Comparative safety and effectiveness of TNF inhibitors, IL6 inhibitors and methotrexate for the treatment of immune checkpoint inhibitor-associated arthritis.

OBJECTIVES: To compare the safety and effectiveness of biologic and conventional disease-modifying antirheumatic drugs (DMARDs) for immune checkpoint inhibitor-associated inflammatory arthritis (ICI-IA). METHODS: The retrospective multicentre observational study included patients with a diagnosis of ICI-IA treated with a tumour necrosis factor inhibitor (TNFi), interleukin-6 receptor inhibitor (IL6Ri) and/or methotrexate (MTX); patients with pre-existing autoimmune disease were excluded. The primary outcome was time to cancer progression from ICI initiation; the secondary outcome was time to arthritis control from DMARD initiation. Cox proportional hazard models were used to compare medication groups, adjusting for confounders. RESULTS: 147 patients were included (mean age 60.3 (SD 11.9) years, 66 (45%) women). ICI-IA treatment was TNFi in 33 (22%), IL6Ri 42 (29%) and MTX 72 (49%). After adjustment for time from ICI initiation to DMARD initiation, time to cancer progression was significantly shorter for TNFi compared with MTX (HR 3.27 (95% CI 1.21 to 8.84, p=0.019)) while the result for IL6Ri was HR 2.37 (95% CI 0.94 to 5.98, p=0.055). Time to arthritis control was faster for TNFi compared with MTX (HR 1.91 (95% CI 1.06 to 3.45, p=0.032)) while the result for IL6Ri was HR 1.66 (95% CI 0.93 to 2.97, p=0.089). A subset analysis in patients with melanoma gave similar results for both cancer progression and arthritis control. CONCLUSION: The treatment of ICI-IA with a biologic DMARD is associated with more rapid arthritis control than with MTX, but may be associated with a shorter time to cancer progression.

Can Patients With Controlled Rheumatoid Arthritis Taper Methotrexate From Targeted Therapy and Sustain Remission? A Systematic Review and Metaanalysis.

OBJECTIVE: To determine the risk of not being able to sustain remission after tapering methotrexate (MTX) from targeted therapy in patients with controlled rheumatoid arthritis (RA). METHODS: A systematic literature search was conducted in MEDLINE, Embase, and the Cochrane Library for studies reporting remission outcomes after tapering MTX from targeted therapies in RA. Full-text articles and abstracts reported in English were included. Metaanalyses were conducted using random-effects models. Forest and funnel plots were created. RESULTS: A total of 10 articles were included. Studies evaluated MTX being tapered from combination treatment with tumor necrosis factor inhibitors, tocilizumab, abatacept, and tofacitinib. A total of 9 studies used a randomized design and 1 was observational. Out of 10 studies, 3 focused on early RA (ie, < 1 yr). The MTX-tapering strategy was gradual in 2 studies and rapid in 8 studies. Follow-up ranged from 3 to 18 months in randomized trials and up to 3 years in the observational study. Our metaanalysis, which included 2000 participants with RA from 10 studies, showed that patients who tapered MTX from targeted therapy had a 10% reduction in the ability to sustain remission and an overall pooled risk ratio of 0.90 (95% CI 0.84-0.97). There was no heterogeneity (I 2 = 0%, P = 0.94). Our funnel plot indicated minimal publication bias. CONCLUSION: Patients with controlled RA may taper MTX from targeted therapy with a 10% reduction in the ability to sustain remission for up to 18 months. Longer follow-up studies with attention to radiographic, functional, and patient-reported outcomes are needed. The risk of disease worsening should be discussed with the patient with careful follow-up and prompt retreatment of disease worsening.

Tumors Constitute a Majority of Total Knee Arthroplasty in Patients <21 Years Old: A United States Nationwide Analysis.

BACKGROUND: Total knee arthroplasty (TKA) is rarely performed in patients under 21 years old, but the frequency of utilization of TKA in this population in the United States is not known. The purpose of this study was to evaluate trends in the use of TKA in patients <21 in the United States. Additionally, we aimed to determine the characteristics of these patients and the hospitals in which this procedure is performed. METHODS: We retrospectively reviewed the Kids' Inpatient Database, a national weighted sample of all inpatient hospital admissions in the United States in patients <21 years of age. We used International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes to identify patients undergoing TKA from 2000 to 2019 and determine a primary diagnosis. Descriptive statistics were calculated using the appropriate sample weights. RESULTS: The total weighted number of TKAs performed in patients <21 years from 2000 to 2019 was 1,535. There were 70.9% of TKAs performed for a primary diagnosis of tumor, and the use of TKA for malignant tumors has increased. In contrast, the use of TKA for inflammatory arthritis/juvenile idiopathic arthritis decreased significantly over the study period. The majority of TKAs were performed in urban teaching hospitals with a large bed size. CONCLUSION: Approximately 1,535 TKAs have been performed in patients <21 years from 2000 to 2019 in the United States. The majority of these procedures were performed for reconstruction after resection of a malignant tumor. The rate of TKA for inflammatory arthritis/juvenile idiopathic arthritis has decreased over the past two decades.

Prevalence of misdiagnosis of cellulitis: A systematic review and meta-analysis.

BACKGROUND: There is no gold standard test to accurately identify patients with cellulitis and therefore misdiagnosis is common. Using the clinical impression of a dermatology or an infectious disease specialist as a reference standard, we sought to determine the prevalence of misdiagnosis of cellulitis among nonspecialist physicians. METHODS: A systemic search was performed using MEDLINE, Cochrane Library, and EMBASE databases for studies reporting diagnostic accuracy of cellulitis. Inclusion criteria required dermatology or infectious disease consultation for all patients diagnosed with cellulitis by generalist physicians. We used random effects modeling to estimate the prevalence of misdiagnosis using consultant diagnosis as a reference standard. RESULTS: Eight studies contributed to the analysis. For the seven studies involving inpatients, the results were sufficiently homogeneous to justify pooling data. Of 858 inpatients initially diagnosed with cellulitis, 335 (39%, 95% confidence interval: 31-47) received an alternative diagnosis from the specialist. Heterogeneity was large (I2 = 74%) and the greatest contributor to between-study variance was the year of publication. Alternative diagnoses were mostly noninfectious (68%, 221/327), with stasis dermatitis (18%, 60/327) being the most common. An abscess was the most common alternative infectious diagnosis (10%, 32/327). DISCUSSION: Cellulitis is commonly misdiagnosed among inpatients, leading to unnecessary hospital admissions and antibiotic overuse. Most alternative diagnoses are noninfectious. Continuing medical education among general practitioners and urgent care providers will likely reduce cellulitis misdiagnoses.

Capitated versus fee-for-service reimbursement and quality of care for chronic disease: a US cross-sectional analysis.

BACKGROUND: Upcoming alternative payment models Primary Care First (PCF) and Kidney Care Choices (KCC) incorporate capitated payments for chronic disease management. Prior research on the effect of capitated payments on chronic disease management has shown mixed results. We assessed the patient, physician, and practice characteristics of practices with capitation as the majority of revenue, and evaluated the association of capitated reimbursement with quality of chronic disease care. METHODS: We performed a cross-sectional analysis of visits in the United States' National Ambulatory Medical Care Survey (NAMCS) for patients with hypertension, diabetes, or chronic kidney disease (CKD). Our predictor was practice reimbursement type, classified as 1) majority capitation, 2) majority FFS, or 3) other reimbursement mix. Outcomes were quality indicators of hypertension control, diabetes control, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEi/ARB) use, and statin use. RESULTS: About 9% of visits were to practices with majority capitation revenue. Capitated practices, compared with FFS and other practices, had lower visit frequency (3.7 vs. 5.2 vs. 5.2, p = 0.006), were more likely to be located in the West Census Region (55% vs. 18% vs. 17%, p < 0.001), less likely to be solo practice (21% vs. 37% vs. 35%, p = 0.005), more likely to be owned by an insurance company, health plan or HMO (24% vs. 13% vs. 13%, p = 0.033), and more likely to have private insurance (43% vs. 25% vs. 19%, p = 0.004) and managed care payments (69% vs. 23% vs. 26%, p < 0.001) as the majority of revenue. The prevalence of controlled hypertension, controlled diabetes, ACEi/ARB use, and statin use was suboptimal across practice reimbursement types. Capitated reimbursement was not associated with differences in hypertension, diabetes, or CKD quality indicators, in multivariable models adjusting for patient, physician, and practice characteristics. CONCLUSIONS: Practices with majority capitation revenue differed substantially from FFS and other practices in patient, physician, and practice characteristics, but were not associated with consistent quality differences. Our findings establish baseline estimates of chronic disease quality of care performance by practice reimbursement composition, informing chronic disease care delivery within upcoming payment models.

Use of Total Hip Arthroplasty in Patients Under 21 Years Old: A US Population Analysis.

BACKGROUND: The purpose of this study is to evaluate trends in the use of total hip arthroplasty (THA) in the United States in patients under 21 years of age. Specifically, we examined the frequency of THA in this patient population over the past 2 decades, the epidemiologic characteristics of patients under 21 who underwent THA, and the characteristics of the hospitals where these procedures were performed. METHODS: We retrospectively reviewed the Kids' Inpatient Database, an inpatient US national weighted sample of hospital admissions in patients under 21 from approximately 4200 hospitals in 46 states. We queried the database using Current Procedural Terminology codes for elective and non-elective primary THA for the years 2000-2016. We utilized the International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes to determine primary diagnoses. RESULTS: The weighted total number of THAs performed in patients under 21 in the Kids' Inpatient Database increased from 347 in 2000 to 551 in 2016. The most common diagnoses were osteonecrosis, osteoarthritis, and inflammatory arthritis. The frequency of THA for osteonecrosis increased from 24% in 2000 to 38% in 2016, while the frequency of THA for inflammatory arthritis decreased from 27% in 2000 to 4% in 2016. CONCLUSION: The number of THAs in patients under 21 in the United States has increased over the past 2 decades and these procedures are increasingly performed in urban teaching hospitals. The decrease in THA for inflammatory arthritis in this population likely reflects improvements in medical management during the study period.

COVID-19 in Hospitalized Adults With HIV.

BACKGROUND: The spread of SARS-CoV-2 and the COVID-19 pandemic have caused significant morbidity and mortality worldwide. The clinical characteristics and outcomes of hospitalized patients with SARS-CoV-2 and HIV co-infection remain uncertain. METHODS: We conducted a matched retrospective cohort study of adults hospitalized with a COVID-19 illness in New York City between March 3, 2020, and May 15, 2020. We matched 30 people with HIV (PWH) with 90 control group patients without HIV based on age, sex, and race/ethnicity. Using electronic health record data, we compared demographic characteristics, clinical characteristics, and clinical outcomes between PWH and control patients. RESULTS: In our study, the median age (interquartile range) was 60.5 (56.6-70.0) years, 20% were female, 30% were black, 27% were white, and 24% were of Hispanic/Latino/ethnicity. There were no significant differences between PWH and control patients in presenting symptoms, duration of symptoms before hospitalization, laboratory markers, or radiographic findings on chest x-ray. More patients without HIV required a higher level of supplemental oxygen on presentation than PWH. There were no differences in the need for invasive mechanical ventilation during hospitalization, length of stay, or in-hospital mortality. CONCLUSIONS: The clinical manifestations and outcomes of COVID-19 among patients with SARS-CoV-2 and HIV co-infection were not significantly different than patients without HIV co-infection. However, PWH were hospitalized with less severe hypoxemia, a finding that warrants further investigation.

Time-Varying Depressive Symptoms and Cardiovascular and All-Cause Mortality: Does the Risk Vary by Age or Sex?

Background Depressive symptoms are associated with mortality. Data regarding moderation of this effect by age and sex are inconsistent, however. We aimed to identify whether age and sex modify the association between depressive symptoms and all-cause and cardiovascular disease (CVD) mortality. Methods and Results The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study is a prospective cohort of Black and White individuals recruited between 2003 and 2007. Associations between time-varying depressive symptoms (Center for Epidemiologic Studies Depression scale score ≥4 versus <4) and all-cause and CVD mortality were measured using Cox proportional hazard models adjusting for demographic and clinical risk factors. All results were stratified by age or sex and by self-reported health status. Of 29 491 participants, 3253 (11%) had baseline elevated depressive symptoms. Mean age was 65 (9.4) years, with 55.1% of participants female, 41.1% Black, and 46.4% had excellent/very good health. Depressive symptoms were measured at baseline, on average 4.9 (SD, 1.5), then 2.1 (SD, 0.4) years later. Neither age nor sex moderated the association between elevated time-varying depressive symptoms and all-cause or CVD mortality (all-cause: age 45-64 years adjusted hazard ratio [aHR], 1.38; 95% CI, 1.18-1.61 versus age ≥65 years aHR,1.36; 95% CI, 1.23-1.50; P=0.05; CVD: age 45-64 years aHR, 1.17; 95% CI, 0.90-1.53 versus age ≥65 years aHR, 1.26; 95% CI, 1.06-1.50; P=0.54; all-cause: males aHR, 1.46; 95% CI, 1.29-1.64 versus female aHR, 1.34; 95% CI, 1.19-1.50; P=0.35; CVD: male aHR, 1.32; 95% CI, 1.08-1.62 versus female aHR, 1.22; 95% CI, 1.00-1.47; P=0.64). Similar results were observed when stratified by self-reported health status. Conclusions Depressive symptoms confer mortality risk regardless of age and sex, including individuals who report excellent/very good health.

Depressive symptoms do not discriminate: racial and economic influences between time-varying depressive symptoms and mortality among REGARDS participants.

PURPOSE: Depressive symptoms relapse and remit over time, perhaps differentially by race and income. Few studies have examined whether time-varying depressive symptoms (TVDS) differentially predict mortality. We sought to determine whether race (white/black) and income (

Impact of diagnostic bone biopsies on the management of non-vertebral osteomyelitis: A retrospective cohort study.

Optimal antibiotic management of patients with osteomyelitis remains a challenge for many clinicians. Although image-guided bone biopsy (IGB) remains the gold standard, its role in confirming diagnosis and guiding antibiotic management is not clear in patients with non-vertebral osteomyelitis.To determine the diagnostic yield of IGB and its impact on antibiotic management in non-vertebral osteomyelitis.Retrospective cohort study.Urban academic medical center.Patients admitted for non-vertebral osteomyelitis who underwent image-guided bone biopsy.Primary outcomes were microbiologic and histopathological results. We evaluated the impact of IGB on clinician-initiated changes in antibiotic regimen before and after biopsy.We evaluated 203 bone biopsies in 185 patients with clinical suspicion of osteomyelitis. 79% of patient received antibiotics prior to biopsy. Bone cultures were positive in 28% and histopathology confirmed osteomyelitis in 29%, but concordance was poor. Furthermore, clinical suspicion of infection was much higher, given that 68% received empiric antibiotics. Leukocytosis was significantly associated with positive cultures in multivariate analysis. There was no statistically significant correlation between antibiotic management and bone culture results. When culture yielded an organism, empiric regimens were kept the same, broadened or narrowed with equal frequency; targeted regimens were chosen only in 4 cases. Despite negative cultures in 98/138 cases having received empiric treatment, antibiotics were discontinued in only 8 cases. Even when empiric treatment was not given, negative cultures did not dissuade clinicians from eventual antibiotic use in a significant number of cases (17/48). In 46/71 patients whose final regimen included vancomycin, there was no evidence of current or past infection with MRSA.In patients with non-vertebral osteomyelitis, the diagnostic yield of image-guided bone biopsy is low, and clinicians frequently make decisions regarding antibiotic management that are not aligned with culture results.

Treating loss-to-follow-up as a missing data problem: a case study using a longitudinal cohort of HIV-infected patients in Haiti.

BACKGROUND: HIV programs are often assessed by the proportion of patients who are alive and retained in care; however some patients are categorized as lost to follow-up (LTF) and have unknown vital status. LTF is not an outcome but a mixed category of patients who have undocumented death, transfer and disengagement from care. Estimating vital status (dead versus alive) among this category is critical for survival analyses and program evaluation. METHODS: We used three methods to estimate survival in the cohort and to ascertain factors associated with death among the first cohort of HIV positive patients to receive antiretroviral therapy in Haiti: complete case (CC) (drops missing), Inverse Probability Weights (IPW) (uses tracking data) and Multiple Imputation with Chained Equations (MICE) (imputes missing data). Logistic regression was used to calculate odds ratios and 95% confidence intervals for adjusted models for death at 10 years. The logistic regression models controlled for sex, age, severe poverty (living on <$1 USD per day), Port-au-Prince residence and baseline clinical characteristics of weight, CD4, WHO stage and tuberculosis diagnosis. RESULTS: Age, severe poverty, baseline weight and WHO stage were statistically significant predictors of AIDS related mortality across all models. Gender was only statistically significant in the MICE model but had at least a 10% difference in odds ratios across all models. CONCLUSION: Each of these methods had different assumptions and differed in the number of observations included due to how missing values were addressed. We found MICE to be most robust in predicting survival status as it allowed us to impute missing data so that we had the maximum number of observations to perform regression analyses. MICE also provides a complementary alternative for estimating survival among patients with unassigned vital status. Additionally, the results were easier to interpret, less likely to be biased and provided an alternative to a problem that is often commented upon in the extant literature.

Differences in Risk of Sudden Cardiac Death Between Blacks and Whites.

BACKGROUND: Prior studies have consistently demonstrated that blacks have an approximate 2-fold higher incidence of sudden cardiac death (SCD) than whites; however, these analyses have lacked individual-level sociodemographic, medical comorbidity, and behavioral health data. OBJECTIVES: The purpose of this study was to evaluate whether racial differences in SCD incidence are attributable to differences in the prevalence of risk factors or rather to underlying susceptibility to fatal arrhythmias. METHODS: The Reasons for Geographic and Racial Differences in Stroke study is a prospective, population-based cohort of adults from across the United States. Associations between race and SCD defined per National Heart, Lung, and Blood Institute criteria were assessed. RESULTS: Among 22,507 participants (9,416 blacks and 13,091 whites) without a history of clinical cardiovascular disease, there were 174 SCD events (67 whites and 107 blacks) over a median follow-up of 6.1 years (interquartile range: 4.6 to 7.3 years). The age-adjusted SCD incidence rate (per 1,000 person-years) was higher in blacks (1.8; 95% confidence interval [CI]: 1.4 to 2.2) compared with whites (0.7; 95% CI: 0.6 to 0.9), with an unadjusted hazard ratio of 2.35; 95% CI: 1.74 to 3.20. The association of black race with SCD risk remained significant after adjustment for sociodemographics, comorbidities, behavioral measures of health, intervening cardiovascular events, and competing risks of non-SCD mortality (hazard ratio: 1.97; 95% CI: 1.39 to 2.77). CONCLUSIONS: In a large biracial population of adults without a history of cardiovascular disease, SCD rates were significantly higher in blacks as compared with whites. These racial differences were not fully explained by demographics, adverse socioeconomic measures, cardiovascular risk factors, and behavioral measures of health.

Stress, Socializing, and Other Motivations for Smoking Among the Lesbian, Gay, Bisexual, Transgender, and Queer Community in New York City.

PURPOSE: This study contributes to the emerging literature on lesbian, gay, bisexual, transgendered, and queer (LGBTQ) health disparities and tobacco use by examining the motivations for smoking among the New York City (NYC) LGBTQ population. APPROACH: We used grounded theory and blended methods from 3 grounded theorists-Strauss, Corbin, and Charmaz-for data collection, coding, and analysis. SETTING: NYC has extensive legislation to prevent smoking; however, the current smoking prevalence of homosexuals is double that of heterosexuals. PARTICIPANTS: Study participants were leaders from 23 NYC LGBTQ organizations. Leaders were chosen to establish a relationship with community and to ensure cultural sensitivity. Eligibility criteria required holding a leadership position in an organization serving the NYC LGBTQ community. METHODS: Interviews were transcribed verbatim and uploaded into Dedoose for analysis. An initial code list was developed from the interview guide. Key themes were identified as the themes with the most number of quotes. RESULTS: Three key themes emerged from our interviews: image, socializing, and stress. Smoking was reported to be a socialization aid and a maladaptive coping technique for stress arising from interactions of conflicting identities. CONCLUSION: Future smoking cessation interventions among the LGBTQ community should equip smokers with healthy coping mechanisms that address the stressors that arise from the intersections of smokers' many identities.

A Comparison of Alternative Tobacco Product Usage, Knowledge and Beliefs Between the New York City Lesbian, Gay, Bisexual, and Transgendered Community and Heterosexuals.

Within the United States, alternative tobacco product (ATP) and varies by geographic region, gender and age. Few articles have been published on the usage of these products among the lesbian, gay, bisexual, transgender or queer (LGBTQ) population. A web-based anonymous survey administered through Google Forms, was used to collect data on current tobacco usage, knowledge and beliefs from adult heterosexuals, homosexuals, bisexuals and transgendered persons residing in New York City from May 2014 to July 2014. Sixty-four individuals completed the survey; 30 were heterosexual and 32 identified as either lesbian, gay, bisexual, transgender or queer. Heterosexuals were found to have tried cigarettes, on average, almost a year before the LGBTQ respondents. Social networks were influential to LGBTQ respondents for an introduction to smoking; 48.00% were introduced by friends, 28.00% by family, 12.00% by a significant other and 9.09% by someone else. For heterosexuals, 73.68% reported that friends introduced them to smoking. More heterosexuals reported trying hookah (N = 10), snus (N = 4) and roll your own cigarettes (N = 5). On average respondents knew of eight different tobacco products, regardless of sexual identity. To our knowledge, we present for the first time a comparison of people who tried, current and former users of ATPs, beliefs and knowledge about ATPs, and sources of knowledge of ATPs by sexual identity from NYC. More research is needed to examine the impact of social networks and the upcoming FDA regulations on ATPs have on the overall prevalence of usage among the LGBTQ community.

Dentists' self-perceived role in offering tobacco cessation services: results from a nationally representative survey, United States, 2010-2011.

INTRODUCTION: Dental visits represent an opportunity to identify and help patients quit smoking, yet dental settings remain an untapped venue for treatment of tobacco dependence. The purpose of this analysis was to assess factors that may influence patterns of tobacco-use-related practice among a national sample of dental providers. METHODS: We surveyed a representative sample of general dentists practicing in the United States (N = 1,802). Multivariable analysis was used to assess correlates of adherence to tobacco use treatment guidelines and to analyze factors that influence providers' willingness to offer tobacco cessation assistance if reimbursed for this service. RESULTS: More than 90% of dental providers reported that they routinely ask patients about tobacco use, 76% counsel patients, and 45% routinely offer cessation assistance, defined as referring patients for cessation counseling, providing a cessation prescription, or both. Results from multivariable analysis indicated that cessation assistance was associated with having a practice with 1 or more hygienists, having a chart system that includes a tobacco use question, having received training on treating tobacco dependence, and having positive attitudes toward treating tobacco use. Providers who did not offer assistance but who reported that they would change their practice patterns if sufficiently reimbursed were more likely to be in a group practice, treat patients insured through Medicaid, and have positive attitudes toward treating tobacco dependence. CONCLUSION: Findings indicate the potential benefit of increasing training opportunities and promoting system changes to increase involvement of dental providers in conducting tobacco use treatment. Reimbursement models should be tested to assess the effect on dental provider practice patterns.

Antimicrobial-resistant nocardia isolates, United States, 1995-2004.

We conducted a 10-year retrospective evaluation of the epidemiology and identification of Nocardia isolates submitted to the Centers for Disease Control and Prevention for antimicrobial susceptibility testing. The species most commonly identified were N. nova (28%), N. brasiliensis (14%), and N. farcinica (14%). Of 765 isolates submitted, 61% were resistant to sulfamethoxazole and 42% were resistant to trimethoprim-sulfamethoxazole.

Gordonia araii infection associated with an orthopedic device and review of the literature on medical device-associated Gordonia infections.

Gordonia infections in humans are rare and usually affect immunocompromised patients. We present the first case of Gordonia araii infection associated with a medical device in an immunocompetent patient. Sequencing was required for conclusive identification. We compared our case to the 16 Gordonia species-associated medical device infections reported to date.