There is a need for new systemic sclerosis subset criteria. A content analytic approach.

OBJECTIVES: Systemic sclerosis (SSc) is heterogenous. The objectives of this study were to evaluate the purpose, strengths and limitations of existing SSc subset criteria, and identify ideas among experts about subsets. METHODS: We conducted semi-structured interviews with randomly sampled international SSc experts. The interview transcripts underwent an iterative process with text deconstructed to single thought units until a saturated conceptual framework with coding was achieved and respondent occurrence tabulated. Serial cross-referential analyses of clusters were developed. RESULTS: Thirty experts from 13 countries were included; 67% were male, 63% were from Europe and 37% from North America; median experience of 22.5 years, with a median of 55 new SSc patients annually. Three thematic clusters regarding subsetting were identified: research and communication; management; and prognosis (prediction of internal organ involvement, survival). The strength of the limited/diffuse system was its ease of use, however 10% stated this system had marginal value. Shortcomings of the diffuse/limited classification were the risk of misclassification, predictions/generalizations did not always hold true, and that the elbow or knee threshold was arbitrary. Eighty-seven percent use more than 2 subsets including: SSc sine scleroderma, overlap conditions, antibody-determined subsets, speed of progression, and age of onset (juvenile, elderly). CONCLUSIONS: We have synthesized an international view of the construct of SSc subsets in the modern era. We found a number of factors underlying the construct of SSc subsets. Considerations for the next phase include rate of change and hierarchal clustering (e.g. limited/diffuse, then by antibodies).

Effect of biologics on depressive symptoms in patients with psoriasis: a systematic review.

BACKGROUND: Twenty to fifty percent of patients with psoriasis have depressive symptoms. OBJECTIVE: To describe the effects of biologics (tumour necrosis factor inhibitors [TNFi] or interleukin 12/23 inhibitors [IL-12/23i]) on depressive symptoms in patients with psoriasis. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) examining the effects of biologics on depressive symptoms in adults with psoriasis. RESULTS: Of the 305 publications identified, three RCTs were included in a systematic review. In a trial evaluating ustekinumab, mean change in Hospital and Anxiety Depression Rating Scale at 24 weeks from baseline was 3.1 with ustekinumab (P < 0.001) vs. 0.21 with placebo (not significant). In a trial evaluating adalimumab, mean change in Zung Self-Rating Depression Scale at 12 weeks from baseline was -6.7 with adalimumab vs. -1.5 with placebo. In a trial evaluating etanercept, the between-group difference at 12 weeks in Beck Depression Inventory Scale was 1.8 (95% CI: 0.6, 2.90) in favour of etanercept over placebo. Limitations are that diagnostic criteria for depression were not used and scales and data from individual RCTs could not be combined. CONCLUSION: Adalimumab, etanercept and ustekinumab were associated with statistically significant reductions in depressive symptom scores using various scales in patients with moderate-to-severe psoriasis.

Myopathy is a poor prognostic feature in systemic sclerosis: results from the Canadian Scleroderma Research Group (CSRG) cohort.

OBJECTIVE: To determine the clinical impact of muscle involvement in a large systemic sclerosis (SSc) cohort. METHOD: Using the Canadian Scleroderma Research Group (CSRG) database, SSc patients with either elevated creatine kinase (CK) or a prior history of myositis/myopathy were identified. Regression and Kaplan-Meier analyses were performed to determine characteristics associated with muscle involvement in SSc and survival outcome. RESULTS: In 1145 patients with SSc, 5.6% had an elevated CK. This subset was more likely to be male (24.5% in elevated CK vs. 12.6% in normal CK, p < 0.013), younger (52 vs. 56 years, p < 0.045), have diffuse cutaneous SSc (dcSSc; 40.4% vs. 37.9%, p < 0.002), tendon friction rubs (30.0% vs. 13.4%, p < 0.001), and forced vital capacity (FVC) < 70% (23.9% vs. 13.1%, p < 0.039), be ribonucleoprotein (RNP) antibody positive (12.0% vs. 5.0%, p < 0.032), topoisomerase1 (topo1)-antibody positive (26.0% vs. 14.4%, p < 0.026), have a higher modified Rodnan skin score (MRSS; 16.14 vs. 9.81, p < 0.001), and a higher Health Assessment Questionnaire (HAQ) score (0.98 vs. 0.79, p < 0.011). Survival was reduced for patients with elevated CK (p < 0.025). Nearly 10% of patients in the CSRG cohort had a prior history of myositis/myopathy. This subset also had findings similar to those with elevated CK and increased mortality (p < 0.003). CONCLUSIONS: Muscle involvement in SSc has a poor prognosis impacting survival, especially in men with early dcSSc with topo1 and RNP autoantibodies and interstitial lung disease (ILD).

The frequency of and associations with hospitalization secondary to lupus flares from the 1000 Faces of Lupus Canadian cohort.

OBJECTIVES: Hospitalization is a major factor in health care costs and a surrogate for worse outcomes in chronic disease. The aim of this study was to determine the frequency of hospitalization secondary to lupus flare, the causes of hospitalization, and to determine risk factors for hospitalization in patients with systemic lupus erythematosus (SLE). METHODS: Data were collected as part of the 1000 Canadian Faces of Lupus, a prospective cohort study, where annual major lupus flares including hospitalizations were recorded over a 3-year period. RESULTS: Of 665 patients with available hospitalization histories, 68 reported hospitalization related to a SLE flare over 3 years of follow-up. The average annual hospitalization rate was 7.6% (range 6.6-8.9%). The most common reasons for hospitalization were: hematologic (22.1%), serositis (20.6%), musculoskeletal (MSK) (16.2%), and renal (14.7%). Univariate risk factors for lupus hospitalization included (OR [95% CI]; p < 0.05): juvenile-onset lupus (2.2 [1.1-4.7]), number of ACR SLE criteria (1.4 [1.1-1.7], baseline body mass index (BMI) (1.1 [1.0-1.1]), psychosis (3.4 [1.2-9.9]), aboriginal race (3.2 [1.5-6.7]), anti-Smith (2.6 [1.2-5.4]), erythrocyte sedimentation rate >25 mm/hr (1.9 [1.1-3.4]), proteinuria >0.5 g/d (4.2 [1.9-9.3], and SLAM-2 score (1.1 [1.0-1.2]). After multivariate regression only BMI, number of ACR criteria, and psychosis were associated with hospitalization for lupus flare. CONCLUSIONS: The mean annual rate of hospitalization attributed to lupus was lower than expected. Hematologic, serositis, MSK and renal were the most common reasons. In a regression model elevated BMI, more ACR criteria and psychosis were associated with hospitalization.

Patterns and predictors of change in outcome measures in clinical trials in scleroderma: an individual patient meta-analysis of 629 subjects with diffuse cutaneous systemic sclerosis.

OBJECTIVE: To examine the range and responsiveness to change of clinical outcome measures and study predictors of clinical response in patients with diffuse cutaneous systemic sclerosis (dcSSc) in the context of clinical trials. METHODS: Data were combined from 629 patients with dcSSc who participated in 7 multicenter clinical therapeutic trials. Trials used common outcome measures: modified Rodnan skin thickness score (MRSS), Health Assessment Questionnaire disability index (HAQ DI), patient's global assessment of disease activity, pulmonary function tests (forced vital capacity, diffusing capacity for carbon monoxide), hand span, and oral aperture. RESULTS: The combined database included 629 patients (82% women, mean ± SD age 46.5 ± 11.8 years, mean ± SD disease duration 19.4 ± 15.9 months). Outcomes tended to improve during trials for patients with more severe disease at study entry and to worsen for patients with less severe disease at entry. Disease duration was mildly negatively predictive of change in MRSS at 6 months (r = -0.27, P < 0.001), and substantial bidirectional variation in change in MRSS and HAQ DI score was seen across the spectrum of disease duration. Sixty-three percent of patients with "early" disease (disease duration <18 months) had a decline in MRSS, and 37% had an increase in MRSS. Eighty-one percent of patients with "late" disease (disease duration ≥ 18 months) had a decline in MRSS, and 19% had an increase in MRSS. Multivariate mixed models did not demonstrate that any baseline variables were strongly predictive of subsequent outcome. CONCLUSION: Among patients with dcSSc enrolled in clinical trials, standard outcome measures tend to improve in those with more severe disease at study entry and to worsen in those with less severe disease at entry. Overall, the MRSS improves during trials, while HAQ DI scores and lung function are mostly static. None of these variables, including disease duration, reliably identifies groups of subjects whose MRSS will predictably increase or decrease in the course of a clinical trial. These findings have important implications for clinical trial design in scleroderma.

A targeted association study in systemic lupus erythematosus identifies multiple susceptibility alleles.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Multiple genetic and environmental factors contribute to the pathogenesis of this disease. Recent genome-wide association studies have added substantially to the number of genes associated with SLE. To replicate some of these susceptibility loci, single-nucleotide polymorphisms reported to be associated to SLE were evaluated in a cohort of 245 well-phenotyped Canadian SLE trios. Our results replicate previously reported associations to alleles of interferon regulatory factor 5 (IRF5), major histocompatibility complex (MHC), tumor necrosis factor (ligand) superfamily member 4 (TNFSF4), Kell blood group complex subunit-related family member 6 (XKR6), B-cell scaffold protein with ankyrin repeats 1 (BANK1), protein tyrosine phosphatase non-receptor type 22 (PTPN22), ubiquitin-conjugating enzyme E2L 3 (UBE2L3) and islet cell autoantigen 1 (ICA1). We also identify putative associations to cytotoxic T-lymphocyte-associated protein 4 (CTLA4), a gene associated with several autoimmune disorders, and ERBB3, a locus on 12q13 that was previously reported to be associated with type 1 diabetes. This study confirms the existence of multiple genetic risk factors for SLE, and supports the notion that some risk factors for SLE are shared with other inflammatory disorders.

The minimally important difference (MID) for patient-reported outcomes including pain, fatigue, sleep and the health assessment questionnaire disability index (HAQ-DI) in primary Sjögren's syndrome.

OBJECTIVES: We wanted to determine the MID for the HAQ, pain, fatigue, sleep and global VAS (0-100mm) in Sjögren's syndrome (SS) using a patient-reported overall health status anchor. METHODS: Patients with a diagnosis of primary Sjögren's syndrome (pSS) who had answered a standardised questionnaire at two consecutive visits including an overall health status question: 'How would you describe your overall status since your last visit: much better, better, the same, worse, much worse?' were included. The MID was calculated as the mean change between visits for those who rated their disease as better or worse. Scales on VAS were from 0 (best) to 100 (worst). RESULTS: Forty patients met the inclusion criteria (97% female, mean age 58 years, mean disease duration 10 years). The mean baseline HAQ was 0.68. Ten rated their status as better and 14 as worse than the previous visit. MID estimates for improvemenT/worsening (SD) respectively were: -7.4 (27.8) / 20.7 (20.0) for pain VAS, -6.2 (28.3) / 15.2 (21.8) for fatigue VAS, -24.0 (24.0) / 15.2 (28.0) for sleep VAS, -0.18 (0.23) / 0.14 (0.30) for HAQ and -23.1 (21.6) / 16.4 (20.9) for global VAS. Spearman's rho correlation coefficients for the patient-reported outcomes were 0.38 (pain VAS), 0.54 (fatigue VAS), 0.55 (sleep VAS), 0.39 (HAQ), and 0.57 (global VAS), p<0.05. CONCLUSIONS: The MID for pain and fatigue are greater for worsening than improvement. A small change in the HAQ is detected as a change in status by the patient. This knowledge may aid those who treat SS and in designing intervention studies.

Health Assessment Questionnaire at One Year Predicts All-Cause Mortality in Patients With Early Rheumatoid Arthritis.

OBJECTIVE: Higher self-reported disability (high Health Assessment Questionnaire [HAQ] score) has been associated with hospitalizations and mortality in established rheumatoid arthritis (RA), but associations in early RA are unknown. METHODS: Patients with early RA (symptom duration <1 year) enrolled in the Canadian Early Arthritis Cohort who initiated disease-modifying antirheumatic drugs and had completed HAQ data at baseline and 1 year were included in the study. Discrete-time proportional hazards models were used to estimate crude and multi-adjusted associations of baseline HAQ and HAQ at 1 year with all-cause mortality in each year of follow-up. RESULTS: A total of 1,724 patients with early RA were included. The mean age was 55 years, and 72% were women. Over 10 years, 62 deaths (3.6%) were recorded. Deceased patients had higher HAQ scores at baseline (mean ± SD 1.2 ± 0.7) and at 1 year (0.9 ± 0.7) than living patients (1.0 ± 0.7 and 0.5 ± 0.6, respectively; P < 0.001). Disease Activity Score in 28 joints (DAS28) was higher in deceased versus living patients at baseline (mean ± SD 5.4 ± 1.3 versus 4.9 ± 1.4) and at 1 year (mean ± SD 3.6 ± 1.4 versus 2.8 ± 1.4) (P < 0.001). Older age, male sex, lower education level, smoking, more comorbidities, higher baseline DAS28, and glucocorticoid use were associated with mortality. Contrary to HAQ score at baseline, the association between all-cause mortality and HAQ score at 1 year remained significant even after adjustment for confounders. For baseline HAQ score, the unadjusted hazard ratio (HR) was 1.46 (95% confidence interval [95% CI] 1.02-2.09), and the adjusted HR was 1.25 (95% CI 0.81-1.94). For HAQ score at 1 year, the unadjusted HR was 2.58 (95% CI 1.78-3.72), and the adjusted HR was 1.75 (95% CI 1.10-2.77). CONCLUSION: Our findings indicate that higher HAQ score and DAS28 at 1 year are significantly associated with all-cause mortality in a large early RA cohort.

Digital ulcers: overt vascular disease in systemic sclerosis.

RP is an almost universal manifestation of SSc, with 95% of all patients being affected, and resulting in digital ulcers (DUs) in approximately 30% of the patients each year. DUs are a major clinical problem, being associated with substantial morbidity (reduced quality of life, pain, disability and disfigurement) that can escalate to gangrene and amputation. Ideally, the treatment of DUs would improve tissue integrity and viability, promote ulcer healing and reduce the formation of new ulcers. Treatments that have shown potential include calcium channel blockers, prostacyclin analogues and endothelin receptor antagonists. However, until recently, management was based on empirical experience. The recent approval (in Europe) of the dual endothelin receptor antagonist, bosentan, to reduce the number of new DUs in patients with SSc and ongoing DU disease, means that there is now an approved therapy--and new hope--for the treatment of DUs in these severely afflicted patients.

A systematic review of viral exposures as a risk for rheumatoid arthritis.

OBJECTIVE: Different viral exposures have been implicated in the etiology of rheumatoid arthritis (RA). Evidence relating to the association between putative viral exposures and the development of RA was reviewed. METHODS: A systematic literature search was conducted using MEDLINE-OVID, EMBASE-OVID, PUBMED and Cochrane library databases. Articles were included if they were case-controls, cross-sectional or cohort studies and were published in English. Case-series were included if there was a lack of other study designs. RESULTS: Of 6724 citations, 48 were included in meta-analysis. Studies had poor quality. PBV19 infection was increased in RA compared to controls [N = 12, odds ratio (OR) 1.77 (95% CI: 1.11; 2.80) p = 0.02 for PVB19 IgG]. IgG anti-EBNA antibodies were not increased in RA (N = 17, p = 0.75), but anti-VCA [N = 18, OR 1.5 (95% CI: 1.07; 2.10), p = 0.02] and anti-EA antibodies [N = 11, OR 2.74 (95% CI: 1.27; 5.94), p = 0.01] were increased in RA. CMV was not associated with RA (N = 13, p = 0.42), nor was HBV (N = 5, p = 0.09). HCV was associated with RA in 7 case-control studies [OR 2.82 (95% CI: 1.35; 5.90), p = 0.006] and one cohort study [hazard ratio (HR) 2.03 (95% CI: 1.27, 3.22), p < 0.01]. Persistent arthritis was increased after Chikungunya fever [N = 2, OR 90 (95% CI: 15.2, 134.3), p = 0.047]. CONCLUSIONS: Studies of RA after viral exposures have poor quality. There is a risk of RA after Parvo B19, HCV and possibly EBV infection. CMV and HBV infections are not associated with RA. CHIKV is associated with the persistent inflammatory arthritis.

Palindromic Rheumatism Frequently Precedes Early Rheumatoid Arthritis: Results From an Incident Cohort.

BACKGROUND: This multicenter incident cohort aimed to characterize how often early rheumatoid arthritis (ERA) patients self-report episodic joint inflammation (palindromic rheumatism) preceding ERA diagnosis and which characteristics differentiate these patients from those without prior episodic symptoms. METHODS: Data were from patients with early confirmed or suspected RA (more than 6 weeks and less than 12 months) enrolled in the Canadian Early ArThritis CoHort (CATCH) between April 2017 to March 2018 who completed study case report forms assessing joint pain and swelling prior to ERA diagnosis. Chi-square and t tests were used to compare characteristics of patients with and without self-reported episodic joint inflammation prior to ERA diagnosis. Multivariable logistic regression was used to identify sociodemographic and clinical measures associated with past episodic joint inflammation around the time of ERA diagnosis. RESULTS: A total of 154 ERA patients were included; 66% were female, and mean (SD) age and RA symptom duration were 54 (15) years and 141 (118) days. Sixty-five (42%) ERA patients reported a history of episodic joint pain and swelling, half of whom reported that these symptoms preceded ERA diagnosis by over 6 months. ERA patients with past episodic joint inflammation were more often female, had higher income, were seropositive, had more comorbidities, fewer swollen joints, and lower Clinical Disease Activity Index (CDAI) around the time of ERA diagnosis (P < 0.05). These associations remained significant in multivariable regression adjusting for other sociodemographic and RA clinical measures. CONCLUSION: Almost half of ERA patients experienced episodic joint inflammation prior to ERA diagnosis. These patients were more often female, had higher income, and presented with milder disease activity at ERA diagnosis.

Prevalence and Characteristics of Metabolic Syndrome Differ in Men and Women with Early Rheumatoid Arthritis.

Objective: Metabolic syndrome (MetS) prevalence in early rheumatoid arthritis (ERA) is conflicting. The impact of sex, including menopause, has not been described. We estimated the prevalence and factors associated with MetS in men and women with ERA. Methods: A cross-sectional study of the Canadian Early Arthritis Cohort (CATCH) was performed. Participants with baseline data to estimate key MetS components were included. Sex-stratified logistic regression identified baseline variables associated with MetS. Results: The sample included 1543 participants; 71% were female and the mean age was 54 (SD 15) years. MetS prevalence was higher in men 188 (42%) than women 288 (26%, P < 0.0001) and increased with age. Frequent MetS components in men were hypertension (62%), impaired glucose tolerance (IGT, 40%), obesity (36%), and low high-density lipoprotein cholesterol (36%). Postmenopausal women had greater frequency of hypertension (65%), IGT (32%), and high triglycerides (21%) compared with premenopausal women (P < 0.001). In multivariate analysis, MetS was negatively associated with seropositivity and pulmonary disease in men. Increasing age was associated with MetS in women. In postmenopausal women, corticosteroid use was associated with MetS. Psychiatric comorbidity was associated with MetS in premenopausal women. MetS status was not explained by disease activity or core RA measures. Conclusion: The characteristics and associations of MetS differed in men and women with ERA. Sex differences, including postmenopausal status, should be considered in comorbidity screening. With this knowledge, the interplay of MetS, sex, and RA therapeutic response on cardiovascular outcomes should be investigated.

Long-term effects of bosentan on quality of life, survival, safety and tolerability in pulmonary arterial hypertension related to connective tissue diseases.

OBJECTIVES: This study investigated the long-term effects of bosentan, an oral endothelin ET(A)/ET(B) receptor antagonist, in patients with pulmonary arterial hypertension (PAH) exclusively related to connective tissue diseases (CTD). METHODS: A total of 53 patients with PAH related to connective tissue diseases (PAH-CTD) in World Health Organization (WHO) functional class III received bosentan 62.5 mg twice a day for 4 weeks and then 125 mg twice a day for 44 weeks in this open non-comparative study. Assessments at weeks 16 and 48 included WHO class, clinical worsening, quality of life (Short-Form Health Survey (SF-36) and health assessment questionnaire (HAQ) modified for scleroderma), and survival (week 48 only). Safety and tolerability were monitored throughout the study. RESULTS: At week 48, WHO class improved in 27% of patients (95% CI 16-42%) and worsened in 16% (95% CI 7-29%). Kaplan-Meier estimates were 68% (95% CI 55-82%) for absence of clinical worsening and 92% (95% CI 85-100%) for survival. Overall changes in quality of life were minimal. There were no unexpected side effects observed during the study. CONCLUSIONS: In most patients, bosentan was associated with improvement or stability of clinical status. The 92% estimate for survival at 48 weeks is a significant achievement in this patient population.

Learning from past mistakes: assessing trial quality, power and eligibility in non-renal systemic lupus erythematosus randomized controlled trials.

OBJECTIVES: To evaluate the post hoc study power of randomized controlled trials (RCTs) in the treatment of non-renal SLE and to determine the generalizability of these RCTs using an SLE database. METHODS: RCTs in non-renal SLE were identified using PubMed (1975-2007). Inclusion/exclusion criteria, trial quality (5-point scale) and results of each study were recorded. The inclusion/exclusion criteria were compared with an SLE database to determine the proportion of patients from the database who would theoretically be eligible for these trials. For each negative study, we calculated the post hoc study power. We also looked for temporal improvements of trials in the literature and examined if pharmaceutical involvement influenced trial quality. RESULTS: Sixty-four articles were included; the mean power of 30 negative studies was 24.6 +/- s.e.m. 3.9% (range 2.5-81.1%). Only one study had a power > 80%. Overall, potential eligibility of SLE patients in the database was 45.1 +/- s.e.m. 3.6%. Only 14 studies (21.9%) were of good quality. Fortunately, RCT quality is improving over time (trials <1995, compared with 1996-2002 and >2003; P < 0.001). Trials with pharmaceutical involvement had a significantly higher number of enrollees and better study quality. CONCLUSIONS: Negative RCTs in SLE were mostly underpowered but the generalizability of these trials was high. Determination of study power and the impact of eligibility criteria on generalizability of study results are crucial in the design of clinical trials to ensure applicability to clinical practice.

Arthritis risk after acute bacterial gastroenteritis.

OBJECTIVES: Reactive arthritis (ReA) may occur from bacterial gastroenteritis. We studied the risk of arthritis after an outbreak of Escherichia coli O157:H7 and Campylobacter species within a regional drinking water supply to examine the relationship between the severity of acute diarrhoea and subsequent symptoms of arthritis. METHODS: Participants with no known history of arthritis before the outbreak participated in a long-term follow-up study. Of the 2299 participants, 788 were asymptomatic during the outbreak, 1034 had moderate symptoms of acute gastroenteritis and 477 had severe symptoms that necessitated medical attention. The outcomes of interest were new arthritis by self-report and a new prescription of medication for arthritis during the follow-up period. RESULTS: After a mean follow-up of 4.5 yrs after the outbreak, arthritis was reported in 15.7% of participants who had been asymptomatic during the outbreak, and in 17.6 and 21.6% of those who had moderate and severe symptoms of acute gastroenteritis, respectively (P-value for trend = 0.009). Compared with the asymptomatic participants, those with moderate and severe symptoms of gastroenteritis had an adjusted relative risk of arthritis of 1.19 [95% confidence interval (CI) 0.99-1.43] and 1.33 (95% CI 1.07-1.66), respectively. No association was observed between gastroenteritis and the subsequent risk of prescription medication for arthritis (P = 0.49). CONCLUSIONS: Acute bacterial gastroenteritis necessitating medical attention was associated with a higher risk of arthritic symptoms, but not arthritic medications, up to 4 yrs afterwards. The nature and chronicity of these arthritic symptoms requires further study.

Lack of correlation of the health assessment questionnaire disability index with lung parameters in systemic sclerosis associated pulmonary arterial hypertension.

OBJECTIVE: Pulmonary arterial hypertension (PAH) affects the quality of life (QoL) and the ability to perform the activities of daily living (ADLs) in patients with systemic sclerosis (SSc). We determined whether the Health Assessment Questionnaire-Disability Index (HAQ-DI), a self-assessment measure of function, correlates with a patient's PAH status in a population of SSc patients with PAH. METHODS: Forty-one patients from one centre with systemic scleroderma, dyspnea and PAH were included. All patients filled in a HAQ-DI, and underwent evaluation with pulmonary function tests (PFTs), 6-minute walk distance (6MWD), degree of dyspnea (Borg dyspnea index), NYHA functional class, and expert PAH physician global assessment every 6 months. Change in HAQ DI was studied to determine relationship to changes in PAH. RESULTS: The HAQ-DI scores had no significant correlation with PAH, including NYHA functional class (r=0.38, p=0.39), Borg dyspnea index (r=0.60, p=0.37), 6MWD (r=-0.04, p=0.86), % predicted DLCO (r=0.31, p=0.25), % predicted FVC (r=0.02, p=0.93), and expert PAH physician global assessment (r=0.06, p=0.97). CONCLUSION: HAQ-DI is not an adequate measure of PAH status in SSc patients with PAH. Although PAH causes severe morbidity and death, changes in PAH severity were not reflected in an overall functional status change as assessed by the HAQ-DI. Thus, HAQ-DI changes do not reflect PAH status in SSc.

The Pharmacology of Spinal Opioids and Ziconotide for the Treatment of Non-Cancer Pain.

BACKGROUND: Intrathecal drug delivery has undergone a revitalization following a better understanding of this delivery route and its pharmacokinetics. Driven by patient safety and outcomes, clinicians are motivated to rethink the traditional spinal infusion pump patient selection criteria and indications. We review the current understanding of the pharmacology of commonly employed intrathecal agents and the clinical relevance. METHODS: Search strategies for data acquisition included Medline database, PubMed, Google scholar, along with international and national professional meeting content, with key words including pharmacology of opioids, intrathecal therapy, ziconotide, pharmacokinetics, and intrathecal drug delivery. The search results were limited to the English language. RESULTS: Over 300 papers were identified. The literature was condensed and digested to evaluate the most commonly used medications in practice, sto serve as a foundation for review. We review on-label medications: ziconotide and morphine, and off label medications including fentanyl, sufentail, and hydromorphine. CONCLUSION: Intrathecal therapy has level-one evidence for use for malignant pain and nonmalignant pain, with continued cost savings and improved safety. To most effectively serve our patients, a clear appreciation for the pharmacology of these commonly employed medication is paramount.