Katherine Milette

The Scleroderma Patient-centered Intervention Network (SPIN) Cohort: protocol for a cohort multiple randomised controlled trial (cmRCT) design to support trials of psychosocial and rehabilitation interventions in a rare disease context

Introduction Psychosocial and rehabilitation interventions are increasingly used to attenuate disability and improve health-related quality of life (HRQL) in chronic diseases, but are typically not available for patients with rare diseases. Conducting rigorous, adequately powered trials of these interventions for patients with rare diseases is difficult. The Scleroderma Patient-centered Intervention Network (SPIN) is an international collaboration of patient organisations, clinicians and researchers. The aim of SPIN is to develop a research infrastructure to test accessible, low-cost self-guided online interventions to reduce disability and improve HRQL for people living with the rare disease systemic sclerosis (SSc or scleroderma). Once tested, effective interventions will be made accessible through patient organisations partnering with SPIN. Methods and analysis SPIN will employ the cohort multiple randomised controlled trial (cmRCT) design, in which patients consent to participate in a cohort for ongoing data collection. The aim is to recruit 1500–2000 patients from centres across the world within a period of 5 years (2013–2018). Eligible participants are persons ≥18 years of age with a diagnosis of SSc. In addition to baseline medical data, participants will complete patient-reported outcome measures every 3 months. Upon enrolment in the cohort, patients will consent to be contacted in the future to participate in intervention research and to allow their data to be used for comparison purposes for interventions tested with other cohort participants. Once interventions are developed, patients from the cohort will be randomly selected and offered interventions as part of pragmatic RCTs. Outcomes from patients offered interventions will be compared with outcomes from trial-eligible patients who are not offered the interventions. Ethics and dissemination The use of the cmRCT design, the development of self-guided online interventions and partnerships with patient organisations will allow SPIN to develop, rigourously test and effectively disseminate psychosocial and rehabilitation interventions for people with SSc.

Reporting of Conflicts of Interest in Meta-analyses of Trials of Pharmacological Treatments

CONTEXT Disclosure of conflicts of interest (COIs) from pharmaceutical industry study funding and author-industry financial relationships is sometimes recommended for randomized controlled trials (RCTs) published in biomedical journals. Authors of meta-analyses, however, are not required to report COIs disclosed in original reports of included RCTs. OBJECTIVE To investigate whether meta-analyses of pharmacological treatments published in high-impact biomedical journals report COIs disclosed in included RCTs. DATA SOURCES AND STUDY SELECTION We selected the 3 most recent meta-analyses of patented pharmacological treatments published January 2009 through October 2009 in each general medicine journal with an impact factor of at least 10; in high-impact journals in each of the 5 specialty medicine areas with the greatest 2008 global therapeutic sales (oncology, cardiology, respiratory medicine, endocrinology, and gastroenterology); and in the Cochrane Database of Systematic Reviews. DATA EXTRACTION Two investigators independently extracted data on disclosed study funding, author-industry financial ties, and author employment from each meta-analysis, from RCTs included in each meta-analysis, and on whether meta-analyses reported disclosed COIs of included RCTs. RESULTS Of 29 meta-analyses reviewed, which included 509 RCTs, only 2 meta-analyses (7%) reported RCT funding sources; and 0 reported RCT author-industry ties or employment by the pharmaceutical industry. Of 318 meta-analyzed RCTs that reported funding sources, 219 (69%) were industry funded; and 91 of 132 (69%) that reported author financial disclosures had 1 or more authors with pharmaceutical industry financial ties. In 7 of the 29 meta-analyses reviewed, 100% of included RCTs had at least 1 form of disclosed COI (pharmaceutical industry funding, author-industry financial ties, or employment), yet only 1 of these 7 meta-analyses reported RCT funding sources, and 0 reported RCT author-industry ties or employment. CONCLUSION Among a group of meta-analyses of pharmacological treatments published in high-impact biomedical journals, information concerning primary study funding and author COIs for the included RCTs were only rarely reported.

Comparison of the PHQ-9 and CES-D depression scales in systemic sclerosis: internal consistency reliability, convergent validity and clinical correlates

OBJECTIVE The reported rates of depressive symptoms in patients with SSc are high. The Center for Epidemiologic Studies Depression Scale (CES-D) is the only measure of depressive symptoms validated for SSc patients. The objective of this study was to assess the internal consistency reliability, convergent validity and strength of association with clinical correlates of the 9-item version of the Patient Health Questionnaire depression scale (PHQ-9) compared with the CES-D in SSc. METHODS We conducted a cross-sectional, multicentre study of 566 SSc patients who were assessed with the PHQ-9 and CES-D scales, and through clinical histories and medical examinations. Internal consistency reliability was assessed with Cronbachs alpha, convergent validity with Pearsons correlation and the relationship of socio-demographic and clinical variables with the PHQ-9 and CES-D scores using multiple linear regression. RESULTS Scale reliability was good for the PHQ-9 (alpha = 0.87) and similar to the CES-D (alpha = 0.90). Correlations of the PHQ-9 total score were -0.68 with mental health, -0.43 with physical health, 0.44 with disability, 0.40 with pain and 0.79 with fatigue, which were all in the expected direction and similar to the results with the CES-D. Regression coefficients of clinical correlates did not differ significantly between models using the PHQ-9 and CES-D. CONCLUSION The PHQ-9 is reliable and valid for use as a measure of depressive symptom severity in patients with SSc and performs similarly to the CES-D. However, the PHQ-9 is advantageous because it is half the length of the CES-D, easily administered and scored, and is increasingly used across many patient groups for assessment in research and clinical settings.

Effects of screening for psychological distress on patient outcomes in cancer: A systematic review

OBJECTIVE Several practice guidelines recommend routine screening for psychological distress in cancer care. The objective was to evaluate the effect of screening cancer patients for psychological distress by assessing the (1) effectiveness of interventions to reduce distress among patients identified as distressed; and (2) effects of screening for distress on distress outcomes. METHODS CINAHL, Cochrane, EMBASE, ISI, MEDLINE, PsycINFO, and SCOPUS databases were searched through April 6, 2011 with manual searches of 45 relevant journals, reference list review, citation tracking of included articles, and trial registry reviews through June 30, 2012. Articles in any language on cancer patients were included if they (1) compared treatment for patients with psychological distress to placebo or usual care in a randomized controlled trial (RCT); or (2) assessed the effect of screening on psychological distress in a RCT. RESULTS There were 14 eligible RCTs for treatment of distress, and 1 RCT on the effects of screening on patient distress. Pharmacological, psychotherapy and collaborative care interventions generally reduced distress with small to moderate effects. One study investigated effects of screening for distress on psychological outcomes, and it found no improvement. CONCLUSION Treatment studies reported modest improvement in distress symptoms, but only a single eligible study was found on the effects of screening cancer patients for distress, and distress did not improve in screened patients versus those receiving usual care. Because of the lack of evidence of beneficial effects of screening cancer patients for distress, it is premature to recommend or mandate implementation of routine screening.

Psychological health and well-being in systemic sclerosis: State of the science and consensus research agenda.

Introduction Systemic sclerosis (SSc; scleroderma) is a multisystem disorder characterized by disturbance in fibroblast function, microvascular disease, and immune system activation, culminating in fibrosis of the skin and internal organs (1,2). SSc is associated with extensive morbidity, including disfiguring skin thickening, finger ulcers, joint contractures, pulmonary hypertension, interstitial lung disease, chronic diarrhea, and renal failure (1,2). The rate of disease onset is highest between 30 and 50 years of age, with the risk for women being 4 to 5 times higher than for men (3,4). Median survival time from diagnosis is 11 years, and patients are 3.7 times more likely to die within 10 years of diagnosis (44.9% mortality) than age-, sex-, and race-matched individuals without SSc (12.0% mortality) (3).

Depression Screening and Patient Outcomes in Cancer: A Systematic Review

Background Several practice guidelines recommend screening for depression in cancer care, but no systematic reviews have examined whether there is evidence that depression screening benefits cancer patients. The objective was to evaluate the potential benefits of depression screening in cancer patients by assessing the (1) accuracy of depression screening tools; (2) effectiveness of depression treatment; and (3) effect of depression screening, either alone or in the context of comprehensive depression care, on depression outcomes. Methods Data sources were CINAHL, Cochrane, EMBASE, ISI, MEDLINE, PsycINFO and SCOPUS databases through January 24, 2011; manual journal searches; reference lists; citation tracking; trial registry reviews. Articles on cancer patients were included if they (1) compared a depression screening instrument to a valid criterion for major depressive disorder (MDD); (2) compared depression treatment with placebo or usual care in a randomized controlled trial (RCT); (3) assessed the effect of screening on depression outcomes in a RCT. Results There were 19 studies of screening accuracy, 1 MDD treatment RCT, but no RCTs that investigated effects of screening on depression outcomes. Screening accuracy studies generally had small sample sizes (median = 17 depression cases) and used exploratory methods to set sample-specific cutoff scores that varied substantially across studies. A nurse-delivered intervention for MDD reduced depressive symptoms moderately (effect size = 0.37). Conclusions The one treatment study reviewed reported modest improvement in depressive symptoms, but no evidence was found on whether or not depression screening in cancer patients, either alone or in the context of optimal depression care, improves depression outcomes compared to usual care. Depression screening in cancer should be evaluated in a RCT in which all patients identified as depressed, either through screening or via physician recognition and referral in a control group, have access to comprehensive depression care.

Transparency of outcome reporting and trial registration of randomized controlled trials in top psychosomatic and behavioral health journals: A systematic review

OBJECTIVE The extent that randomized controlled trials (RCTs) accurately reflect intervention effectiveness depends on the completeness and accuracy of published results. A previous study found that only 40% of 63 RCTs published in top behavioral health journals in 2008-2009 clearly declared primary and secondary outcomes and only 21% were registered. The objective of this study was to conduct a five-year follow-up to assess outcome reporting clarity, proportion of registered trials, and adequacy of outcome registration in RCTs in top behavioral health journals. METHOD Eligible studies were RCTs published in Annals of Behavioral Medicine, Health Psychology, Journal of Psychosomatic Research, and Psychosomatic Medicine from January 2013 to October 2014. RESULTS Of 76 RCT publications reviewed, only 25 (32.9%) adequately declared primary or secondary outcomes, whereas 51 (67.1%) had multiple primary outcomes or did not define outcomes. Of the 76 trials, 40 (52.6%) had been registered. Only 3 studies registered a single primary outcome and time point of assessment prior to enrolling patients, and registered and published outcomes were discrepant in 1 of the 3 studies. No studies were adequately registered as per Standard Protocol Items: Recommendation for Interventional Trials guidelines. Compared to 5 years prior, the proportion of published trials with adequate outcome declaration decreased from 39.7% to 32.9% (p=0.514). The proportion of registered trials increased from 20.6% to 52.6% (p<0.001). CONCLUSION The quality of published outcome declarations and trial registrations remains largely inadequate. Greater attention to trial registration and outcome definition in published reports is needed.

Clinical correlates of sleep problems in systemic sclerosis: the prominent role of pain

OBJECTIVE Problems with sleep are common in patients with SSc and impact daily function. Little research, however, has examined factors associated with sleep disruption in SSc. Therefore, the objective of this study was to investigate socio-demographic and medical factors associated with sleep disruption in SSc. METHODS Cross-sectional study of 70 patients from one Canadian Scleroderma Research Group site who were assessed with a 100-mm sleep disruption visual analogue scale (VAS). Patients also completed measures of pain and depressive symptoms and underwent clinical histories and medical examinations. Pearsons correlations were used to assess bivariate association of socio-demographic and medical variables with sleep VAS scores. Multivariable associations of socio-demographic (Step 1) and medical (Step 2) variables with sleep VAS scores were assessed using hierarchical multiple linear regression. RESULTS The mean (s.d.) sleep disruption VAS score was 38.5 (29.9). In bivariate analyses, sleep disruption was associated with marital status (r = -0.24, P = 0.042), smoking (r = 0.27, P = 0.025), gastrointestinal symptoms (r = 0.27, P = 0.023), breathing problems (r = 0.31, P = 0.009), pain (r = 0.53, P < 0.001) and symptoms of depression (r = 0.34, P = 0.004). In multivariate analysis, only marital status (standardized β = -0.24, P = 0.049) and pain (standardized β = 0.50, P < 0.001) were significantly associated with sleep disruption. CONCLUSION Sleep disruption scores were as high in SSc as in RA and higher than in the general population. Pain was robustly associated with sleep disruption. Additional research is needed on sleep in SSc so that well-informed sleep interventions can be developed and tested.

Psychosocial Aspects of Scleroderma.

Patients with systemic sclerosis (SSc; also called scleroderma) have to cope with not only the physical impacts of the disease but also the emotional and social consequences of living with the condition. Because there is no cure for SSc, improving quality of life is a primary focus of treatment and an important clinical challenge. This article summarizes significant problems faced by patients with SSc, including depression, anxiety, fatigue, sleep disruption, pain, pruritus, body image dissatisfaction, and sexual dysfunction, and describes options to help patients cope with the consequences of the disease.

Sleep disturbances in systemic sclerosis: evidence for the role of gastrointestinal symptoms, pain and pruritus

OBJECTIVE SSc is a rare autoimmune CTD characterized by thickening and fibrosis of skin and internal organs. There is significant mortality and no cure. Sleep disturbance has been identified as an important contributor to poor quality of life. The objective was to investigate socio-demographic and medical factors potentially associated with sleep disturbance in SSc. METHODS The sample consisted of patients from the Canadian Scleroderma Research Groups (CSRG) 15-centre, pan-Canadian Registry assessed with the 8-item Patient-Reported Outcome Measurement Information System (PROMIS) sleep disturbance scale short form, version 1.0. Pearsons correlations were used to assess bivariate association of socio-demographic and medical variables with PROMIS sleep scores. The independent association of PROMIS sleep disturbance scores and factors previously identified as associated with sleep disturbance in the general population, in SSc and other rheumatic diseases, was assessed using multiple linear regression. RESULTS Among 397 patients in the study (88% female, mean age 57.5 years), 25% (n = 98) had diffuse cutaneous SSc. Mean duration since onset of non-RP symptoms was 10.6 years. Number of gastrointestinal symptoms (standardized regression coefficient β = 0.19, P = 0.001), pain severity (β = 0.21, P < 0.001) and pruritus severity (β = 0.13, P = 0.024) were independently associated with more severe sleep disturbance. CONCLUSION Gastrointestinal symptoms, pain and pruritus were associated with sleep disturbance in SSc. Additional research is needed on sleep in SSc so that well-informed sleep interventions can be developed and tested.