The Gender Wage Gap Among Early-Career Family Physicians.

PURPOSE: Numerous studies have documented salary differences between male and female physicians. For many specialties, this wage gap has been explored by controlling for measurable factors that influence pay such as productivity, work-life balance, and practice patterns. In family medicine where practice activities differ widely between physicians, it is important to understand what measurable factors may be contributing to the gender wage gap, so that employers and policymakers and can address unjust disparities. METHODS: We used data from the 2017 to 2020 American Board of Family Medicine (ABFM) National Graduate Survey (NGS) which is administered to family physicians 3 years after residency (n = 8608; response rate = 63.9%, 56.2% female). The survey collects clinical income and practice patterns. Multiple linear regression analysis was performed, which included variables on hours worked, degree type, principal professional activity, rural/urban, and region. RESULTS: Although early-career family physician incomes averaged $225,278, female respondents reported incomes that were $43,566 (17%) lower than those of male respondents (P = .001). Generally, female respondents tended toward lower-earning principal professional activities and US regions; worked fewer hours (2.9 per week); and tended to work more frequently in urban settings. However, in adjusted models, this gap in income only fell to $31,804 (13% lower than male respondents, P = .001). CONCLUSION: Even after controlling for measurable factors such as hours worked, degree type, principal professional activity, population density, and region, a significant wage gap persists. Interventions should be taken to eliminate gender bias in wage determinations for family physicians.

Data Disaggregation of Asian-American Family Physicians.

The singular label of "Asian" obscures socioeconomic differences between Asian ethnic groups that affect matriculation into the field of medicine. Using data from American Board of Family Medicine Examination candidates in 2023, we found that compared to the US population, among Asian-American family physicians, Indians were present at higher rates, while Chinese and Filipinos were underrepresented, suggesting the importance of continued disaggregation of Asian ethnicities in medicine.

Early-Career Compensation Trends Among Family Physicians.

PURPOSE: Family medicine incomes are often cited as a key reason for shortages of family physicians. The purpose of this study was to identify family physician income trends and to test how income varies among early-career family physicians. METHODS: We used data from the 2016 to 2020 American Board of Family Medicine National Graduate Survey (NGS) collected from early-career family physicians (n = 9566; response rate = 63.9%). The NGS asked practice income, practice activities, practice site, and setting. We performed an income trend analysis and conducted multivariate regression to test for associations of personal and workplace characteristics with income. RESULTS: Average income across the full sample of early-career family physicians (after inflation adjustments) was $224,292. Overall, income growth outpaced inflation from 2016 to 2020. There are significant differences in income based on personal and work characteristics, and income growth varied dramatically. Notably, women respondents reported earnings of $33,522 below those of men respondents in adjusted models. In addition, the incomes of several groups lagged behind inflation, including those practicing geriatrics (-0.67%), employed by the Indian Health Service (-1.72%), and respondents who identified as Black or African American (-0.85%). Greatest increases in inflation-adjusted incomes were observed among those in palliative care (4.61%) and at nonfederal government clinics (4.46%). CONCLUSIONS: Though income is only one factor physicians consider in deciding where and how to work, it is concerning to see lower incomes among groups that traditionally experience shortages (eg, geriatrics and government-associated practice sites). Differences in expected income among family physicians choosing different work may exacerbate workforce challenges.

Exploring the Association Between Physician Continuity of Care and Diagnosing Hypertension.

Context. The American Board of Family Medicine was funded by the Gordon Betty Moore Foundation to study the association between physician continuity of care, a clinical quality measure, and its impact on accurate, timely, efficient, and cost-effective diagnosis of target conditions that contribute to cardiovascular disease. In this exploratory analysis, we used electronic health records data from the PRIME registry to examine the association of continuity with factors leading to a hypertension diagnosis. Objective. 1) to determine the rate and timeliness of hypertension diagnosis, 2) to investigate the number of hypertension-level blood pressure (BP) readings in the 12 months prior to the diagnosis, and 3) to explore the association between physician continuity of care and these variables. Study Design and Population Studied. In this cohort study, we created two patient cohorts. Our prospective cohort consisted of patients who had 2 or more BP readings greater than SBP of 130 or DBP of 80 mm Hg in 2017-2018 and who did not have a hypertension diagnosis prior to the date of the second reading. Our retrospective cohort consisted of patients who had a hypertension diagnosis in 2018-2019. Dataset. Electronic health records extracted from the PRIME registry Outcome Measures. The rate of diagnosis was calculated by dividing the number of patients with a hypertension diagnosis by the number of patients whose BP readings exceeded the thresholds for hypertension per clinical guidelines. We investigated the timeliness of diagnosis by counting the average days between the second reading and the diagnosis dates. We also identified the number of hypertension-level BP readings in the past 12 months for patients diagnosed with hypertension. Results. Of 7,615 eligible patients from 4 pilot practices, the rate of hypertension diagnosis varied from 39.6% (solo practice) to 11.5% (large practice). The average days until diagnosis ranged from 142 days (solo practice) to 247 days (medium practice). Among patients diagnosed with hypertension (n=104,727), 25.7% had 0, 39.8% had 1, 14.7% had 2 and 19.7 had 3 or more hypertension-level BP readings in the 12 months prior to the diagnosis. We found no significant association between physician continuity of care and the rate or timeliness of the hypertension diagnosis. Conclusions. Factors leading to a hypertension diagnosis may be influenced more by other unobserved variables than by physician continuity of care.

Efficacy of biologics and oral small molecules for atopic dermatitis: a systematic review and meta-analysis.

BACKGROUND: As new targeted therapies continue to emerge for atopic dermatitis (AD), comparisons between agents are necessary to inform clinical decision-making. OBJECTIVES: Assess the efficacy of biologics and oral small molecules on the clinical signs, symptoms, and quality of life in AD. METHODS: A systematic literature review identified phase II and III randomized clinical trials of biologics and oral small molecules in AD. Clinical benefit was assessed for three outcome measures: Eczema Area and Severity Index (EASI), Dermatology Life Quality Index (DLQI), and Peak Pruritus Numerical Rating Scale (PP-NRS) by performing a meta-analysis using the inverse variance heterogeneity model ((IVhet)). RESULTS: The highest achievement of 75% reduction in EASI was seen with the higher dose of upadacitinib (30 mg) followed by abrocitinib and lebrikizumab, which outperformed dupilumab. Similarly, the highest proportion achieving at least a 4-point reduction of PP-NRS was seen with lebrikizumab followed by upadacitinib and abrocitinib which had greater reduction of itch than dupilumab. Abrocitinib had the greatest improvement in DLQI. CONCLUSIONS: Upadacitinib, abrocitinib, and lebrikizumab had greater improvement of clinical signs, symptoms, and quality of life in AD compared to dupilumab and other targeted therapies.

Anti-interleukin-6 signalling therapy rebalances the disrupted cytokine production of B cells from patients with active rheumatoid arthritis.

Rheumatoid arthritis (RA) is associated with abnormal B cell-functions implicating antibody-dependent and -independent mechanisms. B cells have emerged as important cytokine-producing cells, and cytokines are well-known drivers of RA pathogenesis. To identify novel cytokine-mediated B-cell functions in RA, we comprehensively analysed the capacity of B cells from RA patients with an inadequate response to disease modifying anti-rheumatic drugs to produce cytokines in comparison with healthy donors (HD). RA B cells displayed a constitutively higher production of the pathogenic factors interleukin (IL)-8 and Gro-α, while their production of several cytokines upon activation via the B cell receptor for antigen (BCR) was broadly suppressed, including a loss of the expression of the protective factor TRAIL, compared to HD B cells. These defects were partly erased after treatment with the IL-6-signalling inhibitor tocilizumab, indicating that abnormal IL-6 signalling contributed to these abnormalities. Noteworthy, the clinical response of individual patients to tocilizumab therapy could be predicted using the amounts of MIP-1ß and ß-NGF produced by these patients' B cells before treatment. Taken together, our study highlights hitherto unknown abnormal B-cell functions in RA patients, which are related to the unbalanced cytokine network, and are potentially relevant for RA pathogenesis and treatment.

Solar radiation and the incidence and mortality of leading invasive cancers in the United States.

Invasive cancer risk is inversely related to ultraviolet light exposure. This study explores relationships between cancer and the satellite-derived sunlight energy. We obtained the North America Land Data Assimilation System (NLDAS) daily average sunlight for the continental United States from 1999-2011. US Cancer Statistics age-adjusted-incidence and mortality was also obtained from the Centers for Disease Control and Prevention (CDC). We found that cancer incidence for all invasive cancers and for 11 of 22 leading cancers significantly decreased with increased solar radiation. Cancer mortality for all invasive cancers was not significantly associated with solar radiation, but for 7 of 22 leading cancers, including cancers of the uterus, leukemias, lung, ovary, and urinary bladder, increased solar radiation predicted decreased mortality. With increasing solar radiation, increased incidence and cancer mortality was observed for liver cancer and increased incidence but not mortality was observed for cervical cancer. The current study confirms studies relating UV radiation to the incidence and mortality of a variety of cancer types. We find associations between solar radiation energy and the incidence and mortality of a number of types of cancers.

Engagement of CD22 on B cells with the monoclonal antibody epratuzumab stimulates the phosphorylation of upstream inhibitory signals of the B cell receptor.

The binding of antigen to the B cell receptor (BCR) results in a cascade of signalling events that ultimately drive B cell activation. Uncontrolled B cell activation is regulated by negative feedback loops that involve inhibitory co-receptors such as CD22 and CD32B that exert their functions following phosphorylation of immunoreceptor tyrosine-based inhibition motifs (ITIMs). The CD22-targeted antibody epratuzumab has previously been shown to inhibit BCR-driven signalling events, but its effects on ITIM phosphorylation of CD22 and CD32B have not been properly evaluated. The present study therefore employed both immunoprecipitation and flow cytometry approaches to elucidate the effects of epratuzumab on direct phosphorylation of key tyrosine (Tyr) residues on both these proteins, using both transformed B cell lines and primary human B cells. Epratuzumab induced the phosphorylation of Tyr(822) on CD22 and enhanced its co-localisation with SHP-1. Additionally, in spite of high basal phosphorylation of other key ITIMs on CD22, in primary human B cells epratuzumab also enhanced phosphorylation of Tyr(807), a residue involved in the recruitment of Grb2. Such initiation events could explain the effects of epratuzumab on downstream signalling in B cells. Finally, we were able to demonstrate that epratuzumab stimulated the phosphorylation of Tyr(292) on the low affinity inhibitory Fc receptor CD32B which would further attenuate BCR-induced signalling. Together, these data demonstrate that engagement of CD22 with epratuzumab leads to the direct phosphorylation of key upstream inhibitory receptors of BCR signalling and may help to explain how this antibody modulates B cell function.

SIGLEC1 is a biomarker of disease activity and indicates extraglandular manifestation in primary Sjögren's syndrome.

OBJECTIVES: To evaluate the interferon (IFN) biomarkers sialic acid binding Ig like lectin 1 (SIGLEC1, CD169) and IFN-γ-inducible protein-10 (IP-10) in patients with primary Sjögren's syndrome (pSS). METHODS: 31 patients fulfilling the American-European criteria for pSS were included. Disease activity was obtained by EULAR Sjögren's syndrome disease activity index (ESSDAI). SIGLEC1 expression on monocytes was analysed using flow cytometry. IP-10 concentrations were determined using Bioplex human Cytokine 27-plex kit. Spearman rank test (SRT) was used for correlation analysis and Mann-Whitney U (MWU) to test for differences between glandular and extraglandular manifestations. RESULTS: An activated IFN system was detected by an upregulation of SIGLEC1 expression in 64.5% and by elevated serum level of IP-10 in 78.9% of our patients with pSS. In a subsequent analysis SIGLEC1 expression was found to be upregulated more frequently in patients with extraglandular manifestations (16/16, 100%) compared to patients with exclusively glandular involvement (4/15, 27%). SIGLEC1 expression could significantly discriminate between these two disease subgroups (p=0.0001, MWU) with a positive predictive value (PPV) of 80% for extraglandular disease. Moreover, the expression correlated with disease activity (p=0.005, r=0.54, SRT). Serum IP-10 levels neither differed significantly between glandular and extraglandular disease nor correlated with ESSDAI. CONCLUSIONS: Our results indicate that increased SIGLEC1 expression characterises patients with systemic involvement and high disease activity. Therefore, SIGLEC1 determination might be of value for subset definition, risk stratification and differential therapeutic considerations in pSS.

Enhanced Tyrosine Phosphatase Activity Underlies Dysregulated B Cell Receptor Signaling and Promotes Survival of Human Lupus B Cells.

OBJECTIVE: Systemic lupus erythematosus (SLE) is associated with hyperactivity of B cells and abnormalities of B cell receptor (BCR) signaling. To address the linkage between dysregulated BCR signaling and increased B cell function, we assessed immediate phosphorylation events in lupus B cells. METHODS: B cells from SLE patients and healthy donors were analyzed by flow cytometry to assess phosphorylated CD22, Syk, and Akt as well as the basal expression of the BCR coreceptors CD22 and CD19. Confocal microscopy studies determined the recruitment of CD22 and the tyrosine phosphatase SH2 domain-containing phosphatase 1 to the activated BCR complex. Additionally, phosphatase activity in SLE versus healthy donor B cells was measured. RESULTS: B cells from SLE patients showed diminished Syk phosphorylation and reduced intracellular calcium release after BCR activation as compared to B cells from healthy donors. This was related to an enhanced activity of tyrosine, but not serine/threonine, phosphatases and was corrected by inhibition of tyrosine phosphatase activity. In contrast to reduced Syk phosphorylation after BCR activation, phosphorylation of Akt was significantly increased in SLE B cells. The disturbed balance between Syk and Akt phosphorylation was significantly correlated with B cell survival following BCR engagement. Furthermore, CD27-, but not CD27+, B cells from SLE patients displayed increased expression and phosphorylation of the inhibitory BCR coreceptor CD22. CONCLUSION: These results indicate that an imbalance between serine and tyrosine phosphatases in SLE contributes to an intrinsically disturbed balance of BCR-initiated signaling pathways, resulting in enhanced survival of lupus B cells and differentiation into plasma cells.

Epratuzumab inhibits the production of the proinflammatory cytokines IL-6 and TNF-α, but not the regulatory cytokine IL-10, by B cells from healthy donors and SLE patients.

INTRODUCTION: Cytokines produced by B cells are believed to play important roles in autoimmune diseases. CD22 targeting by epratuzumab has been demonstrated to inhibit phosphorylation of B cell receptor (BCR) downstream signaling in B cells. It has been shown that other sialoadhesin molecules related to CD22 have immunoregulatory functions; therefore, in the present study, we addressed the role of epratuzumab on the production of key cytokines by B cells of patients with systemic lupus erythematosus (SLE) and of healthy donors (HD). METHODS: Peripheral blood B cells were purified and activated by BCR with or without Toll-like receptor 9 (TLR9) stimulation in the presence or absence of epratuzumab. Cytokine production by B cells (interleukin [IL]-6, tumor necrosis factor [TNF]-α and IL-10) in the supernatant and the induction of IL-10(+) B cells from patients with SLE and HD were analyzed. RESULTS: The secretion of the proinflammatory cytokines TNF-α and IL-6 by anti-BCR and BCR- and/or TLR9-activated B cells from HD and patients with SLE was inhibited by epratuzumab. In contrast, the production of IL-10 by B cells was not affected by epratuzumab under either stimulation condition. Consistently, the induction of IL-10-producing B cells in culture was not affected by epratuzumab. CONCLUSIONS: Epratuzumab, by targeting CD22, was able to inhibit the production of the proinflammatory cytokines IL-6 and TNF-α by B cells, in contrast to IL-10, in vitro. These data suggest that targeting CD22 alters the balance between proinflammatory cytokines (TNF-α, IL-6) and the regulatory cytokine IL-10 as another B cell effector mechanism.

Active systemic lupus erythematosus is associated with a reduced cytokine production by B cells in response to TLR9 stimulation.

INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune disease associated with a break in self-tolerance reflected by a production of antinuclear autoantibodies. Since autoantibody production can be activated via nucleic acid Toll-like receptor 9 (TLR9), the respective pathway has been implicated in the development of SLE and pathogenic B cell responses. However, the response of B cells from SLE patients to TLR9 stimulation remains incompletely characterized. METHODS: In the current study, the response of B cells from SLE patients and healthy donors upon TLR9 stimulation was analyzed in terms of proliferation and cytokine production and correlated with the lupus disease activity and anti-dsDNA titers. RESULTS: B cells from SLE patients showed a reduced response to TLR9 agonist compared to B cells from healthy donors in terms of proliferation and activation. B cells from SLE patients with higher disease activity produced less interleukin (IL)-6, IL-10, vascular endothelial growth factor, and IL-1ra than B cells from healthy donors. Further analyses revealed an inverse correlation of cytokines produced by TLR9-stimulated B cells with lupus disease activity and anti-dsDNA titer, respectively. CONCLUSION: The capacity of B cells from lupus patients to produce cytokines upon TLR9 engagement becomes less efficient with increasing disease activity, suggesting that they either enter an exhausted state or become tolerant to TLR stimulation for cytokine production when disease worsens.

Increased frequency of a unique spleen tyrosine kinase bright memory B cell population in systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is characterized by B cell hyperactivity and autoantibody production. As spleen tyrosine kinase (Syk) is pivotal in B cell activation, these experiments aimed to examine the extent to which Syk was abnormally expressed in SLE B cells and the nature of the B cell subset that differently expressed Syk. METHODS: B cells from healthy donors and SLE patients were analyzed by flow cytometry to assess basal expression of Syk and phosphorylated Syk. B cell subsets expressing higher levels of Syk were found, and their detailed phenotype, in vitro differentiation into plasmablasts/plasma cells, and Syk induction by cytokines were determined. RESULTS: Syk expression was higher in CD27+ memory B cells than in naive B cells from SLE patients. However, a significantly increased frequency of CD27- B cells with bright expression of Syk (Syk++) was found in SLE patients. CD27-Syk++ B cells showed enhanced basal expression of p-Syk and stronger Syk phosphorylation upon B cell receptor (BCR) engagement as compared to CD27-Syk+ B cells. CD27-Syk++ B cells were CD38- as well as CD19++, CD20++, and mainly CD21-, with decreased ABCB1 transporter activity. In contrast to CD27-Syk+ B cells, CD27-Syk++ B cells exhibited enhanced differentiation into CD27++ IgG-secreting cells and expressed somatically mutated BCR gene rearrangements. Syk++ B cells were inducible in vitro by stimulation with interferon-γ, lipopolysaccharide, or tumor necrosis factor α. CONCLUSION: SLE patients exhibit an increased frequency of hitherto unknown CD27-Syk++ memory-like B cells, indicating that intracellular Syk density could distinguish CD27- memory B cells from truly naive B cell subsets. Furthermore, the CD27-Syk++ subset is a candidate for a source of increased plasma cells in SLE.

Status epilepticus after stroke is associated with increased long-term case fatality.

PURPOSE: The aim of this study was to determine the long-term case fatality of patients with a first episode of status epilepticus (SE group) of cerebrovascular etiology, as compared with that in acute stroke patients without SE (AS group). METHODS: Patients with SE who had been prospectively admitted to an epidemiologic study were retrospectively compared with a cohort of patients from the local stroke registry. The main outcome end point was overall survival. Survival curves were generated according to the Kaplan-Meier method and compared by using the log-rank test. An extended Cox model was used to examine the impact of patient group on the risk of death. Covariates considered potential confounders included age at diagnosis, sex, type of stroke, affected hemisphere, and localization of lesions. RESULTS: Of 166 patients who entered the study, 93 patients were in the SE group, and 73 patients were in the AS group; 53 SE patients and 35 AS patients died during the study. Patient group (SE vs. AS) showed no significant impact on survival (p=0.0832) in univariate analysis. In contrast, the results from a multivariable analysis suggest that after 6 months, patients with SE were at about twice the risk of death as were patients with AS [hazard ratio of 2.12 with 95% confidence interval, 1.04-4.32, p=0.0392]. CONCLUSIONS: The occurrence of SE in patients with cerebrovascular disease indicates a high risk of death within 3 years. In contrast, the case fatality risk attributable to recurrent status or seizures is lower.