Health related quality of life in cystic fibrosis: To work or not to work?

AbstractBackgroundThe present study investigated whether patients with CF who are studying or working report a better HRQoL in comparison to non-working/studying patients.Methods57 adult CF patients completed the Cystic Fibrosis Questionnaire—Revised, a CF-specific measure of HRQoL. Medical condition was quantified in terms of FEV1 % predicted, BMI, Pseudomonas aer. status, pancreatic status (PS), having an indwelling catheter device (PAC), CF Related Diabetes Mellitus and nutritional status.ResultsMean age was 26.7 years (SD 8.1), mean FEV1 % predicted was 65.09 (SD 22.18), mean BMI was 21.23 (SD 3.45). FEV1 % predicted was related to HRQoL domains Physical Functioning and General Health (r=0.27 and 0.38 respectively, p<0.05). A higher BMI was associated with better scores on Eating Disturbances (= fewer problems; r=0.44, p<0.01) and a better perception of Weight (r=0.43, p<0.01) and Body Image (r=0.28, p<0.05). Analysis of variance showed that specific domains of HRQoL were related to diabetes (Weight), taking caloric supplements (Body Image and Weight) and/or PAC (Physical Functioning, Treatment Burden, Role, Weight). Twenty-four patients worked/studied, these patients had a higher FEV1, and fewer had Pseudomonas aer. or a PAC or took high caloric supplements, compared to non-working/studying patients. After controlling for medical parameters, patients who were working/studying scored higher than non-working/studying patients on Physical Functioning, Role Functioning and Social Functioning.ConclusionsCF patients' HRQoL is related to medical status. The non-working/studying CF patients in this sample had greater disease severity and reported a lower quality of life than their working/studying peers, even after controlling for relevant medical parameters. The decision to stop work/study for CF patients is difficult and affects patients' personal, social and financial well-being

Risk factors for morbidity and death in non-cystic fibrosis bronchiectasis: a retrospective cross-sectional analysis of CT diagnosed bronchiectatic patients

<p>Abstract</p> <p>Introduction</p> <p>There is a relative lack of information about the death rate and morbidity of non-cystic fibrosis bronchiectasis and most studies are limited due to referral bias. We wanted to assess death rate and morbidity in those patients at our hospital.</p> <p>Methods</p> <p>Adult patients seen at our department between June 2006 and November 2009 were recruited if the key string <it>"bronchiect</it>-" was mentioned in electronic clinical records and if chest CT imaging was available. Clinical records of all patients with confirmed radiologic diagnosis of bronchiectasis were reviewed and clinical characteristics were analyzed.</p> <p>Results</p> <p>539 patients with a radiographic diagnosis of non-cystic fibrosis bronchiectasis were identified in a retrospective cross-sectional analysis giving a prevalence of 2.6% in our hospital population. A wide range of etiologies was found with idiopathic bronchiectasis in 26%. In the 41 months interval, 57 patients (10.6%) died. We found a median exacerbation rate of 1.94 per year. Bacterial colonization status was associated with more deaths, exacerbation rate, symptoms and reduced pulmonary function. Pulmonary hypertension was found in 48% of our patients.</p> <p>Conclusions</p> <p>We evaluated a large non-cystic fibrosis bronchiectasis population, and provided new epidemiological data on associations between clinical characteristics and deaths and morbidity in these patients.</p

A cohort description and analysis of the effect of gabapentin on idiopathic cough

BACKGROUND: Chronic idiopathic cough (known as cough hypersensitivity syndrome) is defined by cough in the absence of an identifiable cause. Gabapentin has been suggested as a treatment but evidence is scarce. The aim of our study was to describe the clinical features of patients with unexplained chronic cough and to investigate the effect of gabapentin (600 mg twice a day for a minimal duration of 4 weeks) in reducing cough symptoms. METHODS: A patient cohort analysis was performed. Patients were retrieved using a query in our medical database for the words ‘cough’ and ‘gabapentin’ in 2011. Patients without a clear etiology of cough despite having performed a stepwise diagnostic approach, were included. Medical records of these patients were analyzed. A telephonic survey was performed and patients were asked to retrospectivally rate their cough when they attended the outpatient clinic. They were then asked to rate their cough after treatment with gabapentin. A scale from one to ten was used to score cough severity. They were also questioned about the triggers inducing cough. To evaluate the cough severity score, the results were correlated with questions of the Leicester Cough Questionnaire. RESULTS: We recruited 51 patients (87% female) with a mean age of onset of 47 years (± 14 y) and an average cough duration of 48 months. The most frequently reported cough triggers included change of temperature (57%), talking (49%) and odours (45%). In 67% of patients, the urge to cough was located in the throat area. Thirty-five patients effectively took the prescribed gabapentin. The average improvement in cough score was 2.8/10 (p<0.0001). Of the 35 patients, 20 achieved improvement of their cough symptoms. Responders had a higher pre-treatment cough severity score (p=0.02) and were more likely to have a history of pre-cough airway infection (p=0.04). Current cough severity score negatively correlated with the Leicester Cough Questionnaire scores (p=0.05). CONCLUSION: Chronic idiopathic cough were predominantly middle-aged women, frequently reporting various cough triggers. We also demonstrated that gabapentin can significantly improve cough in these patients. Responders tend to have higher pre-treatment severity scores and have a history of an airway infection

Usage of inhalation devices in asthma and chronic obstructive pulmonary disease: a Delphi consensus statement.

peer reviewedOBJECTIVES: The study aimed to assess usage of inhalation devices in asthma and chronic obstructive pulmonary disease (COPD). METHODS: In this two-round Delphi survey, 50 experts in asthma and COPD completed a 13-item, Internet-based, self-administered questionnaire about choice of inhalation device, training and monitoring of inhalation techniques, the interchangeability and the role of costs in the selection of inhalation devices. For each item, the median (central tendency) and interquartile ranges (degree of consensus) were calculated. RESULTS: Experts considered that the choice of inhalation device was as important as that of active substance (very good consensus) and should be driven by ease of use (good to very good consensus) and teaching (very good consensus). Experts recommended giving oral and visual instructions (good consensus) and systematic monitoring inhalation techniques. Pulmonologists and paramedics have predominantly educational roles (very good consensus). Experts discouraged inhalation device interchangeability (good consensus) and switching for cost reasons (good to very good consensus) without medical consultation (good consensus). CONCLUSIONS: The results of this survey thus suggested that inhalation devices are as important as active substances and training and monitoring are essential in ensuring effective treatment of asthma and COPD. Inhalation device switching without medical consultation should be avoided

Broncho-alveolar lavage fluid recovery correlates with airway neutrophilia in lung transplant patients

SummaryBroncho-alveolar lavage (BAL) is important to assess airway inflammation. There is debate about the volume instilled, but the variation of BAL fluid recovery (BFR) has received little attention. We investigated the association between BFR and rejection/infection status after lung transplantation (LTx).We combined clinical findings, FEV1, transbronchial biopsies and BAL analysis (BFR, interleukin-8 (IL8), cell counts, microbiology) of 115 samples/LTx patients. The patients were divided into 4 groups: stable (subdivided in colonized and non-colonized), acute rejection (AR), Bronchiolitis Obliterans Syndrome (BOS) and infection.BFR was significantly lower in AR, BOS and infection, and correlated with the severity of AR and BOS. A 10ml decrease of BFR was associated with a FEV1 decrease of 4.4% and a %neutrophils and IL8 increase of 9.6% and 9.7pg/ml, respectively. Colonized stable patients had no significant differences in airway inflammation, FEV1 and BFR compared to the non-colonized stable patients.We conclude that a low BFR is an indicator of lung rejection or infection. BFR variation is related to airway obstruction and neutrophilic inflammation, which can cause an increased compliance of the airway wall, making it more collapsible. Airway colonization in stable patients had no effect on airway inflammatory parameters, BFR and FEV1

Bronchiectasis Rheumatoid Overlap Syndrome Is an Independent Risk Factor for Mortality in Patients With Bronchiectasis:A Multicenter Cohort Study

BACKGROUND: This study assessed if bronchiectasis (BR) and rheumatoid arthritis (RA), when manifesting as an overlap syndrome (BROS), were associated with worse outcomes than other BR etiologies applying the Bronchiectasis Severity Index (BSI). METHODS: Data were collected from the BSI databases of 1,716 adult patients with BR across six centers: Edinburgh, United Kingdom (608 patients); Dundee, United Kingdom (n = 286); Leuven, Belgium (n = 253); Monza, Italy (n = 201); Galway, Ireland (n = 242); and Newcastle, United Kingdom (n = 126). Patients were categorized as having BROS (those with RA and BR without interstitial lung disease), idiopathic BR, bronchiectasis-COPD overlap syndrome (BCOS), and "other" BR etiologies. Mortality rates, hospitalization, and exacerbation frequency were recorded. RESULTS: A total of 147 patients with BROS (8.5% of the cohort) were identified. There was a statistically significant relationship between BROS and mortality, although this relationship was not associated with higher rates of BR exacerbations or BR-related hospitalizations. The mortality rate over a mean of 48 months was 9.3% for idiopathic BR, 8.6% in patients with other causes of BR, 18% for RA, and 28.5% for BCOS. Mortality was statistically higher in patients with BROS and BCOS compared with those with all other etiologies. The BSI scores were statistically but not clinically significantly higher in those with BROS compared with those with idiopathic BR (BSI mean, 7.7 vs 7.1, respectively; P < .05). Patients with BCOS had significantly higher BSI scores (mean, 10.4), Pseudomonas aeruginosa colonization rates (24%), and previous hospitalization rates (58%). CONCLUSIONS: Both the BROS and BCOS groups have an excess of mortality. The mechanisms for this finding may be complex, but these data emphasize that these subgroups require additional study to understand this excess mortality

Cost effectiveness review of text messaging, smartphone application, and website interventions targeting T2DM or hypertension

Digital health interventions have been shown to be clinically-effective for type 2 diabetes mellitus (T2DM) and hypertension prevention and treatment. This study synthesizes and compares the cost-effectiveness of text-messaging, smartphone application, and websites by searching CINAHL, Cochrane Central, Embase, Medline and PsycInfo for full economic or cost-minimisation studies of digital health interventions in adults with or at risk of T2DM and/or hypertension. Costs and health effects are synthesised narratively. Study quality appraisal using the Consensus on Health Economic Criteria (CHEC) list results in recommendations for future health economic evaluations of digital health interventions. Of 3056 records identified, 14 studies are included (7 studies applied text-messaging, 4 employed smartphone applications, and 5 used websites). Ten studies are cost-utility analyses: incremental cost-utility ratios (ICUR) vary from dominant to €75,233/quality-adjusted life year (QALY), with a median of €3840/QALY (interquartile range €16,179). One study finds no QALY difference. None of the three digital health intervention modes is associated with substantially better cost-effectiveness. Interventions are consistently cost-effective in populations with (pre)T2DM but not in populations with hypertension. Mean quality score is 63.0% (standard deviation 13.7%). Substandard application of time horizon, sensitivity analysis, and subgroup analysis next to transparency concerns (regarding competing alternatives, perspective, and costing) downgrades quality of evidence. In conclusion, smartphone application, text-messaging, and website-based interventions are cost-effective without substantial differences between the different delivery modes. Future health economic studies should increase transparency, conduct sufficient sensitivity analyses, and appraise the ICUR more critically in light of a reasoned willingness-to-pay threshold

HTA programme response to the challenges of dealing with orphan medicinal products:Process evaluation in selected European countries

Background Challenges commonly encountered in HTA of orphan medicinal products (OMPs) were identified in Advance-HTA. Since then, new initiatives have been developed to specifically address issues related to HTA of OMPs. Objective and methods This study aimed to understand why these new HTA initiatives in England, Scotland and at European-level were established and whether they resolve the challenges of OMPs. The work of Advance-HTA was updated with a literature review and a conceptual framework of clinical, regulatory and economic challenges for OMPs was developed. The new HTA programmes were critiqued against the conceptual framework and outstanding challenges identified. Results The new programmes in England and Scotland recognise the challenges identified in demonstrating the value of ultra-OMPs (and OMPs) and that they require a different process to standard HTA approaches. Wider considerations of disease and treatment experiences from a multi-stakeholder standpoint are needed, combined with other measures to deal with uncertainty (e.g. managed entry agreements). While approaches to assessing this new view of value of OMPs, extending beyond cost/QALY frameworks, differ, their criteria are similar. These are complemented by a European initiative that fosters multi-stakeholder dialogue and consensus about value determinants throughout the life-cycle of an OMP. Conclusion New HTA programmes specific to OMPs have been developed but questions remain about whether they sufficiently capture value and manage uncertainty in clinical practice

Recommendations from the European Working Group for Value Assessment and Funding Processes in Rare Diseases (ORPH-VAL)

International audienceAbstractRare diseases are an important public health issue with high unmet need. The introduction of the EU Regulation on orphan medicinal products (OMP) has been successful in stimulating investment in the research and development of OMPs. Despite this advancement, patients do not have universal access to these new medicines. There are many factors that affect OMP uptake, but one of the most important is the difficulty of making pricing and reimbursement (P&R) decisions in rare diseases. Until now, there has been little consensus on the most appropriate assessment criteria, perspective or appraisal process. This paper proposes nine principles to help improve the consistency of OMP P&R assessment in Europe and ensure that value assessment, pricing and funding processes reflect the specificities of rare diseases and contribute to both the sustainability of healthcare systems and the sustainability of innovation in this field. These recommendations are the output of the European Working Group for Value Assessment and Funding Processes in Rare Diseases (ORPH-VAL), a collaboration between rare disease experts, patient representatives, academics, health technology assessment (HTA) practitioners, politicians and industry representatives. ORPH-VAL reached its recommendations through careful consideration of existing OMP P&R literature and through a wide consultation with expert stakeholders, including payers, regulators and patients. The principles cover four areas: OMP decision criteria, OMP decision process, OMP sustainable funding systems and European co-ordination. This paper also presents a guide to the core elements of value relevant to OMPs that should be consistently considered in all OMP appraisals. The principles outlined in this paper may be helpful in drawing together an emerging consensus on this topic and identifying areas where consistency in payer approach could be achievable and beneficial. All stakeholders have an obligation to work together to ensure that the promise of OMP’s is realised

Allogeneic Hematopoietic Stem Cell Transplantation After Prior Lung Transplantation for Hereditary Pulmonary Alveolar Proteinosis: A Case Report

Pulmonary alveolar proteinosis (PAP) is a rare, diffuse lung disorder characterized by surfactant accumulation in the small airways due to defective clearance by alveolar macrophages, resulting in impaired gas exchange. Whole lung lavage is the current standard of care treatment for PAP. Lung transplantation is an accepted treatment option when whole lung lavage or other experimental treatment options are ineffective, or in case of extensive pulmonary fibrosis secondary to PAP. A disadvantage of lung transplantation is recurrence of PAP in the transplanted lungs, especially in hereditary PAP. The hereditary form of PAP is an ultra-rare condition caused by genetic mutations in genes encoding for the granulocyte macrophage-colony stimulating factor (GM-CSF) receptor, and intrinsically affects bone marrow derived-monocytes, which differentiate into macrophages in the lung. Consequently, these macrophages typically display disrupted GM-CSF receptor-signaling, causing defective surfactant clearance. Bone marrow/hematopoietic stem cell transplantation may potentially reverse the lung disease in hereditary PAP. In patients with hereditary PAP undergoing lung transplantation, post-lung transplant recurrence of PAP may theoretically be averted by subsequent hematopoietic stem cell transplantation, which results in a graft-versus-disease (PAP) effect, and thus could improve long-term outcome. We describe the successful long-term post-transplant outcome of a unique case of end-stage respiratory failure due to hereditary PAP-induced pulmonary fibrosis, successfully treated by bilateral lung transplantation and subsequent allogeneic hematopoietic stem cell transplantation. Our report supports treatment with serial lung and hematopoietic stem cell transplantation to improve quality of life and prolong survival, without PAP recurrence, in selected patients with end-stage hereditary PAP