Multimorbidity in Psoriasis as a Risk Factor for Psoriatic Arthritis: A Population-Based Study.

OBJECTIVES: To examine multimorbidity in psoriasis and its association with the development of PsA. METHODS: A retrospective cohort study was performed using the Rochester Epidemiology Project. Population-based incidence (2000-2009) and prevalence (Jan 1, 2010) cohorts of psoriasis were identified by manual chart review. A cohort of individuals without psoriasis (comparators) were identified (1:1 matched on age, sex, and county). Morbidities were defined using ≥2 Clinical Classification Software codes ≥30 days apart within prior five years. PsA was defined using ClASsification of Psoriatic ARthritis (CASPAR) criteria. χ2 and rank-sum tests were used to compare morbidities, and age-, sex-, and race-adjusted Cox models to examine the association of baseline morbidities in psoriasis with development of PsA. RESULTS: Among 817 incident psoriasis patients, the mean age was 45.2 years with 52.0% females, and 82.0% moderate/severe psoriasis. No multimorbidity differences were found between incident psoriasis patients and comparators. However, in the 1,088 prevalent psoriasis patients, multimorbidity was significantly more common compared with 1,086 comparators (OR : 1.35 and OR : 1.48 for ≥2 and ≥5 morbidities, respectively). Over a median 13.3-year follow-up, 23 patients (cumulative incidence: 2.9% by 15 years) developed PsA. Multimorbidity (≥2 morbidities) was associated with a 3-fold higher risk of developing PsA. CONCLUSION: Multimorbidity was more common in the prevalent but not incident cohort of psoriasis compared with the general population, suggesting patients with psoriasis may experience accelerated development of multimorbidity. Moreover, multimorbidity at psoriasis onset significantly increased the risk of developing PsA, highlighting the importance of monitoring multimorbid psoriasis patients for the development of PsA.

Multimorbidity in systemic lupus erythematosus in a population-based cohort: the lupus Midwest network.

OBJECTIVES: To assess the prevalence and incidence of multimorbidity and the association with the SLICC/ACR damage index (SDI) among patients with systemic lupus erythematosus (SLE). METHODS: Using prevalent and incident population-based cohorts of patients with SLE and their matched comparators, we assessed 57 chronic conditions. Chronic conditions were categorized as SDI-related or SDI-unrelated. Multimorbidity was defined as the presence of 2+ chronic conditions. Multimorbidity at prevalence and incidence/index was compared between cohorts using logistic regression. Cox models were used to examine development of multimorbidity after SLE incidence. RESULTS: The prevalent cohort included 449 patients with established SLE on January 1, 2015. They were three times more likely to have multimorbidity compared with non-SLE comparators (OR 2.98, 95% CI 2.18-4.11). The incident cohort included 270 patients with new-onset SLE. At SLE incidence, patients with SLE were more likely to have multimorbidity than comparators (OR 2.27, 95% CI 1.59-3.27). After incidence, the risk of developing multimorbidity was 2-fold higher among patients with SLE than comparators (hazard ratio (HR) 2.11, 95% CI 1.59-2.80). Development of multimorbidity was higher in patients with SLE based on SDI-related (HR 2.91, 95% CI 2.17-3.88) and SDI-unrelated conditions (HR 1.73, 95% CI, 1.32-2.26). CONCLUSION: Patients with SLE have a higher burden of multimorbidity, even before the onset of the disease. The risk disparity continues after SLE classification and is also seen in a prevalent SLE cohort. Multimorbidity is driven both by SDI-related and unrelated conditions.

Lower Frequency of Comorbidities Prior to Onset of Giant Cell Arteritis: A Population-Based Study.

OBJECTIVE: To assess the frequency of comorbidities and metabolic risk factors at and prior to giant cell arteritis (GCA) diagnosis. METHODS: This is a retrospective case control study of patients with incident GCA between January 1, 2000, and December 31, 2019, in Olmsted County, Minnesota. Two age- and sex-matched controls were identified, and each assigned an index date corresponding to an incidence date of GCA. Medical records were manually abstracted for comorbidities and laboratory data at incidence date, 5 years, and 10 years prior to incidence date. Twenty-five chronic conditions using International Classification of Diseases, 9th revision, diagnosis codes were also studied at incidence date and 5 years prior to incidence date. RESULTS: One hundred and twenty-nine patients with GCA (74% female) and 253 controls were identified. At incidence date, the prevalence of diabetes mellitus (DM) was lower among patients with GCA (5% vs 17%; P = 0.001). At 5 years prior to incidence date, patients were less likely to have DM (2% vs 13%; P < 0.001) and hypertension (27% vs 45%; P = 0.002) and had a lower mean number (SD) of comorbidities (0.7 [1.0] vs 1.3 [1.4]; P < 0.001) compared to controls. Moreover, patients had significantly lower median fasting blood glucose (FBG; 96 mg/dL vs 104 mg/dL; P < 0.001) and BMI (25.8 vs 27.7; P = 0.02) compared to controls. Multivariable logistic regression analysis revealed negative associations for FBG with GCA at 5 and 10 years prior to diagnosis/index date. CONCLUSION: DM prevalence and median FBG and BMI were lower in patients with GCA up to 5 years prior to diagnosis, suggesting that metabolic factors influence the risk of GCA.

Evaluation of hearing loss in young adults after exposure to 3.0T MRI with standard hearing protection.

Standard clinical protocols require hearing protection during magnetic resonance imaging (MRI) for patient safety. This investigation prospectively evaluated the auditory function impact of acoustic noise exposure during a 3.0T MRI in healthy adults. Twenty-nine participants with normal hearing underwent a comprehensive audiologic assessment before and immediately following a clinically indicated head MRI. Appropriate hearing protection with earplugs (and pads) was used per standard of practice. To characterize noise hazards, current sound monitoring tools were used to measure levels of pulse sequences measured. A third audiologic test was performed if a significant threshold shift (STS) was identified at the second test, within 30 days post MRI. Some sequences produced high levels (up to 114.5 dBA; 129 dB peak SPL) that required hearing protection but did not exceed 100% daily noise dose. One participant exhibited an STS in the frequency region most highly associated with noise-induced hearing loss. No participants experienced OSHA-defined STS in either ear. Overall, OAE measures did not show evidence of changes in cochlear function after MRI. In conclusion, hearing threshold shifts associated with hearing loss or OAE level shifts reflecting underlying cochlear damage were not detected in any of the 3.0T MRI study participants who used the current recommended hearing protection.

Comparison of non-contrast vessel wall imaging and 3-D time-of-flight MRA for atherosclerotic stenosis and plaque characterization within intracranial arteries.

PURPOSE: We compared the ability of intracranial high-resolution vessel wall imaging (VWI) without gadolinium and 3-D time-of-flight (3D-TOF) MRA techniques to characterize intracranial arterial stenosis and arterial wall plaque consistent with atherosclerotic plaque. METHODS: Consecutive intracranial VWI examinations performed within 2 months of a 3D-TOF exam with at least 1 noted plaque was included. Examinations assessed 17 vessel segments for plaque and diameters of stenotic and normal segments using double oblique reformatted images. Results were compared with the VWI and 3D-TOF exams considered the reference standard for plaque and luminal stenosis, respectively. RESULTS: Assessed segments totaled 286 from 17 patients. Proximal segment sensitivity and specificity for luminal stenosis detection with VWI was 92.5% and 82.1%, respectively, whereas for assessing plaque with 3D-TOF it was 59.4% and 98.3%, respectively. The mean intra-rater difference in luminal diameter measurements between VWI and 3D-TOF at normal segments and at the area of maximal stenosis was 0.02mm (SD 0.51mm) and 0.08mm (SD 0.66mm), respectively. CONCLUSIONS: Intracranial VWI demonstrated reasonably high sensitivity and specificity for luminal stenosis assessment using 3D-TOF as a reference standard, while 3D-TOF demonstrated low sensitivity for plaque detection. Our results suggest that VWI can be used for simultaneous assessment of luminal stenosis and plaque in the intracranial arteries.

Procedure-Related Pain During Image-Guided Percutaneous Biopsies: A Retrospective Study of Prevalence and Predictive Factors.

OBJECTIVE. The purpose of this study was to evaluate the prevalence and severity of pain reported during image-guided percutaneous biopsies and to identify factors associated with increased reported pain. MATERIALS AND METHODS. In this retrospective study, a database of adult patients who underwent CT- or ultrasound-guided percutaneous core needle biopsy between July 22, 2013, and February 1, 2018, was reviewed. Data collected included patient age and sex, biopsy site, biopsy type (lesion or parenchymal), needle gauge, number of passes, use of sedation, and whether it was the patient's first recorded biopsy. The maximum procedure-related pain reported on a 0-10 numeric rating scale was recorded. Multivariable logistic regression with generalized estimating equations was used to assess the association between covariates and patient-reported pain. RESULTS. A total of 13,344 biopsy procedures were performed in 10,474 patients. Patients reported no pain (0 of 10 scale) during 9765 (73.2%) procedures. Female sex, younger age at biopsy, undergoing IV sedation, and larger needle diameter were all associated with increases in patient-reported pain. Biopsies of renal allografts were the least likely to be painful, followed by hepatic allografts. CONCLUSION. Patients typically report mild or no pain from image-guided biopsy performed by radiologists. Younger patients and women report greater pain. This information can assist preprocedural counseling and reassurance of patients and may help them predict procedure-related patient needs.

Frequency of Bleeding Complications After Percutaneous Core Needle Biopsy and the Association With Aspirin Usage and Length of Aspirin Discontinuation.

OBJECTIVE. The purpose of this study is to report the frequency of major bleeding after percutaneous image-guided core biopsy and its association with aspirin usage and duration of prebiopsy aspirin abstinence. MATERIALS AND METHODS. A retrospective review of percutaneous image-guided core biopsies performed at our institution between September 1, 2005, and September 1, 2016, was performed (n = 30,966). Patients were excluded if aspirin usage data were missing (n = 633). Bleeding complications were defined using the Common Terminology Criteria for Adverse Events and were considered significant if they were grade 3 or higher. Multivariate models were adjusted for age, sex, platelet count, international normalized ratio, and biopsy target. Three categorizations of aspirin use were examined: any use within 10 days before biopsy, duration of abstinence (> 10 days or no aspirin, 8-10 days, 4-7 days, and 0-3 days before biopsy), and use on the day of biopsy. Associations with bleeding complications were modeled using logistic regression models. A p < 0.05 was considered significant. RESULTS. The study included 30,333 biopsies in 21,938 subjects (57% male; median age, 60 years; interquartile range, 49-70 years). Of the biopsies, 7921 (26.1%) were performed in patients who received aspirin within 10 days of biopsy, and 3761 (47.5%) of those biopsies were performed in patients who took aspirin within 3 days. Ninety-eight (0.32%) significant bleeding complications occurred overall, including 34 (0.43%) in patients who used aspirin within 10 days before biopsy (odds ratio, 1.5; 95% CI, 0.96-2.3; p = 0.08). Duration of abstinence was associated with a significantly increased bleeding risk only between 0-3 days versus more than 10 days or no aspirin (odds ratio, 2.1; 95% CI, 1.3-3.6; p = 0.004). Aspirin use on the day of biopsy showed the greatest increase in risk (1.9%; odds ratio, 6.6; 95% CI, 3.8-11.5; p < 0.001). CONCLUSION. Significant bleeding complications after biopsy remain rare even among patients with recent aspirin usage, although shorter duration of prebiopsy abstinence increases bleeding risk, most significantly if aspirin is taken the day of biopsy.

Early Intravascular Events Are Associated with Development of Acute Respiratory Distress Syndrome. A Substudy of the LIPS-A Clinical Trial.

RATIONALE: Acute respiratory distress syndrome (ARDS) is a devastating illness with limited therapeutic options. A better understanding of early biochemical and immunological events in ARDS could inform the development of new preventive and treatment strategies. OBJECTIVES: To determine select peripheral blood lipid mediator and leukocyte responses in patients at risk for ARDS. METHODS: Patients at risk for ARDS were randomized as part of a multicenter, double-blind clinical trial of aspirin versus placebo (the LIPS-A [Lung Injury Prevention Study with Aspirin] trial; NCT01504867). Plasma thromboxane B2 (TXB2), aspirin-triggered lipoxin A4 (15-epi-LXA4, ATL), and peripheral blood leukocyte number and activation were determined on enrollment and after treatment with either aspirin or placebo. MEASUREMENTS AND MAIN RESULTS: Thirty-three of 367 subjects (9.0%) developed ARDS after randomization. Baseline ATL levels, total monocyte counts, intermediate monocyte counts, and monocyte-platelet aggregates were associated with the development of ARDS. Peripheral blood neutrophil count and monocyte-platelet aggregates significantly decreased over time. Of note, nine subjects developed ARDS after randomization yet before study drug initiation, including seven subjects assigned to aspirin treatment. Subjects without ARDS at the time of first dose demonstrated a lower incidence of ARDS with aspirin treatment. Compared with placebo, aspirin significantly decreased TXB2 and increased the ATL/TXB2 ratio. CONCLUSIONS: Biomarkers of intravascular monocyte activation in at-risk patients were associated with development of ARDS. The potential clinical benefit of early aspirin for prevention of ARDS remains uncertain. Together, results of the biochemical and immunological analyses provide a window into the early pathogenesis of human ARDS and represent potential vascular biomarkers of ARDS risk. Clinical trial registered with www.clinicaltrials.gov (NCT01504867).

Accumulation of Gadolinium in Human Cerebrospinal Fluid after Gadobutrol-enhanced MR Imaging: A Prospective Observational Cohort Study.

Purpose To determine whether gadolinium accumulates within cerebrospinal fluid (CSF) in patients recently exposed to the macrocyclic agent gadobutrol and identify factors that may affect this accumulation. Materials and Methods In this prospective observational cohort study, gadolinium was quantified by using inductively coupled plasma mass spectrometry of CSF samples from patients who underwent gadobutrol-enhanced magnetic resonance (MR) imaging followed by lumbar puncture within 30 days (gadobutrol group) or patients who underwent lumbar puncture without history of gadolinium-enhanced MR imaging (control group). CSF total protein level of 35 mg/dL or lower was used as a surrogate marker of an intact blood-brain barrier (BBB). Associations between gadolinium CSF concentration and patient characteristics were examined by using log (e)-linear regression models. Results A total of 82 patients (68 in gadobutrol group, 14 in control group; 42 male and 40 female patients; median age, 47 years [interquartile range, 25-65 years]) were included in this study. Gadolinium was detected in the CSF of all 68 patients in the gadobutrol group (100% [95% confidence interval: 94.7, 100]; range, 0.2-1494 ng/mL). CSF total protein level higher than 35 mg/dL and patient age of at least 18 years were associated with higher gadolinium concentrations (estimate: 1.1, with standard error [SE] of 0.26 [P < .001] and 0.91, with SE of 0.37 [P = .02], respectively). Conclusion Intravenous administration of the macrocyclic agent gadobutrol results in gadolinium accumulation within the CSF, even in the setting of normal renal function and no BBB dysfunction.

Influence of Injection Volume on Rate of Subsequent Intervention in Carpal Tunnel Syndrome Over 1-Year Follow-Up.

PURPOSE: The optimal volume and dose of corticosteroid injections for treatment of carpal tunnel syndrome (CTS) have not yet been established. It is unknown whether the volume of injectate influences the outcome of carpal tunnel injection. The purpose of this study was to assess whether there is an association between the volume of injectate and subsequent intervention in the treatment of CTS. METHODS: This study evaluated residents of Olmsted County, MN, who were treated with a corticosteroid injection for CTS between 2001 and 2010. Failure of treatment was the primary outcome, defined as a subsequent intervention: either a second injection or carpal tunnel release within 1 year of initial injection. General estimating equations logistic regression was used to assess the association between injectate volume and rate of treatment failure, adjusting for age, sex, effective dose of steroid, type of steroid injected, electrodiagnostic severity, and the presence of comorbidities such as rheumatoid arthritis, diabetes mellitus, peripheral neuropathy, and radiculopathy. RESULTS: There were 856 affected hands in 651 patients. A total of 56% (n = 484) of treated hands received subsequent treatment within 1 year. Multivariable analysis showed that a larger injectate volume was significantly associated with reduced rate of treatment failure within 1 year. Rheumatoid arthritis and ultrasound-guided procedures were also associated with a reduced rate of treatment failure, whereas severe electrodiagnostic results were associated with an increased rate of failure. CONCLUSIONS: This study showed that a larger volume of corticosteroid injection is associated with reduced odds of subsequent intervention after a single corticosteroid injection in CTS. Further research is needed to determine the optimal volume for steroid injections in the treatment of CTS. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Effects of Aspirin Therapy on Ultrasound-Guided Renal Allograft Biopsy Bleeding Complications.

PURPOSE: To determine if patient aspirin exposure and timing affect bleeding risk after renal allograft biopsy. MATERIALS AND METHODS: Review of 6,700 renal allograft biopsies (in 2,362 unique patients) was performed. Median patient age was 53.0 years [interquartile range 43.0, 62.0]; 56.2% of patients were male. Of biopsies, 4,706 (70.2%) were performed in patients with no aspirin exposure within 10 days of biopsy; 664 (9.9%), were performed within 8-10 days of aspirin exposure; 855 (12.8%), within 4-7 days; and 475 (7.1%), within 0-3 days. Follow-up to 3 months after the procedure was completed in all patients. Biopsies were categorized as protocol or indication; 19.7% were indication biopsies. Bleeding complications were graded based on SIR criteria. Logistic regression models examined the association between aspirin use and bleeding events. RESULTS: Rate [95% confidence interval] of major bleeding complications was 0.24% [0.14, 0.39], and rate of any bleeding complication was 0.66% [0.46, 0.90]. Bleeding events were significantly associated with patients undergoing indication biopsies compared with protocol biopsies (odds ratio [OR] 2.27, P = .012). Patient factors associated with major bleeding complications in multivariate models included estimated glomerular filtration rate (OR 0.61, P = .016) and platelet count (OR 0.64, P = .033). Aspirin use was not significantly associated with increased risk of bleeding complication except for use of 325 mg of aspirin within 3 days of biopsy (any complication OR 3.87 [1.12, 13.4], P = .032; major complication OR 6.30 [1.27, 31.3], P = .024). CONCLUSIONS: Renal allograft biopsy bleeding complications are very rare, particularly for protocol biopsies. Use of 325 mg of aspirin within 3 days of renal allograft biopsy was associated with increased bleeding complications.

AKI after Transcatheter or Surgical Aortic Valve Replacement.

Transcatheter aortic valve replacement (TAVR) is an alternative to surgical aortic valve replacement (SAVR) for patients with symptomatic severe aortic stenosis who are at high risk of perioperative mortality. Previous studies showed increased risk of postoperative AKI with TAVR, but it is unclear whether differences in patient risk profiles confounded the results. To conduct a propensity-matched study, we identified all adult patients undergoing isolated aortic valve replacement for aortic stenosis at Mayo Clinic Hospital in Rochester, Minnesota from January 1, 2008 to June 30, 2014. Using propensity score matching on the basis of clinical characteristics and preoperative variables, we compared the postoperative incidence of AKI, defined by Kidney Disease Improving Global Outcomes guidelines, and major adverse kidney events in patients treated with TAVR with that in patients treated with SAVR. Major adverse kidney events were the composite of in-hospital mortality, use of RRT, and persistent elevated serum creatinine ≥200% from baseline at hospital discharge. Of 1563 eligible patients, 195 matched pairs (390 patients) were created. In the matched cohort, baseline characteristics, including Society of Thoracic Surgeons risk score and eGFR, were comparable between the two groups. Furthermore, no significant differences existed between the TAVR and SAVR groups in postoperative AKI (24.1% versus 29.7%; P=0.21), major adverse kidney events (2.1% versus 1.5%; P=0.70), or mortality >6 months after surgery (6.0% versus 8.3%; P=0.51). Thus, TAVR did not affect postoperative AKI risk. Because it is less invasive than SAVR, TAVR may be preferred in high-risk individuals.

First PET Imaging Studies With 63Zn-Zinc Citrate in Healthy Human Participants and Patients With Alzheimer Disease.

Abnormalities in zinc homeostasis are indicated in many human diseases, including Alzheimer disease (AD). 63Zn-zinc citrate was developed as a positron emission tomography (PET) imaging probe of zinc transport and used in a first-in-human study in 6 healthy elderly individuals and 6 patients with clinically confirmed AD. Dynamic PET imaging of the brain was performed for 30 minutes following intravenous administration of 63Zn-zinc citrate (∼330 MBq). Subsequently, body PET images were acquired. Urine and venous blood were analyzed to give information on urinary excretion and pharmacokinetics. Regional cerebral 63Zn clearances were compared with 11C-Pittsburgh Compound B (11C-PiB) and 18F-fluorodeoxyglucose (18F-FDG) imaging data. 63Zn-zinc citrate was well tolerated in human participants with no adverse events monitored. Tissues of highest uptake were liver, pancreas, and kidney, with moderate uptake being seen in intestines, prostate (in males), thyroid, spleen, stomach, pituitary, and salivary glands. Moderate brain uptake was observed, and regional dependencies were observed in 63Zn clearance kinetics in relationship with regions of high amyloid-ß plaque burden (11C-PiB) and 18F-FDG hypometabolism. In conclusion, zinc transport was successfully imaged in human participants using the PET probe 63Zn-zinc citrate. Primary sites of uptake in the digestive system accent the role of zinc in gastrointestinal function. Preliminary information on zinc kinetics in patients with AD evidenced regional differences in clearance rates in correspondence with regional amyloid-ß pathology, warranting further imaging studies of zinc homeostasis in patients with AD.

An efficient algorithm to explore liquid association on a genome-wide scale.

BACKGROUND: The growing wealth of public available gene expression data has made the systemic studies of how genes interact in a cell become more feasible. Liquid association (LA) describes the extent to which coexpression of two genes may vary based on the expression level of a third gene (the controller gene). However, genome-wide application has been difficult and resource-intensive. We propose a new screening algorithm for more efficient processing of LA estimation on a genome-wide scale and apply its use to a Saccharomyces cerevisiae data set. RESULTS: On a test subset of the data, the fast screening algorithm achieved >99.8% agreement with the exhaustive search of LA values, while reduced run time by 81-93 %. Using a well-known yeast cell-cycle data set with 6,178 genes, we identified triplet combinations with significantly large LA values. In an exploratory gene set enrichment analysis, the top terms for the controller genes in these triplets with large LA values are involved in some of the most fundamental processes in yeast such as energy regulation, transportation, and sporulation. CONCLUSION: In summary, in this paper we propose a novel, efficient algorithm to explore LA on a genome-wide scale and identified triplets of interest in cell cycle pathways using the proposed method in a yeast data set. A software package named fastLiquidAssociation for implementing the algorithm is available through http://www.bioconductor.org .

Sex Differences in Aging-related Myocardial Stiffening Quantitatively Measured with MR Elastography.

Purpose To investigate the feasibility of using quantitative MR elastography (MRE) to characterize the influence of aging and sex on left ventricular (LV) shear stiffness. Materials and Methods In this prospective study, LV myocardial shear stiffness was measured in 109 healthy volunteers (age range: 18-84 years; mean age, 40 years ± 18 [SD]; 57 women, 52 men) enrolled between November 2018 and September 2019, using a 5-minute MRE acquisition added to a clinical MRI protocol. Linear regression models were used to estimate the association of cardiac MRI and MRE characteristics with age and sex; models were also fit to assess potential age-sex interaction. Results Myocardial shear stiffness significantly increased with age in female (age slope = 0.03 kPa/year ± 0.01, P = .009) but not male (age slope = 0.008 kPa/year ± 0.009, P = .38) volunteers. LV ejection fraction (LVEF) increased significantly with age in female volunteers (0.23% ± 0.08 per year, P = .005). LV end-systolic volume (LVESV) decreased with age in female volunteers (-0.20 mL/m2 ± 0.07, P = .003). MRI parameters, including T1, strain, and LV mass, did not demonstrate this interaction (P > .05). Myocardial shear stiffness was not significantly correlated with LVEF, LV stroke volume, body mass index, or any MRI strain metrics (P > .05) but showed significant correlations with LV end-diastolic volume/body surface area (BSA) (slope = -3 kPa/mL/m2 ± 1, P = .004, r2 = 0.08) and LVESV/BSA (-1.6 kPa/mL/m2 ± 0.5, P = .003, r2 = 0.08). Conclusion This study demonstrates that female, but not male, individuals experience disproportionate LV stiffening with natural aging, and these changes can be noninvasively measured with MRE. Keywords: Cardiac, Elastography, Biological Effects, Experimental Investigations, Sexual Dimorphisms, MR Elastography, Myocardial Shear Stiffness, Quantitative Stiffness Imaging, Aging Heart, Myocardial Biomechanics, Cardiac MRE Supplemental material is available for this article. Published under a CC BY 4.0 license.

Using Unsupervised Machine Learning Methods to Cluster Comorbidities in a Population-Based Cohort of Patients With Rheumatoid Arthritis.

OBJECTIVE: To identify clusters of comorbidities in patients with rheumatoid arthritis (RA) using 4 methods and to compare to patients without RA. METHODS: In this retrospective, population-based study, residents of 8 Minnesota counties with prevalent RA as of January 1, 2015 were identified. Age-, sex-, and county-matched non-RA comparators were selected from the same underlying population. Diagnostic codes were retrieved for 5 years before January 1, 2015. Using 2 codes ≥30 days apart, 44 previously defined morbidities and 11 nonoverlapping chronic disease categories based on Clinical Classifications Software were defined. Unsupervised machine learning methods of interest included hierarchical clustering, factor analysis, K-means clustering, and network analysis. RESULTS: Two groups of 1,643 patients with and without RA (72% female; mean age 63.1 years in both groups) were studied. Clustering of comorbidities revealed strong associations among mental/behavioral comorbidities and among cardiovascular risk factors and diseases. The clusters were associated with age and sex. Differences between the 4 clustering methods were driven by comorbidities that are rare and those that were weakly associated with other comorbidities. Common comorbidities tended to group together consistently across approaches. The instability of clusters when using different random seeds or bootstrap sampling impugns the usefulness and reliability of these methods. Clusters of common comorbidities between RA and non-RA cohorts were similar. CONCLUSION: Despite the higher comorbidity burden in patients with RA compared to the general population, clustering comorbidities did not identify substantial differences in comorbidity patterns between the RA and non-RA cohorts. The instability of clustering methods suggests caution when interpreting clustering using 1 method.

Clinical and Imaging Outcomes of Surgically Repaired Cerebrospinal Fluid-Venous Fistulas Identified by Lateral Decubitus Digital Subtraction Myelography.

OBJECTIVE: To describe clinical and radiographic outcomes of surgical repair of cerebrospinal fluid-venous fistula (CVF), an increasingly recognized cause of spontaneous intracranial hypotension that is poorly responsive to epidural blood patch (EBP). METHODS: Retrospective review identified adult patients who had lateral decubitus digital subtraction myelography indicative of cerebrospinal fluid leak at Mayo Clinic between November 2018 and February 2020, with clearly localized CVF, followed by surgical treatment. Patients without available imaging before or after surgery were excluded. History of EBP and clinical response to EBP were evaluated along with surgical outcomes. RESULTS: Of 25 patients with CVF who met protocol criteria and were included in the data analysis, 22 (88%) received EBP, but clinical benefit lasting ≥4 weeks occurred in only 2 of 22 (9%). Headache was the most prominent preoperative feature among patients (24/25; 96%). Following surgery, 18 of 24 (75%) patients had complete headache improvement, 4 (17%) had partial improvement, and 2 (8%) had no improvement. Ten of 25 (40%) patients reported cognitive disturbance at baseline; at follow-up, 5 of 10 (50%) had complete improvement, 3 (30%) had partial improvement, and 2 (20%) had no improvement. On postoperative brain magnetic resonance imaging, 6 of 25 (24%) patients had complete resolution of findings by Bern score criteria, 18 (72%) showed partial improvement, and 1 (4%) patient showed no improvement. Adverse events were minor and included surgical site pain and paresthesias. CONCLUSIONS: Surgical repair of CVF resulted in improvements in headache and other symptoms, with few side effects.

COVID-19 Vaccine Uptake Among Patients With Systemic Lupus Erythematosus in the American Midwest: The Lupus Midwest Network (LUMEN).

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) are at higher risk of poor outcomes from coronavirus disease 2019 (COVID-19). The vaccination rate among such patients is unknown. We aimed to assess COVID-19 vaccine uptake among patients with SLE. METHODS: We included 342 patients with SLE from the Lupus Midwest Network (LUMEN) and 350 age-, sex-, race-, and county-matched comparators. Vaccination uptake for influenza, pneumococcal, and zoster vaccines before pandemic restrictions began (up to February 29, 2020) was assessed. First-dose COVID-19 vaccine uptake was electronically retrieved and manually ascertained (December 15, 2020, to July 31, 2021). Time to COVID-19 vaccination, demographics, SLE manifestations, medications, Charlson Comorbidity Index, Area Deprivation Index, and Rural-Urban Commuting Area codes were compared. RESULTS: On July 31, 2021, 83.3% of patients with SLE and 85.5% of comparators were vaccinated against COVID-19. The COVID-19 vaccination rates were similar among SLE and comparators (hazard ratio 0.93, 95% CI 0.79-1.10). Unvaccinated patients with SLE were more likely than vaccinated patients to be men (27.3% vs 14.1%), younger (mean age 54.1 vs 58.8 yrs), have a shorter SLE duration (median 7.3 vs 10.7 yrs), and be less frequently vaccinated with influenza and pneumococcal vaccines. CONCLUSION: Patients with SLE in the Lupus Midwest Network had similar COVID-19 vaccination uptake as matched comparators, most of whom were vaccinated early when the vaccine became available. One in 6 patients with SLE remain unvaccinated.

Comprehensive assessment of multimorbidity burden in a population-based cohort of patients with rheumatoid arthritis.

OBJECTIVE: To comprehensively assess multimorbidity burden in patients with rheumatoid arthritis (RA) in order to unify the multimorbidity definition for RA research and clinical practice. METHODS: In this population-based study, residents of eight Minnesota counties with prevalent RA on 1 January 2015 were identified. Age, sex and county-matched non-RA comparators were selected from the same population. Diagnostic codes were retrieved for 5 years before 1 January 2015. Using two codes ≥30 days apart, 44 previously defined morbidities and 78 non-overlapping chronic disease categories based on Clinical Classification Software were defined. Prevalence of each morbidity in the RA versus non-RA cohorts was compared using false discovery rate to adjust for multiple comparisons. Morbidities more common in RA than non-RA and those with prevalence ≥5% were retained. RESULTS: 1643 patients with RA and 1643 non-RA subjects (72% women; mean age 63.1 years) were studied. Using the 44 morbidities, multimorbidity (defined as 2+ morbidities) was present in 1411 (86%) of RA and 1164 (71%) of non-RA subjects (p<0.001) with 5+ morbidities present in 907 (55%) of RA and 619 (38%) of non-RA (p<0.001). Patients with RA had significantly higher prevalence of 24 of the 44 morbidities compared with non-RA, especially interstitial lung disease, fibromyalgia, osteoarthritis and osteoporosis. Among the additional 78 categories, 7 were significantly higher in RA than non-RA, including organic sleep disorders, vitamin D deficiency and foot ulcers. CONCLUSION: Patients with RA have a higher prevalence of multimorbidity compared with non-RA subjects. These results confirm the list of 44 morbidities and add several other morbidities of interest in RA.

Utilization of preventive services in a systemic lupus erythematosus population-based cohort: a Lupus Midwest Network (LUMEN) study.

BACKGROUND: Systemic lupus erythematosus (SLE) is a disease that can lead to damage of multiple organs and, along with certain treatments, increase the risk of developing cancer, cardiovascular disease, diabetes, osteoporosis, and infections. Preventive services are particularly important in patients with SLE to mitigate the aforementioned risks. We aimed to evaluate the trends of preventive services utilization in patients with systemic lupus erythematosus, compared with non-SLE population. METHODS: All ≥19-year-old patients in the Lupus Midwest Network (LUMEN) registry, a population-based cohort, with SLE on January 1, 2015, were included and matched (1:1) by sex, age, race, and county to non-SLE comparators. Among both groups, we compared the rates of screenings for breast and cervical cancer, hypertension, hyperlipidemia, diabetes mellitus, and osteoporosis as well as immunizations. RESULTS: We included 440 SLE patients and 430 non-SLE comparators. The probability of breast cancer screening among women with SLE was similar to comparators (hazard ratio [HR] 1.09, 95% CI 0.85-1.39), while cervical cancer screening was lower (HR 0.75, 95% CI 0.58-0.96). Hypertension screening was higher among patients with SLE (HR 1.35, 95% CI 1.13-1.62); however, hyperlipidemia screening was similar to comparators (HR 1.16, 95% CI 0.96-1.41). Diabetes and osteoporosis screenings were more likely to be performed for SLE patients than for comparators (HR 2.46, 95% CI 2.11-2.87; and HR 3.19, 95% CI 2.31-4.41; respectively). Influenza and pneumococcal immunizations were higher among SLE patients (HR 1.31, 95% CI 1.12-1.54; and HR 2.06, 95% CI 1.38-3.09; respectively), while zoster vaccination was similar (HR 1.17, 95% CI 0.81-1.69). CONCLUSIONS: The trends of utilization of preventive services by SLE patients vary according to screening or vaccine compared with the general population. Considering these differences, we demonstrate an opportunity for improvement, particularly in cervical cancer, hyperlipidemia, and osteoporosis screenings and vaccinations.