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.

Prevalence of Psychopathological Symptoms and Their Determinants in Four Healthcare Workers' Categories during the Second Year of COVID-19 Pandemic.

Highly stressful situations, such as the current COVID-19 pandemic, induce constant changes in the mental state of people who experience them. In the present study, we analyzed the prevalence of some psychological symptoms and their determinants in four different categories of healthcare workers during the second year of the pandemic. A total of 265 physicians, 176 nurses, 184 other healthcare professionals, and 48 administrative employees, working in different Italian healthcare contexts, answered a questionnaire including variables about their mental status and experience with the pandemic. The mean scores for anxiety and depressive symptoms measured more than one year after the onset of the pandemic did not reach the pathological threshold. In contrast, post-traumatic and burnout symptoms tended toward the critical threshold, especially in physicians. The main determinant of psychological distress was perceived stress, followed by job satisfaction, the impact of COVID-19 on daily work, and a lack of recreational activities. These results increase the knowledge of which determinants of mental distress would be important to act on when particularly stressful conditions exist in the workplace that persist over time. If well-implemented, specific interventions focused on these determinants could lead to an improvement in employee well-being and in the quality of care provided.

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.

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.

The role of kidney dysfunction in COVID-19 and the influence of age.

COVID-19 is strongly influenced by age and comorbidities. Acute kidney injury (AKI) is a frequent finding in COVID-19 patients and seems to be associated to mortality and severity. On the other hand, the role of kidney dysfunction in COVID-19 is still debated. We performed a retrospective study in a cohort of 174 hospitalized COVID-19 patients in Italy from March 3rd to May 21st 2020, to investigate the role of kidney dysfunction on COVID-19 severity and mortality. Moreover, we examined in depth the relationship between kidney function, age, and progression of COVID-19, also using different equations to estimate the glomerular filtration rate (GFR). We performed logistic regressions, while a predictive analysis was made through a machine learning approach. AKI and death occurred respectively in 10.2% and 19.5%, in our population. The major risk factors for mortality in our cohort were age [adjusted HR, 6.2; 95% confidence interval (CI) 1.8-21.4] and AKI [3.36 (1.44-7.87)], while, in these relationships, GFR at baseline mitigated the role of age. The occurrence of AKI was influenced by baseline kidney function, D-dimer, procalcitonin and hypertension. Our predictive analysis for AKI and mortality reached an accuracy of ≥ 94% and ≥ 91%, respectively. Our study scales down the role of kidney function impairment on hospital admission , especially in elderly patients. BIS-1 formula demonstrated a worse performance to predict the outcomes in COVID-19 patients when compared with MDRD and CKD-EPI.

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.

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 Challenge of Reorganizing Rehabilitation Services at the Time of COVID-19 Pandemic: A New Digital and Artificial Intelligence Platform to Support Team Work in Planning and Delivering Safe and High Quality Care.

Introduction: The COVID-19 pandemic has posed great challenges in inpatient rehabilitation services, not only to implement the preventative measures to avoid the spreading of the virus in a highly interactive, multidisciplinary setting but also to create a rehabilitation pathway for post-COVID-19 patients. The aim of this retrospective study was to describe the role of a digital and artificial intelligence platform (DAIP) in facilitating the implementation of changes in a rehabilitation service during the COVID-19 pandemic. Materials and Methods: We gathered qualitative and quantitative descriptors of the DAIP, including measures to assess its efficiency in scheduling therapy sessions, and staff satisfaction using two simple numeric rating scales and the System Usability Scale. We describe how the volume of activity and the quality of care of our rehabilitation service have changed when the DAIP was implemented by comparing the pre-COVID-19 and the pandemic periods for patients' [sex, age, co-morbidities, diagnosis, and Functional Independence Measure (FIM) gain] and service's (bed occupancy, patients' length of stay, and staff capacity) characteristics. Results: Bed occupancy and the impact of rehabilitation on patients' outcome remained stable between the two periods. The DAIP provided a qualitative support for goal setting from remote; 95% of the planned sessions were delivered; the time for scheduling and registering sessions dropped by 50%. Staff satisfaction was about 70% for the easiness and 60% for the usefulness, and the mean "usability" score was close to the cut off for sufficient usability (mean score 65 where 68 is the cut off). Conclusion: By applying the DAIP to rehabilitation treatment, it was shown that the management of rehabilitation can be efficiently performed even in the COVID-19 pandemic. Staff satisfaction reflected a good acceptance of the changes considering the turbulent changes and the stress burden occurring at the time of the pandemic.

Hand rehabilitation with sonification techniques in the subacute stage of stroke.

After a stroke event, most survivors suffer from arm paresis, poor motor control and other disabilities that make activities of daily living difficult, severely affecting quality of life and personal independence. This randomized controlled trial aimed at evaluating the efficacy of a music-based sonification approach on upper limbs motor functions, quality of life and pain perceived during rehabilitation. The study involved 65 subacute stroke individuals during inpatient rehabilitation allocated into 2 groups which underwent usual care dayweek) respectively of standard upper extremity motor rehabilitation or upper extremity treatment with sonification techniques. The Fugl-Meyer Upper Extremity Scale, Box and Block Test and the Modified Ashworth Scale were used to perform motor assessment and the McGill Quality of Life-it and the Numerical Pain Rating Scale to assess quality of life and pain. The assessment was performed at baseline, after 2 weeks, at the end of treatment and at follow-up (1 month after the end of treatment). Total scores of the Fugl-Meyer Upper Extremity Scale (primary outcome measure) and hand and wrist sub scores, manual dexterity scores of the affected and unaffected limb in the Box and Block Test, pain scores of the Numerical Pain Rating Scale (secondary outcomes measures) significantly improved in the sonification group compared to the standard of care group (time*group interaction < 0.05). Our findings suggest that music-based sonification sessions can be considered an effective standardized intervention for the upper limb in subacute stroke rehabilitation.

Prevalence, incidence and clinical features of SARS-CoV-2 infection in adult coeliac patients.

OBJECTIVES: Data on SARS-CoV-2 disease (COVID-19) in adult coeliac disease (CD) are lacking. The aim of the present study is to evaluate the epidemiology and clinical features of COVID-19 in adult coeliac patients regularly followed-up at our centre since January 2015. METHODS: Data about general health status and clinical features of laboratory-confirmed COVID-19 were prospectively collected over the phone. Data about CD were retrospectively collected from clinical notes. Prevalence and incidence of COVID-19 were compared between the coeliac cohort and the figures in the general population of Lombardy, Northern Italy between 20 February to 5 June 2020 provided by the Italian National Institute of Health (Istituto Superiore di Sanità) and the Lombardy regional government. RESULTS: Nine out of 324 patients contracted COVID-19, thus resulting in a prevalence of 2.78% [95% confidence interval (CI) 0.98-4.58] and an incidence rate of 8.15/1000 person-month (95% CI 4.24-15.66). Prevalence of COVID-19 ascertained by means of nasal swab was 1.79% (95% CI 0.22-3.35) and the incidence rate 5.26/1000 person-month (95% CI 2.19-12.63), without difference from the general population. Clinical type of CD, age, sex, duration and adherence to a gluten-free diet, and mucosal healing did not differ between coeliac patients with and without COVID-19. None of the 9 patients with COVID-19 required hospitalization. CONCLUSION: Patients with CD do not seem to carry an increased risk of COVID-19 compared to the general population and their disease course is mild.

Machine learning techniques to predict the effectiveness of music therapy: A randomized controlled trial.

BACKGROUND: The literature shows the effectiveness of music listening, but which factors and what types of music produce therapeutic effects, as well as how music therapists can select music, remain unclear. Here, we present a study to establish the main predictive factors of music listening's relaxation effects using machine learning methods. METHODS: Three hundred and twenty healthy participants were evenly distributed by age, education level, presence of musical training, and sex. Each of them listened to music for nine minutes (either to their preferred music or to algorithmically generated music). Relaxation levels were recorded using a visual analogue scale (VAS) before and after the listening experience. The participants were then divided into three classes: increase, decrease, or no change in relaxation. A decision tree was generated to predict the effect of music listening on relaxation. RESULTS: A decision tree with an overall accuracy of 0.79 was produced. An analysis of the structure of the decision tree yielded some inferences as to the most important factors in predicting the effect of music listening, particularly the initial relaxation level, the combination of education and musical training, age, and music listening frequency. CONCLUSIONS: The resulting decision tree and analysis of this interpretable model makes it possible to find predictive factors that influence therapeutic music listening outcomes. The strong subjectivity of therapeutic music listening suggests the use of machine learning techniques as an important and innovative approach to supporting music therapy practice.

Galacto-Oligosaccharide/Polidextrose Enriched Formula Protects against Respiratory Infections in Infants at High Risk of Atopy: A Randomized Clinical Trial.

BACKGROUND: Early nutrition affects the risk of atopy and infections through modifications of intestinal microbiota. The Prebiotics in the Prevention of Atopy (PIPA) study was a 24-month randomised, double-blind, placebo-controlled trial. It aimed to evaluate the effects of a galacto-oligosaccharide/polydextrose (GOS/PDX)-formula (PF) on atopic dermatitis (AD) and common infections in infants who were born to atopic parents and to investigate the relationship among early nutrition, gut microbiota and clinical outcomes. METHODS: A total of 201 and 199 infants were randomized to receive a PF and standard formula (SF), respectively; 140 infants remained on exclusive breastfeeding (BF). RESULTS: The cumulative incidence of AD and its intensity and duration were not statistically different among the three groups. The number of infants with at least one episode of respiratory infection (RI) and the mean number of episodes until 48 weeks of age were significantly lower in the PF group than in the SF group. The number of patients with recurrent RIs and incidence of wheezing lower RIs until 96 weeks were lower in the PF group than the SF group, but similar to the BF group. Bifidobacteria and Clostridium cluster I colonization increased over time in the PF group but decreased in the SF and BF groups. Bifidobacteria had a protective role in RIs, whereas Clostridium cluster I was associated with atopy protection. CONCLUSION: The early administration of PF protects against RIs and mediates a species-specific modulation of the intestinal microbiota. TRIAL REGISTRATION: clinicaltrial.gov Identifier: NCT02116452.

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.

Pattern of complications and burden of disease in patients affected by beta thalassemia major.

OBJECTIVES: Despite the correct application of blood transfusions and chelation treatments, beta thalassemia patients have many complications. Systematic population analyses on types and frequency of these complications are very few. The aim of this study is to characterize the complications, their risk factors and their clinical and economic impact. METHODS: Complications at baseline and events occurring during one observational year were analyzed in 272 patients aged >12 years. Risk factors were analyzed through chi-squared and unpaired t tests. Logistic regression was applied to perform the risk factors multivariate analysis. RESULTS: A total of 554 complications (1-6 per patient) affected 82.3% of patients. Cardiac complications were less represented than expected. Musculoskeletal diseases were the most represented complications followed by hepatic, sexual and endocrine diseases. Splenectomized patients, born before 1970 and aged >40 years, starting iron chelation therapy when aged >4 years or after receiving more than 20 blood transfusions, presented a significantly higher number of complications. A total of 885 adverse events requiring 34125 additional medical services occurred in 1 year. Of these, 34.9% were related to treatments and 65.1% to other causes. Event numbers, additional medical interventions and cost increased progressively in patients affected by one or more complication compared to patients with no complications. CONCLUSIONS: The pattern of complications changes according to birth cohort and differentiates older from younger patients. The burden of the disease and its costs increase after the onset of the first complication, therefore prevention of complications is fundamental in these patients.

Comparing airways clearance techniques in chronic obstructive pulmonary disease and bronchiectasis: positive expiratory pressure or temporary positive expiratory pressure? A retrospective study.

BACKGROUND: Airway clearance techniques include positive expiratory pressure, commonly used in our clinical practice, and a recently introduced temporary positive expiratory pressure device called UNIKO®. It is unclear which one provides the best benefit to patients. OBJECTIVES: The aim of this observational 4-year study was to retrospectively compare the efficacy of and specific indications for temporary positive expiratory pressure compared to positive expiratory pressure in a standard rehabilitation program. METHOD: We retrospectively collected data from 162 subjects (107 males, mean age 70±9 years, 97 with primary diagnosis of chronic obstructive pulmonary disease, 65 with bronchiectasis), 51 treated with temporary positive expiratory pressure and 111 with positive expiratory pressure. RESULTS: Subjects showed significant improvement in ratio of partial pressure arterial oxygen and fraction of inspired oxygen (p<0.001), forced vital capacity, forced expiratory volume in one second, peak expiratory flow, arterial oxygen saturation, and partial pressure arterial oxygen with no significant difference between positive expiratory pressure and temporary positive expiratory pressure groups apart from forced expiratory flow, which increased only in the positive expiratory pressure group. Evaluating specific subgroups, temporary positive expiratory pressure was more effective than positive expiratory pressure in improving gas transfer in subjects with emphysema and in those on oxygen therapy, as the effective supplement oxygen flow decreased significantly (p=0.034 and 0.046 respectively for temporary positive expiratory pressure vs. positive expiratory pressure). In subjects on mechanical ventilation, positive expiratory pressure was superior to temporary positive expiratory pressure in increasing forced expiratory flow (p=0.018). CONCLUSION: The physiological parameters of both groups improved significantly and similarly. Subgroup analysis suggests that temporary positive expiratory pressure could provide some advantage to subjects with emphysema and those on oxygen therapy, while positive expiratory pressure would benefit patients on mechanical ventilation. Randomized clinical trials are necessary to confirm our preliminary results indicating that different subgroups/phenotypes can benefit more from one type of treatment.

Orphan medicinal products in Europe and United States to cover needs of patients with rare diseases: an increased common effort is to be foreseen.

BACKGROUND: In the European Union (EU) and United States (US), specific regulations have been released to provide incentives to develop and sell orphan medicinal products. We analysed the status of orphan drugs designated that not yet received a marketing authorisation or already marketed for patients affected by rare diseases in the EU and US up to December 2015. For each drug, the following data were extracted: designation date, active substance(s), orphan condition and indication, trade name, approved therapeutic indication, approved ages, genetic nature of disease and if affects children. RESULTS: In the EU, 1264 Orphan Drug Designations have been granted and 133 medicinal products were approved covering a total of 179 indications and 122 rare conditions. Among these, 79 were approved under Regulation (EC)141/2000 (65 still listed in the Orphan Medicinal Products Register and 14 lost the orphan designation but still authorised) and 23 were approved centrally by the European Agency before the Orphan Regulation entered into force. On the other hand, in the US 3082 designations and 415 orphan products, covering a total of 521 indications and 300 rare conditions, were granted. As a result, the mean of designations per year is 79 in the EU and 93.4 in the US, while the mean of approved indications per year is 8.5 in the EU and 15.8 in the US. No orphan product is marketed in the EU for bone and connective tissue, ophthalmic, poisoning/overdose, renal, urinary and reproductive rare diseases. Among the marketed medicinal products, only 46.6% in the EU and 35.2% in the US are approved for children. If all the existing market approvals were merged, 362 additional therapeutic indications in the EU and 72 in the US would be covered. CONCLUSIONS: Our data show that notwithstanding the incentives issued, the number of medicines for rare diseases is still limited, and this is more evident in certain therapeutic areas. However, by merging all the existing approvals, patients would benefit of substantial advantages in both geographic areas. Efforts and cooperation between EU and US seem the only way to speed up the development and marketing of drugs for rare diseases.

The Maugeri Stress Index - reduced form: a questionnaire for job stress assessment.

INTRODUCTION AND OBJECTIVES: A multidimensional self-report questionnaire to evaluate job-related stress factors is presented. The questionnaire, called Maugeri Stress Index - reduced form (MASI-R), aims to assess the impact of job strain on a team or on a single worker by considering four domains: wellness, resilience, perception of social support, and reactions to stressful situations. MATERIAL AND METHODS: The reliability of a first longer version (47 items) of the questionnaire was evaluated by an internal consistency analysis and a confirmatory factor analysis. An item reduction procedure was implemented to obtain a short form of the instrument, and the psychometric properties of the resulting instrument were evaluated using the Rasch measurement model. RESULTS: A total of 14 items from the initial pool were deleted because they were not productive for measurement. The analysis of internal consistency led to the exclusion of eight items, while the analysis performed using structural equation models led to the exclusion of another six items. According to the Rasch model, item properties and the reliability of the instruments appear good, especially for the scales for wellness and resilience. In contrast, the scales for perception of social support and negative coping styles show a lower internal consistency. CONCLUSIONS: The Maugeri Stress Index - reduced form provides a reliable and valid measure, useful for early identification of stress levels in workers or in a team along the eustress-vadistress continuum.

Illness denial questionnaire for patients and caregivers.

PURPOSE: Interest in assessing denial is still present, despite the criticisms concerning its definition and measurement. We tried to develop a questionnaire (Illness Denial Questionnaire, IDQ) assessing patients' and caregivers' denial in relation to their illness/disturbance. PATIENTS AND METHODS: After a preliminary study, a final version of 24 dichotomous items (true/false) was selected. We hypothesized a theoretical model with three dimensions: denial of negative emotions, resistance to change, and conscious avoidance, the first two composing the actual Denial and the last representing an independent component of the illness denial behavior. The IDQ was administered to 400 subjects (219 patients and 181 caregivers) together with the Anxiety-Depression Questionnaire - Reduced form (AD-R), in order to assess concurrent validity. Confirmatory factor analysis (CFA), internal consistency indices (Cronbach's α and McDonald's ω), and test-retest analysis were performed. RESULTS: CFA and internal consistency indices (Cronbach's α: 0.87-0.96) indicated a clear and meaningful three-factor structure of IDQ, for both patients and caregivers. Further analyses showed good concurrent validity, with Denial and its subscale negatively associated with anxiety and depression and avoidance positively associated with anxiety and depression. The IDQ also showed a good stability (r from 0.71 to 0.87). CONCLUSION: The IDQ demonstrated good psychometric properties. Denial of negative emotions and resistance to change seem to contribute to a real expression of denial, and conscious avoidance seems to constitute a further step in the process of cognitive-affective elaboration of the illness.