Early diagnosis of lupus: A possibilty. A multicentric study from SLE Special Interest Group (SIG) of Indian Rheumatology Association (IRA).

INTRODUCTION: Systemic Lupus Erythematosus (SLE) warrants an early diagnosis and prompt management. Delay in diagnosis can result in repeated flares, permanent damage, and even death. There is a large variability in the time taken to diagnose SLE across the world. We undertook this study to determine the time taken for diagnosis of SLE in India and to identify the factors associated. METHODS: Patients with SLE diagnosed within the previous 1 year as per Systemic Lupus Erythematosus International Collaborating Clinics criteria (SLICC) 2012 criteria were included in a cross-sectional multicentre questionnaire-based survey. Demographic profile, self-reported socioeconomic status as per Kuppuswamy classification of socioeconomic status (version 2022) (SES), and several healthcare related parameters including referral pattern were recorded. Median time taken for diagnosis was used to demarcate early or late diagnosis and associated factors were explored. RESULTS: We included 488 patients with SLE from 10 rheumatology centres. The median time to diagnosis was 6 months Interquartile Range (IQR 3,14.7) and within 3 months in about one third [150(30.7%)]. Very early diagnosis (<1 month) was established in 78(16.0%) patients. The mean SLE Disease Activity Index (SLEDAI) at diagnosis was 10.28+7.24. In univariate analysis, an older age, lower SES, non-southern state of residence and larger family size were significantly associated with late diagnosis. In the multivariate analysis, higher SES (AOR 0.95, 95% CI: 0.92-0.98), multiple organ system involvement at initial presentation (AOR1.75 95%CI: 1.08-2.84) and place of residence in south Indian states (AOR1.92 95%CI: 1.24-2.97) had lesser odds of being associated with late diagnosis. Distance from the closest medical centre/professional did not influence the time to diagnosis. Majority of patients had first consulted a medical graduate (42.5%) or postgraduate doctor (48.2%), and referral to rheumatologist was largely done by postgraduate (65%) doctors. More than half of our patients (61%) self-finance their treatment. CONCLUSION: Median time to diagnosis of SLE was 6 months, 1/3rd being diagnosed within 3 months and 78(16.0%) with 1 month of symptom onset. Delay in diagnosis was noted in those belonging to lower socioeconomic strata and those with single organ disease. Distance to the health care facility did not influence time to diagnosis.

Risk factors associated with COVID-19 in systemic lupus erythematosus: Results from a longitudinal prospective cohort.

INTRODUCTION: Patients with SLE (systemic lupus erythematosus) have a higher risk of infection due to dysregulated immune system as well as long-term use of immunosuppressants (IS). This could influence the risk of COVID-19 and its outcome. METHODS: We conducted a longitudinal prospective study across 15 rheumatology centres during the first wave of the pandemic to understand the risk factors contributing to COVID-19 in SLE patients. During the 6 months follow-up, those who tested positive for COVID-19, their clinical course and outcome information were recorded. RESULTS: Through the study period (April-December 2020), 36/1379 lupus patients (2.9%) developed COVID-19. On analysing the COVID-19 positive versus negative cohort during the study period, male gender (adjusted RR 3.72, 95% C.I. 1.85,7.51) and diabetes (adjusted RR 2.94, 95% C.I. 1.28, 6.79) emerged as the strongest risk factors for COVID-19, in the adjusted analysis. There was no significant influence of organ involvement, hydroxychloroquine, glucocorticoid dosage (prednisolone< 7.5 mg or ≥ 7.5 mg/day) or IS on the risk of COVID-19. There was only one death (1/36) among the lupus patients due to COVID-19. CONCLUSION: Traditional risk factors rather than lupus disease process or IS influenced the risk of COVID-19 in our cohort.

Update on cancer therapy-induced atherosclerosis.

PURPOSE OF REVIEW: Recent advances in oncologic therapies have significantly improved overall survival for patients with malignancy. However, cardiovascular complications have not only increased in this population due to shared risk factors and pathophysiology, but also due to the therapies themselves. One key mechanism that warrants further attention is accelerated atherosclerosis due to these agents. RECENT FINDINGS: Here we review recent studies focusing on four classes of anticancer agents with the potential to accelerate atherosclerosis, including breakpoint cluster region-Ableson (BCR-ABL) tyrosine kinase inhibitors, immunotherapies, androgen deprivation therapies, and vascular endothelial growth factor inhibitors. In addition to drug therapy, radiation therapy may also accelerate atherosclerosis. SUMMARY: In order to optimize outcomes for patients with malignancy, enhanced efforts need to focus on mitigating common risk factors, but also recognizing enhanced atherosclerotic risk with certain oncologic therapies. For patients exposed to these agents, risk reduction with agents such as aspirin and/or statins prior to, during, and after cancer treatment may provide opportunities to improve overall outcomes.

Current Controversies in Radiology on Cost, Reimbursement, and Price Transparency: AJR Expert Panel Narrative Review.

Many believe that fundamental reform of the U.S. health care system is overdue and necessary given rising national health care expenditures, poor performance on key population health metrics, meaningful health disparities, concerns about potential financial toxicity of care, inadequate price transparency, pending insolvency of Medicare Part A, increasing commercial insurance premiums, and large uninsured and underinsured populations. The Medicare Payment Advisory Commission, an independent congressional agency, believes that part of this reform includes redistribution of reimbursements away from specialties such as radiology. Thus, despite an increase in the Medicare population and spending, Medicare payments for medical imaging have been decreasing for years. Further, the No Surprises Act, a federal law intended to curb the problem of surprise medical billing, was repurposed in federal rulemaking to reduce reimbursement from commercial payers to certain specialties, including radiology. In this article, we examine challenges facing the U.S. health care system, focusing on cost, reimbursement, and price transparency and the role of radiology in addressing such challenges. Medical imaging is a minor contributor to national health care expenditures but has an outsized impact on patient care. The radiology community should work together to reinforce the value of medical imaging and reduce inappropriate utilization of low-value care.

Radiology in the Era of Value-based Healthcare: A Multi-Society Expert Statement from the ACR, CAR, ESR, IS3R, RANZCR, and RSNA.

Background The Value-Based Healthcare (VBH) concept is designed to improve individual healthcare outcomes without increasing expenditure, and is increasingly being used to determine resourcing of and reimbursement for medical services. Radiology is a major contributor to patient and societal healthcare at many levels. Despite this, some VBH models do not acknowledge radiology's central role; this may have future negative consequences for resource allocation. Methods, findings and interpretation This multi-society paper, representing the views of Radiology Societies in Europe, the USA, Canada, Australia, and New Zealand, describes the place of radiology in VBH models and the health-care value contributions of radiology. Potential steps to objectify and quantify the value contributed by radiology to healthcare are outlined. Published under a CC BY 4.0 license.

Radiology in the Era of Value-Based Healthcare: A Multi-Society Expert Statement From the ACR, CAR, ESR, IS3R, RANZCR, and RSNA.

BACKGROUND: The Value-Based Healthcare (VBH) concept is designed to improve individual healthcare outcomes without increasing expenditure, and is increasingly being used to determine resourcing of and reimbursement for medical services. Radiology is a major contributor to patient and societal healthcare at many levels. Despite this, some VBH models do not acknowledge radiology's central role; this may have future negative consequences for resource allocation. METHODS, FINDINGS AND INTERPRETATION: This multi-society paper, representing the views of Radiology Societies in Europe, the USA, Canada, Australia, and New Zealand, describes the place of radiology in VBH models and the health-care value contributions of radiology. Potential steps to objectify and quantify the value contributed by radiology to healthcare are outlined.

Trends in Diagnostic Imaging Utilization among Medicare and Commercially Insured Adults from 2003 through 2016.

Background Trends in noninvasive diagnostic imaging (NDI) utilization rates have predominantly been reported in Medicare enrollees. To the authors' knowledge, there has been no prior direct comparison of utilization rates between Medicare and commercially insured patients. Purpose To analyze trends in NDI utilization rates by modality, comparing Medicare fee-for-service and commercially insured enrollees. Materials and Methods This study was a retrospective trend analysis of NDI performed between 2003 and 2016 as reported in claims databases for all adults enrolled in fee-for-service Medicare and for roughly 9 million commercially insured patients per year. The commercially insured patients were divided into two populations: those aged 18-44 years and those aged 45-64 years. The same procedure code definitions for NDI were applied to both Medicare and commercial claims, rates were calculated per 1000 enrollees, and trends were reported over time in aggregate followed by modality (CT, MRI, nuclear imaging, echocardiography, US, radiography). Join-point regression was used to model annual rates and to identify statistically significant (P < .05) changes in trends. Results In almost all instances, Medicare enrollees had the highest utilization rate for each modality, followed by commercially insured patients aged 45-64 years, then aged 18-44 years. All three populations showed utilization growth through the mid to late 2000s (images per 1000 enrollees per year for Medicare: 91 [95% confidence interval {CI}: 34, 148]; commercially insured patients aged 45-64 years: 158 [95% CI: 130, 186]; aged 18-44 years: 83 [95% CI: 69, 97]), followed by significant declining trends from the late 2000s through early 2010s (images per 1000 enrollees per year for Medicare: -301 [95% CI: -510, -92]; commercially insured patients aged 45-64 years: -54 [95% CI: -69, -39]; aged 18-44 years: -26 [95% CI: -31, -21]) coinciding with code-bundling events instituted by Medicare (CT, nuclear imaging, echocardiography). There were significant trend changes in modalities without code bundling (MRI, radiography, US), although flat trends mostly were exhibited. After the early 2010s, there were significant trend changes largely showing flat utilization growth. The notable exception was a significant trend change to renewed growth of CT imaging among commercially insured patients aged 45-64 years and Medicare enrollees after 2012, although at half the prior rate (images per 1000 enrollees per year for Medicare: 17 [95% CI: 6, 28]; commercially insured patients aged 45-64 years: 11 [95% CI: 2, 20]). Conclusion Noninvasive diagnostic imaging utilization trends among commercially insured individuals are similar to those in Medicare enrollees, although at lower rates. Earlier rapid growth has ceased and, except for CT, utilization has stabilized since the early 2010s. © RSNA, 2019 See also the editorial by Hentel and Wolk in this issue.

Enhanced Response to Drug-Induced QT Interval Lengthening in Patients with Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Patients with heart failure (HF) with reduced ejection fraction demonstrate enhanced response to drug-induced QT interval lengthening and are at increased risk for torsades de pointes. The influence of HF with preserved ejection fraction (HFpEF) on response to drug-induced QT lengthening is unknown. METHODS AND RESULTS: We administered intravenous ibutilide 0.003 mg/kg to 10 patients with HFpEF and 10 age- and sex-matched control subjects without HF. Serial 12-lead electrocardiograms were obtained for determination of QT intervals. Demographics, maximum serum ibutilide concentrations, area under the serum ibutilide concentration vs time curves, and baseline Fridericia-corrected QT (QTF) (417 ± 14 vs 413 ± 15 ms, P = .54) were similar in the HFpEF and control groups. Area under the effect (QTFvs time) curve (AUEC) from 0 to 1.17 hours during and following the ibutilide infusion was greater in the HFpEF group (519 ± 19 vs 497 ± 18 ms·h, P= .04), as was AUEC from 0 to 8.17 hours (3576 ± 125 vs 3428 ± 161 ms·h, P = .03) indicating greater QTF interval exposure. Maximum QTF (454 ± 15 vs 443 ± 22 ms, P = .18) and maximum percent increase in QTF from baseline (8.2 ± 2.1 vs 6.7 ± 1.9%, P = .10) in the 2 groups were not significantly different. CONCLUSIONS: HFpEF is associated with enhanced response to drug-induced QT interval lengthening.

Maternal and fetal outcomes of lupus pregnancies: A collective effort by Karnataka Rheumatologists.

INTRODUCTION: Identifying factors predicting adverse pregnancy outcomes involving systemic lupus erythematosus (SLE) is a research priority. The aims of this study were to investigate (a) the maternal and fetal outcomes of pregnant lupus patients and the factors associated with adverse pregnancy outcomes, and (b) the effect of pregnancy on lupus disease activity of these patients. METHODS: This was an ambi-directional study collecting information from five multi-specialist referral centres across the state of Karnataka, India over 5 years (2013-2018). Clinical details of pregnancies and outcomes that were temporally associated with lupus disease were recorded using a structured pro forma. The Safety of Estrogen in SLE National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) was used to assess lupus activity during the 6 months prior to pregnancy and the intra- and post-partum periods. Modifications suggested in the SLE Pregnancy Disease Activity Index were considered while scoring. RESULTS: A total of 121 pregnancies in 80 SLE patients with a mean age of 27.1 (±4.5) years and with a mean disease duration of 4.6 (±4.1) years were reviewed. Largely patients were in clinical remission (109/121; 90.1%). Antiphospholipid antibody positivity was seen in 45/121 (37.2%) patients. A history of lupus nephritis was noted in 29/121 (24%) patients. Maternal complications (32%) were mainly due to hypertensive disorders of pregnancy (HDP; 19/121; 15.7%). Adverse fetal outcomes (58%) were mainly in the form of spontaneous first-trimester abortions (21/121; 16%), stillbirth (14/121; 11.6%) and prematurity (24/121; 20%). HDP is strongly associated with stillbirth and prematurity and is independent of active lupus. Disease activity was associated with a three-fold increased risk of adverse fetal outcome in univariate analysis. The risk of major flare during pregnancy is low (4.1%) when conception occurs during stable disease. Hydroxychloroquine (HCQ) use was associated with reduced risk of flare (p = 0.001) in patients in remission at the time of conception. CONCLUSIONS: The risk of major flare during pregnancy is low when conception happens during stable disease. HCQ use was associated with reduced risk of flare in patients in remission at the time of conception. HDP was strongly associated with stillbirth and prematurity and are independent of active lupus in our cohort.

Advanced Imaging Interpretation by Radiologists and Nonradiologist Physicians: A Training Issue.

OBJECTIVE. The purpose of this study was to examine the degree to which nonradiologist physicians provide formal interpretations for advanced imaging and to consider whether adequate training can be achieved for those physicians. This investigation assumed that hospitals are the only places where formal imaging training occurs. MATERIALS AND METHODS. The CMS Physician/Supplier Procedure Summary Master Files (PSPSMFs) of the Medicare Part B datasets for 2015 were reviewed. We selected the Current Procedural Terminology (CPT) codes for four categories of noninvasive diagnostic imaging: CT, MRI, PET, and general nuclear imaging. Medicare place-of-service codes allowed us to determine the location of each study interpretation. We narrowed our analysis to data from the three major hospital places of service: inpatient facilities, hospital outpatient departments, and emergency departments. Provider specialties were determined using Medicare's 108 specialty codes. Procedure volumes among nonradiologist physicians were compared with those among radiologists. RESULTS. Of the 17,824,297 hospital-based CT examinations performed in the Medicare fee-for-service population, radiologists interpreted 17,698,360 (99.29%) and nonradiologists interpreted 125,937 (0.71%). Of the 4,512,627 MRI examinations performed, radiologists interpreted 4,469,275 (99.04%) and nonradiologist physicians interpreted 43,352 (0.96%). Of 391,688 PET studies performed, radiologists interpreted 368,913 (94.19%) and nonradiologist physicians interpreted 22,775 (5.81%). Of the 2,070,861 general nuclear medicine studies performed, radiologists interpreted 1,307,543 (63.14%) and nonradiologist physicians interpreted 763,318 (36.86%). Cardiologists had the largest involvement of nonradiologist physicians, contributing approximately 3% of all advanced imaging interpretations. All other nonradiologist physicians interpreted a tiny fraction of advanced imaging studies. CONCLUSION. Besides radiologists and cardiologists, no other medical specialty provides sufficient education for their trainees and practitioners in advanced imaging interpretation to justify allowing them to interpret these studies in practice, except under carefully controlled circumstances.

Utilization Trends in Abdominal Imaging, 2004-2016.

OBJECTIVE. The purpose of this study was to analyze recent trends in abdominal imaging utilization in the Medicare population. MATERIALS AND METHODS. Medicare Part B databases for 2004-2016 were reviewed, and all Current Procedural Terminology codes pertaining to noninvasive imaging of the abdomen and pelvis were identified. Codes were grouped into six categories: CT and CT angiography (CTA), MRI and MR angiography (MRA), ultrasound, radionuclide imaging, radiography, and gastrointestinal fluoroscopy. Annual utilization rates per 1000 Medicare beneficiaries were calculated. Medicare physician specialty codes were used to identify studies performed by radiologists versus nonradiologist physicians. Reimbursements were determined. RESULTS. Total abdominal imaging utilization decreased from 558.0 examinations per 1000 Medicare beneficiaries in 2004 to 441.9 in 2016 (-20.8%). CT and CTA examinations increased by 22.5% from 2004 to 2010, followed by a sharp drop in 2011 caused by code bundling. From 2011 to 2016, CT and CTA use increased by only 7.2%. Radiography utilization decreased from 129.6 examinations per 1000 Medicare beneficiaries in 2004 to 91.5 in 2016 (-29.4%). Radionuclide studies decreased from 14.0 to 9.5 (-32.1%), and gastrointestinal fluoroscopy decreased from 37.8 examinations to 22.5 (-40.5%). Utilization of ultrasound increased slightly (1.5%), whereas MRI and MRA utilization sharply increased on a percentage basis (81.2%). Reimbursements peaked in 2009 at $1.704 billion, dropped substantially in 2011 because of code bundling, and remained relatively stable thereafter. The radiologists' market share of abdominal imaging was approximately 87% in both 2004 and 2016. CONCLUSION. Abdominal imaging utilization rates have declined in recent years, in part due to code bundling, but also largely because of a decrease in the use of abdominal radiography, gastrointestinal fluoroscopy, and nuclear imaging. Reimbursements have also declined. This study also showed that most of the abdominal imaging was performed by radiologists.

Recent Trends in Endovascular and Surgical Treatment of Peripheral Arterial Disease in the Medicare Population.

OBJECTIVE. Although radiologists developed endovascular treatment of peripheral arterial disease (PAD) in the 1960s, vascular surgeons and cardiologists have become increasingly involved in its application. The purpose of this study was to examine utilization trends in endovascular and surgical treatment of PAD in recent years in the Medicare population. CONCLUSION. Surgical treatment of PAD has decreased each year from 2011 to 2016, whereas endovascular treatment has increased each year. By 2016, Medicare patients who needed revascularization for PAD were more than four times as likely to undergo endovascular as they were to undergo surgical treatment. Between 2011 and 2016, radiologists, vascular surgeons, and cardiologists all increased their endovascular volume, but by 2016, vascular surgeons and cardiologists performed three of every four endovascular procedures for the Medicare population. While only 12% of the total endovascular procedures for PAD were performed in 2016, radiology has grown its procedural volume each year from 2011 through 2016.

Incidence of infection other than tuberculosis in patients with autoimmune rheumatic diseases treated with bDMARDs: a real-time clinical experience from India.

Biologic disease-modifying anti-rheumatic drugs (bDMARD) have transformed the treatment paradigm of chronic autoimmune rheumatic diseases (ARDs), but they are often associated with adverse drug reactions. The present study evaluated the frequency, characteristics and type of infections, other than tuberculosis (TB), in ARD patients receiving bDMARDs. The multicentre, cross-sectional, retrospective, observational study was conducted across 12 centers in Karnataka, India, between January to August 2016. The study included patients receiving bDMARD therapy for various ARDs. Outcome variables considered were any infection, minor infections and major infections, other than TB. Clinical variables were compared between infection and no infection group, and the increase in the likelihood of infection with respect to various clinical variables was assessed. The study involved 209 subjects with a median (range) age of 41 (16-84) years and male to female ratio of 0.97:1. A total of 29 (13.88%) subjects developed infection following bDMARD therapy, out of whom a majority had minor infection (n = 26). The likelihood of developing any infection was noted to be more in subjects receiving anti-TNF (golimumab, P = 0.03) and those on three or more conventional synthetic (cs) DMARDs (P < 0.01). Infection risk was higher in patients with systemic lupus erythematosus (P = 0.04), other connective tissue disease (P < 0.01) and in patients with comorbidities (P = 0.13). The risk of infection was associated with the use of anti-TNF therapy and more than three csDMARDs, co morbidities and Adds such as systemic lupus erythematosus and connective tissue disease.

Inferior Vena Cava Filter Placement and Retrieval Rates among Radiologists and Nonradiologists.

PURPOSE: To evaluate inferior vena cava (IVC) filter placement and retrieval rates among radiologists, vascular surgeons, cardiologists, other surgeons, and all other health care providers for Medicare fee-for-service beneficiaries in the years 2012-2015. MATERIALS AND METHODS: The nationwide Medicare Physician/Supplier Procedure Summary Master Files were used to determine the volume and utilization rate of IVC filter placement, IVC filter repositioning, and IVC filter retrieval, which correspond to procedure codes 37191, 37192, and 37193, respectively. Procedural code 37193 was not available before 2012, so data were reviewed for the years 2012-2015. RESULTS: The total volume of Medicare IVC filter placement decreased from 57,785 in 2012 to 44,378 in 2015, with radiologists responsible for 60% of all filter placements. Volume of IVC filter placement declined across all specialties, including radiologists, who placed 33,744 in 2012 and 27,957 in 2015. In contrast, total retrieval of IVC filters increased from 4,060 removals in 2012 to 6,166 in 2015. Retrieval rate per 100,000 Medicare beneficiaries increased from 11 in 2012 to 16 in 2015. Radiologists removed the bulk of the filters: 64% in both 2012 and 2015. Vascular surgeons, cardiologists, and other surgeons retrieved, respectively, 20%, 10%, and 5% of all IVC filters in 2012 and 22%, 9%, and 5% in 2015. CONCLUSIONS: From 2012 to 2015, IVC filter placement steadily decreased across all specialties. Retrieval rate of IVC filters continued to rise over the same period. Radiologists were responsible for the majority of IVC filter placements and retrievals.

Coronary CT Angiography: Use in Patients With Chest Pain Presenting to Emergency Departments.

OBJECTIVE: Previously published reports have shown that coronary CT angiography (CCTA) is a more efficient method of diagnosis than myocardial perfusion imaging (MPI) and stress echocardiography for patients presenting to emergency departments (EDs) with acute chest pain. In light of this evidence, the objective of this study was to examine recent trends in the use of these techniques in EDs. MATERIALS AND METHODS: The nationwide Medicare Part B databases for 2006-2015 were the data source. The Current Procedural Terminology, version 4, codes for CCTA, MPI, and stress echocardiography were selected. Medicare place-of-service codes were used to determine procedure volumes in EDs. Medicare specialty codes were used to ascertain how many of these examinations were interpreted by radiologists, cardiologists, and other physicians as a group. RESULTS: From 2006 to 2015, there was essentially no change in the number of MPI examinations performed in EDs for patients using Medicare (22,342 in 2006, 22,338 in 2015) or in the number of stress echocardiograms (3544 in 2006, 3520 in 2015). By contrast, the number of CCTA examinations increased rapidly, from 126 in 2006 to 1919 in 2015 (compound annual growth rate, 35%). Despite this rapid growth, patients in EDs underwent 11.6 times as many MPI as CCTA examinations in 2015. In that last year of the study, radiologists interpreted 78% of ED MPI and 83% of ED CCTA examinations. CONCLUSION: Use of CCTA in EDs has increased rapidly, but far more MPI examinations are still being performed. This finding suggests that recently acquired evidence is not yet being fully acted upon.

Screening Mammography and Digital Breast Tomosynthesis: Utilization Updates.

OBJECTIVE: There have been many recent developments in breast imaging, including the 2009 revision of the U.S. Preventive Services Task Force's breast cancer screening guidelines and the approval of digital breast tomosynthesis (DBT) for clinical use in 2011. The objective of this study is to evaluate screening mammography utilization trends among the Medicare population from 2005 to 2015 and examine the volume of DBT studies performed in 2015, the first year for which procedural billing codes for DBT are available. MATERIALS AND METHODS: We reviewed national Medicare Part B Physician/Supplier Procedure Summary master files from 2005 to 2015, to determine the annual utilization rate of screening mammography on the basis of procedure codes used for film-screen and digital screening mammography. We also used the Physician/Supplier Procedure Summary master files to determine the volume of screening and diagnostic DBT studies performed in 2015. RESULTS: The utilization rate of screening mammography per 1000 women in the Medicare fee-for-service population increased gradually every year, from 311.5 examinations in 2005 to a peak of 322.9 examinations in 2009, representing a compound annual growth rate of 0.9%. In 2010, the utilization rate abruptly decreased by 4.3% to 309.2 examinations, and it has not since recovered to pre-2010 levels. In 2015, 18.9% of screening and 16.2% of diagnostic digital mammography examinations included DBT as an add-on procedure. CONCLUSION: In contrast to the annual increase in screening mammography utilization from 2005 to 2009, an abrupt sustained decline in screening occurred beginning in 2010, coinciding with the release of U.S. Preventive Services Task Force recommendations. DBT utilization was somewhat limited in 2015, occurring in conjunction with less than 20% of digital mammography examinations.

Troponin I Mutations R146G and R21C Alter Cardiac Troponin Function, Contractile Properties, and Modulation by Protein Kinase A (PKA)-mediated Phosphorylation.

Two hypertrophic cardiomyopathy-associated cardiac troponin I (cTnI) mutations, R146G and R21C, are located in different regions of cTnI, the inhibitory peptide and the cardiac-specific N terminus. We recently reported that these regions may interact when Ser-23/Ser-24 are phosphorylated, weakening the interaction of cTnI with cardiac TnC. Little is known about how these mutations influence the affinity of cardiac TnC for cTnI (KC-I) or contractile kinetics during ß-adrenergic stimulation. Here, we tested how cTnI(R146G) or cTnI(R21C) influences contractile activation and relaxation and their response to protein kinase A (PKA). Both mutations significantly increased Ca(2+) binding affinity to cTn (KCa) and KC-I. PKA phosphorylation resulted in a similar reduction of KCa for all complexes, but KC-I was reduced only with cTnI(WT). cTnI(WT), cTnI(R146G), and cTnI(R21C) were complexed into cardiac troponin and exchanged into rat ventricular myofibrils, and contraction/relaxation kinetics were measured ± PKA phosphorylation. Maximal tension (Tmax) was maintained for cTnI(R146G)- and cTnI(R21C)-exchanged myofibrils, and Ca(2+) sensitivity of tension (pCa50) was increased. PKA phosphorylation decreased pCa50 for cTnI(WT)-exchanged myofibrils but not for either mutation. PKA phosphorylation accelerated the early slow phase relaxation for cTnI(WT) myofibrils, especially at Ca(2+) levels that the heart operates in vivo. Importantly, this effect was blunted for cTnI(R146G)- and cTnI(R21C)-exchanged myofibrils. Molecular dynamics simulations suggest both mutations inhibit formation of intra-subunit contacts between the N terminus and the inhibitory peptide of cTnI that is normally seen with WT-cTn upon PKA phosphorylation. Together, our results suggest that cTnI(R146G) and cTnI(R21C) blunt PKA modulation of activation and relaxation kinetics by prohibiting cardiac-specific N-terminal interaction with the cTnI inhibitory peptide.

Hydroxychloroquine-related retinal toxicity.

HCQ is widely used for the treatment of rheumatic diseases, particularly lupus and RA. It is generally well tolerated, but retinopathy is a concern. Retinopathy is rare, but is sight threatening, generally irreversible and may progress even after cessation of therapy. Damage may be subclinical. Although a number of risk factors have been proposed (such as duration of therapy and cumulative dose), the many exceptions (e.g. retinopathy on low-dose HCQ, or no retinopathy after a very large cumulative dose of HCQ) highlight our limited understanding of the disease process. Novel technologies such as optical coherence tomography (OCT), fundus autofluorescence (FAF) and multifocal electroretinogram (mfERG) may provide the earliest structural and functional evidence of toxicity in these stages. Along with the well-established technique of central visual field testing (10-2 visual fields), these modalities are increasingly being used as part of screening programmes. The ideal single test with high sensitivity and high specificity for HCQ retinopathy has still not been achieved. Screening for HCQ retinopathy remains an area of considerable debate, including issues of when, who and how to screen. Commonly accepted risk factors include receiving >6.5 mg/kg/day or a cumulative dose of >1000 g of HCQ, being on treatment for >5 years, having renal or liver dysfunction, having pre-existing retinopathy and being elderly. HCQ continues to be a valuable drug in treating rheumatic disease, but clinicians need to be aware of the associated risks and to have arrangements in place that would enable early detection of toxicity.

Provider Distribution Changes in Dual-Energy X-Ray Absorptiometry in the Medicare Population Over the Past Decade.

Both radiologists as well as nonimaging physicians perform dual-energy X-ray absorptiometry (DXA) imaging in the United States. This study aims to compare provider distribution between these physician groups on the Medicare population, which is the predominant age group of patients evaluated by this imaging procedure. Using the 2 relevant Current Procedural Terminology, Fourth Edition codes for DXA scans, source data were obtained from the CMS Physician Supplier Procedure Summary Master Files from 2003 through 2013. DXA scan procedure volumes for radiologists and nonradiologists on Medicare patients were tabulated. Utilization rates were calculated. From 2003 to 2013, the total number of DXA scans performed on Medicare patients decreased by 2%. However, over the same period, the number of scans performed by radiologists had increased by 25% over nonimaging specialists, whose utilization had declined by approximately the same amount. From 2003 to 2013, the rate of utilization of DXA scans in the Medicare fee-for-service population declined somewhat. However, radiologists continue to gain market share from other specialists and now predominate in this type of imaging by a substantial margin.