Exploring the Burden of X-Linked Hypophosphataemia: An Opportunistic Qualitative Study of Patient Statements Generated During a Technology Appraisal.

INTRODUCTION: Capturing the patient experience of living with a rare disease such as X-linked hypophosphataemia (XLH) is critical for a holistic understanding of the burden of a disease. The complexity of the disease coupled with the limited population makes elicitation of the patient burden methodologically challenging. This study used qualitative information direct from patient and caregiver statements to assess the burden of XLH. METHODS: A thematic analysis was conducted on statements received during a National Institute for Health and Care Excellence (NICE) online public open consultation from 15 June to 6 July 2018. Researchers and clinical experts generated themes and codes based on expected aspects of XLH burden. Statements were independently coded by two reviewers, adding additional codes as required, and analysed by frequency and co-reporting across age groups. RESULTS: The majority of responses were submitted from UK-based patients with some from the USA and Australia, and the statements related to children, adolescents and adults. The findings suggest that the greatest burden experienced by children is associated with conventional therapy, co-reported with dosing regimen, adherence, distress and pain. During adolescence, the burden becomes increasingly complex and multi-factorial, with an increasing psychological burden. In adults, conventional therapy co-reported with bone deformity and orthopaedic surgery, as well as pain, mobility, fatigue and dental problems, featured highly. DISCUSSION: Whilst our study was opportunistic in nature, it has highlighted the clear and distinctive evolution of the burden of XLH, transitioning from being therapy-oriented in childhood to multi-factorial in adolescence, and finally to adulthood with its high impact on need for other interventions, function and mobility. This qualitative thematic analysis enhances the understanding of the symptom and treatment burden of XLH.

Inhaled corticosteroids for asthma: impact of practice level device switching on asthma control.

BACKGROUND: As more inhaled corticosteroid (ICS) devices become available, there may be pressure for health-care providers to switch patients with asthma to cheaper inhaler devices. Our objective was to evaluate impact on asthma control of inhaler device switching without an accompanying consultation in general practice. METHODS: This 2-year retrospective matched cohort study used the UK General Practice Research Database to identify practices where ICS devices were changed without a consultation for > or =5 patients within 3 months. Patients 6-65 years of age from these practices whose ICS device was switched were individually matched with patients using the same ICS device who were not switched. Asthma control over 12 months after the switch was assessed using a composite measure including short-acting beta-agonist and oral corticosteroid use, hospitalizations, and subsequent changes to therapy. RESULTS: A total of 824 patients from 55 practices had a device switch and could be matched. Over half (53%) of device switches were from dry powder to metered-dose inhalers. Fewer patients in switched than matched cohort experienced successful treatment based on the composite measure (20% vs. 34%) and more experienced unsuccessful treatment (51% vs. 38%). After adjusting for possible baseline confounding factors, the odds ratio for treatment success in the switched cohort compared with controls was 0.29 (95% confidence interval [CI], 0.19 to 0.44; p < 0.001) and for unsuccessful treatment was 1.92 (95% CI, 1.47 to 2.56; p < 0.001). CONCLUSION: Switching ICS devices without a consultation was associated with worsened asthma control and is therefore inadvisable.

Psychometric development of the Upper Limb Lymphedema Quality of Life Questionnaire demonstrated the patient-reported outcome measure to be a robust measure for breast cancer-related lymphedema.

OBJECTIVES: To develop and undertake initial validation of a patient-reported outcome measure to assess health-related quality of life in patients with breast cancer-related upper limb lymphedema (ULL). STUDY DESIGN AND SETTING: We developed and validated the Upper Limb Lymphedema Quality of Life (ULLQoL) scale in two stages: devising the items and pretesting with patients and clinicians; longitudinal validation to test its psychometric properties-underlying dimensions, internal consistency, test-retest reliability, construct validity, and responsiveness. Patients with ULL were recruited from two outpatient clinics. RESULTS: We derived the ULLQoL scale from a pool of 98 items generated by patients. After further consultation, we produced the draft ULLQoL scale. For validation, 103 patients with ULL completed the draft scale and two generic health measures: SF-36 and ED-5D-3L. Psychometric analysis identified two components, physical and emotional well-being, with good internal consistency and test-retest reliability. Significant correlations with SF-36, EQ-5D-3L, and percentage excess limb volume confirmed construct validity. The ULLQoL scale showed good responsiveness to change reported by lymphedema patients and moderate to large effect sizes. CONCLUSION: The 14-item ULLQoL scale is a robust ULL-specific measure that is feasible and valid to use in both the clinical and research settings.

Salmeterol/fluticasone stable-dose treatment compared with formoterol/budesonide adjustable maintenance dosing: impact on health-related quality of life.

BACKGROUND: Improving patients' health-related quality of life (HRQoL) is recognized as a fundamental part of asthma management. The aims of this study were to evaluate the long-term efficacy (including symptom-free days and exacerbations) and impact on HRQoL of a stable-dose regimen of salmeterol/fluticasone propionate (SAL/FP) and an adjustable maintenance dosing (AMD) regimen of formoterol/budesonide (FOR/BUD) where treatment is adjusted based on symptoms [SAM40056]. METHODS: A total of 688 outpatients with asthma receiving regular low-dose inhaled corticosteroids (ICS) plus a long-acting beta2-agonist, or medium dose ICS alone participated in this randomized, double-blind, double-dummy, parallel-group, 1-year trial, which was conducted in 91 centers in 15 countries. Patients were randomized to receive 1 inhalation of SAL/FP 50/250 mug BID or 2 inhalations of FOR/BUD 6/200 mug BID during Weeks 1-4. For Weeks 5-52, patients meeting strict continuation criteria for stable asthma at Week 4 received AMD with FOR/BUD or stable-dose SAL/FP. RESULTS: The percentage of symptom-free days was significantly greater (58.8% vs 52.1%; p = 0.034) and the annual exacerbation rate was significantly lower (47%; p = 0.008) with stable-dose SAL/FP compared with FOR/BUD AMD. A total of 568 patients completed the Asthma Quality of Life Questionnaire (AQLQ) at least once during the study. The mean change from baseline in AQLQ overall score was numerically greater with SAL/FP than FOR/BUD at week 28 and week 52, but did not reach statistical significance (p = 0.121 at Week 52). However, in a post hoc logistic regression analyses for any AQLQ improvement, significant benefits with SAL/FP were seen at both time points (p = 0.038 and p = 0.009, respectively). The minimally important difference of >/= 0.5-point improvement in AQLQ overall score was achieved by a significantly greater number of patients receiving SAL/FP at Week 28 (68% vs 60%; p = 0.049); a trend for this difference remained at Week 52 (71% vs 65%) (p = 0.205). CONCLUSION: In this population of patients with persistent asthma, stable-dose SAL/FP resulted in significantly greater increases in symptom-free days, a reduction in exacerbation rates, and provided greater HRQoL benefits compared with FOR/BUD AMD. TRIAL REGISTRATION: Clinical Trials registration number NCT00479739.

Symptoms and Association with Health Outcomes in Relapsing-Remitting Multiple Sclerosis: Results of a US Patient Survey.

Background. A variety of symptoms have been reported, but the prevalence of specific symptoms in relapsing-remitting multiple sclerosis (RRMS), how they are related to one another, and their impact on patient reported outcomes is not well understood. Objective. To describe how symptoms of RRMS cooccur and their impact on patient-reported outcomes. Methods. Individuals who reported a physician diagnosis of RRMS in a large general health survey in the United States indicated the symptoms they experience because of RRMS and completed validated scales, including the work productivity and activity impairment questionnaire and either the SF-12v2 or SF-36v2. Symptom clusters were identified through hierarchical cluster analysis, and the relationship between clusters and outcomes was assessed through regression. Results. Fatigue, difficulty walking, and numbness were the most commonly reported symptoms. Seven symptom clusters were identified, and several were significantly related to patient reported outcomes. Pain, muscle spasms, and stiffness formed a cluster strongly related to physical quality of life; depression was strongly related to mental quality of life and cognitive difficulty was associated with work impairment. Conclusions. Symptoms in RRMS show a strong relationship with quality of life and should be taken into consideration in treatment decisions and evaluation of treatment success.

Long-term disease history, clinical symptoms, health status, and healthcare utilization in patients suffering from Lambert Eaton myasthenic syndrome: Results of a patient interview survey in Germany.

INTRODUCTION: The burden of disease in Lambert-Eaton myasthenic syndrome (LEMS) patients is unclear. This study focused on the patient's perspective to obtain patient-reported information on clinical symptoms, burden of illness, impact of LEMS on activities of daily living (ADL), and management of LEMS. METHODS: Semi-structured, face-to-face interviews with LEMS patients from two specialized centres in Germany between September and December 2010. RESULTS: Twelve patients participated; mean age 66.7 ± 9.8 years. First symptoms occurred at age 52.5 ± 14.0 years. Mean time between first symptoms and diagnosis was 4.4 ± 6.2 years. Patients reported neuromuscular, cranial, and autonomic symptoms plus general fatigue. Two-thirds of patients reported 10 or more symptoms. The most frequent symptoms were leg weakness (91.7%) and general fatigue (83.3%). Restrictions in ADL were reported always or often in 75% of patients. Over half of the patients (n = 7) reported poor or very poor health status. Mean EQ-5D utility scores were 0.34 ± 0.35, with little day-to-day variation. Patients visited a number of different clinicians; most had been hospitalized at some point in the course of their disease. The most frequent drug treatments were 3,4-diaminopyridine (3,4-DAP) (83.3%) and pyridostigmine (41.5%). The study has several limitations, including small sample size and the potential influence of recall bias. CONCLUSION: LEMS patients report long individual disease histories. Most patients suffer multiple symptoms which are frequently severe and troublesome, and almost all are restricted in ADL with poor health status. There is high utilization of healthcare resources from diagnosis to ongoing treatment. Physicians should be aware of this rare disease to ensure that patients receive an early diagnosis and prompt and appropriate treatment.

How does patients' quality of life guide their preferences regarding aspects of asthma therapy?: a patient-preference study using discrete-choice experiment methodology.

BACKGROUND AND OBJECTIVE: Previous work has suggested that people with poor health-related quality of life (HR-QOL) as a result of asthma are willing to pay the most for successful therapy. There is also evidence that preferences are an important influence on adherence to therapy. We report a patient preference study using a discrete-choice experiment (DCE) to elicit willingness to pay (WTP) of patients with asthma in Spain, the Netherlands, and the UK. METHODS: The DCE survey included different attributes of asthma therapy (days with symptoms, days needing reliever medication, asthma attacks [none, attack that does not require doctor/emergency room {ER} visit, attack that requires doctor/ER visit], risk of adverse effects, number of preventer inhalers, and monthly out-of-pocket costs). Participants indicated which attribute combinations they preferred. The questionnaire survey included the mini Asthma Quality of Life Questionnaire (mAQLQ). The validity of the choice experiment has been supported by two pilot studies conducted in the UK. Preferences and WTP were estimated using a random effects probit model. Symptom days and asthma attack attributes were segmented by mAQLQ score. RESULTS: Demographic and clinical data were compared between the three country samples (UK, n = 124; Spain, n = 86; the Netherlands, n = 269). All study attributes were independently significant predictors of choice. People were willing to pay €35 per month to avoid a day with symptoms, and €109 per month (year 2005 values) to avoid experiencing asthma attacks that required emergency visits to their doctor or hospital. People with the worst HR-QOL were willing to pay the least to avoid days with symptoms and asthma attacks that required visits to their doctor/ER. This was not an income-related effect. CONCLUSION: Patients who reported higher HR-QOL were willing to pay more to avoid days with symptoms and asthma attacks that required visits to their doctor/ER. Hypotheses were explored to explain this effect. It is possible that people with the least impairment of HR-QOL place the greatest value on avoiding the effects of asthma and so are most willing to alter their behavior. People with the worst HR-QOL may be exhibiting a response shift type of effect whereby their internal values are shifted down by the burden of their disease. These findings may help to illuminate why there are differences in asthma treatment adherence.

Comparison of the clinical efficacy and safety of salmeterol/fluticasone propionate versus current care in the management of persistent asthma in Korea.

OBJECTIVES: In the Asia-Pacific region there is a general preference for prescribing oral over inhaled medications for the treatment of asthma. This study compared inhaled salmeterol/fluticasone propionate therapy (SFC) with physician-determined current care (CC) in the management of persistent asthma in Korea. METHODS: Adult patients with a documented history of reversibility in FEV(1) (>or= 12%) or PEF (>or= 15%), were randomised in a 2:1 ratio to unblinded treatment with SFC (50/250 microg bd or 50/500 microg bd) via Diskus (N = 284) or CC (N = 140) for 52 weeks. Morning peak expiratory flow (PEF) (primary endpoint), exacerbations, asthma symptoms and patient-reported outcome measures were recorded. TRIAL REGISTRATION: GSK study number:100614. RESULTS: At baseline, mean morning PEF in the SFC and CC group was 374 and 401 L/min respectively. The adjusted mean morning PEF at 52 weeks was 423 +/- 3 and 396 +/- 4 L/min for SFC and CC respectively (treatment difference of 27 +/- 5 in favour of SFC; 95% CI 17, 37; p < 0.0001). The mean rate of exacerbations over 52 weeks was significantly lower in the SFC group (SFC/CC odds ratio 0.57; 95% CI 0.44, 0.74; p < 0.0001). Treatment with SFC also resulted in a significantly greater improvement in asthma symptoms, in the number of patients assessed to have well controlled asthma (Asthma Control Test score >or= 20), and in a clinically significant improvement in overall Quality of Life. The incidence of adverse events was low and similar between the two groups and events were of the type expected in this population. CONCLUSIONS: The results of this open-label, randomised study showed that SFC provided greater asthma control than CC in the management of persistent asthma.

Survey of pharmacists' attitudes towards interchangeable use of dry powder inhalers.

BACKGROUND: It is a common cost-containment practice in some countries to dispense a cheaper, generic version of a prescribed medication. This presents few problems for most medications. However, dry powder inhalers used in asthma and COPD vary markedly in design and method of operation, so generic substitution may not be acceptable to patients or healthcare professionals. Patients dispensed an unfamiliar device in which they have received no training, risk poor inhalation technique with the potential for inadequate dosing and loss of disease control. OBJECTIVE: To assess the views of pharmacists towards interchangeable use of dry powder inhalers. SETTING: Community pharmacists in Australia, Canada, France, Germany, and the UK. METHOD: Following exploration of the key issues with international opinion leaders in respiratory management, a structured web questionnaire was developed for use in computer assisted web interviews. Fieldwork was carried out in March and April 2005. MAIN OUTCOME MEASURE: Responses to the web questionnaire were analysed by percentage of respondents or by mean or median score, as appropriate to the question. RESULTS: A total of 254 pharmacists were included in the study. Just 6% of pharmacists considered that dry powder inhalers are interchangeable, with a high level of concern shown about interchangeable use (median score of 6 on a scale of 1, not at all concerned, to 7, extremely concerned). Patient confusion was the main concern, expressed by 77% of respondents. Pharmacists also envisaged substitution having an adverse impact on pharmacy stock levels (72%), patient device handling (70%), pharmacist workload (63%), patient compliance (56%) and outcomes for the patient (51%), with pharmacists in Germany having a particularly negative view and those in France generally the most positive. Despite the generally negative view of pharmacists about interchangeable use of dry powder inhalers, overall only 22% would contact the prescribing physician often/very often for approval of the substitution. CONCLUSION: The study showed that only a small minority of pharmacists believe that dry powder inhalers can be used interchangeably, with the majority concerned about generic substitution of these products. Pharmacists in Germany were particularly negative about the interchangeable use of dry powder inhalers.

Defining COPD exacerbations: impact on estimation of incidence and burden in primary care.

AIMS: To investigate the impact of definition on the incidence of chronic obstructive pulmonary disease (COPD) exacerbations in primary care. METHODS: In a one-year prospective, observational study, data from diary cards were used to determine the incidence of symptom- and healthcare-defined exacerbations. One hundred and twenty seven patients completed > or =80% of days in the diary card and were included in the analysis. RESULTS: Incidence of COPD exacerbation varied according to definition. Mean yearly rates were 2.3 for symptom- and 2.8 for healthcare-defined exacerbations. Although patients with FEV(1) <50% had a higher mean yearly rate of healthcare-defined exacerbations than those with FEV(1) > or =50% (3.2 vs 2.3; p=0.003), patients with less severe disease reported recurrent exacerbations. There was limited agreement between symptom- and healthcare-defined exacerbations. CONCLUSION: Lung function does not appear to be a valid criterion for assigning COPD management directed at patients with recurrent exacerbation.