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.

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.

Development of a Barthel Index based on dyspnea for patients with respiratory diseases.

BACKGROUND: As Barthel Index (BI) quantifies motor impairment but not breathlessness, the use of only this index could underestimate disability in chronic respiratory disease (CRD). To our knowledge, no study evaluates both motor and respiratory disability in CRD during activities of daily living (ADLs) simultaneously and with a unique tool. The objective of this study was to propose for patients with CRD an additional tool for dyspnea assessment during ADLs based on BI items named Barthel Index dyspnea. METHODS: Comprehensibility, reliability, internal consistency, validity, responsiveness, and ability to differentiate between disease groups were assessed on 219 subjects through an observational study performed in an in-hospital rehabilitation setting. RESULTS: Good comprehensibility, high reliability (interrater intraclass correlation coefficient was 0.93 [95% confidence interval 0.892-0.964] and test-retest intraclass correlation coefficient was 0.99 [95% confidence interval 0.983-0.994]), good internal consistency (Cronbach's alpha 0.89), strong concurrent validity with 6 minute walking distance (Pearson r=-0.538, P<0.001) and Medical Research Council (Spearman r S=0.70, P<0.001), good responsiveness after rehabilitation (P<0.001), and good appropriateness of the index were found evidencing patients with different dyspnea severity. Divergent validity showed weak correlation (Pearson r=-0.38) comparing Barthel Index dyspnea and BI. CONCLUSION: The BI based on dyspnea perception proved to be reliable, sensitive, and adequate as a tool for measuring the level of dyspnea perceived in performing basic daily living activities. A unique instrument simultaneously administered may provide a global assessment of disability during ADLs incorporating both motor and respiratory aspects.

Cost-effectiveness treatment with Rituximab in patients with rheumatoid arthritis in real life.

The cost-effectiveness of treatments that have the potential to change the "natural history" of a chronic progressive disease has to be evaluated over the long term. Cost-effectiveness estimates have been based on the concept that, with treatment, patients will not progress to the next level(s) of disease severity or will take a longer time to progress, thus avoiding or delaying the high costs and low utility associated with more severe disease. This analysis focused on the use of Rituximab in treating patients with moderate to severe RA for whom at least one anti-TNFα blocking agent had failed. The aim of our study was to evaluate the cost-effectiveness in 32 patients with rheumatoid arthritis in therapy with a single infusion of Rituximab 1,000 mg given on days 1 and 15 of each month for 1 year. After 6 months of treatment, we observed for all 32 patients a total quality-adjusted life year (QALY) gained of 11,840 with an average of 0.37 QALY for a single patient, a treatment cost of euro 5,610 and a QALY/cost ICER (incremental cost-effectiveness ratio) of euro 15,114. After 1 year of treatment, we observed data for 28 patients with a total QALY gained of 11,480 with an average of 0.41 QALY for a single patient, a treatment cost of euro 9,690 and a QALY/cost ICER (incremental cost-effectiveness ratio) of euro 23,696. The benefit of using Rituximab is cost-effectiveness with a QALY/gained under the acceptable threshold of euro 50,000 in our observational study. These are important data for discussion from the economic point of view when we choose a biologic therapy for rheumatoid arthritis in clinical practice.

Early rheumatoid arthritis in Italy: study of incidence based on a two-level strategy in a sub-area of Florence (Scandicci-Le Signe).

The concept of Early Arthritis represents a new diagnostic-therapeutic strategy in modern rheumatology. Even if many Early Arthritis clinics are starting up, we do not yet know the frequency of this pathology in the Italian population. With the collaboration of 20 general practictioners (GPs) operating in the municipalities of Scandicci, Lastra a Signa and Signa, we assessed the incidence of rheumatoid arthritis and of new cases of Early Rheumatoid Arthritis (ERA) in the period from 1.09.2005 to 31.08.2006. The general population over 18 years old in the three municipalities according to the political electoral lists in April 2006 was as follows: Scandicci 42,474 (Males 20,290; Females 22,184), Lastra a Signa 15,368 (M 7,458; F 7,910) and Signa 13,372 (M 6,439; F 6,933). The total number of patients followed by the 20 GPs was 32,521 according to the records of ASL10 Florence. In one year 920 patients were referred by their GPs to a rheumatologist with suspected early undifferentiated arthritis according to Emery's criteria. The patients underwent a rheumatological examination and the rheumatoid factor IgM, hidden rheumatoid factors (IgG and IgA) and IgG antibodies anti-CCP (anti-cyclic citrullinate peptides) with a semiquantitative immuno-enzymatic test ELISA were investigated. In one year we observed 32 new cases of Rheumatoid Arthritis, of which 8 were males and 24 were females. The rate of incidence with respective intervals of confidence of 95% was 0.98 per thousand (0.64-1.32 per thousand). The average age was 47.7 +/- 10.5 in the females and 54.9 +/- 10.3 in the males. The patients had an average history of illness in months of 5.2 +/- 1.3 F versus 4.6 +/- 1.1 M, number of tender joints 6.2 +/- 2.3 F versus 5.3 +/- 2.2 M, number of swollen joints 4.8 +/- 1.4 F versus 4.2 +/- 1.5 M, a global assessment of 64.3 +/- 10 F versus 53 +/- 12 M, ESR (mm/h) 49.2 +/- 11.3 F versus 43.3 +/- 12.5 M, CRP (mg/dl) 2.8 +/- 1.3 F versus 2.3 +/- 1.4 M, DAS28 5.55 +/- 1.2 F versus 5.19 +/- 1.3 M, HAQ 2.5 +/- 0.4 F, 2.2 +/- 0.3 M. The rates of incidence in the Italian population affected by early rheumatoid arthritis are higher than those found in some European populations, such as those of the UK and Finland, but less than those found in the population of USA. The different data reported in the literature seem to be due to the different methods of assessing ERA and to the different types of samples studied.

Access to information supporting availability of medicines for patients suffering from rare diseases looking for possible treatments: the EuOrphan Service.

Currently in Europe, approximately 30 million people suffer from rare diseases, and a major problem is that many patients do not have access to quality healthcare for their disorders. Moreover, there is also a lack of quality information and a networking system aimed at supporting interaction among patients, clinicians, researchers, pharmaceutical industries, and governmental bodies. The purpose of this article is to inform physicians, public health care professionals, and other health care providers about EuOrphan service, the aim of which is to ensure easier access to quality information on rare diseases and their treatment. A set of web-based services is available at www.euorphan.com where information for target-users on treatments and products available worldwide for rare disease care as well as indications about healthcare centers are provided. Moreover, the service aims at providing consultancies for pharmaceutical companies to ultimately support the European legislation in bringing new drugs of a high ethical standard to the market and to exert a positive impact on the large population of patients suffering from rare diseases in Europe. The services provided by EuOrphan can facilitate concrete networking among patients, patient associations, doctors, and companies and also support the organization of clinical trials. In this perspective, EuOrphan could become a very valuable tool for globalizing the information about the availability of treatment (authorized or under development) of orphan patients.

Update on the family strain questionnaire: a tool for the general screening of caregiving-related problems.

BACKGROUND: The growing prevalence of chronic diseases and home-based treatments has led to the introduction of a large number of instruments for assessing the caregiving-related problems associated with specific diseases, but our Family Strain Questionnaire (FSQ) was designed to provide a basis for general screening and comparison regardless of the disease. We here describe the final validation of its psychometric characteristics. METHODS: The FSQ consists of a brief semi-structured interview and 44 dichotomic items, and has now been administered to 811 caregivers (285 were simultaneously administered other questionnaires assessing anxiety and depressive symptoms). After a factorial analysis confirmed the 5-factor structure identified in previous studies (emotional burden, problems in social involvement, need for knowledge about the disease, satisfaction with family relationships, and thoughts about death), we undertook correlation and reliability analyses, and a receiver operating characteristics curve analysis designed to determine the cut-off point for the emotional problems identified by the first factor. Finally, univariate ANOVA with Bonferroni's post-hoc test was used to compare the disease-specific scores. RESULTS: The validity and reliability of the FSQ is good, and its factorial structure refers to areas that are internationally considered as being of general importance. The semi-structured interview collects information concerning the socio-economic status of caregivers and their convictions/interpretations concerning the diseases of their patients. CONCLUSIONS: The FSQ can be used as a single instrument for the general assessment of caregiving-related problems regardless of the reference disease. This makes it possible to reduce administration and analysis times, and compare the problems experienced by the caregivers of patients with different diseases.

Noninvasive cardiac output assessment during heart surgery.

OBJECTIVE: To evaluate the reliability of a new noninvasive method for the assessment of cardiac output with the partial carbon dioxide rebreathing technique. METHODS: This technique was applied to patients undergoing heart surgery. Values of cardiac index obtained with this equipment were compared with the artero-venous CO2 gradient, a reliable index of cardiovascular status. Positive and negative predictive values of the test were assessed. RESULTS: A total of 21 simultaneous measurement of the cardiac index and of the artero-venous CO2 gradient were obtained. The positive predictive value of the test was 67% while the negative predictive value was 100%, indicating that a normal value of cardiac index recorded with the rebreathing technique predicts with a good reliability a normal cardiovascular state. CONCLUSIONS: Working through a series of mathematical algorithms, accuracy in the computation of cardiac output can be decreased with this equipment; however, this limitation seems to be outweighed by the simplicity and noninvasive nature of the methods.