Health related quality of life in chronic liver diseases.

BACKGROUND & AIMS: The impact of chronic liver diseases (CLDs) on health-related quality of life (HRQoL) is relevant to understand the burden of these conditions and inform decision-making processes related to their care. Studies simultaneously comparing the HRQoL of patients affected by the major CLDs to that of the general population are still lacking and are the subject of this study. METHODS: Using the EQ-5D-3L questionnaire, we analysed and compared HRQoL data from 2962 Italian patients affected by CLDs and forming a representative sample of the general Italian population (6800 individuals). Exploratory analyses were conducted to investigate the effects of each CLD on HRQoL, using the general population as reference and adjusting for possible confounders. RESULTS: Patients with CLDs (HBV, HCV, PSC, PBC, AIH, NAFLD/NASH) in the chronic hepatitis stage and with compensated cirrhosis (CC) showed HRQoL similar to the general population. However, AIH were more likely to report problems in self-care and lower EQ-5D VAS score, while NAFLD/NASH and HCV showed an increased risk of anxiety/depression. On the other hand, with progression to more advanced stages of liver disease (DC or HCC), HRQoL decreased significantly with higher risk of reporting problems in the physical domains, and significant reductions in the VAS and utility index scores. CONCLUSIONS: Different subtypes of CLD affected different QoL domains. This study therefore provides a real estimate of the impact of CLDs on patients' HRQoL, and represents a much needed tool to inform decision-making while assessing the effectiveness and cost-effectiveness of the care of these patients.

Clinical outcome indicators in chronic hepatitis B and C: A primer for value-based medicine in hepatology.

BACKGROUND & AIMS: Chronic liver diseases (CLDs) are major health problems that require complex and costly treatments. Liver-specific clinical outcome indicators (COIs) able to assist both clinicians and administrators in improving the value of care are presently lacking. The Value-Based Medicine in Hepatology (VBMH) study aims to fill this gap, devising and testing a set of COIs for CLD, that could be easily collected during clinical practice. Here we report the COIs generated and recorded for patients with HBV or HCV infection at different stages of the disease. METHODS/RESULTS: In the first phase of VBMH study, COIs were identified, based on current international guidelines and literature, using a modified Delphi method and a RAND 9-point appropriateness scale. In the second phase, COIs were tested in an observational, longitudinal, prospective, multicentre study based in Lombardy, Italy. Eighteen COIs were identified for HBV and HCV patients. Patients with CLD secondary to HBV (547) or HCV (1391) were enrolled over an 18-month period and followed for a median of 4 years. The estimation of the proposed COIs was feasible in the real-word clinical practice and COI values compared well with literature data. Further, the COIs were able to capture the impact of new effective treatments like direct-acting antivirals (DAAs) in the clinical practice. CONCLUSIONS: The COIs efficiently measured clinical outcomes at different stages of CLDs. While specific clinical practice settings and related healthcare systems may modify their implementation, these indicators will represent an important component of the tools for a value-based approach in hepatology and will positively affect care delivery.

Health-related quality of life and psychological wellbeing of children with Specific Learning Disorders and their mothers.

BACKGROUND: Literature suggests that Specific Learning Disorders (SpLD) can cause impairment of Health-Related Quality of Life (HRQoL) and psychological well-being of children, and that this condition potentially affects parents' quality of life and well-being too. AIMS: This study aims first to explore HRQoL and psychological well-being among children with SpLD and second among mothers of children with SpLD. METHODS AND PROCEDURES: Thirty children aged 8-14 years diagnosed as having SpLD and their mothers completed a battery of scales to assess children's HRQoL and psychological well-being. Mothers also completed a battery of instruments to explore their personal HRQoL and psychological well-being. RESULTS: Compared with the general population, children with SpLD reported significantly lower level of psychosocial health, and mothers had a higher probability of being anxious and/or depressed. CONCLUSIONS AND IMPLICATIONS: This study supports previous research about impaired HRQoL, symptoms of generalized anxiety, school-related anxiety and depressed mood in children with SpLD. Moreover, it provides evidence that mothers of children with SpLD may experience stress in coping with their child's disability and develop socio-emotional symptoms such as anxiety. Implications concern the need to implement effective supportive services among children with SpLD and their parents.

Patients', physicians', nurses', and pharmacists' preferences on the characteristics of biologic agents used in the treatment of rheumatic diseases.

OBJECTIVE: To estimate preferences in relevant treatment characteristics evaluated by different groups involved in the management of patients with rheumatic diseases. SUBJECTS AND METHODS: We surveyed patients with rheumatic diseases, and rheumatologists, nurses, and pharmacists with experience in treatment with/provision of biologic drugs for these patients. Through a discrete choice experiment, participants evaluated 16 possible scenarios in which pairs of similarly efficacious treatments were described with six characteristics: 1) frequency of administration; 2) mode and place of administration; 3) manner, helpfulness, efficiency, and courtesy of health personnel; 4) frequency of reactions at the site of drug administration; 5) severity of generalized undesired/allergic reactions; and 6) additional cost. The direction and strength of preferences toward each characteristic level and the relative importance of each characteristic were estimated through a random-effects conditional logistic regression model. RESULTS: In total, 513 patients, 110 rheumatologists, 51 nurses, and 46 pharmacists from 30 centers in Italy participated. Characteristics 3, 4, and 6 were the most important for every subgroup; 1 was least important for patients and rheumatologists, 2 was least important for pharmacists, and 2 and 5 were least important for nurses. For characteristic 2, pharmacists preferred subcutaneous self-injection with a syringe; nurses preferred assisted infusion at an infusion center close to the patient's home; patients and rheumatologists preferred subcutaneous self-injection with a pen. CONCLUSION: The different preferences for some characteristics shown by the different groups can play an important role, together with purely clinical aspects, in the choice and consequent benefit of treatments, contributing also to a more satisfactory use of resources.

Benefits in pain perception, ability function and health-related quality of life in patients with failed back surgery syndrome undergoing spinal cord stimulation in a clinical practice setting.

BACKGROUND: Failed back surgery syndrome (FBSS) represents one main cause of chronic neuropathic or mixed pain, functional disability and reduced Health Related Quality of Life (HRQoL). Spinal Cord Stimulation (SCS) can be a value for money option to treat patients refractory to conventional medical management (CMM). We estimated from real-world data: 1) the amount of reduced levels of HRQoL of target patients compared to general population, 2) the relationship between pain intensity, functional disability, and overall HRQoL, and 3) the improvement of patients' health from SCS intervention, and 4) we give some insights and make some suggestions on the selection of a battery of patients' reported health instruments for use in routine clinical practice. METHODS: At recruitment (before SCS) and every 6 months for 2 years after SCS a battery of questionnaires/tests were completed: the generic EQ-5D and SF-36 for HRQoL, the specific Numerical Rating Scale (NRS) to measure pain intensity, and Oswestry Disability Index (ODI) to measure functional disability. We conducted multilevel regression analyses to investigate the association of HRQoL with the NRS and ODI indexes; multiple regression analyses to compare EQ-5D data with those of the general population adjusted for age, sex and education, and statistical tests to compare the changes of HRQoL, NRS and ODI estimates at baseline with those measured during the follow-up. RESULTS: Eighty patients (40% male, mean age = 58 years) participated. HRQoL was significantly worse in the patients than in the corresponding general population. Pain, functional disability and HRQoL significantly related each other during follow-up, Significant improvements (p < 0.001) in pain intensity, functional capability and HRQoL were reached after 6 months from SCS and generally remained stable during follow-up. Specific instruments provided detailed information on disability and pain, while generic instruments assessed the overall HRQoL and allowed a comparison with the general population's one. CONCLUSIONS: SCS + CMM treatment reaches a statistically significant and probably a clinically relevant improvement in pain perception, functional disability and HRQoL in patients with FBSS refractory to CMM. An appropriate selection of instruments for use in clinical practice is crucial for a routine assessment of health perception in patients, aimed to guide decisions for optimal treatment.

Optimising the clinical strategy for autoimmune liver diseases: Principles of value-based medicine.

BACKGROUND: Autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis represent the three major autoimmune liver diseases (AILDs). Their management is highly specialized, requires a multidisciplinary approach and often relies on expensive, orphan drugs. Unfortunately, their treatment is often unsatisfactory, and the care pathway heterogeneous across different centers. Disease-specific clinical outcome indicators (COIs) able to evaluate the whole cycle of care are needed to assist both clinicians and administrators in improving quality and value of care. Aim of our study was to generate a set of COIs for the three AILDs. We then prospectively validated these indicators based on a series of consecutive patients recruited at three tertiary clinical centers in Lombardy, Italy. METHODS: In phase I using a Delphi method and a RAND 9-point appropriateness scale a set of COIs was generated. In phase II the indicators were applied in a real-life dataset. RESULTS: Two-hundred fourteen patients were enrolled and followed-up for a median time of 54months and the above COIs were recorded using a web-based electronic medical record program. The COIs were easy to collect in the clinical practice environment and their values compared well with the available natural history studies. CONCLUSIONS: We have generated a comprehensive set of COIs which sequentially capture different clinical outcome of the three AILDs explored. These indicators represent a critical tool to implement a value-based approach to patients with these conditions, to monitor, compare and improve quality through benchmarking of clinical performance and to assess the significance of novel drugs and technologies. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.

Parsing the phenotype of obsessive-compulsive tic disorder (OCTD): a multidisciplinary consensus.

Obsessive-Compulsive Disorder (OCD) and Tic Disorder (TD) are highly disabling and often comorbid conditions. Of note, the DSM-5 acknowledged a new 'tic-related' specifier for OCD, which might be referred to as Obsessive-Compulsive Tic Disorder (OCTD), raising new interest toward a better clinical characterisation of affected patients. Available literature indicates that early onset, male gender, sensory phenomena and obsessions of symmetry, aggressiveness, hoarding, exactness and sounds as well as comorbidity with Attention Deficit Hyperactivity Disorder (ADHD) may be of more frequent observation in patients with OCTD. In order to share expertise in the field from different perspectives, a multidisciplinary panel of Italian clinicians, specifically involved in the clinical care of OCD and TD patients, participated into a consensus initiative, aimed to produce a shared document. As a result, after having examined the most relevant literature, authors sought to critically identify and discuss main epidemiologic, socio-demographic and clinical features characterising OCTD patients, along with other specific aspects including Health-Related Quality-of-Life (HRQoL), economic consequences related with the condition and its management, as well as treatment-related issues, that need to be further investigated.

Feasibility, acceptability and construct validity of EQ-5D in systemic sclerosis.

BACKGROUND: Systemic sclerosis is a chronic disabling disease that is often associated with severe physical and psychological impairment. Nonetheless, health-related quality of life (HRQoL) in patients with systemic sclerosis is often left behind in clinical practice and research. One of the reasons for this lack of evaluation is the current use of tools, such as the short form-36 (SF-36) questionnaire, that are complete but complicated to use in everyday routine. Other self-reported outcome measures such as the health assessment questionnaire (HAQ) are simple, but specifically designed for physical disability. STUDY AIMS AND METHODS: Our aim was to evaluate the feasibility, acceptability and construct validity of EQ-5D, a simple and quick self-assessment tool, and to compare its performance with SF-36 and HAQ. We investigated 119 consecutive patients with systemic sclerosis (94% female; age: median 63 years, interquartile range 53-70 years) at three different rheumatology centres. Acceptability was evaluated from comments made by the patients and feasibility on the basis of the number of patients needing assistance or not answering questions (missing data). Construct validity was based on both convergent and divergent validity between conceptually similar and dissimilar domains, respectively, of the compared instruments. RESULTS: EQ-5D was well accepted by patients. The percentage of patients missing data in at least one EQ-5D domain was 2.5%. Spearman's correlation coefficients between similar dimensions of EQ-5D vs SF-36 and vs HAQ were moderate (≥0.30) to strong (≥0.50); in contrast, correlation coefficients between less comparable dimensions were weak. As expected, the EQ-5D anxiety/depression domain did not correlate with any of the HAQ domains. The EQ-5D visual analogue scale (VAS) concordance with SF-36 general health domain and HAQ total score was strong (≥0.50 for both). Median value for the EQ-5D index (interquartile range) was 0.81 (0.75-0.86). The EQ-5D index had correlation coefficients >0.40 with all SF-36 domains and with all HAQ domains, HAQ total and HAQ VAS. CONCLUSIONS: Our data demonstrate good acceptability, feasibility and construct validity of EQ-5D in patients with systemic sclerosis. We suggest the use of EQ-5D in systemic sclerosis patients as an HRQoL measure in clinical practice, in randomised clinical trials and/or in pharmacoeconomic evaluations.

The societal burden of chronic liver diseases: results from the COME study.

OBJECTIVE: Chronic liver diseases (CLDs) impose a significant socioeconomic burden on patients and the healthcare system, but to what extent remains underexplored. We estimated costs and health-related-quality-of-life (HRQoL) among patients with CLDs at different stages and with different aetiologies. DESIGN: A cost-of-illness study was conducted. Direct costs, productivity loss and HRQoL were estimated in patients with chronic hepatitis, cirrhosis hepatocellular carcinoma (HCC) or where orthotopic liver transplantation (OLT) had been performed, for hepatitis C virus (HCV) infection, hepatitis B virus (HBV) infection, or in those with liver disease from other causes. Patients were retrospectively observed for 6 months. The societal perspective was adopted to calculate costs. RESULTS: In total, 1088 valid patients (median age=59.5 years, 60% men) were enrolled. 61% had chronic hepatitis, 20% cirrhosis, 8% HCC and 12% underwent OLT. HCV infection was identified in 52% and HBV infection in 29% of the patients. Adjusted mean direct costs increased from <€200/patient-month in HCV-infected patients with hepatitis to >€3000/patient-month in HBV infected patients with OLT. Antiviral treatment was the cost driver in patients with hepatitis, while hospital costs were the driver in the other subgroups. Absenteeism increased from HBV-infected patients with hepatitis (0.7 day/patient-month) to patients with OLT with other aetiologies (3.7 days/patient-month). HRQoL was on average more compromised in cirrhosis and patients with HCC, than in hepatitis and patients with OLT. HBV-infected patients generated higher direct costs, patients with other aetiologies generated the highest productivity loss and HCV-infected patients reported the worst HRQoL levels. CONCLUSIONS: The present study can be considered a benchmark for future research and to guide policies aimed at maximising the cost-effective of the interventions.

Reliability and validity of the Italian version of the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument in patients with systemic sclerosis.

OBJECTIVES: To test the acceptability, feasibility, reliability and validity of the Italian translated version of the UCLA Scleroderma Clinical Trial Consortium GIT (UCLA-SCTC GIT) 2.0. Gastrointestinal tract (GIT) involvement is frequent in systemic sclerosis (SSc). The UCLA-SCTC GIT 2.0 is a validated instrument for measuring the presence and impact of GIT symptoms in SSc patients. METHODS: Acceptability and feasibility of the questionnaire were evaluated based on the input from the patients. Internal consistency was evaluated by Cronbach's alpha. External consistency was measured by comparing with the Short Form (SF)-36 and EQ-5D by Spearman's rho, meaningful if ≥0.30. RESULTS: Sixty-two consecutive SSc patients (mean age 60.6) were recruited, 88.5% were female. The UCLA-SCTC GIT 2.0 was well accepted. Percentage of missing data in UCLA-SCTC GIT total score was 2 %. Internal consistency was acceptable (alpha≥0.70) for all domains. Cronbach's alpha was ≥0.70 for all domains. UCLA-SCTC GIT 2.0 discriminated between patients with or without gastroesophageal reflux disease whether diagnosed clinically or by objective testing (p<0.01 for both). UCLA-SCTC GIT emotional well-being was correlated with the conceptually equivalent SF-36 mental health domains (correlation coefficient>0.35) and with the EQ-5D usual activities domain (0.38), thus reflecting the impact on everyday activities. The distention/bloating domain strongly correlated with the EQ-5D anxiety/depression domain (0.51) and reflux domain with role emotional of SF-36 (0.44). CONCLUSIONS: This is the first validation study of the Italian version of UCLA-SCTC GIT 2.0. Our data support its feasibility, reliability, and validity in Italian SSc patients.

Cost-Effectiveness and Cost-Utility Analysis of Spinal Cord Stimulation in Patients With Failed Back Surgery Syndrome: Results From the PRECISE Study.

OBJECTIVE: To assess the cost-effectiveness and cost-utility of Spinal Cord Stimulation (SCS) in patients with failed back surgery syndrome (FBSS) refractory to conventional medical management (CMM). MATERIALS AND METHODS: We conducted an observational, multicenter, longitudinal ambispective study, where patients with predominant leg pain refractory to CMM expecting to receive SCS+CMM were recruited in 9 Italian centers and followed up to 24 months after SCS. We collected data on clinical status (pain intensity, disability), Health-Related Quality-of-Life (HRQoL) and on direct and indirect costs before (pre-SCS) and after (post-SCS) the SCS intervention. Costs were quantified in € 2009, adopting the National Health Service's (NHS), patient and societal perspectives. Benefits and costs pre-SCS versus post-SCS were compared to estimate the incremental cost-effectiveness and cost utility ratios. RESULTS: 80 patients (40% male, mean age 58 years) were recruited. Between baseline and 24 months post-SCS, clinical outcomes and HRQoL significantly improved. The EQ-5D utility index increased from 0.421 to 0.630 (p < 0.0001). Statistically significant improvement was first observed six months post-SCS. Societal costs increased from €6600 (pre-SCS) to €13,200 (post-SCS) per patient per year. Accordingly, the cost-utility acceptability curve suggested that if decision makers' willingness to pay per Quality-Adjusted-Life-Years (QALYs) was €60,000, SCS implantation would be cost-effective in 80% and 85% of cases, according to the NHS's and societal point of views, respectively. CONCLUSIONS: Our results suggest that in clinical practice, SCS+CMM treatment of FBSS patients refractory to CMM provides good value for money. Further research is encouraged in the form of larger, long-term studies.

Values for health states with different life durations.

BACKGROUND: Recent research suggests that the value of health states may depend on their duration, implying a more complex relationship between quality and quantity of life than the standard linear relationship assumed in the quality-adjusted life years (QALY) model. OBJECTIVE: This study models how duration affects the value of health states, using discrete choice data. METHODS: A study was conducted comprising health profiles including various durations. Health states were described with the EQ-5D. Duration was introduced as a sixth domain with six levels (1, 5, 10, 15, 30, 50 years). Sixty pairs of health profiles were selected, applying a Bayesian approach. Two hundred eight university students self-completed the computerized response tasks. Data were analyzed with a conditional logistic regression model. RESULTS: There is clear evidence for non-linear values for duration, that is, preferences for duration are more accurately described by a logarithmic function. CONCLUSIONS: In discrete choice experiments using health states with different durations, these data present the first evidence for decreasing marginal utility for duration. Our results suggest that refinement of the standard QALY framework may be needed for states with a long duration.

Burden of diabetes mellitus estimated with a longitudinal population-based study using administrative databases.

OBJECTIVE: To assess the epidemiologic and economic burden of diabetes mellitus (DM) from a longitudinal population-based study. RESEARCH DESIGN AND METHODS: Lombardy Region includes 9.9 million individuals. Its DM population was identified through a data warehouse (DENALI), which matches with a probabilistic linkage demographic, clinical and economic data of different Healthcare Administrative databases. All individuals, who, during the year 2000 had an hospital discharge with a IDC-9 CM code 250.XX, and/or two consecutive prescriptions of drugs for diabetes (ATC code A10XXXX) within one year, and/or an exemption from co-payment healthcare costs specific for DM, were selected and followed up to 9 years. We calculated prevalence, mortality and healthcare costs (hospitalizations, drugs and outpatient examinations/visits) from the National Health Service's perspective. RESULTS: We identified 312,223 eligible subjects. The study population (51% male) had a mean age of 66 (from 0.03 to 105.12) years at the index date. Prevalence ranged from 0.4% among subjects aged ≤45 years to 10.1% among those >85 years old. Overall 43.4 deaths per 1,000 patients per year were estimated, significantly (p<0.001) higher in men than women. Overall, 3,315€/patient-year were spent on average: hospitalizations were the cost driver (54.2% of total cost). Drugs contributed to 31.5%, outpatient claims represented 14.3% of total costs. Thirty-five percent of hospital costs were attributable to cerebro-/cardiovascular reasons, 6% to other complications of DM, and 4% to DM as a main diagnosis. Cardiovascular drugs contributed to 33.5% of total drug costs, 21.8% was attributable to class A (16.7% to class A10) and 4.3% to class B (2.4% to class B01) drugs. CONCLUSIONS: Merging different administrative databases can provide with many data from large populations observed for long time periods. DENALI shows to be an efficient instrument to obtain accurate estimates of burden of diseases such as diabetes mellitus.

Cost and quality of life in patients with severe chronic hand eczema refractory to standard therapy with topical potent corticosteroids.

BACKGROUND: Little is known about the socio-economic burden of severe chronic hand eczema in patients refractory to treatment with potent corticosteroids. OBJECTIVES: To estimate the socio-economic burden of severe chronic hand eczema refractory to potent topical corticosteroids, and to establish an algorithm for the estimation of the health-related quality of life EuroQol five-dimensional (EQ-5D) utility index from the Dermatology Life Quality Index (DLQI) summary score. METHODS: A multicentre cost of illness study was conducted, adopting the societal perspective. Adult patients with severe and refractory chronic hand eczema were enrolled. Direct (e.g. drug treatment and travel) and indirect (i.e. loss of productivity) mean costs/patient-month were estimated. Health-related quality of life was assessed with the EQ-5D and DLQI questionnaires. An ordinary least square regression model was used to investigate relationships between health-related quality of life scores. RESULTS: One hundred and four valid patients (mean age 44.5 years, 39.4% male) participated. Overall mean costs were €418.3/patient-month: loss of productivity contributed 43.7%, followed by hospitalization (16.1%) and travel (10.3%). Health-related quality of life scores were, on average, 0.50 (EQ-5D utility) and 11.3 (DLQI). Utility and DLQI summary were significantly related to each other. CONCLUSIONS: Wellbeing and loss of productivity are the most important consequences in these patients. Appropriate treatment is necessary to improve patient health and productivity, which will contribute to reducing societal costs.

Italian population-based values of EQ-5D health states.

OBJECTIVE: To estimate a value set for the calculation of Italian-specific quality-adjusted life years (QALYs), based on preferences elicited on EuroQol five-dimensional (EQ-5D) questionnaire health states using the time trade-off technique. METHODS: The revised standard Measurement and Valuation of Health protocol was followed. Twenty-five health states, divided into three groups and given to 450 subjects, were selected to obtain 300 observations per state. Subjects aged 18 to 75 years were recruited to be representative of the Italian general adult population for age, sex, and geographical distribution. To improve efficiency, face-to-face interviews were conducted by using the Computer Assisted Personal Interviewing approach. Several random effects regression models were tested to predict the full set of EQ-5D questionnaire health states. Model selection was based on logical consistency of the estimates, sign and magnitude of the regression coefficients, goodness of fit, and parsimony. RESULTS: The model that satisfied the criteria of logical consistency and was more efficient includes 10 main effect dummy variables for the EQ-5D questionnaire domain levels and the D1 interaction term, which accounts for the number of dimensions at levels 2 or 3 beyond the first. This model has an R(2) of 0.389 and a mean absolute error of 0.03, which are comparable to or better than those of models used in other countries. The utility estimates after state 11111 range from 0.92 (21111) to -0.38 (33333). Italian utility estimates are higher than those estimated in the United Kingdom and Spain and used so far to assess QALYs and conduct cost-utility evaluations in Italy. CONCLUSIONS: A specific value set is now available to calculate QALYs for the conduction of health economic studies targeted at the Italian health care system.