major public health concern in several low- and middle-income countries (LMICs)-current attention to the problem is lacking. AIM: This review discusses prevalence of thiamin insufficiency and thiamin-deficiency disorders (TDDs) in LMICs, outlines programmatic experience with thiamin interventions, and offers recommendations to improve public-health and research attention to thiamin in LMICs. DISCUSSION: Thiamin insufficiency, i.e. low-blood-thiamin status, is endemic among several Southeast Asian countries: Cambodia (70-100% of infants and 27-100% of reproductive-age women); Laos (13% of hospitalized infants); Thailand (16-25% of children and 30% of elderly adults). Thiamin deficiency accounts for up to 45% of under-5 deaths in Cambodia, 34% of infant deaths in Laos, and 17% of infant deaths in Myanmar. Deficiency also exists in Africa, Asia, and the Americas, but these instances have typically been isolated. Exclusively breastfed infants of thiamin-deficient mothers are at highest risk for TDD and related death. Intervention strategies that have been employed to combat thiamin deficiency include food processing, fortification, supplementation, dietary diversification, and dietary behaviors, all of which have shown varying levels of effectiveness. CONCLUSIONS: We recommend universal thiamin-fortification of context-specific staple-foods in LMICs as a promising solution, as well as thiamin supplementation, particularly for pregnant and lactating women. Food processing regulations, dietary diversification, and modification of dietary behaviors to increase consumption of thiamin-rich foods may provide benefits in some circumstances, especially in countries without universal fortification programs or in populations dependent on food aid.

Knowledge of venomous snakes, snakebite first aid, treatment, and prevention among clinicians in northern Nigeria: a cross-sectional multicentre study.

Background: Snakebite envenoming causes considerable morbidity and mortality in northern Nigeria. The clinician's knowledge of snakebite impacts outcome. We assessed clinicians' knowledge of snakebite envenoming to highlight knowledge and practice gaps for possible intervention to improve snakebite outcomes. Methods: This was a cross-sectional multicentre study of 374 doctors selected from the accident and emergency, internal medicine, family medicine/general outpatient, paediatrics and surgery departments of nine tertiary hospitals in northern Nigeria using a multistage sampling technique. A self-administered questionnaire was used to assess their sociodemographics, knowledge of common venomous snakes, snakebite first aid, snake antivenom treatment and prevention. Results: The respondents' mean age was 35.6±5.8 y. They were predominantly males (70.6%) from urban hospitals (71.9%), from the northwest region (35.3%), in family medicine/general outpatient departments (33.4%), of <10 years working experience (66.3%) and had previous experience in snakebite management (78.3%). Although their mean overall knowledge score was 70.2±12.6%, only 52.9% had an adequate overall knowledge score. Most had adequate knowledge of snakebite clinical features (62.3%), first aid (75.7%) and preventive measures (97.1%), but only 50.8% and 25.1% had adequate knowledge of snake species that caused most injuries/deaths and anti-snake venom treatment, respectively. Overall knowledge predictors were ≥10 y working experience (odd ratio [OR] 1.72 [95% confidence interval {CI} 1.07 to 2.76]), urban hospital setting (OR 0.58 [95% CI 0.35 to 0.96]), surgery department (OR 0.44 [95% CI 0.24 to 0.81]), northwest/north-central region (OR 2.36 [95% CI 1.46 to 3.82]) and previous experience in snakebite management (OR 2.55 [95% CI 1.49 to 4.36]). Conclusions: Overall knowledge was low. Improvements in overall knowledge may require clinicians' exposure to snakebite management and training of accident and emergency clinicians in the region.

Pfizer Global Virtual Library (PGVL): a chemistry design tool powered by experimentally validated parallel synthesis information.

An unprecedented amount of parallel synthesis information was accumulated within Pfizer over the past 12 years. This information was captured by an informatics tool known as PGVL (Pfizer Global Virtual Library). PGVL was used for many aspects of drug discovery including automated reactant mining and reaction product formation to build a synthetically feasible virtual compound collection. In this report, PGVL is discussed in detail. The chemistry information within PGVL has been used to extract synthesis and design information using an intuitive desktop Graphic User Interface, PGVL Hub. Several real-case examples of PGVL are also presented.

Variables associated with utilization of a centralized medical post in the Andean community of Pampas Grande, Peru.

CONTEXT: Integral to the location of health resources is the distance decay of utilization observed in a population. In rural Peru, a nongovernmental organization planning to increase the availability of health services needed this information. PURPOSE: To determine variables associated with utilization of a central medical clinic and determine whether, because of the mountainous topography, travel time (TT) would be a better predictor of utilization than distance. METHODS: A door-to-door survey of all available households (81% of total), using a Spanish translation of questions excerpted from the Behavioral Risk Factor Surveillance System Survey, was conducted in the summer of 2008 to determine variables associated with self-reported history of clinic utilization. RESULTS: Utilization was inversely related to TT and distance. Of those living within 5 minutes of the clinic, 61% had been to the clinic whereas only 25% of those living 30 or more minutes away had sought care. Female gender and fever predicted increased odds of clinic utilization. Having a disability reduced one's odds (OR 0.55) of visiting the clinic, after adjusting for gender, TT, and fever. The inverse correlation of utilization with travel distance and TT was not significantly different, thus failing to demonstrate that TT is a better predictor of utilization than distance. CONCLUSION: In health service planning, care for common conditions should be available within 5 minutes' TT or a few kilometers' distance from each person's home in order to improve health care access and reduce health care disparities worsened by disability.

PGVL Hub: An integrated desktop tool for medicinal chemists to streamline design and synthesis of chemical libraries and singleton compounds.

PGVL Hub is an integrated molecular design desktop tool that has been developed and globally deployed throughout Pfizer discovery research units to streamline the design and synthesis of combinatorial libraries and singleton compounds. This tool supports various workflows for design of singletons, combinatorial libraries, and Markush exemplification. It also leverages the proprietary PGVL virtual space (which contains 10(14) molecules spanned by experimentally derived synthesis protocols and suitable reactants) for lead idea generation, lead hopping, and library design. There had been an intense focus on ease of use, good performance and robustness, and synergy with existing desktop tools such as ISIS/Draw and SpotFire. In this chapter we describe the three-tier enterprise software architecture, key data structures that enable a wide variety of design scenarios and workflows, major technical challenges encountered and solved, and lessons learned during its development and deployment throughout its production cycles. In addition, PGVL Hub represents an extendable and enabling platform to support future innovations in library and singleton compound design while being a proven channel to deliver those innovations to medicinal chemists on a global scale.

Self-assessed disability and self-rated health among rural villagers in Peru: a brief report.

CONTEXT: Risks for poor self-rated overall health in rural areas of developing nations have not been thoroughly investigated. PURPOSE: The objective of this study was to assess potential risk factors for poor self-rated health among rural villagers in Peru. METHODS: A door-to-door survey of villagers residing in the Pampas Grande region in Peru, which is in the Andes Mountains, yielded complete data for 337 adults. FINDINGS: Adjusting for age and gender using multiple logistic regression analysis revealed that having self-reported disabilities was inversely and independently related to good self-rated health (OR 0.48 [95% CI, 0.26-0.88]). Joint pain also was related to self-rated health (OR 0.23 [95% CI, 0.13-0.41]). CONCLUSIONS: Increasing access to affordable, effective analgesics may reduce this disparity. Health agencies should consider these actions as possible planning priorities for the region.

Cervical dysplasia in Nigerian women infected with HIV.

OBJECTIVE: To determine the prevalence of and risk factors for cervical dysplasia in HIV-positive women receiving care at the Jos University Teaching Hospital in Nigeria. METHODS: A total of 369 HIV-positive women had cervical cytology performed; HIV-1 RNA viral load and CD4 counts were measured. RESULTS: Of 369 participants, cervical dysplasia was present in 107 (29.0%) women. However, cervical cytology was abnormal in 252 (68.3%). Among those with abnormal cytology, 145 (57.5%) women had ASCUS, 56 (22.2%) had LSIL, and 51 (20.2%) had HSIL. Median CD4 lymphocyte count was lower in women with dysplasia compared with those without (142 vs 170 cells/mm(3); P=0.04), while median HIV RNA viral load was higher in women with dysplasia (101781 vs 77479 copies/mL; P=0.002). Low CD4 count (<200 cells/mm(3)) and evidence of HPV infection were significantly associated with cervical dysplasia. CONCLUSION: A high prevalence of cervical dysplasia was found among HIV-positive Nigerian women, which was associated with increased immune suppression.

Derivation of class II force fields. VIII. Derivation of a general quantum mechanical force field for organic compounds.

A class II valence force field covering a broad range of organic molecules has been derived employing ab initio quantum mechanical "observables." The procedure includes selecting representative molecules and molecular structures, and systematically sampling their energy surfaces as described by energies and energy first and second derivatives with respect to molecular deformations. In this article the procedure for fitting the force field parameters to these energies and energy derivatives is briefly reviewed. The application of the methodology to the derivation of a class II quantum mechanical force field (QMFF) for 32 organic functional groups is then described. A training set of 400 molecules spanning the 32 functional groups was used to parameterize the force field. The molecular families comprising the functional groups and, within each family, the torsional angles used to sample different conformers, are described. The number of stationary points (equilibria and transition states) for these molecules is given for each functional group. This set contains 1324 stationary structures, with 718 minimum energy structures and 606 transition states. The quality of the fit to the quantum data is gauged based on the deviations between the ab initio and force field energies and energy derivatives. The accuracy with which the QMFF reproduces the ab initio molecular bond lengths, bond angles, torsional angles, vibrational frequencies, and conformational energies is then given for each functional group. Consistently good accuracy is found for these computed properties for the various types of molecules. This demonstrates that the methodology is broadly applicable for the derivation of force field parameters across widely differing types of molecular structures. Copyright 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1782-1800, 2001