Alison D. Marshall

Ottawa Panel Evidence-Based Clinical Practice Guidelines for Aerobic Fitness Exercises in the Management of Fibromyalgia: Part 1

Background and Purpose: The objective of this study was to create guidelines for the use of aerobic fitness exercises in the management of adult patients (>18 years of age) with fibromyalgia, as defined by the 1990 American College of Rheumatology criteria. Methods: Following Cochrane Collaboration methods, the Ottawa Methods Group found and synthesized evidence from comparative controlled trials and formed the Ottawa Panel, with nominated experts from key stakeholder organizations. The Ottawa Panel then developed criteria for grading the recommendations based on experimental design (I for randomized controlled trials, II for nonrandomized studies) and strength of evidence (A, B, C+, C, D+, D, or D−). From the rigorous literature search, 13 randomized control trials and 3 controlled clinical trials were selected. Statistical analysis was based on Cochrane Collaboration methods. Continuous data were calculated with weighted mean differences between the intervention and control groups, and dichotomous data were analyzed with relative risks. Clinical improvement was calculated using absolute benefit and relative difference in change from baseline. Clinical significance was attained when an improvement of 15% relative to a control was found. Results: There were 24 positive recommendations: 10 grade A, 1 grade B, and 13 grade C+. Of these 24 positive recommendations, only 5 were of clinical benefit. Discussion and Conclusion: The Ottawa Panel recommends aerobic fitness exercises for the management of fibromyalgia as a result of the emerging evidence (grades A, B, and C+, although most trials were rated low quality) shown in the literature.

Ottawa Panel Evidence-Based Clinical Practice Guidelines for Strengthening Exercises in the Management of Fibromyalgia: Part 2

Background and Purpose: The objective of this study was to create guidelines for the use of strengthening exercises in the management of adult patients (>18 years of age) with fibromyalgia (FM), as defined by the 1990 American College of Rheumatology criteria. Methods: Following Cochrane Collaboration methods, the Ottawa Methods Group found and synthesized evidence from comparative controlled trials and formed the Ottawa Panel, with nominated experts from key stakeholder organizations. The Ottawa Panel then developed criteria for grading the recommendations based on experimental design (I for randomized controlled trials, II for nonrandomized studies) and strength of evidence (A, B, C+, C, D+, D, or D−). From the rigorous literature search, 5 randomized controlled trials were selected. Statistical analysis was based on Cochrane Collaboration methods. Continuous data were calculated with weighted mean differences between the intervention and control groups, and dichotomous data were analyzed with relative risks. Clinical improvement was calculated using absolute benefit and relative difference in change from baseline. Clinical significance was attained when an improvement of 15% relative to a control was found. Results: There were 5 positive recommendations: 2 grade A and 3 grade C+. All 5 were of clinical benefit. Discussion and Conclusion: The Ottawa Panel recommends strengthening exercises for the management of fibromyalgia as a result of the emerging evidence (grades A, B, and C+, although most trials were rated low quality) shown in the literature.

Ottawa Panel evidence-based clinical practice guidelines for the management of osteoarthritis in adults who are obese or overweight.

Background and Purpose The objective of this review was to construct an updated evidence-based clinical practice guideline on the use of physical activity and diet for the management of osteoarthritis (OA) in adults (>18 years of age) who are obese or overweight (body mass index ≥25 kg/m2). Data Sources Articles were extracted from the following databases: MEDLINE, EMBASE (Current Contents), SPORTDiscus, SUM, Scopus, CINAHL, AMED, BIOMED, PubMed, ERIC, the Cochrane Controlled Trials, and PEDro. Study Selection The Ottawa Panel and research assistance team strictly applied the inclusion and exclusion criteria from previous Ottawa Panel publications. Data Extraction An a priori literature search was conducted for articles related to obesity and OA of the lower extremities that were published from January 1, 1966, to November 30, 2010. Inclusion criteria and the methods to grade the recommendations were created by the Ottawa Panel. Data Synthesis Recommendations were graded based on the strength of evidence (A, B, C, C+, D, D+, or D−) as well as experimental design (I for randomized controlled trials and II for nonrandomized studies). In agreement with previous Ottawa Panel methods, Cochrane Collaboration methods were utilized for statistical analysis. Clinical significance was established by an improvement of ≥15% in the experimental group compared with the control group. There were a total of 79 recommendations from 9 articles. From these recommendations, there were 36 positive recommendations: 21 grade A and 15 grade C+. There were no grade B recommendations, and all recommendations were of clinical benefit. Limitations Further research is needed, as more than half of the trials were of low methodological quality. Conclusions This review suggests that physical activity and diet programs are beneficial, specifically for pain relief (9 grade A recommendations) and improved functional status (6 grade A and 7 grade C+ recommendations), for adults with OA who are obese or overweight. The Ottawa Panel was able to demonstrate that when comparing physical activity alone, diet alone, physical activity combined with diet, and control groups, the intervention including physical activity and diet produced the most beneficial results.

Evaluation of the Xpert HCV Viral Load point-of-care assay from venepuncture-collected and finger-stick capillary whole-blood samples: a cohort study

BACKGROUND Point-of-care hepatitis C virus (HCV) RNA testing offers an advantage over antibody testing (which only indicates previous exposure), enabling diagnosis of active infection in a single visit. In this study, we evaluated the performance of the Xpert HCV Viral Load assay with venepuncture and finger-stick capillary whole-blood samples. METHODS Plasma and finger-stick capillary whole-blood samples were collected from participants in an observational cohort enrolled at five sites in Australia (three drug and alcohol clinics, one homelessness service, and one needle and syringe programme). We compared the sensitivity and specificity of the Xpert HCV Viral Load test for HCV RNA detection by venepuncture and finger-stick collection with the Abbott RealTime HCV Viral Load assay (gold standard). FINDINGS Of 210 participants enrolled between Feb 8, 2016, and July 27, 2016, 150 participants had viral load testing results for the three assays tested. HCV RNA was detected in 45 (30% [95% CI 23-38]) of 150 participants based on Abbott RealTime. Sensitivity of the Xpert HCV Viral Load assay for HCV RNA detection in plasma collected by venepuncture was 100·0% (95% CI 92·0-100·0) and specificity was 99·1% (95% CI 94·9-100·0). Sensitivity of the Xpert HCV Viral Load assay for HCV RNA detection in samples collected by finger-stick was 95·5% (95% CI 84·5-99·4) and specificity was 98·1% (95% CI 93·4-99·8). No adverse events caused by the index test or the reference standard were observed. IMPLICATIONS The Xpert HCV Viral Load test can detect active infection from a finger-stick sample, which represents an advance over antibody-based tests that only indicate past or previous exposure. FUNDING National Health and Medical Research Council (Australia), Cepheid, South Eastern Sydney Local Health District (Australia), and Merck Sharp & Dohme (Australia).

Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe

All-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed DAA was ombitasvir, paritaprevir, and ritonavir, with dasabuvir, and with or without ribavirin (33 [94%] countries and jurisdictions). 16 (46%) countries and jurisdictions required patients to have fibrosis at stage F2 or higher, 29 (83%) had no listed restrictions based on drug or alcohol use, 33 (94%) required a specialist prescriber, and 34 (97%) had no additional restrictions for people co-infected with HIV and hepatitis C virus. These findings have implications for meeting WHO targets, with evidence of some countries not following the 2016 hepatitis C virus treatment guidelines by the European Association for the Study of Liver.

Restrictions for reimbursement of direct-acting antiviral treatment for hepatitis C virus infection in Canada: a descriptive study

BACKGROUND In Canada, interferon-free, direct-acting antiviral hepatitis C virus (HCV) regimens are costly. This presents challenges for universal drug coverage of the estimated 220 000 people with chronic HCV infection nationwide. The study objective was to appraise criteria for reimbursement of 4 HCV direct-acting antivirals in Canada. METHODS We reviewed the reimbursement criteria for simeprevir, sofosbuvir, ledipasvir-sofosbuvir and paritaprevir-ritonavir-ombitasvir plus dasabuvir in the 10 provinces and 3 territories. Data were extracted from April 2015 to June 2016. The primary outcomes extracted from health ministerial websites were: 1) minimum fibrosis stage required, 2) drug and alcohol use restrictions, 3) HIV coinfection restrictions and 4) prescriber type restrictions. RESULTS Overall, 85%-92% of provinces/territories limited access to patients with moderate fibrosis (Meta-Analysis of Histologic Data in Viral Hepatitis stage F2 or greater, or equivalent). There were no drug and alcohol use restrictions; however, several criteria (e.g., active injection drug use) were left to the discretion of the physician. Quebec did not reimburse simeprevir and sofosbuvir for people coinfected with HIV; no restrictions were found in the remaining jurisdictions. Prescriber type was restricted to specialists in up to 42% of provinces/territories. INTERPRETATION This review of criteria of reimbursement of HCV direct-acting antivirals in Canada showed substantial interjurisdictional heterogeneity. The findings could inform health policy and support the development and adoption of a national HCV strategy.

Restrictions for reimbursement of interferon-free direct-acting antiviral therapies for HCV infection in Europe

[Marshall, A. D.; Cunningham, E. B.; Dore, G. J.; Grebely, J.] UNSW Sydney, Kirby Inst, Sydney, NSW, Australia. [Nielsen, S.] Freelance Epidemiologist, Madrid, Spain. [Aghemo, A.] Univ Milan, Fdn IRCCS CA Granda Osped Maggiore Policlin, Div Gastroenterol & Hepatol, Milan, Italy. [Alho, H.] Helsinki Univ Hosp, Abdominal Ctr, Helsinki, Finland. [Alho, H.] Univ Helsinki, Helsinki, Finland. [Backmund, M.] Univ Hosp Munich, Dept Med 2, Munich, Germany. [Bruggmann, P.] Arud Ctr Addict Med, Zurich, Switzerland. [Dalgard, O.] Univ Oslo, Akershus Univ Hosp, Dept Infect Dis, Oslo, Norway. [Dalgard, O.] Univ Oslo, Fac Med, Oslo, Norway. [Flisiak, R.] Med Univ Bialystok, Dept Infect Dis & Hepatol, Bialystok, Poland. [Foster, G.] Queen Mary Univ London, London, England. [Gheorghe, L.] Fundeni Clin Inst, Gastroenterol & Hepatol, Bucharest, Romania. [Goldberg, D.] Hlth Protect Scotland, Glasgow, Lanark, Scotland. [Goulis, I.] Dept Internal Med, Thessaloniki, Greece. [Hickman, M.] Univ Bristol, Social Med, Bristol, Avon, England. [Hoffmann, P.] Minist Hlth Luxembourg, Luxembourg, Luxembourg. [Jancoriene, L.] Vilnius Univ Hosp, Santariskiu Klin, Ctr Infect Dis, Vilnius, Lithuania. [Jarcuska, P.] Univ Hosp, Dept Internal Med 1, Kosice, Slovakia. [Jarcuska, P.] Univ Pavol Jozef Safarik, Kosice, Slovakia. [Kaberg, M.] Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden. [Makara, M.] St Istvan & St Laszlo Hosp, Hepatol Ctr, Budapest, Hungary. [Maimets, M.] Univ Tartu, Dept Internal Med, Tartu, Estonia. [Marinho, R.] Hosp Santa Maria, Med Sch Lisbon, Dept Gastroenterol & Hepatol, Lisbon, Portugal. [Maticic, M.] Univ Med Ctr, Clin Infect Dis & Febrile Illnesses, Ljubljana, Slovenia. [Norris, S.; Tait, M.] Dr Steevens Hosp, Natl Hepatitis Treatment Programme C, Hlth Serv Execut, Dublin, Ireland. [Olafsson, S.] Landspitali Univ Hosp, Dept Med, Div Gastroenterol, Reykjavik, Iceland. [Ovrehus, A.] Univ Southern Denmark, Odense Univ Hosp, Dept Infect Dis, Odense, Denmark. [Pawlotsky, J. -M.] Univ Paris Est, Hop Henri Mondor, Creteil, France. [Pocock, J.] Mater Hosp, Gastroenterol Dept, Msida, Malta. [Robaeys, G.] Ziekenhuis Oost Limburg, Dept Gastroenterol & Hepatol, Genk, Belgium. [Robaeys, G.] UHasselt, Dept Med & Life Sci, Hasselt, Belgium. [Robaeys, G.] UZLeuven, Dept Hepatol, Leuven, Belgium. [Roncero, C.] Univ Autonoma Barcelona, Hosp Univ Vall dHebron, Psychiat Serv, Addict & Dual Diag Unit, Barcelona, Spain. [Simonova, M.] Mil Med Acad, Dept Gastroenterol HPB Surg & Transplantol, Sofia, Bulgaria. [Sperl, J.] Inst Clin & Expt Med, Dept Hepatogastroenterol, Prague, Czech Republic. [Tolmane, I.] Infectol Ctr Latvia, Dept Hepatol, Riga, Latvia. [Tomaselli, S.] Off Publ Hlth, Vaduz, Liechtenstein. [van der Valk, M.] Acad Med Ctr, Dept Infect Dis, Amsterdam, Netherlands. [Vince, A.] Univ Zagreb, Sch Med, Univ Hosp Infect Dis, Zagreb, Croatia. [Lazarus, J. V.] Univ Copenhagen, Rigshosp, CHIP, Copenhagen, Denmark. [Lazarus, J. V.] Hosp Clin Barcelona, Barcelona Inst Global Hlth ISGlobal, Barcelona, Spain.

Do women with complex alcohol and other drug use histories want women-only residential treatment?

Abstract Background Women‐only addiction services tend to be provided on a poorly evidenced assumption that women want single‐sex treatment. We draw upon womens expectations and experiences of women‐only residential rehabilitation to stimulate debate on this issue. Methods Semi‐structured interviews were undertaken with 19 women aged 25–44 years [currently in treatment (n = 9), successfully completed treatment (n = 5), left treatment prematurely (n = 5)]. All had histories of physical or sexual abuse, and relapses linked to relationships with men. Interviews were audio‐recorded, transcribed verbatim, coded and analysed inductively following Iterative Categorization. Findings Women reported routinely that they had been concerned, anxious or scared about entering women‐only treatment. They attributed these feelings to previous poor relationships with women, being more accustomed to male company and negative experiences of other women‐only residential settings. Few women said that they had wanted women‐only treatment, although many became more positive after entering the women‐only service. Once in treatment, women often explained that they felt safe, supported, relaxed, understood and able to open up and develop relationships with other female residents. However, they also described tensions, conflicts, mistrust and social distancing that undermined their treatment experiences. Conclusions Women who have complex histories of alcohol and other drug use do not necessarily want or perceive benefit in women‐only residential treatment.

Evaluation of the Xpert HCV Viral Load Finger-Stick Point-of-Care Assay

Point-of-care hepatitis C virus (HCV) RNA testing is advantageous, enabling diagnosis of active infection in a single visit. This study evaluated the sensitivity and specificity of the Xpert HCV Viral Load Finger-Stick assay (Xpert HCV VL FS) for HCV RNA detection (finger-stick) and the Xpert HCV Viral Load assay (plasma) compared with the Abbott RealTime HCV Viral Load assay by venepuncture. Plasma and finger-stick capillary whole-blood samples were collected from participants in an observational cohort in Australia. Of 223 participants enrolled, HCV RNA was detected in 40% of participants (85 of 210) with available Xpert HCV Viral Load testing. Participants receiving HCV therapy were excluded from subsequent analyses (n = 16). Sensitivity of the Xpert HCV Viral Load assay for HCV RNA quantification in plasma collected by venepuncture was 100.0% (95% confidence interval [CI] 96.9%-100.0%) and specificity was 100.0% (95% CI, 94.4%-100.0%). Sensitivity of the Xpert HCV VL FS assay for HCV RNA quantification in samples collected by finger-stick was 100.0% (95% CI, 93.9%-100.0%) and specificity was 100.0% (95% CI, 96.6%-100.0%). The Xpert HCV VL FS test can accurately detect active infection from a finger-stick sample in 1 hour allowing single-visit HCV diagnosis.

The removal of DAA restrictions in Europe – One step closer to eliminating HCV as a major public health threat

Of ∼10.2 million people with chronic HCV infection in Europe, 6.7 million live in Eastern Europe, 2.3 million in Western Europe and 1.2 million in Central Europe. HCV transmission continues to occur in parallel with an increasing HCV-related liver disease burden, the result of an ageing population infected during peak HCV epidemics decades earlier. In 2016, the World Health Organization set targets to eliminate HCV infection as a major public health threat by 2030. Across Europe, an estimated 36% of those living with chronic HCV infection have been diagnosed and ∼5% have been treated. A major barrier to enhancing HCV treatment uptake has been restrictions set by payers, including national governments and others, in response to the initially high list prices of direct-acting antiviral (DAA) therapies. The aims of this article are to discuss DAA restrictions in Europe, why DAA restrictions are still in place, what has facilitated the removal of DAA restrictions, and what challenges remain as we attempt to eliminate HCV as a major public health threat in the region by 2030.