A practical approach to the evaluation and management of gastrointestinal symptoms in patients with systemic sclerosis

The gastrointestinal (GI) tract is the most commonly affected internal organ system in systemic sclerosis (SSc). SSc may lead to impaired function in any region of the GI tract, from the esophagus to the anorectum, which causes significant morbidity as well as mortality in patient subsets. Given the low prevalence of SSc in the community, many rheumatologists may not have a systematic framework for diagnosing or treating the GI complaints in this disease. These practice recommendations aim to summarize and consolidate the current guidelines from the fields of gastroenterology and rheumatology and establish a symptom-based framework for diagnosis and management based on available evidence in the literature. Subject areas that are in need of additional research are also identified.     

The microbiome and systemic sclerosis: A review of current evidence

Systemic sclerosis (SSc) is characterized by immune dysregulation, vasculopathy, and fibrosis of multiple organs. The gastrointestinal (GI) tract is the most common internal organ manifestation, which contributes to significant morbidity and mortality in patients with SSc. Emerging reports have identified unique microbial taxa alterations in the GI microbiome of patients with SSc as compared to healthy controls (HC). These taxa alterations include differences at the phyla (e.g., Bacteroidetes) and genera (e.g., Bacteroides, Clostridium, Faecalibacterium, and Lactobacillus) level. In addition, some genera have been associated with more severe GI symptoms (e.g., Prevotella and Akkermansia). This review summarizes the current evidence on factors influencing the GI microbiome, GI microbiome alterations in SSc as compared to HC, and in SSc subgroups according to disease manifestations. Current exploration in therapeutic interventions that target the GI microbiome is discussed.     

Morbidity and mortality of patients diagnosed with systemic sclerosis after the age of 75: a nested case-control study

This study aims to characterize the clinical features of a cohort of patients diagnosed with systemic sclerosis (SSc) after the age of 75 and compare them to a group diagnosed at a younger age. We record the review of 769 patients diagnosed with SSc over the past 16 years. Utilizing a nested case-control model, we compare demographics, disease severity, morbidity, and mortality data of all patients diagnosed after the age of 75 to sex- and disease-type-matched, randomly selected group of patients diagnosed with SSc before the age of 60. Twelve patients were diagnosed with SSc after the age of 75, seven with the diffuse, and five with the limited form. It took longer to diagnose SSc in the older patients, and comparison of disease severity revealed a worse pulmonary picture and a more frequent development of malignancy in the older patients as compared with the younger ones. During a mean follow-up of 36.2 months, our cohort of patients did not have worsening in their disease severity, though 6 months after the last follow-up, six patients died. We conclude that a diagnosis of SSc at an older age appears to be a poor prognostic indicator related to both disease severity and comorbidities. A higher clinical suspicion will lead to an earlier diagnosis and a potential decrease in morbidity and mortality.     

A systematic review of recommendations and guidelines for the management of osteoarthritis: The Chronic Osteoarthritis Management Initiative of the U.S. Bone and Joint Initiative

Purpose

Although a number of osteoarthritis (OA) management guidelines exist, uptake has been suboptimal. Our aim was to review and critically evaluate existing OA management guidelines to better understand potential issues and barriers.

Methods

A systematic review of the literature in MEDLINE published from January 1, 2000 to April 1, 2013 was performed and supplemented by bibliographic reviews, following PRISMA guidelines and a written protocol. Following initial title and abstract screening, 2 authors independently reviewed full-text articles; a third settled disagreements. Two independent reviewers extracted data into a standardized form. Two authors independently assessed guideline quality using the AGREE II instrument; three generated summary recommendations based on the extracted guideline data.

Results

Overall, 16 articles were included in the final review. There was broad agreement on recommendations by the various organizations. For non-pharmacologic modalities, education/self-management, exercise, weight loss if overweight, walking aids as indicated, and thermal modalities were widely recommended. For appropriate patients, joint replacement was recommended; arthroscopy with debridement was not recommended for symptomatic knee OA. Pharmacologic modalities most recommended included acetaminophen/paracetamol (first line) and NSAIDs (topical or oral, second line). Intra-articular corticosteroids were generally recommended for hip and knee OA. Controversy remains about the use of acupuncture, knee braces, heel wedges, intra-articular hyaluronans, and glucosamine/chondroitin.

Conclusions

The relative agreement on many OA management recommendations across organizations indicates a problem with dissemination and implementation rather than a lack of quality guidelines. Future efforts should focus on optimizing implementation in primary care settings, where the majority of OA care occurs.     

A comprehensive framework for navigating patient care in systemic sclerosis: A global response to the need for improving the practice of diagnostic and preventive strategies in SSc

Systemic sclerosis (SSc), the most lethal of rheumatologic conditions, is the cause of death in >50% of SSc cases, led by pulmonary fibrosis followed by pulmonary hypertension and then scleroderma renal crisis (SRC). Multiple other preventable and treatable SSc-related vascular, cardiac, gastrointestinal, nutritional and musculoskeletal complications can lead to disability and death.Vascular injury with subsequent inflammation transforming to irreversible fibrosis and permanent damage characterizes SSc. Organ involvement is often present early in the disease course of SSc, but requires careful history-taking and vigilance in screening to detect. Inflammation is potentially reversible provided that treatment intensity quells inflammation and other immune mechanisms. In any SSc phenotype, opportunities for early treatment are prone to be under-utilized, especially in slowly progressive phenotypes that, in contrast to severe progressive ILD, indolently accrue irreversible organ damage resulting in later-stage life-limiting complications such as pulmonary hypertension, cardiac involvement, and malnutrition.A single SSc patient visit often requires much more physician and staff time, organization, vigilance, and direct management for multiple organ systems compared to other rheumatic or pulmonary diseases. Efficiency and efficacy of comprehensive SSc care enlists trending of symptoms and bio-data. Financial sustainability of SSc care benefits from understanding insurance reimbursement and health system allocation policies for complex patients. Sharing care between recognised SSc centers and local cardiology/pulmonary/rheumatology/gastroenterology colleagues may prevent complications and poor outcomes, while providing support to local specialists.As scleroderma specialists, we offer a practical framework with tools to facilitate an optimal, comprehensive and sustainable approach to SSc care. Improved health outcomes in SSc relies upon recogntion, management and, to the extent possible, prevention of SSc and treatment-related complications.     

Health‐related quality of life in systemic sclerosis as measured by the short form 36: Relationship with clinical and biologic markers

Objective

To evaluate health‐related quality of life (HRQOL) in patients with systemic sclerosis (SSc) using the Short Form 36 (SF‐36) and to correlate SF‐36 scores with clinical and biologic markers.

Methods

The SF‐36 was administered to 24 controls and 24 SSc patients. SSc patients also were evaluated for subset (limited SSc [lSSc] and diffuse SSc [dSSc]), age, disease duration, angiotensin‐converting enzyme (ACE) levels, autoantibodies, and skin and internal organ involvement.

Results

The physical summary score (PSS) was lower in SSc patients than in controls (P < 0.05), whereas the mental summary score (MSS) was higher in dSSc than in lSSc patients (P < 0.05). Five of 8 single SF‐36 domain scores were lower in SSc patients than in controls (P < 0.05). Vitality was higher in dSSc than in controls (P < 0.001). In SSc, elder age correlated with lower PSS; low ACE levels and high skin score correlated with higher general mental health and role limitations due to physical problems, respectively (P < 0.05). Patients with heart involvement had higher scores in general health perceptions (P < 0.05).

Conclusion

The SF‐36 shows that HRQOL is impaired in patients with SSc. Higher scores in MSS and vitality in patients with dSSc and correlations of high SF‐36 scores with specific organ involvement suggest that SSc patients with severe disease are more able to cope with HRQOL modification.

     

Assessing disability and quality of life in systemic sclerosis: Construct validities of the Cochin Hand Function Scale,Health Assessment Questionnaire (HAQ), Systemic Sclerosis HAQ,and Medical Outcomes Study 36‐Item Short Form Health Survey

Objective

To assess the construct validity of the Cochin Hand Function Scale (CHFS) and the relevance of using aggregate scores for the scleroderma Health Assessment Questionnaire (sHAQ) and Medical Outcomes Study 36‐Item Short Form Health Survey (SF‐36) in systemic sclerosis (SSc).

Methods

We evaluated 50 patients with SSc (mean ± SD age and disease duration 54 ± 12 years and 9 ± 8 years, respectively), of which 26 had limited cutaneous SSc (lcSSc) and 23 diffuse SSc (dSSc). Quality of life was assessed by the SF‐36, global disability by the Health Assessment Questionnaire (HAQ) and sHAQ, and hand disability by the CHFS. Construct validity was assessed by convergent and divergent validity (Spearman's rank correlation coefficient) and factor analysis.

Results

The CHFS had good construct validity and its total score explained 75% of the variance of the HAQ. The HAQ had better construct validity than the aggregate sHAQ and their scores correlated well (r = 0.88). The aggregate sHAQ was no better than the HAQ in discriminating between lcSSc and dSSc. SF‐36 physical and mental components had acceptable convergent and divergent validity. Factor analysis of the 8 subscales extracted 3 factors explaining 72% of the variance, which differed from the a priori stratification with physical and mental subscales extracted in the same factor.

Conclusion

In patients with SSc, the CHFS has good construct validity, the HAQ should be preferred over the aggregate sHAQ for assessing physical functioning, and use of SF‐36 physical and mental components aggregate scores is questionable.     

A systematic review of recommendations and guidelines for the management of osteoarthritis: The Chronic Osteoarthritis Management Initiative of the U.S. Bone and Joint Initiative

PurposeAlthough a number of osteoarthritis (OA) management guidelines exist, uptake has been suboptimal. Our aim was to review and critically evaluate existing OA management guidelines to better understand potential issues and barriers.MethodsA systematic review of the literature in MEDLINE published from January 1, 2000 to April 1, 2013 was performed and supplemented by bibliographic reviews, following PRISMA guidelines and a written protocol. Following initial title and abstract screening, 2 authors independently reviewed full-text articles; a third settled disagreements. Two independent reviewers extracted data into a standardized form. Two authors independently assessed guideline quality using the AGREE II instrument; three generated summary recommendations based on the extracted guideline data.ResultsOverall, 16 articles were included in the final review. There was broad agreement on recommendations by the various organizations. For non-pharmacologic modalities, education/self-management, exercise, weight loss if overweight, walking aids as indicated, and thermal modalities were widely recommended. For appropriate patients, joint replacement was recommended; arthroscopy with debridement was not recommended for symptomatic knee OA. Pharmacologic modalities most recommended included acetaminophen/paracetamol (first line) and NSAIDs (topical or oral, second line). Intra-articular corticosteroids were generally recommended for hip and knee OA. Controversy remains about the use of acupuncture, knee braces, heel wedges, intra-articular hyaluronans, and glucosamine/chondroitin.ConclusionsThe relative agreement on many OA management recommendations across organizations indicates a problem with dissemination and implementation rather than a lack of quality guidelines. Future efforts should focus on optimizing implementation in primary care settings, where the majority of OA care occurs.     

Quantity and quality of complementary and alternative medicine recommendations in clinical practice guidelines for type 2 diabetes mellitus: A systematic review

AimsApproximately 70% of Americans with diabetes have used complementary and alternative medicine (CAM) in the past year. Healthcare providers often receive minimal training on these therapies and subsequently rely on clinical practice guidelines (CPGs) to supplement their knowledge about the safe and effective use of CAM for the treatment/management of type 2 diabetes mellitus (T2DM). The purpose of this systematic review is to determine the quantity and assess the quality of CAM recommendations in CPGs for the treatment and/or management of T2DM.Data synthesisMEDLINE, EMBASE, and CINAHL were systematically searched from 2009 to 2020, in addition to the Guidelines International Network and the National Center for Complementary and Integrative Health websites. CPGs containing treatment and/or management recommendations for T2DM were eligible; those with CAM recommendations were quality-assessed with the AGREE II instrument twice, once for the overall CPG and once for the CAM sections. Twenty-seven CPGs were deemed eligible, of which 7 made CAM recommendations. Mean scaled domain percentages were (overall, CAM): scope and purpose (89.7%, 79.8%), clarity of presentation (85.7%, 48.4%), stakeholder involvement (67.9%, 28.2%), applicability (54.8%, 20.2%), rigour of development (49.7%, 35.7%), and editorial independence (44.1%, 44.1%).ConclusionsQuality varied within and across CPGs; domain scores across CAM sections generally scored lower than the overall CPG. Given that CAM therapies for T2DM are only represented in one-quarter of eligible CPGs and are of lower quality, a knowledge gap exists for healthcare providers who seek evidence-based information on this topic in order to effectively counsel inquiring patients.     

Lung CT densitometry in systemic sclerosis: correlation with lung function, exercise testing, and quality of life

BACKGROUND: To ascertain if analysis of lung density histograms in thin-section CT was more reproducible than visual assessment of lung changes in systemic sclerosis (SSc), and if such density histogram parameters as mean lung attenuation (MLA), skewness, and kurtosis could more closely reflect pulmonary function as well as exercise and quality of life impairment. METHODS: The intraoperator and interoperator reproducibility of visual and densitometric lung CT analysis in 48 SSc patients examined with CT were evaluated by means of weighted kappa statistics. Univariate and multivariate regression analyses were applied to evaluate the relationship of visual and densitometric CT measurements with functional parameters including functional residual capacity (FRC), FVC, FEV(1), diffusion capacity of the lung for carbon monoxide (Dlco), 6-min walking testing (6MWT), and health-related quality of life questionnaire (QLQ) parameters. RESULTS: The intraoperator and interoperator reproducibility of MLA (intraobserver weighted kappa = 0.97; interobserver weighted kappa = 0.96), skewness (intraobserver weighted kappa = 0.89; interobserver weighted kappa = 0.88), and kurtosis (intraobserver weighted kappa = 0.89; interobserver weighted kappa = 0.88) were higher than those of visual assessment (intraobserver weighted kappa = 0.71; interobserver weighted kappa = 0.69). In univariate analysis, only densitometric measurements were correlated with some exercise and QLQ parameters. In multivariate analysis, MLA (square regression coefficient corrected [R(2)c] = 0.70), skewness (R(2)c = 0.78), and kurtosis (R(2)c = 0.77) were predicted by FRC, FVC, Dlco, 6MWT, and QLQ parameters, while visual assessment was associated only with FRC and FVC (R(2)c = 0.40). CONCLUSIONS: In SSc, densitometric analysis is more reproducible than visual assessment of lung changes in thin-section CT and more closely correlated to pulmonary function testing, 6MWT, and QLQ. Density histogram parameters may be useful for cross-sectional and longitudinal studies of lung involvement in SSc.     

French practical guidelines for the diagnosis and management of relapsing polychondritis

Relapsing polychondritis is a rare systemic disease. It usually begins in middle-aged individuals. This diagnosis is mainly suggested in the presence of chondritis, i.e. inflammatory flares on the cartilage, in particular of the ears, nose or respiratory tract, and more rarely in the presence of other manifestations. The formal diagnosis of relapsing polychondritis cannot be established with certainty before the onset of chondritis, which can sometimes occur several years after the first signs. No laboratory test is specific of relapsing polychondritis, the diagnosis is usually based on clinical evidence and the elimination of differential diagnoses. Relapsing polychondritis is a long-lasting and often unpredictable disease, evolving in the form of relapses interspersed with periods of remission that can be very prolonged. Its management is not codified and depends on the nature of the patient's symptoms and association or not with myelodysplasia/vacuoles, E1 enzyme, X linked, autoinflammatory, somatic (VEXAS). Some minor forms can be treated with non-steroidal anti-inflammatory drugs, or a short course of corticosteroids with possibly a background treatment of colchicine. However, the treatment strategy is often based on the lowest possible dosage of corticosteroids combined with background treatment with conventional immunosuppressants (e.g. methotrexate, azathioprine, mycophenolate mofetil, rarely cyclophosphamide) or targeted therapies. Specific strategies are required if relapsing polychondritis is associated with myelodysplasia/VEXAS. Forms limited to the cartilage of the nose or ears have a good prognosis. Involvement of the cartilage of the respiratory tract, cardiovascular involvement, and association with myelodysplasia/VEXAS (more frequent in men over 50 years of age) are detrimental to the prognosis of the disease.     

International comparisons of the management of patients with non-ST segment elevation acute myocardial infarction in the United Kingdom,Sweden, and the United States: The MINAP/NICOR,SWEDEHEART/RIKS-HIA,and ACTION Registry-GWTG/NCDR registries

Objectives

To compare management of patients with acute non-ST segment elevation myocardial infarction (NSTEMI) in three developed countries with national ongoing registries.

Background

Results from clinical trials suggest significant variation in care across the world. However, international comparisons in “real world” registries are limited.

Methods

We compared the use of in-hospital procedures and discharge medications for patients admitted with NSTEMI from 2007 to 2010 using the unselective MINAP/NICOR [England and Wales (UK); n = 137,009], the unselective SWEDEHEART/RIKS-HIA (Sweden; n = 45,069), and the selective ACTION Registry-GWTG/NCDR [United States (US); n = 147,438] clinical registries.

Results

Patients enrolled among the three registries were generally similar except those in the US who were younger but had higher rates of smoking, diabetes, hypertension, prior heart failure, and prior MI than in Sweden or in UK. Angiography and percutaneous coronary intervention (PCI) were performed more often in the US (76% and 44%) and Sweden (65% and 42%) relative to the UK (32% and 22%). Discharge betablockers were also prescribed more often in the US (89%) and Sweden (89%) than in the UK (76%). In contrast, discharge statins, angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB), and dual antiplatelet agents (among those not receiving PCI) were higher in the UK (92%, 79%, and 71%) than in the US (85%, 65%, 41%) and Sweden (81%, 69%, and 49%).

Conclusions

The care for patients with NSTEMI differed substantially among the three countries. These differences in care among countries provide an opportunity for future comparative effectiveness research as well as identify opportunities for global quality improvement.     

Managing the residual cardiovascular disease risk associated with HDL-cholesterol and triglycerides in statin-treated patients: A clinical update

Cardiovascular disease (CVD) is a significant cause of death in Europe. In addition to patients with proven CVD, those with type 2 diabetes (T2D) are at a particularly high-risk of CVD and associated mortality. Treatment for dyslipidaemia, a principal risk factor for CVD, remains a healthcare priority; evidence supports the reduction of low-density lipoprotein cholesterol (LDL-C) as the primary objective of dyslipidaemia management.While statins are the treatment of choice for lowering LDL-C in the majority of patients, including those with T2D, many patients retain a high CVD risk despite achieving the recommended LDL-C targets with statins. This ‘residual risk’ is mainly due to elevated triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) levels. Following statin therapy optimisation additional pharmacotherapy should be considered as part of a multifaceted approach to risk reduction. Fibrates (especially fenofibrate) are the principal agents recommended for add-on therapy to treat elevated TG or low HDL-C levels. Currently, the strongest evidence of benefit is for the addition of fenofibrate to statin treatment in high-risk patients with T2D and dyslipidaemia. An alternative approach is the addition of agents to reduce LDL-C beyond the levels attainable with statin monotherapy.Here, addition of fibrates and niacin to statin therapy is discussed, and novel approaches being developed for HDL-C and TG management, including cholesteryl ester transfer protein inhibitors, Apo A-1 analogues, mipomersen, lomitapide and monoclonal antibodies against PCSK9, are reviewed.