[COVID-19 and medical publications: How three articles have influenced the media and public decisions in France]. / Littérature médicale et COVID-19 : comment trois articles ont influencé les médias et la décision publique en France.

The present article details the publication process and the vicissitudes of three articles about SARS-CoV-2 and its related disease (COVID-19). The three articles were published one month apart between March and May 2020. Their mediatization led French health authorities to intervene. Our article does not focus on and does not assess the scientific quality of the articles presented, but only aims to open the reflection on medical publication. Beyond the description of these three specific cases, this article raises issues about article retraction, peer-reviewing, preprints, authorship and the dissemination of scientific medical information, including through the mass media. It discusses new publishing modes and the dissemination of published information in clinical research.

The Intestinal Gas Questionnaire: development of a new instrument for measuring gas-related symptoms and their impact on daily life.

BACKGROUND: Although gas-related symptoms (GRS) are common and intrusive, there are no questionnaires to quantitate this problem. This study aimed to develop an instrument to rectify this gap in our knowledge. METHODS: Concepts were initially identified from the literature and interviews with gastroenterologists. Exploratory one-to-one interviews and focus groups with irritable bowel syndrome (IBS) patients (n = 28) and non-IBS subjects (n = 27) with GRS were conducted in UK, France, and Spain leading to a conceptual framework for the questionnaire. Last, iterative rounds of cognitive debriefing were performed with IBS (n = 16) and non-IBS subjects (n = 14). KEY RESULTS: From the first three steps, nine GRS (bloating, distension, flatulence, odorous flatulence, difficult gas evacuation, stomach rumbling, belching, bad breath, and abdominal movement) were identified although abdominal movement was subsequently excluded. Twelve quality of life domains affected by these symptoms were identified as: Clothing, emotional, physical appearance, diet, daily living, work, social life, physical activity, relationships, sex life, sleep, and cognitive function. A 24-h recall for symptoms and a 7-day recall for impact assessment were supported by the qualitative findings. Cognitive debriefing confirmed the understanding of the instrument. Across the three languages, the instrument was conceptually and linguistically consistent. CONCLUSIONS & INFERENCES: The International Gas Questionnaire is a 2-part instrument, developed rigorously and simultaneously in three languages assessing seven symptoms (17 items) and their impact on 12 domains (26 items) in IBS and general population. It is now undergoing psychometric validation and should provide a unique tool for epidemiological surveys and clinical trials for developing new treatments for these symptoms.

The minimally important difference in the Rhinoconjunctivitis Total Symptom Score in grass-pollen-induced allergic rhinoconjunctivitis.

BACKGROUND: The minimally important difference (MID) has been defined as the smallest improvement considered worthwhile by a patient. The MID has not been estimated for the Rhinoconjunctivitis Total Symptom Score (RTSS). METHODS: In a prospective multicentre study, patients consulting for grass-pollen-induced allergic rhinitis (AR) recorded a 15-point global rating of change scale (GRCS) score and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score on a weekly basis and the individual symptom scores comprising the RTSS on a daily basis over two consecutive weeks. The MID in the RTSS was determined with anchor-based methods (using the GRCS and the RQLQ) and a distribution-based method [based on the RTSS' standard deviation (SD)]. RESULTS: The study population comprised 806 patients (253 children, 250 adolescents and 303 adults). During the first week of the study, the mean ± SD RTSSs for these age groups were 6.5 ± 3.3, 6.8 ± 3.4 and 7.0 ± 3.4, respectively. For an improvement of 2 points in the GRCS or 0.5 points in the RQLQ score, the regression analysis yielded MIDs in the RTSS of 1.24 ± 0.17 and 1.12 ± 0.14 in children, 1.33 ± 0.14 and 1.20 ± 0.13 in adolescents and 1.13 ± 0.14 and 0.89 ± 0.12 in adults, respectively. When applying distribution-based methods, the MID ranged from 1.09 to 1.13 (based on 0.33 SDs of the first-week RTSS) and from 1.22 to 1.40 (based on 0.5 SDs of the difference in RTSSs between the first and second weeks). CONCLUSION: The MID in the RTSS was consistently estimated as 1.1-1.3 (and could conceivably be rounded to 1) in patients with grass-pollen-induced AR.

Early antiviral treatment fails to completely prevent herpes-related pain.

OBJECTIVES: Antiviral therapy does not completely relieve herpes zoster (HZ)-related pain, including post-herpetic neuralgia (PHN). The 12-month longitudinal prospective observational ARIZONA study was conducted in primary care in France between November 20, 2006 and September 12, 2008. The ARIZONA study included data from 1358 patients 50 years of age or more, presenting with acute eruptive HZ. This article focuses on the relationship between antiviral therapy and HZ-related pain in this large population. PATIENTS AND METHODS: Six hundred and forty-four family physicians (FPs) consecutively included all patients 50years of age or more presenting with acute HZ in the eruptive phase. The FP documented every patient's demographic and medical characteristics, HZ characteristics, and prescribed drugs at inclusion, and the presence of HZ-related pain on day 15 and at months 1, 3, 6, 9, and 12. RESULTS: One thousand two hundred and fifty-eight (92.6%) of the 1358 included patients (mean 67.7years [SD 10.7]; 62.2% female patients) were given antiviral drugs. The prevalence of HZ-related pain was 43.6%, 27.0%, 11.7%, 8.7%, 7.4%, and 6.0%, on day 15 and at months 1, 3, 6, 9, and 12, respectively. HZ-related pain was at least as frequent in patients treated by antiviral therapy within 72hours following HZ-rash onset as in patients treated later or who did not receive antiviral treatment, and more frequent in patients whose diagnosis was made within 24hours following HZ-rash onset. CONCLUSIONS: Antiviral therapy, even early, does not prevent HZ-related pain and PHN, probably because patients quickly identified and treated were those with severe forms and potentially at high risk of pain. Preventive strategies are thus needed.

Validation of a self-questionnaire for assessing the control of allergic rhinitis.

BACKGROUND: Allergic rhinitis affects the lives of patients for whom discomfort is, in most cases, significantly improved by pharmacological treatment. OBJECTIVE: To develop and validate a self-assessment global score for allergic rhinitis control (five items scored from 1 to 5 assessing the rhinitis over the 2 previous weeks). METHODS: Study of acceptability, reliability, validity and sensitivity to change during a prospective observational study in 902 patients selected by 411 general practitioners or allergists. RESULTS: The score correlated significantly to the clinical picture and to the impact of the rhinitis on social and sports activities at inclusion (P<0.0001). A significant improvement in the score was observed after 15 days of treatment: 14.9 ± 4.0 at inclusion and 21.5 ± 2.9 at re-evaluation after 15 days of treatment (P<0.0001). Using receiver operating characteristics curve, a score of 20 was the cut-off for poor vs. well-controlled rhinitis; a score strictly higher than 20 (best being 25) had a sensitivity of 67%, a specificity of 82%, a negative predictive value of 32% and a positive predictive value of 95%. CONCLUSION AND CLINICAL RELEVANCE: The self-assessment score for allergic rhinitis control appeared to be sensitive to change and correlated to the clinical expression of rhinitis and also to its involvement with treatment. These results suggest that this self-completion questionnaire could be used in daily practice at each consultation to determine, in a standardized manner, the level of control of the allergic rhinitis of an individual patient.

[How can an effective drug to treat irritable bowel syndrome be successfully developed?]. / Développer un médicament dans le syndrome de l'intestin irritable : une mission impossible ?

BACKGROUND: Irritable bowel syndrome (IBS) is a prevalent disorder, and although the pharmaceutical industry knows the potential fallout of a successful drug launch in this area, effective drug treatments are rare. AIM: To give an overview of the main factors interfering with the development of IBS drugs and to provide pertinent methodological indications to improve their investigation in clinical trials. RESULTS: Developing IBS drugs remains a major challenge, as numerous factors, related or unrelated to the nature of the disease itself, interfere with the demonstration of efficacy : the multiplicity of physiopathological mechanisms, wide variation in symptoms across patients and over time, associated psychological traits and environmental aspects, and a very significant placebo effect. There can be no question of developing drugs to target a single receptor in the hope of thereby impacting the whole range of factors involved in the genesis of IBS symptoms. Drug safety is, moreover, a prime consideration, given that this pathology, while certainly disabling, is not life-threatening. If a significant difference between a new treatment and placebo is to be demonstrated on a clinical trial, inclusion and efficacy criteria and study treatment duration must be predefined very precisely. The primary endpoint is abdominal pain, but the assessment of relief of the patient's symptoms has been also recommended, even if there is as yet no consensus as to its definition. The impact of a new IBS drug on patient's quality of life is an important secondary endpoint. CONCLUSION: In IBS more, perhaps, than in other pathologies, study design needs very careful consideration if new IBS drug trials are to be conclusive. However, some critical methodological issues (e.g., definite primary endpoint, interpretation of results, and definition of responders) are still unresolved.

International validation of a health-related quality of life questionnaire in patients with erosive gastro-oesophageal reflux disease.

BACKGROUND: Although erosive gastro-oesophageal reflux disease (GERD) is a highly prevalent condition, there is no specific, valid, reliable and sensitive questionnaire that allows evaluating treatment-induced changes in health-related quality of life (HRQoL). AIM: To design a self-administered questionnaire, the GERD Analyzer (GERDyzer), for use in clinical studies. METHODS: The GERDyzer comprises 10 dimensions each illustrated by pictogram-like drawings, simplifying communication with the patients. Self-assessment is performed by 100 mm Visual Analogue Scales. For validation, a 5-week clinical trial involving 395 patients (per-protocol) with oesophagitis was conducted. Patients were treated with pantoprazole (40 mg o.d.) for 28 days. Psychometric analyses included internal consistency, test-retest reliability, responsiveness and construct validity. RESULTS: Factor analysis showed consistency of the dimensions and no reduction was necessary. Validation of GERDyzer indicated high internal consistency (Cronbach's alpha = 0.95) and test-retest reliability (intraclass correlation coefficient =0.91). Responsiveness of the total score expressed by nonparametric effect size was 1.38. Comparison of scores with other questionnaires resulted in logical correlation levels depending on the respected concepts measured. Conclusions GERDyzer proved to be highly valid, reproducible and responsive. It allows reliably assessing treatment-induced changes in HRQoL in erosive GERD.

Validation of a questionnaire for assessment of asthma patient knowledge and behaviour.

BACKGROUND: For several years, educational programmes have been highlighted because care success depends on patient's knowledge and patient's asthma management. However, no tool is available to assess change in patient knowledge and behaviour before and after completing an educational programme. OBJECTIVE: To validate a questionnaire measuring the knowledge and behaviour of asthmatics participating in an educational programme and to gauge the benefit of such a programme. METHODS: The Asthma Behaviour Change (ABC) questionnaire was generated from literature, patient surveys and clinical situations. It was organized in eight dimensions assessing patient behaviour in seven different clinical situations and two assessing patient (pathophysiology and therapeutic) knowledge. A total of 139 asthmatics filled out the questionnaire before, during and after the educational programme. RESULTS: The principal component analysis confirmed the structure empirically made by clinical situations. Internal consistency analysis yielded high Cronbach's alpha values. Different dimensions and the two global scores were able to discriminate patients according to asthma severity. Finally, the effect size of difference before and after educational programme was at least 0.47, and was larger than 0.74 for both global behaviour and knowledge scores. The difference between visit 1 and 3 for global behaviour and knowledge scores reached 18.84 +/- 20.83 (P < 0.001, 95% CI: 13.18-24.43) and 11.06 +/- 14.98 (P < 0.001, 95% CI: 7.10-15.03), respectively. CONCLUSION: ABC questionnaire is a valid tool to assess asthmatics' knowledge and behaviour. Furthermore, this study confirmed that educational programmes lead to better awareness of asthma by patients.

Systematic review: health-related quality of life (HRQOL) questionnaires in gastro-oesophageal reflux disease.

BACKGROUND: Although gastro-oesophageal reflux disease (GERD) has a well-established pathophysiology, the impact of GERD symptoms on the patients' quality of life can be profound. Therefore, health-related quality of life (HRQOL) questionnaires have become standard instruments to evaluate the effect of treatment in clinical trials. AIM: To evaluate the reliability, validity and responsiveness of available GERD-specific HRQOL. METHODS: A systematic literature search using the Medical Subject Headings terms: 'Gastro-oesophageal reflux', 'Heartburn' and 'Oesophagitis' with 'quality of life' and 'questionnaires' was preformed to identify the available HRQOL questionnaires. To analyse the psychometric properties of the respective tools, the actual guidelines for the use of patient-reported outcomes in clinical trials were applied. RESULTS: We identified five GERD-specific HRQOL questionnaires but none of them fulfilled all quality criteria; either they did not meet the actual standards for psychometric properties (HBQOL, GERD-HRQL, Jasani et al.Aust Fam Physician 1999; 28: 515), or were impracticable to use in clinical trials. The generic and hybrid instruments lack specificity and sensitivity and were not designed for treatment evaluation in GERD patients. CONCLUSION: There is need for a new evaluative tool in the assessment of HRQOL during GERD therapy.

Effect of a fermented milk containing Bifidobacterium animalis DN-173 010 on the health-related quality of life and symptoms in irritable bowel syndrome in adults in primary care: a multicentre, randomized, double-blind, controlled trial.

BACKGROUND: Health-related quality of life (HRQoL) has been rarely evaluated as a primary endpoint in the assessment of the effect of probiotics on the irritable bowel syndrome (IBS). AIM: To study the effects of fermented milk containing Bifidobacterium animalis DN-173 010 and yoghurt strains on the IBS in a multicentre, double-blind, controlled trial. METHODS: A total of 274 primary care adults with constipation-predominant IBS (Rome II) were randomized to consume for 6 weeks either the test fermented milk or a heat-treated yoghurt (control). HRQoL and digestive symptoms were assessed after 3 and 6 weeks on an intention-to-treat population of 267 subjects. RESULTS: The HRQoL discomfort score, the primary endpoint, improved (P < 0.001) in both groups at weeks 3 and 6. The responder rate for the HRQoL discomfort score was higher (65.2 vs. 47.7%, P < 0.005), as was the decrease in bloating score [0.56 +/- (s.d.)1.01 vs. 0.31 +/- 0.87, P = 0.03], at week 3 in the test vs. the control group. In those subjects with <3 stools/week, stool frequency increased (P < 0.001) over 6 weeks in the test vs. control group. CONCLUSIONS: This study suggests a beneficial effect of a probiotic food on discomfort HRQoL score and bloating in constipation-predominant IBS, and on stool frequency in subjects with <3 stools/week.

Acute exacerbation of pain in irritable bowel syndrome: efficacy of phloroglucinol/trimethylphloroglucinol. A randomized, double-blind, placebo-controlled study.

BACKGROUND: Abdominal pain is the predominant symptom in irritable bowel syndrome patients. Phloroglucinol and its methylated derivative are antispasmodic agents acting on smooth muscle. AIM: To evaluate the efficacy of phloroglucinol/trimethylphloroglucinol on pain intensity during an acute exacerbation of pain of irritable bowel syndrome over a 1-week period treatment. METHODS: Irritable bowel syndrome Rome II patients seeking medical advice for an acute exacerbation of abdominal pain were randomized to phloroglucinol/trimethylphloroglucinol (62.2 mg P + 80 mg TMP) two pills three times daily or placebo for 7 days. Patients were included if they had a pain with a minimal intensity of 40 on a 100-mm visual analogue scale, and if pain occurred at least 2 days during the week previous inclusion. RESULTS: Three hundred and seven patients were included by 78 general practitioners. The intent-to-treat population included 300 patients, aged of 46.9 +/- 14.8 years (73% female). The relative decrease of pain intensity at day 7 was 57.8 +/- 31.7% vs. 46.3 +/- 34.7% (Delta = 11.5 +/- 3.8%, [CI(95%): 4.0 ; 19.1], P = 0.0029) and the percentage of patients with at least a 50% decrease of pain intensity was 62% vs. 47% (Delta = 15.3 +/- 5.7%, [CI(95%): 4.1 ; 26.5], P = 0.0078) in phloroglucinol/trimethylphloroglucinol and placebo groups, respectively. CONCLUSIONS: A 1-week phloroglucinol/trimethylphloroglucinol treatment significantly reduces pain intensity in irritable bowel syndrome patients consulting their general practitioners for pain exacerbation.

Impact of pain in health related quality of life of patients with systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) has an heterogenous clinical pattern, with variable organ involvement and degrees of severity. Like in other rheumatic diseases, the self-questionnaires have been used to evaluate SSc globally. The aim of the study is as to evaluate the quality of life (QoL) in patients with either diffuse or limited SSc, and to examine the impact of pain on the QoL scores. METHODS: Patients with SSc, either diffuse or limited SSc, were included in a cross-sectional study. The QoL was evaluated with the short-form 36 (SF-36) and the functional repercussion with the SSc-modified Health Assessment Questionnaire (S-HAQ). RESULTS: A total of 89 patients (67 with diffuse and 22 with limited SSc) were included. The SF-36 score values were lower in SSc patients than those reported in the general population. The physical component scores (PCS) of the SF-36 was significantly worse in diffuse compared with limited SSc (P < 0.05). The PCS was significantly negatively related to the number of clinical manifestations (ANOVA, P < 0.0001). The mental component score (MCS) was not influenced by the type of SSc or the number of clinical manifestations presented by the patient. The QoL of SSc patients was highly correlated with pain (R = 0.69) and disability (R = 0.70). Interestingly, the QoL of SSc patients was only slightly correlated with cutaneous (R = 0.42) and pulmonary involvement (R = 0.57). CONCLUSION: The QoL of patients with SSc is strongly influenced by the type of SSc, the burden of clinical manifestations, the functional disability and by the pain, whatever its cause. The treatment of pain should be considered as priority to improve the QoL of SSc patients.

Validation of French version of the Scleroderma Health Assessment Questionnaire (SSc HAQ).

The modified Scleroderma Health Assessment Questionnaire (SSc HAQ) is a functional score to assess systemic sclerosis (SSc) comprising the HAQ disease index (HAQ-DI) plus five specific visual analogue scales (VAS). Since it was validated in English-speaking patients only, its general use in any other language necessitates prior cross-cultural adaptation and validation. We designed this study to assess its value in French-speaking patients and to validate the French version according to international recommendations. We elaborated a French version using the "forward-backward" method. We then validated its psychometric properties with 100 consecutive SSc French-speaking patients who had undergone simultaneous clinical and paraclinical examination. In addition, we calculated the SSc HAQ score, a new outcome measure, which is obtained by pooling the eight domains from the HAQ-DI with the five organ VAS. Our study confirmed the psychometric properties of the SSc HAQ in non-English-speaking patients with (a) structural validity: the major component analysis, performed on the HAQ-DI and the five VAS, yielding a two-factor structure; (b) convergent validity: with high correlation coefficients between the SSc HAQ score and the physical component score of the SF-36 (r=-0.74, p<0.0001); (c) discriminant validity: the SSc HAQ score was better in patients with limited than with diffuse SSc (0.5+/-0.5 vs 1.1+/-0.7, respectively, p<0.0001) in relation to the number of clinical involvements; (d) reproducibility was high using the test-retest procedure (r=0.98). This study showed the value of the SSc HAQ, which is a simple, discriminant, reproducible self-administered questionnaire to evaluate French-speaking SSc patients. In addition, we suggest the use of a new outcome measure, the SSc HAQ score, to assess this systemic disease more accurately.