Using Health-Related Social Media to Understand the Experiences of Adults With Lung Cancer in the Era of Immuno-Oncology and Targeted Therapies: Observational Study.

BACKGROUND: The treatment of non-small cell lung cancer (NSCLC) has evolved dramatically with the approval of immuno-oncology (IO) and targeted therapies (TTs). Insights on the patient experience with these therapies and their impacts are lacking. Health-related social media has been increasingly used by patients to share their disease and treatment experiences, thus representing a valuable source of real-world data to understand the patient's voice and uncover potential unmet needs. OBJECTIVE: This study aimed to describe the experiences of patients with NSCLC as reported in discussions posted on lung cancer-specific social media with respect to their disease symptoms and associated impacts. METHODS: Publicly available posts (2010-2019) were extracted from selected lung cancer- or NSCLC-specific websites. Social media users (patients and caregivers posting on these websites) were stratified by metastatic- and adjuvant-eligible subgroups and treatment received using natural language processing (NLP) and machine learning methods. Automated identification of symptoms was conducted using NLP. Qualitative data analysis (QDA) was conducted on random samples of posts mentioning pain-related, fatigue-related, respiratory-related, or infection-related symptoms to capture the patient experience with these and associated impacts. RESULTS: Overall, 1724 users (50,390 posts) and 574 users (4531 posts) were included in the metastatic group and adjuvant group, respectively. Among users in the metastatic group, pain, discomfort, and fatigue were the most commonly mentioned symptoms (49.7% and 39.6%, respectively), and in the QDA (258 posts from 134 users), the most frequent impacts related to physical impairments, sleep, and eating habits. Among users in the adjuvant group, pain, discomfort, and respiratory symptoms were the most commonly mentioned (44.8% and 23.9%, respectively), and impacts identified in the QDA (154 posts from 92 users) were mostly related to physical functioning. CONCLUSIONS: Findings from this exploratory observational analysis of social media among patients and caregivers informed the lived experience of NSCLC in the era of novel therapies, shedding light on most reported symptoms and their impacts. These findings can be used to inform future research on NSCLC treatment development and patient management.

Linaclotide utilization and potential for off-label use and misuse in three European countries.

Introduction: Linaclotide is approved for adults with moderate-to-severe irritable bowel syndrome (IBS) with constipation (IBS-C). Linaclotide is not indicated for weight loss or for patients with inflammatory bowel disease (IBD); it is contraindicated in patients with mechanical bowel obstruction (MBO). Some patients with obesity or eating disorders (ED) may use linaclotide off-label for weight loss or as a laxative. Objectives: To describe the use of linaclotide in clinical practice, including patients with potential for off-label use or misuse. Methods: Post-authorization safety study conducted in three databases from the linaclotide launch date to 2017: the Clinical Practice Research Datalink in the United Kingdom (UK), the Information System for Research in Primary Care database in Spain and the linked Patient, Prescription and Causes of Death Registries in Sweden. Cohorts of patients were identified as having IBS using diagnostic and treatment codes; IBS subtypes were identified using symptoms and treatment codes; patients with obesity, ED, MBO, and IBD were identified using diagnostic codes or body mass index. Results: There were 1319, 1981, and 5081 linaclotide users from the United Kingdom, Spain, and Sweden with a median age of 45, 57, and 51 years, respectively; most were females. In the United Kingdom, Spain, and Sweden, respectively: 59.0%, 60.3%, and 31.3% of linaclotide users had an IBS diagnosis recorded, and among those, 68.8%, 61.3%, and 92.7% were classified as IBS-C. The proportions of linaclotide users considered at risk for potential off-label use for weight loss or as a laxative were 17.1%, 29.7%, and 1.7%, and the proportions of users considered at risk of misuse due to a history of MBO or IBD were 3.5%, 4.6%, and 5.7% in the United Kingdom, Spain, and Sweden, respectively. Conclusions: Potential linaclotide off-label use and misuse appears limited, as evidenced by the small sizes of the patient subgroups at risk for off-label use and misuse.

Discontinuation and primary care visits in nonvalvular atrial fibrillation patients treated with apixaban or warfarin.

AIM: Nonvalvular atrial fibrillation (NVAF) requires long-term anticoagulation treatment, which may necessitate frequent primary care visits. MATERIALS & METHODS: NVAF patients initiating warfarin or apixaban in 2012-2017 were identified from linked primary (Clinical Practice Research Datalink) and secondary care (Hospital Episode Statistics) data. A propensity score matched Cox regression model compared discontinuation risk. Primary care visits were compared via negative binomial regression. RESULTS: A total of 2695 apixaban users were matched to warfarin patients. Discontinuation risk was lower with apixaban than warfarin (hazard ratio: 0.40; 95% CI: 0.35-0.46). Apixaban patients averaged 12.2 annual primary care visits, versus 17.1 for warfarin users (p < 0.001). CONCLUSION: Apixaban was associated with reduced rates of discontinuation and primary care visits compared with warfarin.

Validation of the shortened Hunter Syndrome-Functional Outcomes for Clinical Understanding Scale (HS-FOCUS).

BACKGROUND: The rare disease, Hunter Syndrome (mucopolysaccharidosis type II; MPS II), characterized by iduronate-2-sulfatase deficiency, has heterogeneous symptoms often including cognitive impairment (CI). To evaluate physical functioning and daily activity limitations of patients with MPS II, the multidomain shortened Hunter Syndrome-Functional Outcomes for Clinical Understanding Scale (HS-FOCUS) questionnaire was previously developed and preliminarily validated. Here we gather data in a dedicated prospective longitudinal observational study using direct responses to the shortened instrument and assess its psychometric properties further. METHODS: Interview data were collected from eligible self-reporting patients (≥ 12 years of age) or caregivers of patients using respective versions of the instrument at baseline and 2-4 weeks later. Internal consistency, test-retest reliability, convergent and discriminant validity, and validity of known groups were assessed. Participants also completed Child Health Questionnaire (CHQ), Health Utilities Index Mark 3, and Global Impression of Severity (GIS) questionnaires. RESULTS: All patients were male, consisting of 31 caregiver-reported patients (aged 3-26 years) and 20 self-reported patients (aged 12-58 years). Most (77.4%) caregiver-reported patients had CI. Both questionnaire versions demonstrated good internal consistency and test-retest reliability; Cronbach's alpha and intra-class correlation coefficients were > 0.70. Spearman's correlations demonstrated good convergent validity with moderate (> 0.3) to high (> 0.6) correlations of the HS-FOCUS total score with physical functioning, role/social-physical, and bodily pain domains of CHQ. The tool also differentiated between MPS II severity levels based on GIS scores. CONCLUSIONS: The shortened HS-FOCUS questionnaire was found to be a valid and reliable tool to assess the physical functioning impact of MPS II.

A retrospective study to assess resource utilization and costs in patients with post-stroke spasticity in the United Kingdom.

OBJECTIVE: Post-stroke spasticity (PSS) is a common complication following stroke. This study describes the differences in healthcare resource utilization between patients who do and do not develop PSS in the UK. METHODS: Adults registered in The Health Improvement Network database with a recorded stroke between 2007 and 2011 were included. PSS was identified through Read codes; machine learning was used to retrospectively identify unrecorded PSS events. Patients with diagnosed or predicted PSS in the 12 months after stroke were matched to those with no PSS on age, sex, number of strokes, socioeconomic status, and comorbidities using the nearest neighbor algorithm. Utilization and costs associated with general practitioner visits, nurse visits, hospitalizations, referrals to specialists, laboratory tests, and medications in the 12 months after stroke were compared. RESULTS: Overall, 2,951 PSS cases were matched to 37,753 controls. During the first year, more PSS cases visited a physiotherapist (19% vs 7%) and occupational therapist (12% vs 5%) compared to controls. A greater proportion of cases were also referred to specialists (76% vs 64%) and hospitalized (33% vs 9%) compared to controls. Medication for spasticity was, on average, 14.68 prescriptions for cases and 5.64 for controls. Total mean costs per patient were £1,270 (standard deviation [SD] = 772) and £635 (SD = 273) for cases and controls, respectively. CONCLUSION: Costs after stroke for patients developing PSS are twice as high compared to patients who do not develop it, with the major driver being the number of hospital admissions. This highlights the need for better recording and closer management of PSS.

Basal-bolus Therapy in Patients with Type 2 Diabetes Mellitus in the UK: Patient Characteristics, Treatment Patterns and the Effect of Switching to Premixed Insulin.

INTRODUCTION: Increasing emphasis is being placed on insulin use among patients with type 2 diabetes mellitus (T2DM). Basal-bolus (BB) therapy is regarded as the gold standard, but a high frequency of injections and the general complexity of this therapy are seen as barriers in real-world practice. Here we describe the characteristics and treatment patterns of patients with T2DM receiving BB in the UK, with specific focus on those switching to a simplified regimen of premixed insulin. METHODS: Patients with T2DM receiving BB from 1 January 2005 were identified from the Clinical Practice Research Datalink. Characteristics were described at treatment initiation or on 1 January 2005, and treatment patterns were assessed at 12 months of follow-up. Clinical factors were compared in two groups of patients who while receiving BB had one haemoglobin A1c (HbA1c) measurement of ≥53 mmol/mol (7.0%) and remained either on BB or switched to a premixed insulin regimen. RESULTS: Study criteria were met by 12,060 subjects (mean age 59 years; duration diabetes 12.4 years). The mean HbA1c concentration was 76 mmol/mol (9.1% of patients), and 84.0% of patients were overweight. At 12 months of follow-up, 74.5% of the patients who had started BB remained on it. While on BB, 8835 patients had a HbA1c measurement of ≥53 mmol/mol (7.0% of all patients); of these, 95.9% remained on BB and 4.1% switched to premixed insulin. Mean HbA1c levels were consistently higher for patients who switched to premixed insulin than for those who remained on BB, but the levels remained relatively unchanged over time. CONCLUSION: A large proportion of patients receiving insulin did not achieve good glycaemic control in clinical practice. A small subset with higher comorbidities and HbA1c levels switched to a simplified regimen. Little evidence was found that type of insulin therapy was associated with meaningful changes in key clinical factors over time. FUNDING: Eli Lilly and company.

COPD exacerbations by disease severity in England.

OBJECTIVES: Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with accelerated disease progression and are important drivers of health care resource utilization. The study aimed to quantify the rates of COPD exacerbations in England and assess health care resource utilization by severity categories according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013. METHODS: Data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics were used to identify patients with a COPD diagnosis aged ≥40 years. Those with complete spirometric, modified Medical Research Council Dyspnea Scale information, and exacerbation history 12 months prior to January 1, 2011 (index date) were classified into GOLD severity groups. Study outcomes over follow-up (up to December 31, 2013) were exacerbation rates and resource utilization (general practitioner visits, hospital admissions). RESULTS: From the 44,201 patients in the study cohort, 83.5% were classified into severity levels GOLD A: 33.8%, GOLD B: 21.0%, GOLD C: 18.1%, and GOLD D: 27.0%. Mean age at diagnosis was 66 years and 52.0% were male. Annual exacerbation rates per person-year increased with severity, from 0.83 (95% confidence interval [CI]: 0.81-0.85) for GOLD A to 2.51 (95% CI: 2.47-2.55) for GOLD D. General practitioner visit rates per person-year also increased with severity, from 4.82 (95% CI: 4.74-4.93) for GOLD A to 7.44 (95% CI: 7.31-7.61) for GOLD D. COPD-related hospitalization rates per person-year increased from less symptoms (GOLD A: 0.28, GOLD C: 0.39) to more symptoms (GOLD B: 0.52, GOLD D: 0.84). CONCLUSION: Patients in the most severe category (GOLD D) experienced nearly three times the number of exacerbations and COPD-related hospitalizations as those in the least severe category (GOLD A), in addition to increased general practitioner visits. Better patient management to stabilize the disease progression could allow for an improvement in exacerbation frequency and a reduction in health care resource utilization.

Predictive analysis for identifying potentially undiagnosed post-stroke spasticity patients in United Kingdom.

PURPOSE OF THE RESEARCH: Spasticity is one of the well-recognized complications of stroke which may give rise to pain and limit patients' ability to perform daily activities. The predisposing factors and direct effects of post-stroke spasticity also involve high management costs in terms of healthcare resources, and case-control designs are required for establishing such differences. Using 'The Health Improvement Network' (THIN) database, such a study would not provide reliable estimates since the prevalence of post-stroke spasticity was found to be 2%, substantially below the most conservative previously reported estimates. The objective of this study was to use predictive analysis techniques to determine if there are a substantial number of potentially under-recorded patients with post-stroke spasticity. METHODS: This study used retrospective data from adult patients with a diagnostic code for stroke between 2007 and 2011 registered in THIN. Two algorithm approaches were developed and compared, a statistically validated data-trained algorithm and a clinician-trained algorithm. RESULTS: A data-trained algorithm using Random Forest showed better prediction performance than clinician-trained algorithm, with higher sensitivity and only marginally lower specificity. Overall accuracy was 75% and 72%, respectively. The data-trained algorithm predicted an additional 3912 records consistent with patients developing spasticity in the 12months following a stroke. CONCLUSIONS: Using machine learning techniques, additional unrecorded post-stroke spasticity patients were identified, increasing the condition's prevalence in THIN from 2% to 13%. This work shows the potential for under-reporting of PSS in primary care data, and provides a method for improved identification of cases and control records for future studies.

Epidemiology, severity, and treatment of chronic obstructive pulmonary disease in the United Kingdom by GOLD 2013.

OBJECTIVES: In 2013, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) updated the management strategy on COPD based on severity using a combined assessment of symptoms, degree of airflow limitation, and number of exacerbations. This study quantified prevalence and incidence of COPD in the United Kingdom and estimated disease severity by GOLD 2013 categories A/B (low risk) and C/D (high risk). METHODS: The Clinical Practice Research Datalink was used to identify COPD patients ≥40 years. Patient characteristics were described, and prevalence was calculated on December 31, 2013. Five-year incidence (2009-2013) was estimated, with rates standardized using 2011 UK population age and sex. To classify patients by GOLD categories, spirometry results, the modified British Medical Research Council grade, and history of exacerbations were used. RESULTS: The prevalent cohort comprised 49,286 patients with COPD with mean age 70 years; 51.0% were male. Overall prevalence was 33.3 per 1,000 persons (95% confidence interval [CI]: 33.1-33.6); 66.4% were classified as GOLD A/B and 33.6% as C/D. The standardized prevalence of GOLD A/B was 21.9 per 1,000 persons (95% CI: 21.7-22.1) and of C/D was 11.1 (95% CI: 10.9-11.2). A total of 27,224 newly diagnosed COPD patients were identified with mean age 67 years at diagnosis; 53.0% were male. Incidence was 2.2 per 1,000 person-years (95% CI: 2.2-2.3); 68.7% were classified in categories A/B and 31.3% in C/D, of which 17.2% did not receive COPD maintenance medication. CONCLUSION: A third of COPD patients in the UK are considered high risk (GOLD 2013 categories C/D), and a third of patients are diagnosed for the first time at these severe stages. Given the progressive nature of the disease, results suggest that closer attention to respiratory symptoms for early detection, diagnosis, and appropriate treatment of COPD in the UK is warranted.

Clinical burden of pneumonia, meningitis and septicemia in Norway 2 years after 7-valent pneumococcal conjugate vaccine introduction.

AIMS: This population-based, retrospective study quantified the rates of all-cause and pneumococcal pneumonia, meningitis and septicemia in Norway from 2008 to 2009 and determined the proportions of cases caused by pneumococcal vaccine serotypes. METHODS: Data on patients with all-cause and pneumococcal pneumonia, meningitis and septicemia were obtained from the Norwegian Patient Registry, which collects hospitalization data from all Norwegian public hospitals based on International Classification of Diseases codes. Norwegian Patient Registry case records linked to the Norwegian Surveillance System for Communicable Diseases provided serotype data for invasive pneumococcal disease in patients with microbiological cultures. RESULTS: In 2008 and 2009, hospitalization rates were relatively stable for all-cause pneumonia (5.28 and 5.35, respectively, per 1000), meningitis (10.70 and 9.67, respectively, per 100,000), and septicemia (from 171.81 to 161.46 per 100,000). In contrast, rates decreased for International Classification of Diseases-10 diagnosed pneumococcal pneumonia (from 13.66 to 10.52 per 100,000), although these cases may be under-reported because of inclusion in all-cause pneumonia. Rates also decreased in diagnosed pneumococcal meningitis (from 1.60 to 1.19 per 100,000) and diagnosed pneumococcal septicemia (from 9.08 to 7.94 per 100,000). Diagnosed pneumococcal disease rates were highest in younger children and older adults, peaking at ⩾ 60 years old. Pneumococcal pneumonia, meningitis and septicemia caused by serotypes included in the 7-valent pneumococcal conjugate vaccine decreased substantially during the study period, with corresponding serotype replacement by non-7-valent pneumococcal conjugate vaccine serotypes. CONCLUSIONS: From 2008 to 2009, International Classification of Diseases-10 diagnosed pneumococcal pneumonia, meningitis and septicemia decreased in most age groups but remained greatest among subjects aged 0-1 and ⩾ 60 years.

A retrospective study to assess resource utilization in patients with cervical dystonia in the United Kingdom.

PURPOSE: Cervical dystonia (CD) is a hypertonic condition caused by damage to the central nervous system. Very few studies have assessed the overall economic burden of the disease. The objective of this study was to describe the utilization of health care resources of patients with CD in the UK primary care setting, using a large population-based database. PATIENTS AND METHODS: Adults with a first diagnosis of CD between January 1, 2007 and January 31, 2011, who were registered to a general practitioner (GP) practice contributing to The Health Improvement Network (THIN), were included. Sociodemographic and clinical characteristics were assessed at the time of diagnosis. Health care resource utilization and pharmacological treatment were investigated at the end of the first and second year after diagnosis. RESULTS: Overall, 4,024 newly diagnosed patients with CD were identified, with average age at diagnosis of 45 years old; 65.3% were female. Depression in the year prior to diagnosis was the most common comorbidity. Primary care utilization was high in the first year, with 99.2% of patients visiting their GP (on average 6.2 times), and 43% visiting a nurse (on average 2.5 times). Patients were most commonly referred to an orthopedic surgeon, and 15.9% reported at least one physiotherapy visit. In the second year, utilization was similar. Prescriptions of at least one of the investigated treatments were found in 82.0% and 45.3%, in the first and second year, respectively. CONCLUSION: Findings suggest a high number of new CD cases are being identified in primary care, but not all will be referred to secondary care. Health care resource utilization was compared with that of all patients registered in THIN, which is representative of the UK, and the adjusted usage of primary care resources was found to be similar to that of the THIN population.

Retrospective database study to assess the economic impact of hip fracture in the United Kingdom.

OBJECTIVE: Publications containing recent, real-world data on the economic impact of hip fractures in the UK are lacking. This retrospective electronic medical records database analysis assessed medication and healthcare resource use, direct healthcare costs, and factors predicting increased resource use and costs in adult UK hip fracture patients. METHODS: Data were obtained from the Clinical Practice Research Datalink linked to the Hospital Episode Statistics for adult patients hospitalized for their first hip fracture between January 1, 2006 and March 31, 2011 (index event); healthcare costs were calculated from the National Health Service perspective using 2011-2012 cost data. RESULTS: Data from 8028 patients were analyzed. Resource use and costs were statistically significantly higher in the year following fracture (mean total [standard deviation (SD)] cost £7359 [£14,937]) compared with the year before fracture (mean total [SD] cost £3122 [£9435]; p < 0.001), and were similar to the total amount of the index hospitalization (mean total [SD] cost £8330 [£2627]). Multivariate regression analysis (using an estimated generalized linear model) showed that older age, male gender, higher comorbidity, osteoporosis, discharge to another institution compared with home, and pre-index hospitalization and outpatient visits were associated with increased post-index hospitalization healthcare costs (all p < 0.05). CONCLUSIONS: Although we did not capture all pre- and post-index costs and healthcare utilization, this study provides important insights regarding the characteristics of patients with hip fracture, and information that will be useful in burden-of-illness and economic analyses.

The Hunter Syndrome-Functional Outcomes for Clinical Understanding Scale (HS-FOCUS) Questionnaire: item reduction and further validation.

PURPOSE: The Hunter Syndrome-Functional Outcomes for Clinical Understanding Scale (HS-FOCUS) Questionnaire is a patient and parent-completed disease-specific instrument used in Hunter syndrome (mucopolysaccharidosis II), a rare paediatric progressive multi-systemic lysosomal storage disease. The objective of this study was to shorten the number of items of the Questionnaire to reduce response burden while maintaining its content validity. METHODS: Data collected in a clinical trial were used. An iterative process helped identifying redundant or low performing items based on content validity and psychometric properties. Validation on the retained items was assessed using patients and parent's responses in terms of reliability, validity and responsiveness. RESULTS: The HS-FOCUS was completed by 49 patients and 84 parents. Items were mainly removed owing to high floor effects, high inter-item correlations (>0.80) or inadequate content. The shortened patient and parent versions (18 and 21 items) each contained five function domains. Internal consistency and test-retest reliability were >0.70 for most domains, except Breathing and School/work. Concurrent validity was demonstrated by significant correlations (>0.30) with similar concepts of previously validated measures. Significant differences were found in all domain scores across levels of disability. CONCLUSIONS: The shortened HS-FOCUS is a reliable, valid and responsive measure, where burden in answering the Questionnaire was reduced without compromising its validity.

The impact of Hunter syndrome (mucopolysaccharidosis type II) on health-related quality of life.

BACKGROUND: Hunter syndrome (mucopolysaccharidosis type II (MPS II)) is a rare metabolic disease that can severely compromise health, well-being and life expectancy. Little evidence has been published on the impact of MPS II on health-related quality of life (HRQL). The objective of this study was to describe this impact using the Hunter Syndrome-Functional Outcomes for Clinical Understanding Scale (HS-FOCUS) questionnaire and a range of standard validated questionnaires previously used in paediatric populations. METHODS: Clinical and demographic characteristics collected in a clinical trial and responses to four HRQL questionnaires completed both by patients and parents prior to enzyme replacement treatment were used. The association between questionnaire scores and clinical function parameters were tested using Spearman rank-order correlations. Results were compared to scores in other paediatric populations with chronic conditions obtained through a targeted literature search of published studies. RESULTS: Overall, 96 male patients with MPS II and their parents were enrolled in the trial. All parents completed the questionnaires and 53 patients above 12 years old also completed the self-reported versions. Parents' and patients' responses were analysed separately and results were very similar. Dysfunction according to the HS-FOCUS and the CHAQ was most pronounced in the physical function domains. Very low scores were reported in the Self Esteem and Family Cohesion domains in the CHQ and HUI3 disutility values indicated a moderate impact. Scores reported by patients and their parents were consistently lower than scores in the other paediatric populations identified (except the parent-reported Behaviour score); and considerably lower than normative values. CONCLUSIONS: This study describes the impact on HRQL in patients with MPS II and provides a broader context by comparing it with that of other chronic paediatric diseases. Physical function and the ability to perform day-to-day activities were the most affected areas and a considerable impact on the psychological aspects of patients' HRQL was also found, with a higher level of impairment across most dimensions (particularly Pain and Self Esteem) than that of other paediatric populations. Such humanistic data provide increasingly important support for establishing priorities for health care spending, and as a component of health economic analysis.

Time savings associated with C.E.R.A. once monthly: a time-and-motion study in hemodialysis centers in five European countries.

OBJECTIVE: This time-and-motion study aimed to quantify healthcare personnel time associated with routine anemia-management tasks for maintenance therapy with C.E.R.A. (continuous erythropoietin receptor activator) that treats anemia with once-monthly injections versus other erythropoiesis-stimulating agents ('Other ESAs'), including shorter-acting ESAs (epoetin alfa, epeotin beta) and darbepoetin alfa. METHODS AND DESIGN: This was a non-interventional, observational study where patients were treated for anemia according to individual center practices. Time taken to complete frequent anemia-management tasks for both groups (C.E.R.A. vs. 'Other ESAs') was recorded and potential annual time savings per patient and per center following assumed 100% uptake of C.E.R.A. once monthly were estimated. RESULTS: For 'Other ESAs', the average total time spent per patient per year on frequent anemia management-related tasks ranged from 48 minutes in Spain to 265 minutes in Poland. For C.E.R.A. once monthly, the average total time spent per patient per year ranged from 12 minutes in Spain to 39 minutes in Poland, a reduction in actual time spent of 76-89% versus 'Other ESAs'. 100% adoption of C.E.R.A. once monthly may result in average annual time savings of 26-553 hours, a reduction of 67-95% depending on center size and frequency distribution of 'Other ESAs'. LIMITATIONS: Due to variability in treatment practices between centers (differences in task, description and frequency distribution of 'Other ESAs') and the small numbers of centers participating in each country, it is difficult to generalize annual per patient time results to reflect each country. Per center results should be interpreted with caution as they were derived based on specific center sizes that may not reflect typical center sizes in the country. CONCLUSIONS: Adoption of C.E.R.A. once monthly could offer substantial time savings on frequent anemia management-related tasks versus 'Other ESAs'; allowing re-allocation of scarce resources to other aspects of patient care.

The Hunter syndrome-functional outcomes for clinical understanding scale (HS-FOCUS) questionnaire: evaluation of measurement properties.

PURPOSE: This study was to conduct the psychometric validation of the patient and parent versions of the Hunter syndrome-functional outcomes for clinical understanding scale (HS-FOCUS). METHODS: Data collected in a 53-week placebo-controlled multinational trial were used to evaluate item performance and reliability, validity, and ability to detect change of the six HS-FOCUS function domains. RESULTS: HS-FOCUS was completed by 49 patients above 12 years old and 84 parents. Floor effects and high average inter-item correlations suggested that some items were less informative or redundant. For both patients and parents, the internal consistency and test-retest reliability met the >0.70 criteria for all domains except for the breathing, sleeping, and schooling/work in patients. Construct validity showed moderate to high correlations with CHAQ, CHQ, and HUI3 in activity-related concepts. Significant differences in domain scores were found in most domains among severity in disability measured by CHAQ DIS. Significant differences in HS-FOCUS change scores were found in patients whose CHAQ DIS score also changed. CONCLUSIONS: Psychometric validation of the HS-FOCUS demonstrates it is a reliable, valid, and responsive instrument that can be applied in clinical trials or disease registries. Findings on the individual item performance suggest some items could be removed without compromising its validity.

Measuring patient experiences in Fabry disease: validation of the Fabry-specific Pediatric Health and Pain Questionnaire (FPHPQ).

INTRODUCTION: Common symptoms for children with Anderson-Fabry Disease (FD) such as acroparaesthesia and gastrointestinal manifestations can only be objectively assessed in patients using a valid instrument. To date, no such instrument exists. METHODS: A preliminary 40-item measure of symptoms and experience with FD, the Fabry-specific Paediatric Health and Pain Questionnaire (FPHPQ) was developed, but lacked a formal assessment of its measurement properties. The FPHPQ was used in the Fabry Outcome Survey (FOS), a registry for all patients with a confirmed diagnosis of FD who are receiving agalsidase alfa, or are treatment naïve and who are managed by physicians participating in FOS. After an item analysis to explore how items performed and combined into domains, a battery of psychometric analyses was performed to assess the measurement properties of this new instrument. RESULTS: Eighty-seven children (ages 4-18 years) completed the questionnaire. Twenty-three items in three subscales of the questionnaire emerged: pain associated with heat or exertion, pain associated with cold, and abdominal pain and fatigue symptoms. Internal consistency reliability for all three subscales was good (Cronbach alpha ≥ 0.84). Reliability was equally high for all age groups (4-7, 8-12, and 13-18). Test-retest reliability was high for all three subscales (intraclass correlation coefficient ≥ 0.74). Construct validity was demonstrated by moderate correlation with brief pain inventory (BPI), KINDL, and EQ-5D. Known group validity showed all subscales were able to discriminate between Fabry disease severity groups as classified by above or below median of the FOS MSSI (Mainz Severity Score Index) grade. The heat or exertion subscale was responsive to change in symptoms between responders and non-responders as defined by change in EQ-5D index scores between the first and second visit. CONCLUSIONS: Preliminary results indicate that the measurement properties of FPHPQ are valid and reliable for assessing patient-reported symptoms of FD. The questionnaire could be a useful tool for clinicians to understand the progression of disease and monitor treatment effects. FPHPQ will be further validated and refined as the FOS registry is continuously adding more patients.