Nomenclature and diagnosis of seronegative coeliac disease and chronic non-coeliac enteropathies in adults: the Paris consensus.

OBJECTIVE: Differential diagnosis of villous atrophy (VA) without coeliac antibodies in adults includes seronegative coeliac disease (CD) and chronic enteropathies unrelated to gluten, ie. non-coeliac enteropathies (NCEs). There is currently no international consensus on the nomenclature and diagnostic criteria for these enteropathies. In this work, a Delphi process was conducted to address this diagnostic and clinical uncertainty. DESIGN: An international task force of 13 gastroenterologists from six countries was recruited at the 16th International Coeliac Disease Symposium, Paris, 2019. Between September 2019 and July 2021, a Delphi process was conducted through mail surveys to reach a consensus on which conditions to consider in the differential diagnosis of VA with negative coeliac serology and the clinical diagnostic approaches required for these conditions. A 70% agreement threshold was adopted. RESULTS: Chronic enteropathies characterised by VA and negative coeliac serology can be attributed to two main clinical scenarios: forms of CD presenting with negative serology, which also include seronegative CD and CD associated with IgA deficiency, and NCEs, with the latter recognising different underlying aetiologies. A consensus was reached on the diagnostic criteria for NCEs assisting clinicians in differentiating NCEs from seronegative CD. Although in adults seronegative CD is the most common aetiology in patients with VA and negative serology, discriminating between seronegative CD and NCEs is key to avoid unnecessary lifelong gluten-free diet, treat disease-specific morbidity and contrast poor long-term outcomes. CONCLUSION: This paper describes the Paris consensus on the definitions and diagnostic criteria for seronegative CD and chronic NCEs in adults.

Comparison of nuisance parameters in pediatric versus adult randomized trials: a meta-epidemiologic empirical evaluation.

BACKGROUND: We wished to compare the nuisance parameters of pediatric vs. adult randomized-trials (RCTs) and determine if the latter can be used in sample size computations of the former. METHODS: In this meta-epidemiologic empirical evaluation we examined meta-analyses from the Cochrane Database of Systematic-Reviews, with at least one pediatric-RCT and at least one adult-RCT. Within each meta-analysis of binary efficacy-outcomes, we calculated the pooled-control-group event-rate (CER) across separately all pediatric and adult-trials, using random-effect models and subsequently calculated the control-group event-rate risk-ratio (CER-RR) of the pooled-pediatric-CERs vs. adult-CERs. Within each meta-analysis with continuous outcomes we calculated the pooled-control-group effect standard deviation (CE-SD) across separately all pediatric and adult-trials and subsequently calculated the CE-SD-ratio of the pooled-pediatric-CE-SDs vs. adult-CE-SDs. We then calculated across all meta-analyses the pooled-CER-RRs and pooled-CE-SD-ratios (primary endpoints) and the pooled-magnitude of effect-sizes of CER-RRs and CE-SD-ratios using REMs. A ratio < 1 indicates that pediatric trials have smaller nuisance parameters than adult trials. RESULTS: We analyzed 208 meta-analyses (135 for binary-outcomes, 73 for continuous-outcomes). For binary outcomes, pediatric-RCTs had on average 10% smaller CERs than adult-RCTs (summary-CE-RR: 0.90; 95% CI: 0.83, 0.98). For mortality outcomes the summary-CE-RR was 0.48 (95% CIs: 0.31, 0.74). For continuous outcomes, pediatric-RCTs had on average 26% smaller CE-SDs than adult-RCTs (summary-CE-SD-ratio: 0.74). CONCLUSIONS: Clinically relevant differences in nuisance parameters between pediatric and adult trials were detected. These differences have implications for design of future studies. Extrapolation of nuisance parameters for sample-sizes calculations from adult-trials to pediatric-trials should be cautiously done.

Safety and adequacy of percutaneous kidney biopsy performed by nephrology trainees.

BACKGROUND: Recently there has been a progressive loss of specialty related skills for nephrologists. Among the skills we find the kidney biopsy that has a central role in diagnosis of renal parenchymal disease. One of the causes might be the belief that the kidney biopsy should be performed only in larger Centers which can rely on the presence of a renal pathologist and on nephrologists with a large experience. This trend may increase in the short term procedural safety but may limit the chance of in training nephrologists to become confident with the technique. METHODS: We evaluated renal biopsies performed from May 2002 to October 2016 in our Hospital, a mid-sized facility to determine whether the occurrence of complications would be comparable to those reported in literature and whether the increase in the number of biopsy performing physicians including nephrology fellows which took place since January 2012, after our Nephrology Unit became academic, would be associated to an increase of complications or a reduction of diagnostic power of renal biopsies. Three hundred thirty seven biopsies were evaluated. Patients underwent ultrasound guided percutaneous renal biopsy using a 14 G core needle loaded on a biopsy gun. Observation lasted for 24 h, we evaluated hemoglobin levels 6 and 24 h and kidney ultrasound 24 h after the biopsy. RESULTS: Complications occurred in 18.7% of patients, of these only 1,2% were major complications. Complications were more common in female (28%) compared to male patients (14,8%) (p = 0.004). We found no correlation between diagnosis, kidney function and complication rates; hypertension was not associated to a higher risk in complications. The increase of biopsy performing personnel was not associated to an increase in complication rates (18,7% both pre and post 2012) or with an increase of major complications (1.2% vs 1,2%). CONCLUSIONS: Kidney biopsy can be safely performed in mid-sized hospitals. Safety and adequacy are guaranteed even if the procedure is performed by a larger number of less experienced nephrologists as long as under tutor supervision, thus kidney biopsy should become an integral part of a nephrology fellow training allowing more widespread diffusion of this technique.

Determinants of functional outcome in hip fracture: the role of comorbidity.

BACKGROUND AND AIMS: Executed studies did not clearly identify which index of comorbidity was an independent outcome determinant. The aim of this prospective observational cohort study was to address this issue. METHODS: We analyzed 200 consecutive patients with hip fracture. All patients underwent rehabilitation. At admission comorbidity was assessed through the cumulative severity, severity index, and comorbidity index of the Cumulative Illness Rating Scale. Discharge scores and effectiveness in the Functional Independence Measure motor subscale, and discharge destination were the outcome measures. Multivariate regression analyses were performed to identify determinants of outcome. RESULTS: Mini Mental State Examination and comorbidity index of the Cumulative Illness Rating Scale were important independent determinants of final (respectively, ß = 0.46 and -0.25) and effectiveness (respectively, ß = 0.47 and -0.25) in motor Functional Independence Measure scores, while hip strength and Rankin score were determinants of final motor Functional Independence Measure score (respectively, ß = 0.21 and -0.20). Comorbidity index of the Cumulative Illness Rating Scale (odds ratio 8.18 for ≥3 versus < 3 comorbidity score; 95% confidence interval, 1.03-64.7) and Geriatric Depression Scale (odds ratio 4.02 for ≥6 versus ≤5 depression scale score; 95% confidence interval, 1.52-10.63) were risk indicators for nursing home. CONCLUSIONS: Among the indices of the Cumulative Illness Rating Scale, comorbidity index is the sole independent determinant of both motor Functional Independence Measure scores and discharge destination in hip fracture patients. This suggests to specifically evaluate this index to identify the patients who may be admitted to a rehabilitation program.

Active music therapy approach for stroke patients in the post-acute rehabilitation.

Guidelines in stroke rehabilitation recommend the use of a multidisciplinary approach. Different approaches and techniques with music are used in the stroke rehabilitation to improve motor and cognitive functions but also psychological outcomes. In this randomized controlled pilot trial, relational active music therapy approaches were tested in the post-acute phase of disease. Thirty-eight hospitalized patients with ischemic and hemorrhagic stroke were recruited and allocated in two groups. The experimental group underwent the standard of care (physiotherapy and occupational therapy daily sessions) and relational active music therapy treatments. The control group underwent the standard of care only. Motor functions and psychological aspects were assessed before and after treatments. Music therapy process was also evaluated using a specific rating scale. All groups showed a positive trend in quality of life, functional and disability levels, and gross mobility. The experimental group showed a decrease of anxiety and, in particular, of depression (p = 0.016). In addition, the strength of non-dominant hand (grip) significantly increased in the experimental group (p = 0.041). Music therapy assessment showed a significant improvement over time of non-verbal and sonorous-music relationships. Future studies, including a greater number of patients and follow-up evaluations, are needed to confirm promising results of this study.

Predictors of Mortality in Patients with COPD and Chronic Respiratory Failure: The Quality-of-Life Evaluation and Survival Study (QuESS): A Three-Year Study.

UNLABELLED: Previous studies sought to identify survival or outcome predictors in patients with COPD and chronic respiratory failure, but their findings are inconsistent. We identified mortality-associated factors in a prospective study in 21 centers in 7 countries. Follow-up data were available in 221 patients on home mechanical ventilation and/or long-term oxygen therapy. MEASUREMENTS: diagnosis, co-morbidities, medication, oxygen therapy, mechanical ventilation, pulmonary function, arterial blood gases, exercise performance were recorded. Health status was assessed using the COPD-specific SGRQ and the respiratory-failure-specific MRF26 questionnaires. Date and cause of death were recorded in those who died. Overall mortality was 19.5%. The commonest causes of death were related to the underlying respiratory diseases. At baseline, patients who subsequently died were older than survivors (p = 0.03), had a lower forced vital capacity (p = 0.03), a higher use of oxygen at rest (p = 0.003) and a worse health status (SGRQ and MRF26, both p = 0.02). Longitudinal analyses over a follow-up period of 3 years showed higher median survival times in patients with use of oxygen at rest less than 1.75 l/min and with a better health status. In contrast, an increase from baseline levels of 1 liter in O2 flow at rest, 1 unit in SGRQ or MRF26, or 1 year increase in age resulted in an increase of mortality of 68%, 2.4%, 1.3%, and 6%, respectively. In conclusion, the need for oxygen at rest, and health status assessment seems to be the strongest predictors of mortality in COPD patients with chronic respiratory failure.

Single delivery of an adeno-associated viral construct to transfer the CASQ2 gene to knock-in mice affected by catecholaminergic polymorphic ventricular tachycardia is able to cure the disease from birth to advanced age.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia is an inherited arrhythmogenic disorder characterized by sudden cardiac death in children. Drug therapy is still insufficient to provide full protection against cardiac arrest, and the use of implantable defibrillators in the pediatric population is limited by side effects. There is therefore a need to explore the curative potential of gene therapy for this disease. We investigated the efficacy and durability of viral gene transfer of the calsequestrin 2 (CASQ2) wild-type gene in a catecholaminergic polymorphic ventricular tachycardia knock-in mouse model carrying the CASQ2(R33Q/R33Q) (R33Q) mutation. METHODS AND RESULTS: We engineered an adeno-associated viral vector serotype 9 (AAV9) containing cDNA of CASQ2 wild-type (AAV9-CASQ2) plus the green fluorescent protein (GFP) gene to infect newborn R33Q mice studied by in vivo and in vitro protocols at 6, 9, and 12 months to investigate the ability of the infection to prevent the disease and adult R33Q mice studied after 2 months to assess whether the AAV9-CASQ2 delivery could revert the catecholaminergic polymorphic ventricular tachycardia phenotype. In both protocols, we observed the restoration of physiological expression and interaction of CASQ2, junctin, and triadin; the rescue of electrophysiological and ultrastructural abnormalities in calcium release units present in R33Q mice; and the lack of life-threatening arrhythmias. CONCLUSIONS: Our data demonstrate that viral gene transfer of wild-type CASQ2 into the heart of R33Q mice prevents and reverts severe manifestations of catecholaminergic polymorphic ventricular tachycardia and that this curative effect lasts for 1 year after a single injection of the vector, thus posing the rationale for the design of a clinical trial.

Correlation of deglutition in subacute ischemic stroke patients with peripheral blood adaptive immunity: Essential amino acid improvement.

We aimed to document in stroke patients peripheral blood immune cell profiles, their relations with neuro-functional tests, and any possible influence of supplemented essential amino acids (EAAs) may have on both the immune system and the relationship of the latter with neuro-function.Forty-two dysphagic stroke patients (27 men; 71±9 years) underwent bio-humoral measurements, neuro-functional tests, including Functional Independence Measure (FIM) and Dysphagia Outcome and Severity Scale (DOSS), and were randomized to receive EAAs 8 g/d (EAA group) or isocaloric maltodextrin (placebo group).At discharge all measurements were repeated 38±1 days after randomization.At admission, total white cell (TWC), neutrophil (N), and lymphocyte (Lymph) counts were normal and the N/Lymph ratio was higher than normal values (<3.0). At discharge, both TWC and N decreased while Lymph increased significantly. As a result, the N/Lymph ratio significantly decreased (P <0.001) returning to normal levels. Absolute Lymph counts and Lymph % TWC correlated positively with DOSS (r = +0.235, P = 0.04 and r = +0.224, P = 0.05, respectively), negatively with C-reactive protein natural logarithm (ln CRP) (P = 0.02 and P = 0.0001, respectively), which is an inflammation marker. N correlated positively with ln CRP (P = 0.001) and had a slight negative association with FIM (P = 0.07). The N/Lymph ratio was inversely related to FIM (r = -0.262, P = 0.02) and DOSS (r = -0.279, P = 0.01). Finally, FIM correlated with DOSS (r = +0.35, P = 0.05).For the regression analysis, the overtime changes of Lymph % TWC correlated significantly with DOSS (P = 0.01). There was a positive correlation between Lymph % TWC and DOSS for the entire stroke population (P = 0.015). While this correlation was not important for the placebo group (P = 0.27), it was significant in the EAA subgroup (P = 0.018).In the sub-acute stroke stage, there may be slight alterations of peripheral blood immune cells. Lymph cells are associated with improved neuro-function tests with evidence that this association is enhanced by supplementing EAAs.

[Discriminating capacity of the MASI-R questionnaire in the perception of work-stress]. / Validità discriminante del MASI-R nella percezione di stress lavoro-correlato.

INTRODUCTION: Workplace mobbing represents a severe type of occupational stress. The aim of this study is to evaluate the discriminant validity of the Maugeri Stress Index-Revised questionnaire (MASI-R) for the perceived work stress assessment. METHODS: A total of 105 patients were enrolled at the Occupational Medicine Uinit of our Institute for mobbing-related issues; they were compared to a control group matched for age, sex and professional category. Work stress perception was assessed in both samples using the self-report questionnaire MASI-R, which is the Maugeri Stress Index short form. RESULTS: Workers who perceived exposure to mobbing scored significantly lower compared to the control group in the four MASI-R scales (p < 0.001) and in the two visual analogue scales measuring job satisfaction (p < 0.001) and life satisfaction (p < 0.001). Further analyses have identified the items which significant discriminate between the two groups of workers. CONCLUSIONS: These findings show a good discriminant validity of the MASI-R questionnaire: workers who perceived exposure to workplace mobbing reveal higher work stress levels compared to the control group in all aspects measured.

Multidimensional screening and intervention program for neurocognitive disorder in vascular and multimorbid outpatients: Study protocol for a randomized clinical trial.

BACKGROUND: The heightened risk of dementia resulting from multiple comorbid conditions calls for innovative strategies. Engaging in physical and cognitive activities emerges as a protective measure against cognitive decline. This protocol aims to discuss a multidomain intervention targeting individuals with dementias secondary to cerebrovascular or other medical diseases, emphasizing an often underrepresented demographic. METHODS: This study primary objectives are: a) to identify patients affected by Neurocognitive disorder due to vascular disease or multiple etiologies (screening and diagnostic phase) and b) to evaluate the effectiveness of distinct rehabilitation protocols (intervention phase): motor training alone, paper-based cognitive rehabilitation combined with motor training, digital-based cognitive rehabilitation coupled with motor training. DISCUSSION: Identifying cognitive impairment beyond rigid neurological contexts can facilitate timely and targeted interventions. This protocol strives to address the complex interplay of cognitive decline and comorbidities through a multidimensional approach, providing insights that can shape future interventions and enhancing overall well-being in this vulnerable population. TRIAL REGISTRATION: The study has been registered on July 13, 2023 with the ClinicalTrials.gov NCT05954741 registration number (https://classic.clinicaltrials.gov/ct2/show/NCT05954741).

Clarithromycin in rheumatoid arthritis: the addition to methotrexate and low-dose methylprednisolone induces a significant additive value--a 24-month single-blind pilot study.

UNLABELLED: To compare the efficacy of the addition of clarithromycin (CM) to methotrexate (MTX) and methylprednisolone (MP) in active rheumatoid arthritis (RA). 32 patients with RA consecutively randomized. CONTROL GROUP: sixteen patients treated for 24 months with MTX 10-15 mg i.m. weekly and MP 4-6 mg daily. CM group: sixteen patients treated with MTX 10-15 mg i.m. weekly and MP 4-6 mg daily for 24 months; CM therapy added in the first month (500 mg twice a day for the first 15 days followed by 500 mg a day for the remaining 15 days). Evaluation of the improvement following ACR criteria was performed at months 1 (primary endpoint), 3 and 6. Patients were furthermore observed after 12, 18 and 24 months from the study beginning. At month 1, following ACR70 improvement criteria, we found a significant additive value in CM group (10/16 = 63% vs 4/16 = 25%, p = 0.033--chi-square test). After discontinuation of CM, the difference between groups was anymore evident (month 3: CM group 10/16 = 63% vs control group 9/16 = 56%). At month 24, 7/16 (44%) in control group and 12/16 (75%) in CM group completed the follow-up. The addition of CM to MTX and MP can induce the remission ACR 70 in the majority of RA patients within 4 weeks, while MTX and MP alone need about 3 months to achieve the same result.

Humoral immunogenicity of COVID-19 vaccines in patients with coeliac disease and other noncoeliac enteropathies compared to healthy controls.

OBJECTIVES: Data are lacking on the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients affected by coeliac disease, Whipple's disease and other noncoeliac enteropathies (NCE), characterised by primary or drug-related immunosuppression. We aimed to assess humoral response to SARS-CoV-2 vaccination in these patients compared to controls. METHODS: Between December 2021 and January 2022, IgG anti-SARS-CoV-2 spike protein antibodies were measured in serum samples of coeliac disease, Whipple's disease and NCE patients attending our gastroenterology outpatient clinic for follow-up, who had received their first SARS-CoV-2 vaccination dose 3-6-9 (±1) months prior. Humoral response was compared with healthy controls (vaccinated healthcare workers undergoing serological screening), matched for gender, age, and time from first vaccine dose at sample collection. RESULTS: A total of 120 patients [107 coeliac disease; 10 Whipple's disease; 2 common-variable immunodeficiency (CVID); 1 idiopathic villous atrophy; 77 F, 42 ± 16 years] and 240 matched controls (154 F, 43 ± 14 years) were enrolled. At 3, 6 and 9 months, humoral response in coeliac patients was not impaired compared to controls. Inadequate humoral response to vaccination was significantly more common among Whipple's disease patients than controls ( P < 0.001). Patients on immunosuppressive therapy had markedly lower IgG anti-SARS-CoV-2 antibody titres (median 14 vs. 520 BAU/mL, P < 0.001). As expected, patients with CVID showed no humoral response to vaccination. CONCLUSIONS: Humoral immunogenicity of SARS-CoV-2 vaccines was not reduced in coeliac disease patients compared to controls, although it was in Whipple's disease and CVID patients. Post-vaccination humoral response should be monitored in patients with Whipple's disease and chronic enteropathies on immunosuppressive therapy in order to schedule vaccine booster doses.

Late gadolinium enhancement by cardiovascular magnetic resonance is complementary to left ventricle ejection fraction in predicting prognosis of patients with stable coronary artery disease.

BACKGROUND: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) predicts adverse prognosis in patients with stable coronary artery disease (CAD). However, the interaction with conventional risk factors remains uncertain. Our aim was to assess whether the extent of LGE is an independent predictor of adverse cardiac outcome beyond conventional risk factors, including left ventricle ejection fraction (LVEF). METHODS: We enrolled 376 patients (88% males, 64 ± 11 years) with stable CAD, who underwent LGE assessment and a detailed conventional evaluation (clinical and pharmacological history, risk factors, ECG, Echocardiography). During a follow-up of 38 ± 21 months, 56 events occurred (32 deaths, 24 hospitalizations for heart failure). RESULTS: LGE and LVEF showed the strongest univariate associations with end-points (HR: 13.61 [95%C.I.: 7.32-25.31] for LGE ≥ 45% of LV mass; and 12.34 [6.80-22.38] for LVEF ≤ 30%; p < 0.0001). Multivariate analysis identified baseline LVEF, loop diuretic therapy, moderate-severe mitral regurgitation and pulmonary hypertension as significant predictors among conventional risk factors. According to a step-wise approach, LGE showed strong association with prognosis as well (5.25 [2.64-10.43]; p < 0.0001). LGE significantly improved the model predictability (chi-square 239 vs 221, F-test p < 0.0001) with an additive effect on the prognostic power of LVEF, which however retained its prognostic power (4.89 [2.50-09.56]; p < 0.0001). Patients with LGE ≥ 45% and/or LVEF ≤ 30% had much worse prognosis compared to patients without risk factors (annual event rates of 43% vs 3%; p < 0.0001). Interestingly LGE was a significant predictor when all cause mortality was analyzed as the only endpoint. CONCLUSIONS: This study demonstrates that LGE assessed by CMR is a robust independent non-invasive marker of prognosis in stable CAD patients. LGE can integrate the available metrics to substantially improve risk stratification.

Development of the Italian version of the Pain Catastrophising Scale (PCS-I): cross-cultural adaptation, factor analysis, reliability, validity and sensitivity to change.

PURPOSE: The aim of this study was to create an Italian version of the Pain Catastrophising Scale (PCS-I) and evaluate its psychometric properties in a sample with chronic low back pain. METHODS: The PCS was culturally adapted in accordance with international standards. The psychometric testing included factor analysis, reliability by internal consistency (Cronbach's alpha) and test-retest repeatability (intraclass coefficient correlations), and concurrent validity by comparing the PCS-I with a numerical rating scale (NRS), the Tampa Scale of Kinesiophobia (TSK), the Roland Morris Disability Questionnaire (RMDQ), the Hospital Anxiety and Depression Scale (HADS) and the Positive Affect and Negative Affect Scale (PANAS) (Pearson's correlation). RESULTS: It took 4 months to develop an agreed version of the PCS-I, which was satisfactorily administered to 180 subjects with chronic low back pain. Factor analysis revealed a three-factor 13-item solution (68% of explained variance). The questionnaire was internally consistent with one exception (α = 0.92 as a whole; 0.89 for Helplessness, 0.87 for Rumination and 0.56 for Magnification subscales) and showed a high degree of test-retest reliability (ICC = 0.842). Concurrent validity showed moderate correlations with the NRS (r = 0.44), TSK (r = 0.59), RMDQ (r = 0.45), HADS (Anxiety: r = 0.57; Depression r = 0.46) and PANAS (Negative Affect r = 0.54). The minimum detectable change was 10.45. The subscales were also psychometrically analysed. CONCLUSION: The successfully translated Italian version of the PCS has good psychometric properties replicating those of other versions.

Responsiveness of the Oswestry Disability Index and the Roland Morris Disability Questionnaire in Italian subjects with sub-acute and chronic low back pain.

INTRODUCTION: An ability to assess longitudinal changes in health status is crucial for the outcome measures used in treatment efficacy trials. The aim of this study was to verify the responsiveness of the Italian versions of the Oswestry Disability Index (ODI) and the Roland Morris Disability Questionnaire (RMDQ) in subjects with subacute or chronic low back pain (LBP). MATERIAL AND METHODS: At the beginning and end of an 8 week rehabilitation programme, 179 patients completed a booklet containing the ODI, the RMDQ, a 0-10 numerical rating scale (NRS), and the 36-item Short-Form Health Survey (SF-36). A global perception of change scale was also completed at the end of the programme, and collapsed to produce a dichotomous outcome (i.e. improved vs. not improved). Responsiveness was assessed by means of distribution methods [minimum detectable change (MDC); effect size (ES); standardised response mean (SRM)] and anchor-based methods (ROC curves). RESULTS: The MDC for the ODI and RMDQ was, respectively, 13.67 and 4.87; the ES was 0.53 and 0.68; and the SRM was 0.80 and 0.81. ROC analysis revealed an area under the curve of 0.71 for the ODI and 0.64 for the RMDQ, thus indicating discriminating capacity; the best cut-off point for the dichotomous outcome was 9.5 for the ODI (sensitivity 76% and specificity 63%) and 2.5 for the RMDQ (sensitivity 62% and specificity 55%). These estimates were comparable between the subacute and chronic subjects. Both the ODI and the RMDQ moderately correlated with the SF-36 and NRS (Spearman's and Pearson's correlation coefficients of >0.30). CONCLUSION: The Italian ODI and RMDQ proved to be sensitive in detecting clinical changes after conservative treatment for subacute and chronic LBP. Our findings are consistent with those published in the literature, thus allowing cross-cultural comparisons and stimulating cross-national studies.

Chronic neck pain and treatment of cognitive and behavioural factors: results of a randomised controlled clinical trial.

PURPOSE: Although there is growing evidence in favour of the bio-psychosocial approach to the treatment of persistent neck pain, it is questioned whether treating psychological factors can improve patient perceptions of disability, pain and quality of life. This randomised, controlled study with 12 months' follow-up was conducted to evaluate the efficacy of adding cognitive-behavioural principles to exercises for chronic neck pain. METHODS: Eighty patients were randomly assigned to the usual neck exercises plus cognitive-behavioural treatment (PTcb group, 40 subjects) or to treatment based on neck exercises alone (PT group, 40 subjects). Before treatment (T1), at the end of treatment (T2) and 12 months later (T3), all of the patients completed a booklet including the Neck Pain and Disability Scale, a numerical rating scale, and the Short-Form Health Survey Questionnaire (SF-36). RESULTS: The present trial failed to demonstrate its primary end point: the pre- and post-treatment difference in total NPDS scores was not statistically different between groups. Disability improved similarly in both groups over time, remaining stable until T3 in the PTcb group and slightly increasing at the same time in the PT group. Pain trends were comparable, with both groups showing an improvement between T1 and T2, and a slight worsening between T2 and T3. There were significant increases in all of the SF-36 domains except for health in general, and vitality in both groups by the end of treatment. SF-36 showed a between-group difference only for the physical activity domain (10.4; 95% CI 2.4-18.5). CONCLUSION: Disability, pain and quality of life improved at the end of treatment in both groups, without differences between them.

Clodronate and hydroxychloroquine in erosive osteoarthritis: a 24-month open randomized pilot study.

We evaluated the efficacy of clodronate for treating active erosive osteoarthritis of the hand and to compare it with hydroxychloroquine. Group A consisted of 24 patients treated for 24 months with clodronate 300 mg i.v. for 7 days, followed by clodronate i.m. 100 mg for 14 days every 3 months. Group B comprised 14 patients treated with hydroxychloroquine 400 mg daily for 30 days, followed by 200 mg daily for the next 11 months. In group A, 21/24 patients completed the trial and obtained significant pain reduction (p < 0.001), Dreiser's score (p = 0.012), and number of tender joints (p = 0.011). Strength of right (p = 0.04) and left (p = 0.016) hands, physician's global assessment (p ≤ 0.001), and patient's global assessment (p = 0.021) improved. In group B, 8/14 patients completed 12 months of the study, which showed the inefficacy of hydroxychloroquine and its lack of acceptance by patients (worsening pain and patient's global assessment). Therefore, enrolment was stopped. Differences between groups showed a pain decreasing trend for group A and a slightly increasing one for group B (p = 0.018). Physician and patient global assessments showed a strong increase in group A compared with group B (p < 0.001). Clodronate is effective in erosive osteoarthritis; hydroxychloroquine seems to be ineffective.

Is it time to rethink the burden of non-coeliac gluten sensitivity? A systematic review.

INTRODUCTION: Non-coeliac gluten sensitivity (NCGS) is still a poorly defined clinical condition. This review aims to describe the clinical features of subjects with a symptomatic response to gluten intake, and to estimate the prevalence of NCGS. EVIDENCE ACQUISITION: Literature search was conducted in accordance with PRISMA recommendations. The PubMed database was searched for original articles until 1st June 2020. EVIDENCE SYNTHESIS: We identified 30 relevant articles, including 14 studies that investigated NCGS through a double-blind, placebo-controlled crossover trial (DBPCC), and 16 that examined the role of gluten in causing symptoms without a DBPCC. We found that regardless of the diagnostic work up, gluten-sensitive patients were predominately middle-aged females complaining of abdominal pain, bloating and diarrhea. The pooled prevalence of NCGS after DBPCC was 24% (5-34%). Subjects with irritable bowel syndrome or self-reporting gluten intolerance accounted for the vast majority of the patients who did not start a DBPCC. A symptomatic response to a gluten-free diet (GFD) occurred in between 7% and 93% of patients. No data on long-term outcomes of NCGS individuals were reported. CONCLUSIONS: Clinical features of NCGS patients did not differ among all the included studies, whereas prevalence figures are rather heterogeneous. Long-term benefit of a GFD on these patients still needs to be ascertained.

The Clinical Frailty Scale (CFS) employment in the frailty assessment of patients suffering from Non-Communicable Diseases (NCDs): A systematic review.

Background: The Clinical Frailty Scale (CFS) is a well-established tool that has been widely employed to assess patients' frailty status and to predict clinical outcomes in the acute phase of a disease, but more information is needed to define the implications that this tool have when dealing with Non-Communicable Diseases (NCDs). Methods: An electronic literature search was performed on PubMed, Scopus, EMBASE, Web of Science, and EBSCO databases to identify studies employing the CFS to assess frailty in patients with NCDs. Findings: After database searching, article suitability evaluation, and studies' quality assessment, 43 studies were included in the systematic review. Researches were conducted mostly in Japan (37.5%), and half of the studies were focused on cardiovascular diseases (46.42%), followed by cancer (25.00%), and diabetes (10.71%). Simplicity (39.29%), efficacy (37.5%), and rapidity (16.07%) were the CFS characteristics mostly appreciated by the authors of the studies. The CFS-related results indicated that its scores were associated with patients' clinical outcomes (33.92%), with the presence of the disease (12.5%) and, with clinical decision making (10.71%). Furthermore, CFS resulted as a predictor of life expectancy in 23 studies (41.07%), clinical outcomes in 12 studies (21.43%), and hospital admissions/readmissions in 6 studies (10.71%). Discussion: CFS was found to be a well-established and useful tool to assess frailty in NCDs, too. It resulted to be related to the most important disease-related clinical characteristics and, thus, it should be always considered as an important step in the multidisciplinary evaluation of frail and chronic patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.asp? PROSPERO 2021, ID: CRD42021224214.

The GLU-10: a validated ten-point score to identify poorly instructed celiac patients in need of dietary interventions.

BACKGROUND: A standard tool to assess patients' knowledge about gluten and the gluten-free diet (GFD) is lacking. METHODS: We aimed to develop and validate a questionnaire to assess GFD knowledge. A 10-point questionnaire (GLU10) covering different aspects of knowledge about gluten content in food/non-food products and the gluten-free living was developed. To validate this questionnaire, it was administered to adult celiac patients already instructed on gluten and the GFD and non-celiac controls. Patients were prospectively recruited at our Gastroenterology Outpatient Clinic between August 2020 and February 2021. RESULTS: One hundred and six patients (52 celiac patients and 54 controls) participated in the validation phase. Celiac patients scored significantly higher than controls on the GLU10 Questionnaire (median 6 points vs. 2 points, P<0.001). Higher self-reported knowledge of the GFD was related to a higher score (P<0.001). ROC curve confirmed the ability of the GLU10 Questionnaire to discriminate between subjects with good and poor GFD knowledge (AUC=0.94, 95% CI: 0.90-0.98). A score of 5 was identified as the best cut-off (sensitivity 80.8%, specificity 94.4%). On multivariable logistic regression analysis, being a celiac patient (P<0.001) and having a university degree (P=0.04) were associated to a high GLU10 Score (≥5). CONCLUSIONS: GLU10 is the first validated questionnaire for assessing knowledge of a GFD in celiac patients and the general population.