A drug free solution for improving the quality of life of fibromyalgia patients (Fibrepik): study protocol of a multicenter, randomized, controlled effectiveness trial.

BACKGROUND: Fibromyalgia is a form of chronic widespread pain that is defined as a syndrome of chronic symptoms of moderate to severe intensity, including diffuse pain, fatigue, sleep disturbance, cognitive impairment, and numerous somatic complaints. To date, there is no specific drug treatment for fibromyalgia but only symptomatic treatments. A drug free solution based on a wristband that emits millimeter waves associated with a therapeutic coaching program was developed. The application of millimeter waves on an innervated area has been described to have a neuromodulating effect, due to endorphin release stimulation and parasympathetic activation. Coaching is carried out to improve the patient's adherence and to increase compliance and effectiveness of the treatment. Regular use of this solution by fibromyalgia patients is expected to improve sleep quality, reduce anxiety and pain levels, and, at the end, increase the quality of life. METHODS: This trial is performed over 8 French inclusion centers for a total of 170 patients. The effectiveness of the solution is evaluated according to the primary objective, the improvement of the quality of life measured through the dedicated Fibromyalgia Impact Questionnaire after 3 months. Patients are randomized in two groups, Immediate or Delayed. The Immediate group has access to the solution just after randomization in addition to standard care, while Delayed has access to the standard of care and waits for 3 months to have the solution. The purpose of this methodology is to limit deception bias and facilitate inclusion. The solution consists in using the device for three sessions of 30 min per day and four coaching sessions spread over the first 2 months of wristband usage. DISCUSSION: The objective is to confirm the effect of the integrative approach based on endorphin stimulation and a therapeutic coaching program in nociplastic pain and specifically for the patient suffering from fibromyalgia. If the effectiveness of the solution is demonstrated, we will be able to respond to the demand of fibromyalgia patients for access to an effective non-medicinal treatment to improve their quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT05058092.

The impact of pathogen-reduced platelets in acute leukaemia treatment on the total blood product requirement: a subgroup analysis of an EFFIPAP randomised trial.

OBJECTIVE: To evaluate the impact of pathogen-reduced (PR) platelet transfusions on blood products requirement for clinical practice. BACKGROUND: PR platelets are increasing in use as standard blood products. However, few randomised trials have evaluated their impact on bleeding control or prevention. Furthermore, PR platelets recirculate less than untreated platelets. METHODS: A subgroup study of the randomised clinical trial EFFIPAP compared three arms of platelet preparations (PR: P-PRP/PAS, additive solution: P-PAS and plasma P-P arms respectively). The subgroup of acute leukaemia patients, in their chemotherapy induction phase, included 392 patients (133 P-PRP/PAS arm, 132 P-PAS arm and 130 P-P arm). Blood requirements were analysed across over periods of 7 days. RESULTS: The number of platelet transfusions per week was significantly higher in the P-PRP/PAS group 2.3 [1.6-3.3] compared to the control groups 1.9 [1.3-2.8] and 2.0 [1.3-3.0] for P-P and P-PAS groups respectively (p < 0.0001). However, the total number of platelets transfused per week was not different. The number of red blood cell concentrates (RBC) transfusion per week did not differ either. CONCLUSION: In a homogeneous group of patients, platelet pathogen reduction resulted in an increased number of platelet units transfused per week while having no impact on the total number of platelets transfused or the number of RBC transfusion; resulting to an average requirement of 2 RBC and 2-3 platelets transfusions per week of marrow aplasia.

Effect of Prophylactic Embolization on Patients With Blunt Trauma at High Risk of Splenectomy: A Randomized Clinical Trial.

Importance: Splenic arterial embolization (SAE) improves the rate of spleen rescue, yet the advantage of prophylactic SAE (pSAE) compared with surveillance and then embolization only if necessary (SURV) for patients at high risk of spleen rupture remains controversial. Objective: To determine whether the 1-month spleen salvage rate is better after pSAE or SURV. Design, Setting, and Participants: In this randomized clinical trial conducted between February 6, 2014, and September 1, 2017, at 16 institutions in France, 133 patients with splenic trauma at high risk of rupture were randomized to undergo pSAE or SURV. All analyses were performed on a per-protocol basis, as well as an intention-to-treat analysis for specific events. Interventions: Prophylactic SAE, preferably using an arterial approach via the femoral artery, or SURV. Main Outcomes and Measures: The primary end point was an intact spleen or a spleen with at least 50% vascularized parenchyma detected on an arterial computed tomography scan at 1 month after trauma, assessed by senior radiologists masked to the treatment group. Secondary end points included splenectomy and pseudoaneurysm, secondary SAE after inclusion, complications, length of hospital stay, quality-of-life score, and length of time off work or studies during the 6-month follow-up. Results: A total of 140 patients were randomized, and 133 (105 men [78.9%]; median age, 30 years [interquartile range, 23-47 years]) were retained in the study. For the primary end point, data from 117 patients (57 who underwent pSAE and 60 who underwent SURV) could be analyzed. The number of patients with at least a 50% viable spleen detected on a computed tomography scan at month 1 was not significantly different between the pSAE and SURV groups (56 of 57 [98.2%] vs 56 of 60 [93.3%]; difference, 4.9%; 95% CI, -2.4% to 12.1%; P = .37). By the day 5 visit, there were significantly fewer splenic pseudoaneurysms among patients in the pSAE group than in the SURV group (1 of 65 [1.5%] vs 8 of 65 [12.3%]; difference, -10.8%; 95% CI, -19.3% to -2.1%; P = .03), significantly fewer secondary embolizations among patients in the pSAE group than in the SURV group (1 of 65 [1.5%] vs 19 of 65 [29.2%]; difference, -27.7%; 95% CI, -41.0% to -15.9%; P < .001), and no difference in the overall complication rate between the pSAE and SURV groups (19 of 65 [29.2%] vs 27 of 65 [41.5%]; difference, -12.3%; 95% CI, -28.3% to 4.4%; P = .14). Between the day 5 and month 1 visits, the overall complication rate was not significantly different between the pSAE and SURV groups (11 of 59 [18.6%] vs 12 of 63 [19.0%]; difference, -0.4%; 95% CI, -14.4% to 13.6%; P = .96). The median length of hospitalization was significantly shorter for patients in the pSAE group than for those in the SURV group (9 days [interquartile range, 6-14 days] vs 13 days [interquartile range, 9-17 days]; P = .002). Conclusions and Relevance: Among patients with splenic trauma at high risk of rupture, the 1-month spleen salvage rate was not statistically different between patients undergoing pSAE compared with those receiving SURV. In view of the high proportion of patients in the SURV group needing SAE, both strategies appear defendable. Trial Registration: ClinicalTrials.gov Identifier: NCT02021396.

Non-invasive fibrosis tests to predict complications in compensated post-hepatitis C cirrhosis.

BACKGROUND AND AIMS: Markers predicting complications of post-hepatitis C cirrhosis are needed. We asked whether changes in noninvasive markers of fibrosis can predict liver-related complications. METHODS: This was a case-controlled study using a prospective national cohort (ANRS-CO12-CIRVIR) of 1323 HCV-infected patients with compensated cirrhosis: 97 patients who developed liver-related complications such as hepatocellular carcinoma or hepatic decompensation (cases) matched in age, sex and follow-up duration were compared with 257 patients without complications (controls). Actitest/Fibrotest™, Inflameter/Fibrometer™, ELF™ and Fibroscan™ were performed at baseline and yearly. Samples based on Propensity score matching were built and mixed linear models performed. Outcomes in a sustained virological response (SVR) negative population and a SVR-positive population were also described. RESULTS: At baseline, all characteristics of patients were similar between the groups. All fibrosis tests were statistically higher for cases compared to controls, Fibroscan™ excepted: Fibrotest™: 0.83±0.13 vs. 0.77±0.16; Fibrometer™: 0.93±0.07 vs. 0.90±0.11; ELF™: 11.4±1.0 vs. 11.0±1.2 (P<0.02). The mean follow-up was 5.7±1.9 years. Over a 3-year period, the significant difference in fibrosis marker values between cases and controls remained constant; with a trend toward a decrease in inflammation markers in controls, independent of SVR status. CONCLUSIONS: Baseline noninvasive serum fibrosis and inflammation markers were significantly higher in patients developing a complication than in controls. During the follow-up only inflammatory markers decreased in controls, but not in cases, and thus could potentially be used to predict the occurrence of complications in cirrhotic patients.

A generalized additive model to disentangle age and diagnosis-specific cohort effects in psychological and behavioral outcomes in people living with HIV: the French cross-sectional ANRS-VESPA2 survey.

BACKGROUND: Unlike their younger counterparts, some of today's older HIV patients were diagnosed before the advent of highly active antiretroviral therapy (HAART). The psychosocial and behavioral outcomes of people living with HIV (PLWH) have been widely studied, and associated factors are well known. However, their evolution both in terms of age and diagnosis-specific cohort effects is not well understood. METHODS: Data from the ANRS-VESPA2 cross-sectional survey, representative of French PLWH, were used to investigate whether psychosocial and behavioral outcomes such as quality of life, need for support and HIV status disclosure, evolve under both the influence of patients' age and diagnosis-specific cohort effects. A semi-parametric generalized additive model (GAM) was employed. The physical and mental components of health-related quality of life, the need for material and moral support, and HIV-status disclosure, constituted our outcomes. RESULTS: Non-linear diagnosis-specific cohort effects were found for physical and mental QoL and HIV-status disclosure. Overall, physical QoL was better in recently diagnosed patients than in those diagnosed in the early 1980s. An increasing influence of diagnosis-specific cohort effects between 1983 and 1995 was observed. No cohort effects were noticeable between 1996 and 2000, while an increasing influence was apparent for patients diagnosed with HIV from 2000 to 2011 (year of study). For mental QoL, the only increase was observed in participants diagnosed with HIV between 1983 and 2000. The relationship between diagnosis-specific cohort effects and HIV status disclosure was negative overall: participants diagnosed after 2000 were much less likely to disclose than those diagnosed before 1995. The effect of age was significantly associated with all outcomes, with a non-linear influence on mental QoL and with the need for material/moral support. CONCLUSIONS: Psychosocial and behavioral outcomes are complex processes which can be explained in different ways by a combination of the clinical and social contexts which PLWH are exposed to at the time of diagnosis, and by developmental characteristics. A greater understanding of these processes could inform healthcare policy-making for specific HIV generations and different HIV age groups.

Renunciation of health care by people living with HIV in France is still associated with discrimination in health-care services and social insecurity - results from the ANRS-VESPA2 survey.

BACKGROUND: This study aimed to estimate the frequency of renunciation of health care among people living with HIV (PLHIV) in France, including health care unrelated to HIV, and to characterize associated socioeconomic and psychosocial risk factors. METHODS: The cross-sectional ANRS-VESPA2 survey was conducted on adult PLHIV attending French hospitals in 2011. Correlates of health-care renunciation in the 12 months before the survey were assessed through logistic modelling. RESULTS: Among the 3,020 PLHIV included in the sample, 17% declared health-care renunciation during the preceding year and 42% had a high level of social insecurity. During the previous 2 years, 8% and 11%, respectively, were discriminated against by medical staff and family. In multivariate analysis, positive associations were found between health-care renunciation and a high level of social insecurity (adjusted odds ratio [95% CI] 3.44 [2.54, 4.65]; P<0.001), having children (1.52 [1.10, 2.10]; P=0.01), smoking tobacco (1.50 [1.13, 1.98]; P=0.01), discrimination by medical staff (1.53 [1.22, 2.29]; P=0.04) or family (2.48 [1.75, 3.52]; P<0.001), major depressive episodes (1.46 [1.02, 2.09]; P=0.04), past or current drug injection (1.54 [1.03, 2.30]; P=0.04), and younger age (0.98 [0.97, 1.00]; P=0.03). Health-care renunciation was also negatively associated with HIV diagnosis after 1996 (1996-2002: 0.64 [0.46, 0.90]; P=0.01; ≥2003: 0.56 [0.40, 0.77]; P=0.001). CONCLUSIONS: In spite of universal health insurance in France, barrier- and refusal-renunciation of health care by PLHIV remain frequent. Poor psychosocial outcomes and discrimination by families and health-care providers compound the negative effect of social insecurity on health-care seeking in this population. To ensure optimal medical care, strategies are needed to prevent discrimination against PLHIV in health-care services. Special attention must be provided to patients experiencing social insecurity.

Significant reductions in alcohol use after hepatitis C treatment: results from the ANRS CO13-HEPAVIH cohort.

BACKGROUND AND AIMS: Few data exist on changes to substance use patterns before and after hepatitis C virus (HCV) treatment. We used longitudinal data of HIV-HCV co-infected individuals to examine whether receiving pegylated interferon (Peg-IFN)-based therapy irrespective of HCV clearance could modify tobacco, cannabis and alcohol use. DESIGN: A prospective cohort of HIV-HCV co-infected individuals was enrolled from 2006. Participants' clinical data were retrieved from medical records and socio-demographic and behavioural characteristics were collected by yearly self-administered questionnaires. SETTING: Data were collected across 17 hospitals in France. PARTICIPANTS: All HIV-HCV co-infected patients who initiated HCV treatment during follow-up and answered items regarding substance use in at least one yearly questionnaire (258 patients, 671 visits). INTERVENTION: HCV treatment consisted of Peg-IFN-based regimens. MEASUREMENTS: Four time-varying outcomes: hazardous alcohol use (Alcohol Use Disorders Identification Test-C > 3/4 for women/men), number of alcohol units/month, binge drinking, cannabis and tobacco use. Mixed models assessed the effect of HCV treatment status (not yet treated, treated and HCV-cleared, treated and HCV-chronic) on each outcome. FINDINGS: A significant decrease (more than 60% reduction) in both hazardous alcohol use and binge drinking and a reduction of 10 alcohol units/month was observed after HCV treatment (irrespective of HCV clearance). No significant effect of HCV treatment status was found on tobacco use and regular cannabis use, but HCV 'clearers' reported less non-regular use of cannabis. CONCLUSIONS: Hepatitis C virus (HCV) treatment appears to help HIV-HCV co-infected patients reduce alcohol use.

Efficacy and safety of boceprevir-based triple therapy in HCV cirrhotic patients awaiting liver transplantation (ANRS HC29 BOCEPRETRANSPLANT).

BACKGROUND AND AIMS: In this French multicentre, open-label study, we analyzed the efficacy, safety and patient-reported outcomes of a boceprevir-based triple therapy in HCV genotype 1 cirrhotic patients awaiting liver transplantation (LT). METHODS: Patients received PEG-IFN/ribavirin (RBV) for 48 weeks (W) and boceprevir from W4 to W48 or until LT. RESULTS: Fifty-one patients (80% males, median age: 56 years) were included. Fifty-seven percent had hepatocellular carcinoma and 43% end-stage liver disease. At enrolment, the median MELD score was 9 (range: 6-18); the Child-Pugh score was A in 65%, B in 35% and C in 2%. Therapy was discontinued because of severe adverse events (SAEs) in 39% of cases and virological inefficacy in 24%. 16% of patients had undetectable HCV RNA 24 weeks after the end of treatment (SVR24). LT was performed in 18 patients (35%). HCV RNA was undetectable in 16.6% at LT. Seven patients (14%) died and three deaths were attributed to treatment. SAEs (n=129) were observed in 84% of patients. Twenty-four percent of patients developed severe infections. Albumin<35g/L was independently associated with severe infection. Compared with baseline values, a significant decrease (P=0.02) of the physical dimension of health-related quality of life was observed between W4 and W24. The mean (95% CI) number of self-reported symptoms doubled during treatment (from 6.3 [4.8-7.7] to 11.8 [9.3-14.3]; P<0.001). CONCLUSIONS: The safety of the PEG-IFN/RBV/boceprevir combination is poor in patients awaiting LT, with a high risk of severe infection. Moreover, the limited efficacy confirms the indication for IFN-free combinations in these patients.