Non-invasive diagnosis of alcohol-related steatohepatitis in patients ongoing alcohol withdrawal based on cytokeratin 18 and transient elastography.

BACKGROUND AND AIMS: The diagnosis of alcoholic steatohepatitis (ASH) is based on liver biopsy, which is costly and invasive with non-negligible morbidity. The aim of this study was to evaluate the accuracy of circulating cytokeratin 18 M65 fragment (K18-M65) alone or in association with other markers for the non-invasive diagnosis of ASH in patients ongoing alcohol withdrawal. METHODS: This study examined the serum level of K18-M65 in a test cohort of 196 patients. All patients underwent liver biopsy, transient elastography (TE) and serum collection. The diagnostic accuracy of K18-M65 alone or combined with clinico-biological data was assessed and the best defined cut-offs were validated in an independent validation cohort of 58 patients. RESULTS: K18-M65 had an area under the curve (AUC) of 0.82 (test cohort) and 0.90 (validation cohort). Using two cut-off decision points, K18-M65 was able to classify 46.9% (test cohort) and 34.5% (validation cohort) of patients with 95% sensitivity or specificity. Combining K18-M65, alpha-2-macroglobulin, TE, body mass index, and age, we created a score allowing accurate diagnosis of ASH with an AUC of 0.93 (test cohort) and 0.94 (validation cohort). This new score was able to rule out or rule in the diagnosis of steatohepatitis for probability ≤0.135 or ≥0.667 respectively in more than two-thirds of patients. CONCLUSIONS: We propose a new validated non-invasive score for the diagnosis of ASH in patients ongoing alcohol withdrawal. This score can help to identify patients that may benefit from potential therapeutics or motivate them to reduce alcohol consumption.

Switching from natalizumab administration at the day hospital to administration at home. A 1 year prospective study of patient experience and quality of life in 30 consecutive patients with multiple sclerosis (TYSAD-35).

BACKGROUND: In the context of the COVID-19 pandemic, French health authorities allowed the home administration of natalizumab by a healthcare-at-home service. We evaluated the patients' perception of care quality following the transition from day-hospital to home natalizumab administration. METHODS: Thirty relapsing-remitting multiple sclerosis (MS) patients treated with natalizumab were prospectively evaluated for one year after changing onto a home treatment procedure, using MusiCare, the first MS-specific questionnaire to evaluate patient experience and MusiQol. A numerical rating scale score for satisfaction and a dedicated questionnaire concerning patient experience were completed after each infusion. The primary endpoint was the mean difference in MusiCare score between baseline and 12 months. RESULTS: From June 2020 to November 2021, 306 infusions were performed at home. Three patients withdrew from the study (one lost to follow-up and two preferred to return at the day hospital). No worsening of patient experience or quality of life was observed. The mean scores of the Musicare dimensions were higher at 12 months than at baseline, significantly for the "relationship with healthcare professionals" (p = 0.0203). The MusiQol global score remained stable but the coping and friendship dimensions were significantly better at M12 than at baseline (p = 0.0491 and p = 0.0478, respectively). The satisfaction questionnaire highlighted some pain during the infusions (21.8%) and contradictions between healthcare professionals (17.2%). The mean score for satisfaction with care was 9.1/10. No safety concerns were identified. CONCLUSION: The positive experience of patients with home natalizumab administration provides an important opportunity to improve the quality of patient care.

Health-related quality of life as an endpoint in oncology phase I trials: a systematic review.

BACKGROUND: Phase I trials aim to identify the recommended dose for further development. Health-related quality of life (HRQoL) could be a complement to the usual National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) scale to detect adverse events and define the doses. The objective of this study is to review the phase I in oncology which used HRQoL as endpoint. METHODS: A search in PubMed database identified phase I trials in oncology with HRQoL as endpoint, published between January 2012 to May 2016. Hematological and pediatric phase I were excluded. RESULTS: A total of 1333 phase I were identified and 15 trials were identified with HRQoL as endpoint (1.1%). The European Organisation for Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) was the most frequently used instrument: 5 studies (33.3%). The targeted dimensions of HRQoL and the minimal clinically important difference were prespecified in 1 study (6.7%) and 2 studies (13.3%), respectively. Twelve studies (80%) described the statistical approach to analyze HRQoL data. Eight studies used the mean change from baseline (60%) to analyse longitudinal HRQoL data, two the mean score at certain times (13.3%), one the linear mixed model for repeated measures (6.7%), one the time to HRQoL score deterioration (6.7%), one percentage of patient-reported symptoms (6.7%). None of the studies used HRQoL to determine the recommended doses. CONCLUSION: Few phase I studies used HRQoL as endpoint and among studies with HRQoL as endpoint, the methodology of HRQoL measurement and statistical analysis was heterogeneous. HRQoL. endpoint not used for assessing the recommended phase II doses.

Distribution- and anchor-based methods to determine the minimally important difference on patient-reported outcome questionnaires in oncology: a structured review.

BACKGROUND: Interpretation of differences or changes in patient-reported outcome scores should not only consider statistical significance, but also clinical relevance. Accordingly, accurate determination of the minimally important difference (MID) is crucial to assess the effectiveness of health care interventions, as well as for sample size calculation. Several methods have been proposed to determine the MID. Our aim was to review the statistical methods used to determine MID in patient-reported outcome (PRO) questionnaires in cancer patients, focusing on the distribution- and anchor-based approaches and to present the variability of criteria used as well as possible limitations. METHODS: We performed a systematic search using PubMed. We searched for all cancer studies related to MID determination on a PRO questionnaire. Two reviewers independently screened titles and abstracts to identify relevant articles. Data were extracted from eligible articles using a predefined data collection form. Discrepancies were resolved by discussion and the involvement of a third reviewer. RESULTS: Sixty-three articles were identified, of which 46 were retained for final analysis. Both distribution- and anchor-based approaches were used to assess the MID in 37 studies (80.4%). Different time points were used to apply the distribution-based method and the most frequently reported distribution was the 0.5 standard deviation at baseline. A change in a PRO external scale (N = 13, 30.2%) and performance status (N = 15, 34.9%) were the most frequently used anchors. The stability of the MID over time was rarely investigated and only 28.2% of studies used at least 3 assessment timepoints. The robustness of anchor-based MID was questionable in 37.2% of the studies where the minimal number of patients by anchor category was less than 20. CONCLUSION: Efforts are needed to improve the quality of the methodology used for MID determination in PRO questionnaires used in oncology. In particular, increased attention to the sample size should be paid to guarantee reliable results. This could increase the use of these specific thresholds in future studies.

Impact of the occurrence of a response shift on the determination of the minimal important difference in a health-related quality of life score over time.

BACKGROUND: An important challenge of the longitudinal analysis of health-related quality of life (HRQOL) is the potential occurrence of a Response Shift (RS) effect. While the impact of RS effect on the longitudinal analysis of HRQOL has already been studied, few studies have been conducted on its impact on the determination of the Minimal Important Difference (MID). This study aims to investigate the impact of the RS effect on the determination of the MID over time for each scale of both EORTC QLQ-C30 and QLQ-BR23 questionnaires in breast cancer patients. METHODS: Patients with breast cancer completed the EORTC QLQ-C30 and the EORTC QLQ-BR23 questionnaires at baseline (time of diagnosis; T0), three months (T1) and six months after surgery (T2). Four hospitals and care centers participated in this study: cancer centers of Dijon and Nancy, the university hospitals of Reims and Strasbourg At T1 and T2, patients were asked to evaluate their HRQOL change during the last 3 months using the Jaeschke transition question. They were also asked to assess retrospectively their HRQOL level of three months ago. The occurrence of the RS effect was explored using the then-test method and its impact on the determination of the MID by using the Anchor-based method. RESULTS: Between February 2006 and February 2008, 381 patients were included of mean age 58 years old (SD = 11). For patients who reported a deterioration of their HRQOL level at each follow-up, an increase of RS effect has been detected between T1 and T2 in 13/15 dimensions of QLQ-C30 questionnaire, and 4/7 dimensions of QLQ-BR23 questionnaire. In contrast, a decrease of the RS effect was observed in 8/15 dimensions of QLQ-C30 questionnaire and in 5/7 dimensions of QLQ-BR23 questionnaire in case of improvement. At T2, the MID became ≥ 5 points when taking into account the RS effect in 10/15 dimensions of QLQ-C30 questionnaire and in 5/7 dimensions of QLQ-BR23 questionnaire. CONCLUSIONS: This study highlights that the RS effect increases over time in case of deterioration and decreases in case of improvement. Moreover, taking the RS into account produces a reliable and significant MID.