Health care utilization and costs of systemic lupus erythematosus in the United States: A systematic review.

OBJECTIVES: To evaluate health care utilization and costs for patients with systemic lupus erythematosus (SLE) by disease severity. METHODS: We searched PubMed and Embase from January 2000 to June 2020 for observational studies examining health care utilization and costs associated with SLE among adults in the United States. Two independent reviewers reviewed the selected full-text articles to determine the final set of included studies. Costs were converted to 2020 US $. RESULTS: We screened 9224 articles, of which 51 were included. Mean emergency department visits were 0.3-3.5 per year, and mean hospitalizations were 0.1-2.4 per year (mean length of stay 0.4-13.0 days). Patients averaged 10-26 physician visits/year. Mean annual direct total costs were $17,258-$63,022 per patient and were greater for patients with moderate or severe disease ($19,099-$82,391) compared with mild disease ($12,242-$29,233). Mean annual direct costs were larger from commercial claims ($24,585-$63,022) than public payers (Medicare and Medicaid: $18,302-$27,142). CONCLUSIONS: SLE remains a significant driver of health care utilization and costs. Patients with moderate to severe SLE use more health care services and incur greater direct and indirect costs than those with mild disease.

The risk of infections in adult patients with systemic lupus erythematosus: systematic review and meta-analysis.

OBJECTIVES: We conducted a systematic review and meta-analysis to determine the magnitude of infection risk in patients with SLE and evaluate the effect of general and SLE-related factors on infection risk. METHODS: We searched MEDLINE and Embase from inception to July 2018, screening for observational studies that evaluated infection risk in patients with SLE compared with the general population/healthy controls. Outcomes of interest included overall severe infection, herpes zoster infection/reactivation, opportunistic infections, pneumonia and tuberculosis. Random-effects models were used to calculate pooled risk ratios (RRs) for each type of infection. Sensitivity analysis assessed the impact of removing studies with high risk of bias. RESULTS: Eleven retrospective or prospective cohort studies were included in the meta-analysis: overall severe infection (n = 4), pneumonia (n = 6), tuberculosis (n = 3) and herpes zoster (n = 2). Pooled RRs for overall severe infection significantly increased for patients with SLE compared with the general population/healthy controls [RR 2.96 (95% CI 1.28, 6.83)]. Pooled RRs for pneumonia, herpes zoster and tuberculosis showed significantly increased risk compared with the general population/healthy controls [RR 2.58 (1.80, 3.70), 2.50 (2.36, 2.65) and 6.11 (3.61, 10.33), respectively]. Heterogeneity and evidence of publication bias were present for all analyses, except herpes zoster. Sensitivity analyses confirmed robustness of the results. CONCLUSION: Patients with SLE have significantly higher risk of infection compared with the general population/healthy controls. Efforts to strengthen strategies aimed at preventing infections in SLE are needed. PROTOCOL REGISTRATION: PROSPERO number: CRD42018109425.

Persistent CSF but not plasma HIV RNA is associated with increased risk of new-onset moderate-to-severe depressive symptoms; a prospective cohort study.

Major depressive disorder is the most common neuropsychiatric complication in human immunodeficiency virus (HIV) infections and is associated with worse clinical outcomes. We determined if detectable cerebrospinal fluid (CSF) HIV ribonucleic acid (RNA) at threshold ≥50 copies/ml is associated with increased risk of depression. The CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort is a six-center US-based prospective cohort with bi-annual follow-up of 674 participants. We fit linear mixed models (N = 233) and discrete-time survival models (N = 154; 832 observations) to evaluate trajectories of Beck Depression Inventory (BDI) II scores and the incidence of new-onset moderate-to-severe depressive symptoms (BDI ≥ 17) among participants on combination antiretroviral therapy (cART), who were free of depression at study entry and received a minimum of three CSF examinations over 2496 person-months follow-up. Detectable CSF HIV RNA (threshold ≥50 copies/ml) at any visit was associated with a 4.7-fold increase in new-onset depression at subsequent visits adjusted for plasma HIV RNA and treatment adherence; hazard ratio (HR) = 4.76, (95 % CI 1.58-14.3); P = 0.006. Depression (BDI) scores were 2.53 points higher (95 % CI 0.47-4.60; P = 0.02) over 6 months if CSF HIV RNA was detectable at a prior study visit in fully adjusted models including age, sex, race, education, plasma HIV RNA, duration and adherence of CART, and lifetime depression diagnosis by Diagnostic Statistical Manual (DSM-IV) criteria. Persistent CSF but not plasma HIV RNA is associated with an increased risk for new-onset depression. Further research evaluating the role of immune activation and inflammatory markers may improve our understanding of this association.

Cocaine Use May be Associated with Increased Depression in Persons Infected with HIV.

HIV infection, depression, and cocaine use are independently associated with increased inflammatory signal production. There is increasing evidence about the role of inflammation in depression. In HIV disease, cocaine use may increase disease progression as well as alter T cell functioning resulting in cytokine activation and thereby increasing susceptibility to depression. We examined the association between cocaine use and depression among 447 African American persons infected with HIV who were frequent cocaine users or non-users, enrolled in an observational study in Baltimore, Maryland, between August 2003 and December 2012. The overall prevalence of depression was 40.9 % (183 of 447) participants. Among persons who were depressed, the prevalence of cocaine use was 81.4 % (149 of 183), compared to 69.3 % among persons who were not depressed (183 of 264), P = 0.004. Cocaine use was associated with nearly twofold increased odds of depression, unadjusted odds ratio (OR) 1.94, (95 % CI 1.23, 3.06); P = 0.004, compared to never using cocaine, and OR 1.02, (95 % CI 1.10, 1.05); P = 0.04 in adjusted analysis. A dose-response relationship between increasing duration of cocaine use and depression was observed. Frequency and duration of cocaine use may be associated with depression. We speculate that depression among cocaine users with HIV may involve an inflammatory component that needs further examination.

Functional Donor Site Morbidity After Vascularized Toe Transfer Procedures: A Review of the Literature and Biomechanical Consideration for Surgical Site Selection.

BACKGROUND: The purpose of this study was to conduct a systematic review and pooled analysis of vascularized toe-to-hand transfer to determine functional donor site morbidity among different techniques. METHODS: Pubmed MEDLINE, EMBASE, and Cochrane databases search yielded 302 citations, with 56 meeting inclusion criteria. Pooled outcomes and analysis are reported based on donor site morbidity, specific toe transferred, technique used, and foot biomechanical changes. RESULTS: A total of 802 digit transfers (418 isolated great toe transfers, 324 isolated second toe transfers, and 153 toes classified as "other") were included for analysis. Sex was reported in 510 patients (80.2 % men, 19.8% women). The mean patient age was 28.5 ± 8.4 years. Functional impairment analysis found 23.7% (97 digit transfers) experienced gait impairment. Great toe transfer versus second toe transfer versus the "other" group demonstrated morbidity rates of 21.8%, 14.5%, and 23% (P = 0.001), respectively. Donor site reoperative intervention occurred in 11.8% of cases (95 digits): 4.5%, 16.6%, and 16.0% (P < 0.001), respectively. Mean follow-up time was 62.6 months. CONCLUSIONS: Functional foot impairment can occur after various toe transfer procedures due to altered biomechanics of weight distribution and gait. Rigorous biomechanical foot evaluation of this subset of patients is lacking. Great toe transfer appears to have the highest morbidity rate, but lower reoperative intervention as compared to second toe transfer. Preserving ray projection does not prevent biomechanical changes to the foot, but may delay functional impairment leading to favorable functional interpretation by patients and surgeons.

Development and evaluation of a clinical staging system for amyotrophic lateral sclerosis.

BACKGROUND: Staging of disease severity is useful for prognosis, decision-making and resource planning. However, no commonly used, validated staging system exists for amyotrophic lateral sclerosis (ALS). Our purpose was to develop an ALS staging system (ALS Milano-Torino Staging) that captures the observed progressive loss of independence and function. METHODS: Clinical milestones in ALS progression were defined by loss of independence in four key domains on the ALS Functional Rating Scale (ALSFRS): swallowing, walking/self-care, communicating and breathing. Stages were defined as follows: stage 0, functional involvement but no loss of independence on any domain; stages 1-4, number of domains in which independence was lost; and stage 5, death. Staging criteria were applied to patients enrolled in a Quality of Care in ALS (QOC) study; endpoints included function (ALSFRS), quality of life (QOL; Short Form-36) and health service costs. Between-stage transition probabilities were assessed in the QOC study and in a second clinical study of lithium carbonate in ALS. RESULTS: 70/118 (59.3%) participants in the QOC study progressed to higher stages of disease at 12 months compared with their baseline stage. Functional (ALSFRS) and QOL measures were inversely related to disease stage. Health service costs were directly related to increasing disease stages from 0 to 4 (p<0.001). Probabilities for transitioning from a given stage at baseline in both studies were usually greatest for the next highest stage. CONCLUSIONS: The proposed ALS Milano-Torino Staging system correlates well with assessments of function, QOL and health service costs. Further studies are warranted to validate this system.

The cerebrospinal fluid HIV risk score for assessing central nervous system activity in persons with HIV.

Detectable human immunodeficiency virus (HIV) RNA in the cerebrospinal fluid (CSF) is associated with central nervous system (CNS) complications. We developed the CSF HIV risk score through prediction modeling to estimate the risk of detectable CSF HIV RNA (threshold >50 copies/mL) to help identify persons who might benefit most from CSF monitoring. We used baseline data from 1,053 participants receiving combination antiretroviral therapy who were enrolled in the 6-center, US-based CNS HIV Antiretroviral Therapy Effects Research (CHARTER) prospective cohort in 2004-2007. Plasma HIV RNA, CNS penetration effectiveness, duration of combination antiretroviral therapy, medication adherence, race, and depression status were retained correlates of CSF HIV RNA, displaying good discrimination (C statistic = 0.90, 95% confidence interval (CI): 0.87, 0.93) and calibration (Hosmer-Lemeshow P = 0.85). The CSF HIV risk score ranges from 0 to 42 points, with a mean of 15.4 (standard deviation, 7.3) points. At risk scores greater than 25, the probability of detecting CSF HIV RNA was at least 42.9% (95% CI: 36.6, 49.6). For each 1-point increase, the odds of detecting CSF HIV RNA increased by 26% (odds ratio = 1.26, 95% CI: 1.21, 1.31; P < 0.01). The risk score correlates with detection of CSF HIV RNA. It represents an advance in HIV management and monitoring of CNS effects, providing a potentially useful tool for clinicians.

Bone mass in individuals with chronic spinal cord injury: associations with activity-based therapy, neurologic and functional status, a retrospective study.

OBJECTIVE: To describe the prevalence of osteoporosis and its association with functional electrical stimulation (FES) use in individuals with spinal cord injury (SCI)-related paralysis. DESIGN: Retrospective cross-sectional evaluation. SETTING: Clinic. PARTICIPANTS: Consecutive persons with SCI (N=364; 115 women, 249 men) aged between 18 and 80 years who underwent dual-energy x-ray absorptiometry (DXA) examinations. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Prevalence of osteoporosis defined as DXA T score ≤-2.5. RESULTS: The prevalence of osteoporosis was 34.9% (n=127). Use of FES was associated with 31.2% prevalence of osteoporosis compared with 39.5% among persons not using FES. In multivariate adjusted logistic regression analysis, FES use was associated with 42% decreased odds of osteoporosis after adjusting for sex, age, body mass index, type and duration of injury, Lower Extremity Motor Scores, ambulation, previous bone fractures, and use of calcium, vitamin D, and anticonvulsant; (adjusted odds ratio [OR]=.58; 95% confidence interval [CI], .35-.99; P=.039). Duration of injury >1 year was associated with a 3-fold increase in odds of osteoporosis compared with individuals with injury <1 year; (adjusted OR=3.02; 95% CI, 1.60-5.68; P=.001). CONCLUSIONS: FES cycling ergometry may be associated with a decreased loss of bone mass after paralysis. Further prospective examination of the role of FES in preserving bone mass will improve our understanding of this association.

Ictal adiponectin levels in episodic migraineurs: a randomized pilot trial.

OBJECTIVE: To assess ictal adiponectin (ADP) levels before and after acute abortive treatment in women episodic migraineurs. METHODS: Peripheral blood specimens were collected from women episodic migraineurs before and after acute abortive treatment with sumatriptan/naproxen sodium vs placebo. Univariate and multivariate models were utilized to examine the relationship between serum total ADP (T-ADP), ADP oligomers (high molecular weight [HMW], middle molecular weight, and low molecular weight [LMW]-ADP), and ADP ratio levels and pain severity. Paired t-tests and random intercept longitudinal models were utilized to assess the mean changes in T-ADP, ADP oligomers, and ratios over time in treatment responders and nonresponders. RESULTS: Twenty participants (11 responders, 9 nonresponders) have been studied to date. In all participants, increases in the HMW : LMW ADP ratio were associated with an increase in pain severity. For every 1 point increase in the HMW : LMW ratio, pain severity increased by 0.22 (Confidence Interval [CI]: 0.07, 0.37; P = .004). In contrast, for every 0.25 µg/mL increase in LMW-ADP, pain severity decreased by 0.20 (CI: -0.41, -0.002; P = .047). In treatment responders, T-ADP levels were reduced at 30 minutes (12.52 ± 3.4; P = .03), 60 minutes (12.32 ± 3.2; P = .017), and 120 minutes (12.65 ± 3.2; P = .016) after treatment as compared with onset (13.48 ± 3.8). Additionally, in responders, the HMW : LMW ratio level was greater at pain onset (3.70 ± 1.9 µg/mL) as compared with nonresponders (2.29 ± 0.71 µg/mL), P = .050. Responders also showed a decrease in the HMW : LMW ratio at 60 minutes (2.37 ± 1.1; P = .002) and 120 minutes (2.76 ± 1.4; P = .02) after treatment as compared with onset (3.70 ± 1.9). These changes in responders remained significant after adjusting for covariates, including measured body mass index (m-BMI). Although nonresponders showed no significant changes in unadjusted T-ADP or ADP oligomer or ratio levels, the HMW : LMW ratio was increased in nonresponders after adjustments (P = .025). CONCLUSION: In this pilot study of women episodic migraineurs, the HMW : LMW ADP ratio level was associated with migraine severity and predictive of acute treatment response. ADP and the HMW : LMW ratio of ADP represent potential novel biomarkers and drug targets for episodic migraine.

Lower extremity functional electrical stimulation cycling promotes physical and functional recovery in chronic spinal cord injury.

OBJECTIVE: To examine the effect of long-term lower extremity functional electrical stimulation (FES) cycling on the physical integrity and functional recovery in people with chronic spinal cord injury (SCI). DESIGN: Retrospective cohort, mean follow-up 29.1 months, and cross-sectional evaluation. SETTING: Washington University Spinal Cord Injury Neurorehabilitation Center, referral center. PARTICIPANTS: Twenty-five people with chronic SCI who received FES during cycling were matched by age, gender, injury level, and severity, and duration of injury to 20 people with SCI who received range of motion and stretching. INTERVENTION: Lower extremity FES during cycling as part of an activity-based restorative treatment regimen. MAIN OUTCOME MEASURE: Change in neurological function: motor, sensory, and combined motor-sensory scores (CMSS) assessed by the American Spinal Injury Association Impairment scale. Response was defined as ≥ 1 point improvement. RESULTS: FES was associated with an 80% CMSS responder rate compared to 40% in controls. An average 9.6 CMSS point loss among controls was offset by an average 20-point gain among FES subjects. Quadriceps muscle mass was on average 36% higher and intra/inter-muscular fat 44% lower, in the FES group. Hamstring and quadriceps muscle strength was 30 and 35% greater, respectively, in the FES group. Quality of life and daily function measures were significantly higher in FES group. CONCLUSION: FES during cycling in chronic SCI may provide substantial physical integrity benefits, including enhanced neurological and functional performance, increased muscle size and force-generation potential, reduced spasticity, and improved quality of life.

Frequency, severity and costs of flares increase with disease severity in newly diagnosed systemic lupus erythematosus: a real-world cohort study, United States, 2004-2015.

OBJECTIVE: To evaluate frequency, severity and costs of flares in US patients with newly diagnosed SLE. METHODS: Adults diagnosed with SLE between January 2005 and December 2014 were identified from US commercial claims data linked to electronic medical records. Disease and flare severity during 1 year after diagnosis were classified as mild, moderate or severe using a claims-based algorithm. Study outcomes included frequency and severity of flares stratified by disease severity during the 1-year post-diagnosis period and all-cause healthcare costs of flares by severity at 30, 60 and 90 days after flare. RESULTS: Among 2227 patients, 26.3%, 51.0% and 22.7% had mild, moderate and severe SLE, respectively. The overall annual flare rate was 3.5 and increased with disease severity: 2.2, 3.7 and 4.2, respectively, for mild, moderate and severe SLE (p<0.0001). Patients with severe SLE had a higher annual severe flare rate (0.6) compared with moderate (0.1) or mild SLE (0; p<0.0001). Mean total all-cause costs at 30, 60 and 90 days after flare were $16 856, $22 252 and $27 468, respectively, for severe flares (mild flares: $1672, $2639 and $3312; moderate flares: $3831, $6225, $8582; (p<0.0001, all time points)). Inpatient costs were the primary driver of the increased cost of severe flares. CONCLUSIONS: Flare frequency and severity in newly diagnosed patients with SLE increase with disease severity. After a flare, healthcare costs increase over the following 90 days by disease severity. Preventing flares or reducing flare rates and duration may improve outcomes and reduce healthcare costs.

Disease and economic burden increase with systemic lupus erythematosus severity 1 year before and after diagnosis: a real-world cohort study, United States, 2004-2015.

OBJECTIVE: To assess the economic burden of patients with SLE by disease severity in the USA 1 year before and after diagnosis. METHODS: Patients aged ≥18 years with a first SLE diagnosis (index date) between January 2005 and December 2014 were identified from administrative commercial claims data linked to electronic medical records (EMRs). Disease severity during the year after diagnosis was classified as mild, moderate, or severe using claims-based algorithms and EMR data. Healthcare resource utilisation (HCRU) and all-cause healthcare costs (2017 US$) were reported for 1 year pre-diagnosis and post-diagnosis. Generalised linear modelling examined all-cause costs over 1 year post-index, adjusting for baseline demographics, clinical characteristics, Charlson Comorbidity Index and 1 year pre-diagnosis costs. RESULTS: Among 2227 patients, 26.3% had mild, 51.0% moderate and 22.7% severe SLE. Mean per-patient costs were higher for patients with moderate and severe SLE compared with mild SLE during the year before diagnosis: mild US$12 373, moderate $22 559 and severe US$39 261 (p<0.0001); and 1-year post-diagnosis period: mild US$13 415, moderate US$29 512 and severe US$68 260 (p<0.0001). Leading mean cost drivers were outpatient visits (US$13 566) and hospitalisations (US$10 252). Post-diagnosis inpatient utilisation (≥1 stay) was higher for patients with severe (51.2%) and moderate (22.4%) SLE, compared with mild SLE (12.8%), with longer mean hospital stays: mild 0.47 days, moderate 1.31 days and severe 5.52 days (p<0.0001). CONCLUSION: HCRU and costs increase with disease severity in the year before and after diagnosis; leading cost drivers post-diagnosis were outpatient visits and hospitalisations. Earlier diagnosis and treatment may improve health outcomes and reduce HCRU and costs.

The Burden of Systemic Lupus Erythematosus in Germany: Incidence, Prevalence, and Healthcare Resource Utilization.

INTRODUCTION: We evaluated incidence, prevalence, costs, and healthcare utilization associated with systemic lupus erythematosus (SLE) in patients in Germany. METHODS: Adult patients with SLE were identified from the German Betriebskrankenkassen (BKK) health insurance fund database between 2009 and 2014. SLE incidence and prevalence were calculated for each year and extrapolated (age and sex adjusted) to the German population. The 2009 SLE population was followed through 2014. Healthcare utilization and costs for patients with SLE were calculated and compared with controls matched by age, sex, and baseline Charlson Comorbidity Index scores. RESULTS: This analysis included 1160 patients with SLE. Estimated SLE incidence between 2009 and 2014 ranged from 4.59 to 6.89 per 100,000 persons and prevalence ranged from 37.32 to 47.36 per 100,000. SLE incidence in Germany in 2014 was 8.82 per 100,000 persons; prevalence was 55.80 (corrected for right-censored data). At baseline, 12.8, 41.7, and 45.5% of patients were categorized as having mild, moderate, and severe SLE, respectively. Patients with SLE had greater mean (standard deviation [SD]) annual medical costs compared with matched controls 1 year after index diagnosis (€6895 [14,424] vs. €3692 [3994]; P < 0.0001) and in subsequent years. Patients with moderate or severe SLE had significantly more hospitalizations, outpatient visits, and prescription medication use compared with matched controls. Mean annual costs for 5 years ranged from €1890 to 3010, €4867 to 5876, and €8396 to 10,001 for patients with mild, moderate, and severe SLE, respectively. CONCLUSIONS: SLE incidence in Germany increased 1.4-fold over 5 years. Patients with SLE have higher healthcare costs, and costs increase with baseline severity. Early and effective treatments may delay progression and reduce the burden of SLE.

Risk of malignancy in patients with systemic lupus erythematosus: Systematic review and meta-analysis.

BACKGROUND: Malignancy is a potential comorbidity in patients with systemic lupus erythematosus (SLE). However, risk by malignancy type remains to be fully elucidated. We evaluated the risk of malignancy type in SLE patients in a systematic review and meta-analysis. METHODS: MEDLINE and EMBASE were searched from inception to July 2018 to identify observational studies that evaluated malignancy risk in adult SLE patients compared with the general population. Random-effects models were used to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Heterogeneity was quantified using the I2 test. FINDINGS: Forty-one studies reporting on 40 malignancies (one overall, 39 site-specific) were included in the meta-analysis. The pooled RR for all malignancies from 3694 events across 80 833 patients was 1.18 (95% CI: 1.00-1.38). The risk of 24 site-specific malignancies (62%) was increased in SLE patients. For malignancies with ≥6 studies, non-Hodgkin lymphoma and Hodgkin lymphoma risk was increased >3-fold; myeloma and liver >2-fold; cervical, lung, bladder, and thyroid ≥1.5-fold; stomach and brain >1.3-fold. The risk of four malignancies (breast, uterine, melanoma, prostate) was decreased, whereas risk of 11 other malignancies did not differ between SLE patients and the general population. Heterogeneity ranged between 0% and 96%, and 63% were non-significant. INTERPRETATION: The risk of overall and some site-specific malignancies is increased in SLE compared with the general population. However, the risk for some site-specific malignancies is decreased or did not differ. Further examination of risk profiles and SLE patient phenotypes may support guidelines aimed at reducing malignancy risk. FUNDING: AstraZeneca. SYSTEMATIC REVIEW REGISTRATION: PROSPERO number: CRD42018110433.

Healthcare Utilization and Costs of Systemic Lupus Erythematosus by Disease Severity in the United States.

OBJECTIVE: To quantify healthcare utilization and costs by disease severity for patients with systemic lupus erythematosus (SLE) in the United States. METHODS: We conducted descriptive analyses of Humedica electronic health record (EHR) data from 2011 to 2015 (utilization analysis) and integrated Optum administrative claims/Humedica EHR data from 2012 to 2015 (cost analysis) for patients with SLE. All-cause utilization outcomes examined were hospitalizations, outpatient visits, emergency department (ED) visits, and prescription drug use. Analyses of costs stratified by disease severity were limited to patients enrolled in an Optum-participating health insurance plan for ≥ 1 year after the earliest observed SLE diagnosis date. Costs were converted to 2016 US dollars (US$). RESULTS: Healthcare utilization was evaluated in 17,257 patients with SLE. Averaged over the 2011-2015 study period, 13.7% of patients had ≥ 1 hospitalization per year, 25.7% had ≥ 1 ED visit, and 94.4% had ≥ 1 outpatient visit. Utilization patterns were generally similar across each year studied. Annually, 88.0% of patients had ≥ 1 prescription, including 1.3% who used biologics. Biologic treatment doubled between 2011 (0.7%) and 2015 (1.4%). Cost analyses included 397 patients. From 2012 to 2015, patients with severe SLE had mean annual costs of $52,951, compared with $28,936 and $21,052 for patients with moderate and mild SLE, respectively. Patients with severe SLE had increased costs in all service categories: inpatient, ED, clinic/office visits, and pharmacy. CONCLUSION: Patients from the US with SLE, especially individuals with moderate or severe disease, utilize significant healthcare resources and incur high medical costs.

Study protocol for the international Systemic Lupus Erythematosus Prospective Observational Cohort Study (SPOCS): understanding lupus and the role of type I interferon gene signature.

INTRODUCTION: The Systemic Lupus Erythematosus (SLE) Prospective Observational Cohort Study (SPOCS) aims to describe the disease course of SLE and its association with type I interferon gene signature (IFNGS) status. METHODS AND ANALYSIS: SPOCS is an international, multicentre, prospective, observational cohort study designed to follow patients through biannual study visits during a 3-year observation period. Patients ≥18 years old with a physician diagnosis that meets the American College of Rheumatology or Systemic Lupus International Collaborating Clinics SLE classification criteria will be included. SPOCS will comprehensively analyse clinical features, disease progression and treatment, SLE outcomes, health status assessments and quality of life, and healthcare resource utilisation of patients with moderate to severe SLE. A four-gene test will be used to measure IFNGS status; scores will be compared with a pre-established cut-off. Patients will be stratified by low or high IFNGS expression levels. Enrolment began in June 2017, and study completion is expected in 2022. The total number of anticipated patients was initially planned for 1500 patients and was amended to 900 patients owing to slow accrual of eligible patients. ETHICS AND DISSEMINATION: The ethics committee/institutional review board/independent ethics committee at each study site approved the SPOCS protocol prior to study initiation (protocol number: D3461R00001, version 3.0, 26 June 2019). Study findings will be disseminated through peer-reviewed publications and presentations at scientific meetings. TRIAL REGISTRATION NUMBER: NCT03189875.

Association between organ damage and mortality in systemic lupus erythematosus: a systematic review and meta-analysis.

OBJECTIVE: At least half of patients with systemic lupus erythematosus (SLE) develop organ damage as a consequence of autoimmune disease or long-term therapeutic steroid use. This study synthesised evidence on the association between organ damage and mortality in patients with SLE. DESIGN: Systematic review and meta-analysis. METHODS: Electronic searches were performed in PubMed, Embase, Cochrane Library and Latin American and Caribbean Health Sciences Literature for observational (cohort, case-control and cross-sectional) studies published between January 2000 and February 2017. Included studies reported HRs or ORs on the association between organ damage (measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score) and mortality. Study quality was assessed using the modified Newcastle-Ottawa assessment. Pooled HRs were obtained using the DerSimonian and Laird random-effects model. Heterogeneity was assessed using the Cochrane Q (Q) and I2 statistics. RESULTS: The search yielded 10 420 articles, from which 21 longitudinal studies were selected. Most studies (85%) were of high quality. For 10 studies evaluating organ damage (SDI) as a continuous variable and reporting HR as a measure of association, a 1-unit increase in SDI was associated with increased mortality; pooled HR was 1.34 (95% CI: 1.24 to 1.44, p<0.001; Q p=0.027, I2=52.1%). Exclusion of one potential outlying study reduced heterogeneity with minimal impact on pooled HR (1.33 (95% CI: 1.25 to 1.42), p<0.001, Q p=0.087, I2=42.0%). The 11 remaining studies, although they could not be aggregated because of their varying patient populations and analyses, consistently demonstrated that greater SDI was associated with increased mortality. CONCLUSIONS: Organ damage in SLE is consistently associated with increased mortality across studies from various countries. Modifying the disease course with effective therapies and steroid-sparing regimens may reduce organ damage, improve outcomes and decrease mortality for patients with SLE.

Breast Cancer following Augmentation Mammaplasty: A Case-Control Study.

BACKGROUND: The purpose of this study was to determine whether augmentation mammaplasty, implant type, and implant location affect breast cancer detection, stage, and treatment. METHODS: An institutional case-control study was performed of patients with prior breast augmentation undergoing breast cancer treatment from 2000 to 2013. Controls were propensity matched and randomized, and data were retrospectively reviewed. RESULTS: Forty-eight cases and 302 controls were analyzed. Palpable lesions were detected at a smaller size in augmentation patients (1.6 cm versus 2.3 cm; p < 0.001). Fewer lesions in augmented patients were detected by screening mammography (77.8 percent of cases versus 90.7 percent of controls; p = 0.010). Patients with implants were more likely to undergo an excisional biopsy for diagnosis (20.5 percent versus 4.4 percent; p < 0.001), rather than image-guided core needle biopsy (77.3 percent versus 95.3 percent; p < 0.001). Earlier staging in augmented patients approached but did not reach statistical significance (p = 0.073). Augmented patients had higher mastectomy rates (74.5 percent versus 57.0 percent) and lower rates of breast-conservation therapy (25.5 percent versus 43 percent; p = 0.023). Neither implant fill type nor anatomic location affected method of diagnosis, stage, or treatment. CONCLUSIONS: Palpable detection of breast cancer is more likely at a smaller size in augmented patients, yet it is less likely on screening mammography than in controls. Augmentation breast cancer patients have a comparable disease stage and are more likely to undergo mastectomy rather than lumpectomy. Both silicone and saline implants, whether placed submuscularly or subglandularly, have comparable effects on breast imaging, biopsy modality, and surgical intervention. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Functional electrical stimulation as a component of activity-based restorative therapy may preserve function in persons with multiple sclerosis.

OBJECTIVE: To examine the effect of functional electrical stimulation (FES) cycling on disability progression in persons with multiple sclerosis (MS). DESIGN: Retrospective cohort, 40 participants with mean follow-up of 15 months. Setting International Center for Spinal Cord Injury at Kennedy Krieger Institute in Baltimore, a rehabilitation referral center. PARTICIPANTS: Forty consecutive persons with MS undergoing rehabilitation from 2007 to 2011, with at least two evaluations based on the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). Interventions FES cycling as part of activity-based restorative therapy interventions. OUTCOME MEASURES: Change in Expanded Disability Status Scale (EDSS) and ISNCSCI motor, light touch, and pin prick scores from baseline to latest evaluation. RESULTS: In 71% of patients, activity-based rehabilitation included FES cycling. There was no disability progression on the EDSS. Lower extremity motor scores improved or stabilized in 75% of patients with primary progressive MS (PPMS), 71.4% with secondary progressive MS (SPMS), and 54.5% with relapsing remitting MS (RRMS). Among patients with improved or stabilized lower extremity motor function, PPMS recorded a mean 9% improvement, SPMS 3% and RRMS 6%. In PPMS, use of FES showed trend towards improvement in motor scores (P = 0.070). CONCLUSIONS: FES as part of activity-based rehabilitation may help preserve or improve neurological function in patients with MS.