Digital support interventions for the self-management of low back pain: a systematic review

Background: Low back pain (LBP) is a common cause of disability and is ranked as the most burdensome health condition globally. Self-management, including components on increased knowledge, monitoring of symptoms, and physical activity, are consistently recommended in clinical guidelines as cost-effective strategies for LBP management and there is increasing interest in the potential role of digital health. Objective: The study aimed to synthesize and critically appraise published evidence concerning the use of interactive digital interventions to support self-management of LBP. The following specific questions were examined: (1) What are the key components of digital self-management interventions for LBP, including theoretical underpinnings? (2) What outcome measures have been used in randomized trials of digital self-management interventions in LBP and what effect, if any, did the intervention have on these? and (3) What specific characteristics or components, if any, of interventions appear to be associated with beneficial outcomes? Methods: Bibliographic databases searched from 2000 to March 2016 included Medline, Embase, CINAHL, PsycINFO, Cochrane Library, DoPHER and TRoPHI, Social Science Citation Index, and Science Citation Index. Reference and citation searching was also undertaken. Search strategy combined the following concepts: (1) back pain, (2) digital intervention, and (3) self-management. Only randomized controlled trial (RCT) protocols or completed RCTs involving adults with LBP published in peer-reviewed journals were included. Two reviewers independently screened titles and abstracts, full-text articles, extracted data, and assessed risk of bias using Cochrane risk of bias tool. An independent third reviewer adjudicated on disagreements. Data were synthesized narratively. Results: Of the total 7014 references identified, 11 were included, describing 9 studies: 6 completed RCTs and 3 protocols for future RCTs. The completed RCTs included a total of 2706 participants (range of 114-1343 participants per study) and varied considerably in the nature and delivery of the interventions, the duration/definition of LBP, the outcomes measured, and the effectiveness of the interventions. Participants were generally white, middle aged, and in 5 of 6 RCT reports, the majority were female and most reported educational level as time at college or higher. Only one study reported between-group differences in favor of the digital intervention. There was considerable variation in the extent of reporting the characteristics, components, and theories underpinning each intervention. None of the studies showed evidence of harm. Conclusions: The literature is extremely heterogeneous, making it difficult to understand what might work best, for whom, and in what circumstances. Participants were predominantly female, white, well educated, and middle aged, and thus the wider applicability of digital self-management interventions remains uncertain. No information on cost-effectiveness was reported. The evidence base for interactive digital interventions to support patient self-management of LBP remains weak

Number of hospital contacts with alcohol problems predicts later risk of alcoholic liver cirrhosis.

AIMS: Alcoholic liver cirrhosis is usually preceded by years of heavy drinking. We investigated whether the risk of alcoholic liver cirrhosis increases as the number of hospital contacts with alcohol problems goes up. METHODS: This was a supplementary analysis on a nationwide register-based cohort study. All patients in Denmark with an initial hospital contact with alcohol problems (alcohol intoxication, harmful alcohol use or alcohol dependence) 1998-2002, free of liver disease, were followed for diagnosis of alcoholic liver cirrhosis. The number of subsequent hospital contacts with alcohol problems was estimated as a time-dependent variable for each patient. RESULTS: In all, 36,044 hospital patients with an initial hospital contact with alcohol problems were included. These patients had 301,525 subsequent hospital contacts with alcohol problems. Risk of alcoholic liver cirrhosis increased ( p < 0.0001) with number of alcohol hospital contacts in both men and women for up to nine contacts. CONCLUSIONS: The number of prior hospital contacts with alcohol problems might provide clinicians with a helpful metric in deciding whether to offer preventive interventions for alcoholic liver cirrhosis

Impaired platelet aggregation and rebalanced hemostasis in patients with chronic hepatitis C virus infection

Increased risk of both cardiovascular disease (CVD) and bleeding has been found in patients with chronic hepatitis C (CHC) infection, and a re-balanced hemostasis has been proposed. The aim of this study was to investigate functional whole blood coagulation and platelet function in CHC infection. The prospective study included 82 patients with CHC infection (39 with advanced liver fibrosis and 43 with no or mild liver fibrosis) and 39 healthy controls. A total of 33 patients were treated for CHC infection and achieved sustained virological response (SVR). Baseline and post-treatment blood samples were collected. Hemostasis was assessed by both standard coagulation tests and functional whole blood hemostatic assays (thromboelastograhy (TEG), and platelet aggregation (Multiplate). Patients with CHC and advanced fibrosis had impaired platelet aggregation both compared to patients with no or mild fibrosis and to healthy controls. Patients with CHC and advanced fibrosis also had lower antithrombin, platelet count, and coagulation factors II-VII-X compared to healthy controls. In contrast, TEG did not differ between groups. In treated patients achieving SVR, post-treatment platelet count was higher than pre-treatment counts (p = 0.033) and ADPtest, ASPItest, and RISTOhightest all increased post treatment (all p &lt; 0.05). All Multiplate tests values, however, remained below those in the healthy controls. CHC-infected patients displayed evidence of rebalanced hemostasis with only partly hemostatic normalization in patients achieving SVR. The implications of rebalanced hemostasis and especially the impact on risk of CVD and bleeding warrants further studies

Hospital contacts with alcohol problems prior to liver cirrhosis or pancreatitis diagnosis.

AIM: To evaluate prior hospital contacts with alcohol problems in patients with alcoholic liver cirrhosis and pancreatitis. METHODS: This was a register-based study of all patients diagnosed with alcoholic liver cirrhosis or pancreatitis during 2008-2012 in Denmark. Hospital contacts with alcohol problems (intoxication, harmful use, or dependence) in the 10-year period preceding the diagnosis of alcoholic liver cirrhosis and pancreatitis were identified. RESULTS: In the 10 years prior to diagnosis, 40% of the 7719 alcoholic liver cirrhosis patients and 40% of the 1811 alcoholic pancreatitis patients had at least one prior hospital contact with alcohol problems. Every sixth patient (15%-16%) had more than five contacts. A similar pattern of prior hospital contacts was observed for alcoholic liver cirrhosis and pancreatitis. Around 30% were diagnosed with alcohol dependence and 10% with less severe alcohol diagnoses. For the majority, admission to somatic wards was the most common type of hospital care with alcohol problems. Most had their first contact with alcohol problems more than five years prior to diagnosis. CONCLUSION: There may be opportunities to reach some of the patients who later develop alcoholic liver cirrhosis or pancreatitis with preventive interventions in the hospital setting

Review article: The need for more efficient and patient-oriented drug development pathways in NASH—setting the scene for platform trials

Drug development; Non-alcoholic steatohepatitis; Study designsDesenvolupament de fàrmacs; Esteatohepatitis no alcohòlica; Dissenys d'estudiDesarrollo de fármacos; Esteatohepatitis no alcohólica; Diseños de estudioBackground and Aims Non-alcoholic steatohepatitis (NASH) constitutes a significant unmet medical need with a burgeoning field of clinical research and drug development. Platform trials (PT) might help accelerate drug development while lowering overall costs and creating a more patient-centric environment. This review provides a comprehensive and nuanced assessment of the NASH clinical development landscape. Methods Narrative review and expert opinion with insight gained during the EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project. Results Although NASH represents an opportunity to use adaptive trial designs, including master protocols for PT, there are barriers that might be encountered owing to distinct and sometimes opposing priorities held by these stakeholders and potential ways to overcome them. The following aspects are critical for the feasibility of a future PT in NASH: readiness of the drug pipeline, mainly from large drug companies, while there is not yet an FDA/EMA-approved treatment; the most suitable design (trial Phase and type of population, e.g., Phase 2b for non-cirrhotic NASH patients); the operational requirements such as the scope of the clinical network, the use of concurrent versus non-concurrent control arms, or the re-allocation of participants upon trial adaptations; the methodological appraisal (i.e. Bayesian vs. frequentist approach); patients' needs and patient-centred outcomes; main regulatory considerations and the funding and sustainability scenarios. Conclusions PT represent a promising avenue in NASH but there are a number of conundrums that need addressing. It is likely that before a global NASH PT becomes a reality, ‘proof-of-platform’ at a smaller scale needs to be provided.JMP reports having received consulting fees from Boehringer-Ingelheim, MSD and Novo Nordisk. He has received speaking fees from Gilead, Intercept, and Novo Nordisk, and travel expenses from Gilead, Rubió, Pfizer, Astellas, MSD, CUBICIN, and Novo Nordisk. He has received educational and research support from Madrigal, Gilead, Pfizer, Astellas, Accelerate, Novartis, Abbvie, ViiV, and MSD. Funds from European Commission/EFPIA IMI2 853966-2, IMI2 777377, H2020 847989, and ISCIII PI19/01898. NAdP works for Janssen. QMA is Coordinator of the EU IMI-2 LITMUS consortium, which is funded by the EU Horizon 2020 programme and EFPIA. This multistakeholder consortium includes industry partners. He reports research Grant Funding: Allergan/Tobira, AstraZeneca, Boehringer-Ingelheim, Glaxo SmithKline, Glympse Bio, Intercept, Novartis Pharma AG, Pfizer Ltd. Consultancy: 89Bio, Abbvie/Allergan, Akero, Altimentiv, Altimmune, AstraZeneca, Axcella, Blade, BMS, BNN Cardio, Boehringer-Ingelheim, Cirius, CymaBay, EcoR1, E3Bio, Eli Lilly & Company Ltd., Galmed, Genentech, Genfit SA, Gilead, Grunthal, HistoIndex, Indalo, Intercept Pharma Europe Ltd., Inventiva, IQVIA, Janssen, Johnson & Johnson, Madrigal, MedImmune, Medpace, Merck, Metacrine, NGMBio, North Sea Therapeutics, Novartis, Novo Nordisk A/S, PathAI, Pfizer Ltd., Poxel, ProSciento, Raptor Pharma, Roche, Servier, Shionogi, Terns, The Medicines Company, Viking Therapeutics. Speaker: Abbott Laboratories, Allergan/Tobira, BMS, Clinical Care Options, Falk, Fishawack, Genfit SA, Gilead, Integritas Communications, Kenes, Medscape. Royalties: Elsevier Ltd. PM works for Novartis. MSK is an employee of and a shareholder in Novo Nordisk A/S. JG has received consulting fees from Boehringer-Ingelheim, speaking fees from Echosens and travel expenses from Gilead and Abbie. Funds from ISCIII PI18/00947 and PI21/00691. JRE has received speaking fees from Gilead. FT lab’ work has been supported by the German Research Foundation (DFG, CRC/TR 362) and research grants from Gilead, Allergan, Bristol-Myers Squibb and Inventiva. VR consults for and Intercept, Novo Nordisk, Galmed, Poxel, NGM, Madrigal, Enyo, Sagimet, 89 Bio, Prosciento, Terns, and Theratechnologies, and received grants from Intercept and Gilead

Effectiveness of treatment with pegylated interferon and ribavirin in an unselected population of patients with chronic hepatitis C: A Danish nationwide cohort study

<p>Abstract</p> <p>Background</p> <p>The effect of peginterferon and ribavirin treatment on chronic hepatitis C virus (HCV) infection has been established in several controlled clinical studies. However, the effectiveness of treatment and predictors of treatment success in routine clinical practice remains to be established. Our aim was to estimate the effectiveness of peginterferon and ribavirin treatment in unselected HCV patients handled in routine clinical practice. The endpoint was sustained virological response (SVR), determined by the absence of HCV RNA 24 weeks after the end of treatment.</p> <p>Methods</p> <p>We determined the proportion of SVR in a nationwide, population-based cohort of 432 patients with chronic HCV infection who were starting treatment, and analyzed the impact of known covariates on SVR by using a logistic regression analysis.</p> <p>Results</p> <p>The majority of treated patients had genotype 1 (133 patients) and genotype 2/3 (285 patients) infections, with 44% and 72%, respectively, obtaining SVR. Other than genotype, the predictors of SVR were age ≤ 45 years at the start of treatment, completion of unmodified treatment, the absence of cirrhosis and non-European origin.</p> <p>Conclusions</p> <p>The effectiveness of peginterferon and ribavirin treatment for chronic hepatitis C in a routine clinical practice is comparable to that observed in controlled clinical trials, with a higher SVR rate in genotype 2 and 3 patients compared to genotype 1 patients. Our data further indicate that age at start of treatment is a strong predictor of SVR irrespective of HCV genotype, with patients 45 years or younger having a higher SVR rate.</p

Effectiveness of app-delivered, tailored self-management support for adults with lower back pain–related disability

Importance: Lower back pain (LBP) is a prevalent and challenging condition in primary care. The effectiveness of an individually tailored self-management support tool delivered via a smartphone app has not been rigorously tested. Objective: To investigate the effectiveness of selfBACK, an evidence-based, individually tailored self-management support system delivered through an app as an adjunct to usual care for adults with LBP-related disability. Design, Setting, and Participants: This randomized clinical trial with an intention-to-treat data analysis enrolled eligible individuals who sought care for LBP in a primary care or an outpatient spine clinic in Denmark and Norway from March 8 to December 14, 2019. Participants were 18 years or older, had nonspecific LBP, scored 6 points or higher on the Roland-Morris Disability Questionnaire (RMDQ), and had a smartphone and access to email. Interventions: The selfBACK app provided weekly recommendations for physical activity, strength and flexibility exercises, and daily educational messages. Self-management recommendations were tailored to participant characteristics and symptoms. Usual care included advice or treatment offered to participants by their clinician. Main Outcomes and Measures: Primary outcome was the mean difference in RMDQ scores between the intervention group and control group at 3 months. Secondary outcomes included average and worst LBP intensity levels in the preceding week as measured on the numerical rating scale, ability to cope as assessed with the Pain Self-Efficacy Questionnaire, fear-avoidance belief as assessed by the Fear-Avoidance Beliefs Questionnaire, cognitive and emotional representations of illness as assessed by the Brief Illness Perception Questionnaire, health-related quality of life as assessed by the EuroQol-5 Dimension questionnaire, physical activity level as assessed by the Saltin-Grimby Physical Activity Level Scale, and overall improvement as assessed by the Global Perceived Effect scale. Outcomes were measured at baseline, 6 weeks, 3 months, 6 months, and 9 months. Results: A total of 461 participants were included in the analysis; the population had a mean [SD] age of 47.5 [14.7] years and included 255 women (55%). Of these participants, 232 were randomized to the intervention group and 229 to the control group. By the 3-month follow-up, 399 participants (87%) had completed the trial. The adjusted mean difference in RMDQ score between the 2 groups at 3 months was 0.79 (95% CI, 0.06-1.51; P = .03), favoring the selfBACK intervention. The percentage of participants who reported a score improvement of at least 4 points on the RMDQ was 52% in the intervention group vs 39% in the control group (adjusted odds ratio, 1.76; 95% CI, 1.15-2.70; P = .01). Conclusions and Relevance Among adults who sought care for LBP in a primary care or an outpatient spine clinic, those who used the selfBACK system as an adjunct to usual care had reduced pain-related disability at 3 months. The improvement in pain-related disability was small and of uncertain clinical significance. Process evaluation may provide insights into refining the selfBACK app to increase its effectiveness. Trial Registration ClinicalTrials.gov Identifier: NCT0379828