A Pragmatic Approach to Identifying and Profiling Primary Care Clinicians and Primary Care Practices in the USA.

BACKGROUND: There are no consistent data on US primary care clinicians and primary care practices owing to the lack of standard methods to identify them, hampering efforts in primary care improvement. METHODS: We develop a pragmatic framework that identifies primary care clinicians and practices in the context of the US healthcare system, and applied the framework to the IQVIA OneKey Healthcare Professional database to identify and profile primary care clinicians and practices in the USA. RESULTS: Our framework prescribes sequential steps to identify primary care clinicians by cross-examining clinician specialties and organizational affiliations, and then identify primary care practices based on organization types and presence of primary care clinicians. Applying this framework to the 2021 IQVIA data, we identified 365,751 physicians with a primary specialty in primary care, and after excluding those who further specialized (24%), served as hospitalists (5%), or worked in non-primary care settings (41%), we determined that 179,369 (49%) of them were actually practicing primary care. We identified 287,506 nurse practitioners and 134,083 physician assistants and determined that 88,574 (31%) and 29,781 (22%), respectively, were delivering primary care. We identified 94,489 primary care practices, and found that 45% of them were with one primary care physician, 15% had two physicians, 12% employed nurse practitioners or physician assistants only, and 19% employed both primary care physicians and specialists. CONCLUSIONS: Our approach offers a pragmatic and consistent alternative to the diverse methods currently used to identify and profile primary care workforce and organizations in the USA.

Computational Study on the Influence of Mo/V Centers on the Electronic Structure and Hydrazine Reduction Capability of [MFe3S4]3+/2+ Complexes.

[MFe3S4] cubanes have for some time been of interest for their ability to mimic the electronic and geometric structure of the active site of nitrogenase, the enzyme responsible for fixing N2 to NH3. Nitrogenase naturally occurs in three forms, with the major difference being that the metal ion present in the cofactor active site is either molybdenum (FeMoco), vanadium (FeVco), or iron. The molybdenum and vanadium versions of these cofactors are more closely studied, owing to their larger abundance and rate of catalysis. In this study, we compare free energy profiles and electronic properties of the Mo/V cubanes at various stages during the reduction of N2H4 to NH3. Our findings highlight the differences in how the complexes facilitate the reaction, in particular, vanadium's comparatively weaker ability to interact with the Fe/S network and stabilize reducing electrons prior to N-N bond cleavage, which may have implications when considering the lower efficiency of the vanadium-dependent nitrogenase.

Mechanism of Nitrogen Reduction to Ammonia in a Diiron Model of Nitrogenase.

Nitrogenase is a fascinating enzyme in biology that reduces dinitrogen from air to ammonia through stepwise reduction and protonation. Despite it being studied in detail by experimental and computational groups, there are still many unknown factors in the catalytic cycle of nitrogenase, especially related to the addition of protons and electrons and their order. A recent biomimetic study characterized a potential dinitrogen-bridged diiron cluster as a synthetic model of nitrogenase. Using strong acid and reductants, the dinitrogen was converted into ammonia molecules, but details of the mechanism remains unknown. In particular, it was unclear from the experimental studies whether the proton and electron transfer steps are sequential or alternating. Moreover, the work failed to establish what the function of the diiron core is and whether it split into mononuclear iron fragments during the reaction. To understand the structure and reactivity of the biomimetic dinitrogen-bridged diiron complex [(P2P'PhFeH)2(µ-N2)] with triphenylphosphine ligands, we performed a density functional theory study. Our computational methods were validated against experimental crystal structure coordinates, Mössbauer parameters, and vibrational frequencies and show excellent agreement. Subsequently, we investigated the alternating and consecutive addition of electrons and protons to the system. The calculations identify a number of possible reaction channels, namely, same-site protonation, alternating protonation, and complex dissociation into mononuclear iron centers. The calculations show that the overall mechanism is not a pure sequential set of electron and proton transfers but a mixture of alternating and consecutive steps. In particular, the first reaction steps will start with double proton transfer followed by an electron transfer, while thereafter, there is another proton transfer and a second electron transfer to give a complex whereby ammonia can split off with a low energetic barrier. The second channel starts with alternating protonation of the two nitrogen atoms, whereafter the initial double proton transfer, electrons and protons are added sequentially to form a hydrazine-bound complex. The latter split off ammonia spontaneously after further protonation. The various reaction channels are analyzed with valence bond and orbital diagrams. We anticipate the nitrogenase enzyme to operate with mixed alternating and consecutive protonation and electron transfer steps.

Tool to improve patient-provider interactions in adult primary care: Randomized controlled pilot study.

OBJECTIVE: To assess whether an intervention to help patients prioritize goals for their visit would improve patient-provider communication and clinical outcomes. DESIGN: Randomized controlled pilot study. SETTING: Primary care clinic. PARTICIPANTS: There were 120 adult hypertensive patients enrolled. INTERVENTION: Patients were randomized to receive either usual care or a previsit patient activation card developed through a series of focus groups that prompted patients to articulate their needs and set priorities for their clinic visit. Encounters were audiorecorded, transcribed, and assessed using duplicate ratings of patient activation and decision making. MAIN OUTCOME MEASURES: The primary outcome was change in medication adherence as measured by pill count at 4 and 12 weeks after the initial visit. Secondary outcomes evaluated patient-provider interaction quality (patient satisfaction, patient activation, shared decision making, patient trust, and physicians' perceived difficulty of the encounter), functional status, and blood pressure control. RESULTS: Of the 120 enrolled patients, 106 completed the baseline visit (mean age of 66 years, 53% women, 57% Black, 36% White). Participants had multiple comorbidities (median number of medications = 8). During the visit, there was greater patient activation in the intervention arm than in the control arm (4.4 vs 3.8, P = .047; ratings were based on a scale from 1 to 10). However, after the visit there were no differences in medication adherence (4 weeks: 45.8% vs 49.5%; 12 weeks: 49.4% vs 51.1%), blood pressure control (4 weeks: 133/78 mm Hg vs 131/77 mm Hg; 12 weeks: 129/77 mm Hg vs 129/76 mm Hg), or encounter satisfaction (78.6% vs 73.8% fully satisfied; P = .63). There were also no differences in shared decision making, patients' trust, or perceived difficulty of the encounter. CONCLUSION: A single previsit tool designed to prompt patients to set a prioritized agenda improved patient activation during the visit, but did not affect the quality of the interaction or postvisit patient-centred outcomes.

Rationale and design of the Women's Ischemia Trial to Reduce Events in Nonobstructive CAD (WARRIOR) trial.

BACKGROUND: Approximately half of all women with anginal symptoms and/or signs of ischemia and no obstructive coronary artery disease (INOCA) referred for coronary angiography have elevated risk for major adverse cardiac events (MACE), poor quality of life and resource consumption. Yet, guidelines focus on symptom management while clinical practice typically advocates only reassurance. Pilot studies of INOCA subjects suggest benefit with intensive medical therapy (IMT) that includes high-intensity statins and angiotensin converting enzyme inhibitors (ACE-I) or receptor blockers (ARB) to provide the rationale for a randomized pragmatic trial to limit MACE. METHODS: The Women's IschemiA TRial to Reduce Events In Non-ObstRuctive CAD is a multicenter, prospective, randomized, blinded outcome evaluation (PROBE design) of a pragmatic strategy of IMT vs usual care (UC) in 4,422 symptomatic women with INOCA (NCT03417388) in approximately 70 United States sites. The hypothesis is that IMT will reduce the primary outcome of first occurrence of MACE by 20% vs. UC at ∼2.5 year followup. Secondary outcomes include quality of life, time to return to "duty"/work, healthcare utilization, angina, cardiovascular death and individual primary outcome components over 3 years follow-up. The study utilizes web-based data capture, e-consents, single IRB and centralized pharmacy distribution of strategy medications directly to patients' homes to reduce site and patient burden. A biorepository will collect blood samples to assess potential mechanisms. CONCLUSIONS: The results of this trial will provide important data necessary to inform guidelines regarding how best to manage this growing and challenging population of women with INOCA.

Comparison of hospital course and outcome in hospital-acquired vs pre-existing delirium.

BACKGROUND: Delirium is a major source of morbidity in the inpatient hospital setting. This study examined differences between patients with delirium present prior to hospital admission and those with hospitalacquired delirium in several health outcomes. METHODS: A total of 12,529 patients on 2 inpatient units were included in this retrospective cohort study. Outcomes were assessed using chart review. Other variables were compared across groups and included in multivariate models predicting discharge location within the hospitalacquired delirium group. RESULTS: Of 709 patients with delirium, 83% had pre-admission prevalent and 17% had post-admission incident delirium. Compared with patients with preexisting delirium, patients with hospital-acquired delirium had greater hospital durations and mortality and were more likely to receive ICU care, more likely to receive multiple classes of medications, and less likely to be discharged home without home health services. Multivariate analysis in the hospital-acquired delirium group found that several variables independently predicted discharge location. CONCLUSIONS: Patients with hospital-acquired delirium had worse hospital outcomes and a more complicated hospital course than those with preexisting delirium. Administration of various medications, several demographic variables, and some hospital-related variables were independently associated with worse outcomes within the hospital-acquired delirium group. These results demonstrate that patients with hospitalacquired delirium are a vulnerable subgroup deserving special attention.

Women's Preventive Services Initiative recommends screening women for anxiety.

SOURCE CITATION: Gregory KD, Chelmow D, Nelson HD, et al. Screening for anxiety in adolescent and adult women: a recommendation from the Women's Preventive Services Initiative. Ann Intern Med. 2020;173:48-56. 32510990.

Management of Dyslipidemia for Cardiovascular Disease Risk Reduction: Synopsis of the 2020 Updated U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline.

DESCRIPTION: In June 2020, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) released a joint update of their clinical practice guideline for managing dyslipidemia to reduce cardiovascular disease risk in adults. This synopsis describes the major recommendations. METHODS: On 6 August to 9 August 2019, the VA/DoD Evidence-Based Practice Work Group (EBPWG) convened a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions, systematically searched and evaluated the literature (English-language publications from 1 December 2013 to 16 May 2019), and developed 27 recommendations and a simple 1-page algorithm. The recommendations were graded by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. RECOMMENDATIONS: This synopsis summarizes key features of the guideline in 7 crucial areas: targeting of statin dose (not low-density lipoprotein cholesterol goals), additional tests for risk prediction, primary and secondary prevention, laboratory testing, physical activity, and nutrition.

Strategies to maximise patient comfort during extracorporeal shockwave lithotripsy - A randomised controlled trial.

BACKGROUND/PURPOSE OF STUDY: We aim to assess if distraction techniques improve patient comfort tolerability of SWL. METHODS: We carried out a prospective randomised controlled trial of SWL-naïve patients attending for treatment. Patients were randomised into three groups and offered oral analgesia as standard of care. Group 1 (n = 19) received stress balls to squeeze during treatment. Group 2 (n = 19) listened to music during treatment. Group 3 (n = 17) received standard of care only. All patients completed a validated health anxiety inventory score prior to treatment. All patients completed a validated pain questionnaire and visual analogue scale (VAS) after treatment. Primary outcomes were completion of SWL treatment and pain score results. RESULTS: 55 patients attending for SWL were randomised. There was no difference in stone size or position, presence of a stent, height or weight between the groups. VAS scores were lower in controls compared to Group 1 (1.93 vs 3.69, p = 0.08). On subgroup analysis of non-anxious patients, pain questionnaire scores were lower in controls compared to Group 1 (2.58 vs 4.77, p = 0.06). VAS scores were lower in patients who received optional analgesia alone than in patients who received stress balls alone (1.92 vs 4.07, p = 0.05). Across all subgroups, pain scores were lower in the control group compared to the distraction groups, but did not achieve significance. CONCLUSIONS: In conclusion, distraction techniques should not replace standard of care for analgesia during SWL. This study was registered with clinicaltrials.gov (identifier NCT03379922).

Molecular Identification of a High-Spin Deprotonated Intermediate during the S2 to S3 Transition of Nature's Water-Oxidizing Complex.

The identity of a key intermediate in the S2 to S3 transition of nature's water-oxidizing complex (WOC) in Photosystem 2 is presented. Broken-symmetry density functional theory (BS-DFT) calculations and Heisenberg-Dirac-van Vleck (HDvV) spin ladder calculations show that an S2 state open cubane model of the WOC containing a µ-hydroxo O4 changes from an S = 5/2 form to an S = 7/2, form upon deprotonation of W1. Combined with X-band electron paramagnetic resonance (EPR) spectral analysis, this indicates that the g = 4.1 EPR signal corresponds to an S = 5/2 form of the WOC with W1 present as a water ligand to Mn4, while the g = 4.8/4.9 form observed at high pH values corresponds to an S = 7/2 form, with W1 as a hydroxo ligand. The latter is also likely to represent the form needed to progress to S3 in the functioning enzyme.

Localized Bond Orbital Analysis of the Bonds of O2.

A localized bond orbital analysis of the bonding in dioxygen and related species provides a unique fundamental insight into its bonding characteristics. It reveals the coalescence of the molecular orbital and valence bond/Lewis approaches and clearly demonstrates that the often stated inability of valence bond theory to describe the bonding of O2 is a myth. The analysis indicates that the σ-bond strength of 3O2 is not weak as previously believed and accounts for much of its enhanced stability compared with hydroperoxyl. We attribute the stability and persistence of 3O2 to a combination of this attribute and favorable maximization of exchange coupling between the valence electrons.

The great decline in adolescent cigarette smoking since 2000: consequences for drug use among US adolescents.

OBJECTIVE: Adolescent cigarette smoking declined steadily and substantially from 2000 to 2018. This paper considers the potential consequences of this 'great decline' for the prevalence of other drug use among adolescents. METHODS: Data are annual, cross-sectional, nationally representative Monitoring the Future surveys of more than 1.2 million US students in 12th, 10th and 8th grades from 2000 to 2018. Analyses include trends in the past 12 months' non-medical amphetamine, tranquillisers and opioid use overall, among ever and never cigarette smokers, and projected if adolescent cigarette smoking levels had remained at 2000 levels. RESULTS: Within groups of ever and never cigarette smokers, the prevalence for each of the three substances has either changed little or overall increased in 2018 as compared with 2000. When the two groups were combined into one pool, the overall prevalence for each of the drugs declined by about half. The decline resulted from the growing group of never smokers, whose levels of non-medical drug use over the study period were at least four times lower than the levels of ever smokers. CONCLUSIONS: The results support the 'gateway' prediction that declines in cigarette smoking among adolescents pull downward their non-medical use of amphetamines, tranquillisers and opioids. Continuing to reduce adolescent smoking through policy and programmatic prevention efforts should have further positive spillover effects on adolescent drug use.

Changes in the Order of Cigarette and Marijuana Initiation and Associations with Cigarette Use, Nicotine Vaping, and Marijuana Use: U.S. 12th Grade Students, 2000-2019.

This study (a) examined changes in marijuana and cigarette initiation sequencing and (b) considered implications of such changes for prevention efforts by examining associations between initiation sequencing and current adolescent substance use. Analyses used 2000-2019 cross-sectional data from the national Monitoring the Future (MTF) study (78,252 U.S. 12th grade students). Models examined trends in six distinct patterns of initiation order, and multivariable associations between order of initiation and 30-day cigarette and marijuana use prevalence, cigarette and marijuana use frequency among users, and nicotine and marijuana vaping prevalence. While the percentage of students initiating neither cigarettes nor marijuana increased, increases also were observed in marijuana-only initiation (the fastest-growing pattern) and initiation of marijuana before cigarettes; these increases were accompanied by a significant decrease in cigarette-only initiation. Cigarette use prevalence and frequency were highest among students initiating cigarettes before marijuana; marijuana use prevalence and frequency were highest among students initiating marijuana before cigarettes. Cigarette and marijuana prevalence, as well as marijuana frequency, were lowest among students initiating only a single substance. Nicotine vaping was less prevalent among students initiating a single substance versus both substances, but no significant differences were observed in nicotine vaping prevalence between those initiating only cigarettes versus only marijuana. Implications of these findings for prevention efforts are discussed in the frameworks of both the common liability model and route of administration model.

Shifting Age of Peak Binge Drinking Prevalence: Historical Changes in Normative Trajectories Among Young Adults Aged 18 to 30.

BACKGROUND: This study examined the extent to which the developmental pattern of prevalence of binge drinking in the past 2 weeks from ages 18 through 30 has changed across 29 cohorts of U.S. young adults, and whether the changes differed by gender. METHODS: Analyses used national longitudinal data from 58,019 12th-grade students (from graduating high school classes 1976 to 2004) participating in the Monitoring the Future study followed through modal age 30 (with age 29/30 data collected from 1987 to 2016). Weighted time-varying effect modeling was used to model cohort group differences in age-related patterns of binge drinking. RESULTS: The age of peak binge drinking prevalence increased across cohorts (from age 20 in 1976 to 1985 to 22 in 1996 to 2004 for women, and from 21 in 1976 to 1985 to 23 in 1996 to 2004 for men). Historical change in the developmental pattern of binge drinking across all ages of young adulthood differed for men and women. Even after controlling for key covariates, women in the more recent cohort group reported significantly higher binge drinking prevalence than women in earlier cohorts from ages 21 through 30. Men in the more recent cohort group reported higher binge drinking prevalence at ages 25 to 26, but prevalence levels then converged to those seen in earlier cohort groups by age 30. CONCLUSIONS: An older age of peak binge drinking and a decreased rate of decline in the prevalence of binge drinking in later young adulthood among more recent cohorts have resulted in an extension of individual and societal risks associated with binge drinking, particularly for women, across young adulthood. High-risk alcohol use prevention efforts are needed throughout at least the third decade of life.

Recent increases in depressive symptoms among US adolescents: trends from 1991 to 2018.

BACKGROUND: Mental health problems and mental health related mortality have increased among adolescents, particularly girls. These trends have implications for etiology and prevention and suggest new and emerging risk factors in need of attention. The present study estimated age, period, and cohort effects in depressive symptoms among US nationally representative samples of school attending adolescents from 1991 to 2018. METHODS: Data are drawn from 1991 to 2018 Monitoring the Future yearly cross-sectional surveys of 8th, 10th, and 12th grade students (N = 1,260,159). Depressive symptoms measured with four questions that had consistent wording and data collection procedures across all 28 years. Age-period-cohort effects estimated using the hierarchical age-period-cohort models. RESULTS: Among girls, depressive symptoms decreased from 1991 to 2011, then reversed course, peaking in 2018; these increases reflected primarily period effects, which compared to the mean of all periods showed a gradual increase starting in 2012 and peaked in 2018 (estimate = 1.15, p < 0.01). Cohort effects were minimal, indicating that increases are observed across all age groups. Among boys, trends were similar although the extent of the increase is less marked compared to girls; there was a declining cohort effect among recently born cohorts, suggesting that increases in depressive symptoms among boys are slower for younger boys compared to older boys in recent years. Trends were generally similar by race/ethnicity and parental education, with a positive cohort effect for Hispanic girls born 1999-2004. CONCLUSIONS: Depressive symptoms are increasing among teens, especially among girls, consistent with increases in depression and suicide. Population variation in psychiatric disorder symptoms highlight the importance of current environmental determinants of psychiatric disorder risk, and provide evidence of emerging risk factors that may be shaping a new and concerning trend in adolescent mental health.

Joint Effects of Age, Period, and Cohort on Conduct Problems Among American Adolescents From 1991 Through 2015.

Although arrest rates among juveniles have substantially decreased since the 1990s, US national trends in conduct problems are unknown. Population variation in conduct problems would imply changes in the social environment, which would include emergent or receding risk factors. In the present study, we separated age, period, and cohort effects on conduct problems using nationally representative surveys of 375,879 US students conducted annually (1991-2015). The summed score of 7 items measuring the frequency of conduct problems was the outcome. Conduct problems have decreased during the past 25 years among boys; the total amount of the decrease was approximately 0.4 standard deviations (P < 0.01), and by item prevalence, the total amount of the decrease was 8%-11%. Declines are best explained by period effects beginning approximately in 2008, and a declining cohort effect beginning among those born after 1992, which suggests not only declines in population levels, but more rapid declines among younger cohorts of boys. Trends were also consistent with age-period-cohort effects on evenings spent out, which suggest a possible mechanism. Conduct problems among girls were lower than boys and did not demonstrate trends across time. These changes may reflect the changing nature of adolescence toward less unsupervised interaction.

Patterns of simultaneous and concurrent alcohol and marijuana use among adolescents.

BACKGROUND: Alcohol and marijuana are the most commonly used substances among adolescents but little is known about patterns of co-use. OBJECTIVES: This study examined patterns of concurrent (not overlapping) and simultaneous (overlapping) use of alcohol and marijuana among adolescents. METHODS: Data from US-national samples of 12th graders (N = 84,805, 48.4% female) who participated in the Monitoring the Future study from 1976 to 2016 and who used alcohol and/or marijuana in the past 12 months were used to identify latent classes of alcohol use, marijuana use, and simultaneous alcohol and marijuana (SAM) use. RESULTS: A four-class solution indicated four patterns of use among adolescents: (1) Simultaneous alcohol and marijuana (SAM) use with binge drinking and recent marijuana use (SAM-Heavier Use; 11.2%); (2) SAM use without binge drinking and with recent marijuana use (SAM-Lighter Use; 21.6%); (3) Marijuana use and alcohol use but no SAM use (Concurrent Use; 10.7%); and (4) Alcohol use but no marijuana or SAM use (Alcohol-Only Use; 56.4%). Membership in either SAM use class was associated with a higher likelihood of truancy, evenings out, and use of illicit drugs other than marijuana. SAM-Heavier Use, compared to SAM-Lighter Use, class members were more likely to report these behaviors and be male, and less likely to have college plans. CONCLUSIONS: Among 12th graders who use both alcohol and marijuana, the majority use simultaneously, although not all use heavily. Given the recognized increased public health risks associated with simultaneous use, adolescent prevention programming should include focus on particular risks of simultaneous use.