Identification of connective tissue disease autoantibodies and a novel autoantibody anti-annexin A11 in patients with "idiopathic" interstitial lung disease.

BACKGROUND: Autoantibodies are a hallmark feature of Connective Tissue Diseases (CTD). Their presence in patients with idiopathic interstitial lung disease (ILD) may suggest covert CTD. We aimed to determine the prevalence of CTD autoantibodies in patients diagnosed with idiopathic ILD. METHODS: 499 patient sera were analysed: 251 idiopathic pulmonary fibrosis (IPF), 206 idiopathic non-specific interstitial pneumonia (iNSIP) and 42 cryptogenic organising pneumonia (COP). Autoantibody status was determined by immunoprecipitation. RESULTS: 2.4% of IPF sera had a CTD-autoantibody compared to 10.2% of iNSIP and 7.3% of COP. 45% of autoantibodies were anti-synthetases. A novel autoantibody targeting an unknown 56 kDa protein was found in seven IPF patients (2.8%) and two NSIP (1%) patients. This was characterised as anti-annexin A11. CONCLUSION: Specific guidance on autoantibody testing and interpretation in patients with ILD could improve diagnostic accuracy. Further work is required to determine the clinical significance of anti-annexin A11.

Patient outcomes after hospitalisation with COVID-19 and implications for follow-up: results from a prospective UK cohort.

The longer-term consequences of SARS-CoV-2 infection are uncertain. Consecutive patients hospitalised with COVID-19 were prospectively recruited to this observational study (n=163). At 8-12 weeks postadmission, survivors were invited to a systematic clinical follow-up. Of 131 participants, 110 attended the follow-up clinic. Most (74%) had persistent symptoms (notably breathlessness and excessive fatigue) and limitations in reported physical ability. However, clinically significant abnormalities in chest radiograph, exercise tests, blood tests and spirometry were less frequent (35%), especially in patients not requiring supplementary oxygen during their acute infection (7%). Results suggest that a holistic approach focusing on rehabilitation and general well-being is paramount.

Outcome of Hospitalization for COVID-19 in Patients with Interstitial Lung Disease. An International Multicenter Study.

Rationale: The impact of coronavirus disease (COVID-19) on patients with interstitial lung disease (ILD) has not been established.Objectives: To assess outcomes in patients with ILD hospitalized for COVID-19 versus those without ILD in a contemporaneous age-, sex-, and comorbidity-matched population.Methods: An international multicenter audit of patients with a prior diagnosis of ILD admitted to the hospital with COVID-19 between March 1 and May 1, 2020, was undertaken and compared with patients without ILD, obtained from the ISARIC4C (International Severe Acute Respiratory and Emerging Infection Consortium Coronavirus Clinical Characterisation Consortium) cohort, admitted with COVID-19 over the same period. The primary outcome was survival. Secondary analysis distinguished idiopathic pulmonary fibrosis from non-idiopathic pulmonary fibrosis ILD and used lung function to determine the greatest risks of death.Measurements and Main Results: Data from 349 patients with ILD across Europe were included, of whom 161 were admitted to the hospital with laboratory or clinical evidence of COVID-19 and eligible for propensity score matching. Overall mortality was 49% (79/161) in patients with ILD with COVID-19. After matching, patients with ILD with COVID-19 had significantly poorer survival (hazard ratio [HR], 1.60; confidence interval, 1.17-2.18; P = 0.003) than age-, sex-, and comorbidity-matched controls without ILD. Patients with an FVC of <80% had an increased risk of death versus patients with FVC ≥80% (HR, 1.72; 1.05-2.83). Furthermore, obese patients with ILD had an elevated risk of death (HR, 2.27; 1.39-3.71).Conclusions: Patients with ILD are at increased risk of death from COVID-19, particularly those with poor lung function and obesity. Stringent precautions should be taken to avoid COVID-19 in patients with ILD.

No relevant pharmacokinetic drug-drug interaction between nintedanib and pirfenidone.

Nintedanib and pirfenidone are approved treatments for idiopathic pulmonary fibrosis (IPF). This open-label, two-group trial investigated the pharmacokinetic drug-drug interaction between these two drugs in patients with IPF.Subjects not treated with antifibrotics at screening (group 1, n=20) received a single nintedanib dose (150 mg) followed by pirfenidone (titrated to 801 mg thrice daily) for 3 weeks, with a further single nintedanib dose (150 mg) on the last day (day 23). Subjects treated with pirfenidone at screening (group 2, n=17) continued to receive pirfenidone alone (801 mg thrice daily) for 7 days, then co-administered with nintedanib (150 mg twice daily) for a further 7 days, before single doses of both treatments on day 16.In group 1, adjusted geometric mean (gMean) ratios (with/without pirfenidone) were 88.6% and 80.6% for nintedanib area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax), respectively. In group 2, gMean ratios (with/without nintedanib) were 97.2% and 99.5% for pirfenidone AUC and Cmax, respectively. For all parameters, the 90% confidence intervals included 100%, suggesting similar exposure for administration alone and when co-administered. Both treatments were well tolerated.These data indicate there is no relevant pharmacokinetic drug-drug interaction between nintedanib and pirfenidone when co-administered in IPF patients.

Daily Home Spirometry: An Effective Tool for Detecting Progression in Idiopathic Pulmonary Fibrosis.

RATIONALE: Recent clinical trial successes have created an urgent need for earlier and more sensitive endpoints of disease progression in idiopathic pulmonary fibrosis (IPF). Domiciliary spirometry permits more frequent measurement of FVC than does hospital-based assessment, which therefore affords the opportunity for a more granular insight into changes in IPF progression. OBJECTIVES: To determine the feasibility and reliability of measuring daily FVC in individuals with IPF. METHODS: Subjects with IPF were given handheld spirometers and instruction on how to self-administer spirometry. Subjects recorded daily FEV1 and FVC for up to 490 days. Clinical assessment and hospital-based spirometry was undertaken at 6 and 12 months, and outcome data were collected for 3 years. MEASUREMENTS AND MAIN RESULTS: Daily spirometry was recorded by 50 subjects for a median period of 279 days (range, 13-490 d). There were 18 deaths during the active study period. Home spirometry showed excellent correlation with hospital-obtained readings. The rate of decline in FVC was highly predictive of outcome and subsequent mortality when measured at 3 months (hazard ratio [HR], 1.040; 95% confidence interval [CI], 1.021-1.062; P ≤ 0.001), 6 months (HR, 1.024; 95% CI, 1.014-1.033; P < 0.001), and 12 months (HR, 1.012; 95% CI, 1.007-1.016; P = 0.001). CONCLUSIONS: Measurement of daily home spirometry in patients with IPF is highly clinically informative and is feasible to perform for most of these patients. The relationship between mortality and rate of change of FVC at 3 months suggests that daily FVC may be of value as a primary endpoint in short proof-of-concept IPF studies.

Rituximab in autoimmune connective tissue disease-associated interstitial lung disease.

OBJECTIVE: CTD-associated interstitial lung disease (ILD) often fails to respond to conventional immunomodulatory agents. There is now considerable interest in the use of rituximab in systemic autoimmune CTD in patients refractory to standard treatments. The aim of this study was to review the experience of North Bristol NHS Trust managing patients with CTD-associated ILD with rituximab and explore possible associations with treatment response. METHODS: We conducted a retrospective analysis of all patients who received rituximab under the Bristol CTD-ILD service, having failed to respond to other immunomodulatory treatments. Results were collated for pulmonary function and radiological outcomes before and after treatment. RESULTS: Twenty-four patients were treated with rituximab. Their physiological parameters had failed to improve despite other immunomodulatory agents, with a mean change in forced vital capacity (FVC) prior to therapy of - 3.3% (95% CI - 5.6, -1.1) and mean change in diffusing capacity of carbon monoxide of - 4.3% (95% CI - 7.7, -0.9). After rituximab, radiology remained stable or improved for 11 patients, while worsening was observed in 9 patients. The decline in FVC was halted following treatment, with a mean change of + 4.1% (95% CI 0.9, 7.2), while diffusing capacity of carbon monoxide was stable [mean change +2.1% (95% CI - 1.0, 5.2)]. Patients with myositis overlap or antisynthetase syndrome appeared to respond well to treatment, with four patients showing clinically significant improvement in FVC >10%. CONCLUSION: Rituximab is a therapeutic option in treatment-refractory CTD-associated ILD. Some disease subgroups may respond better than others, however, more work is needed to define its role in managing these patients.

Ambulatory and short-burst oxygen for interstitial lung disease.

BACKGROUND: A large subgroup of people with interstitial lung disease (ILD) are normoxic at rest, but rapidly desaturate on exertion. This can limit exercise capacity and worsen dyspnoea. The use of ambulatory or short-burst oxygen when mobilising or during other activities, may improve exercise capacity and relieve dyspnoea. OBJECTIVES: To determine the effects of ambulatory and short-burst oxygen therapy, separately, on exercise capacity, dyspnoea and quality of life in people who have interstitial lung disease (ILD), particularly those with idiopathic pulmonary fibrosis (IPF). SEARCH METHODS: We conducted searches in the Cochrane Airways Group Specialised Register (all years to May 2016), Cochrane Central Register of Controlled Trials (CENTRAL) (all years to May 2016), MEDLINE (Ovid) (1950 to 4th May 2016) and EMBASE (Ovid) (1974 to 4th May 2016). We also searched the reference lists of relevant studies, international clinical trial registries and respiratory conference abstracts for studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs that compared ambulatory or short-burst oxygen with a control group in people with ILD of any origin. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion and assessed risk of bias in the included studies. We extracted data from included studies using a prepared checklist, including study characteristics and results. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria to assess the quality of the included studies. MAIN RESULTS: Three studies (including 98 participants, all of whom had IPF) met the inclusion criteria of this review. These studies were conducted in hospital respiratory physiology laboratories. Two studies did not demonstrate any beneficial effect of supplemental oxygen on exercise capacity or exertional dyspnoea. Neither of these studies titrated oxygen requirements to prevent ongoing exertional desaturation. One study showed an increase in exercise capacity as assessed by endurance time with supplemental oxygen. We did not identify any studies that examined the effect of ambulatory oxygen on health-related quality of life, survival, costs or time to exacerbation or hospitalisation. No study reported any adverse events. The quality of evidence for all three studies, as assessed by GRADE criteria, was low. AUTHORS' CONCLUSIONS: This review found no evidence to support or refute the use of ambulatory or short burst oxygen in ILD due to the limited number of included studies and data. Further research is needed to examine the role of this treatment.

Pulmonary Langerhans cell histiocytosis (PLCH): a new UK register.

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial lung disease of unknown aetiology. We aimed to characterise a UK-wide cohort of patients with PLCH and compare diagnostic and management methods in specialist and non-specialist centres. 106 cases (53 hospitals) identified. Complete data received in 67 cases (53.7% female, age 37.1±14.4 years). 96% current or ex-smokers. Treatment; smoking cessation (79%), corticosteroids (30.6%), cytotoxic therapy (26.9%) and lung transplant (6%). Patients at specialist centres received cytotoxic drugs more often (p=0.0001) and survival appeared higher. This dataset indicates a more even gender distribution than previously documented. It suggests variation in clinical management and outcomes achieved dependent on clinical experience.

The Impact of Integrated Palliative Care on Survival in Idiopathic Pulmonary Fibrosis: A Retrospective Multicenter Comparison.

Background: Early and integrated palliative care is recommended for patients with idiopathic pulmonary fibrosis. Unfortunately, palliative care delivery remains poor due to various barriers in practice. This study describes various palliative care delivery models in a real-world cohort of patients with idiopathic pulmonary fibrosis, examines the predictors of survival in this cohort of patients, and explores the impact of palliative care on survival. Design: Charts were reviewed retrospectively and analyzed. The primary outcome was survival during a 4-year follow-up period. Two multivariable models were created to examine the impact of therapeutic strategies including palliative intervention on survival. Results: 298 patients with idiopathic pulmonary fibrosis were enrolled from 3 interstitial lung disease clinics with different palliative care models in Edmonton, Canada; Bristol, UK; and Kingston, Canada. 200 (67%) patients received palliative care and 119 (40%) died during follow up. Primary palliative care models (Edmonton and Bristol) delivered palliative care to 96% and 100% respectively compared 21% in the referral model (Queens). Palliative care [adjusted hazard ratio (aHR) .28 (.12-.65)] along with the use of antifibrotics [aHR .56 (.37-.84)], and body mass index >30 [aHR .47 (.37-.85)] reduced the risk of death in our idiopathic pulmonary fibrosis cohort. Opioid use was associated with worse survival [aHR 2.11 (1.30-23.43)]. Conclusions: Both palliative care and antifibrotic use were associated with survival benefit in this cohort of patients with idiopathic pulmonary fibrosis after adjusting for covariates. The benefit was seen despite differences in disease severity and different palliative care delivery models.

Assessment of the impact of social deprivation, distance to hospital and time to diagnosis on survival in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive condition associated with a variable prognosis. The relationship between socioeconomic status or distance travelled to respiratory clinics and prognosis is unclear. RESEARCH QUESTION: To determine whether socioeconomic status, distance to hospital and time to referral affects survival in patients with IPF. STUDY DESIGN AND METHODS: In this retrospective cohort study, we used data collected from the British Thoracic Society Interstitial Lung Diseases Registry, between 2013 and 2021 (n = 2359) and calculated the quintile of Index of Multiple Deprivation 2019 score, time from initial symptoms to hospital attendance and distance as the linear distance between hospital and home post codes. Survival was assessed using Cox proportional hazards models. RESULTS: There was a significant association between increasing quintile of deprivation and duration of symptoms prior to hospital presentation, Gender Age Physiology (GAP) index and receipt of supplemental oxygen and antifibrotic therapies at presentation. The most deprived patients had worse overall survival compared to least deprived after adjusting for smoking status, GAP index, distance to hospital and time to referral (HR = 1.39 [1.11, 1.73]; p = 0.003). Patients living furthest from a respiratory clinic also had worse survival compared to those living closest (HR = 1.29 [1.01, 1.64]; p = 0.041). INTERPRETATION: The most deprived patients with IPF have more severe disease at presentation and worse outcomes. Living far from hospital was also associated with poor outcomes. This suggests inequalities in access to healthcare and requires consideration in delivering effective and equitable care to patients with IPF.

The impact of targeted local outreach clinics to improve COVID-19 vaccine uptake: controlled interrupted time series in South West England.

BACKGROUND: Outreach clinics were part of efforts to maximise uptake in COVID-19 vaccination. METHODS: We used controlled interrupted time series, matching on age, sex, deprivation and vaccination eligibility date, to determine the effect of outreach clinics on time to first COVID-19 vaccine, using a population-based electronic health record database of 914,478 people, from December 2020 to December 2021; people living within 1 mile of each outreach clinics were exposed. RESULTS: 50% of 288,473 exposed citizens were white British, and 71% were aged 0-49 years. There was no evidence for an overall statistically significant increase in cumulative percentage vaccinated due to the outreach clinic at 6 weeks, with an overall pooled effect estimate of -0.07% (95% CI: -1.15%, 1.02%). The pooled estimate for increased cumulative vaccine uptake varied slightly depending on how the analysis was stratified; by ethnic group it was - 0.12% (95% CI: -0.90%, 0.66%); by age group it was - 0.06% (95% CI: -0.41%, 0.28%); and by deprivation it was 0.03% (95% CI: -0.74%, 0.79%). CONCLUSIONS: Living within a mile of an outreach clinic was not associated with higher vaccine uptake. Evaluation of future outreach clinics should consider the relative importance of travel amongst other barriers to accessing vaccines.

A Retrospective Analysis of 2-Year Follow-Up of Patients with Incidental Findings of Sarcoidosis.

INTRODUCTION: Sarcoidosis is a multi-system granulomatous disease most commonly involving the lungs. It may be incidentally diagnosed during imaging studies for other conditions or non-specific symptoms. The appropriate follow-up of incidentally diagnosed asymptomatic stage 1 disease has not been well defined. OBJECTIVE: To define the clinical course of incidentally diagnosed asymptomatic stage 1 sarcoidosis and propose an algorithm for the follow-up of these patients. METHODOLOGY: A retrospective case note analysis was performed of all EBUS-TBNA (endobronchial ultrasound-guided transbronchial needle aspiration)-confirmed cases of stage 1 sarcoidosis presenting incidentally to Bristol and Liverpool Interstitial Lung Disease services. Clinical history, serology results, imaging scans, and lung function parameters were examined at baseline, 12, and 24 months. A cost analysis was performed comparing the cost of the current 2-year follow-up guidance to a 1 year follow-up period. RESULTS: Sixty-seven patients were identified as the final cohort. There was no significant change in the pulmonary function tests over the two-year follow-up period. Radiological disease stability was observed in the majority of patients (58%, n = 29), and disease regression was evidenced in 40% (n = 20) at 1 year. Where imaging was performed at 2 years, the majority (69.8%, n = 37) had radiological evidence of disease regression, and 30.2% (n = 16) showed radiological evidence of stability. All patients remained asymptomatic and did not require therapeutic intervention over the study period. CONCLUSIONS: Our results show that asymptomatic patients with incidental findings of thoracic lymph nodal non-caseating granulomas do not progress over a 2-year period. Our results suggest that the prolonged secondary-care follow-up of such patients may not be necessary. We propose that these patients are followed up for 1 year with a further year of patient-initiated follow-up (PIFU) prior to discharge.

Real-world experience of nintedanib for progressive fibrosing interstitial lung disease in the UK.

Background: Nintedanib slows progression of lung function decline in patients with progressive fibrosing (PF) interstitial lung disease (ILD) and was recommended for this indication within the United Kingdom (UK) National Health Service in Scotland in June 2021 and in England, Wales and Northern Ireland in November 2021. To date, there has been no national evaluation of the use of nintedanib for PF-ILD in a real-world setting. Methods: 26 UK centres were invited to take part in a national service evaluation between 17 November 2021 and 30 September 2022. Summary data regarding underlying diagnosis, pulmonary function tests, diagnostic criteria, radiological appearance, concurrent immunosuppressive therapy and drug tolerability were collected via electronic survey. Results: 24 UK prescribing centres responded to the service evaluation invitation. Between 17 November 2021 and 30 September 2022, 1120 patients received a multidisciplinary team recommendation to commence nintedanib for PF-ILD. The most common underlying diagnoses were hypersensitivity pneumonitis (298 out of 1120, 26.6%), connective tissue disease associated ILD (197 out of 1120, 17.6%), rheumatoid arthritis associated ILD (180 out of 1120, 16.0%), idiopathic nonspecific interstitial pneumonia (125 out of 1120, 11.1%) and unclassifiable ILD (100 out of 1120, 8.9%). Of these, 54.4% (609 out of 1120) were receiving concomitant corticosteroids, 355 (31.7%) out of 1120 were receiving concomitant mycophenolate mofetil and 340 (30.3%) out of 1120 were receiving another immunosuppressive/modulatory therapy. Radiological progression of ILD combined with worsening respiratory symptoms was the most common reason for the diagnosis of PF-ILD. Conclusion: We have demonstrated the use of nintedanib for the treatment of PF-ILD across a broad range of underlying conditions. Nintedanib is frequently co-prescribed alongside immunosuppressive and immunomodulatory therapy. The use of nintedanib for the treatment of PF-ILD has demonstrated acceptable tolerability in a real-world setting.

Mucin 5B promoter polymorphism is associated with idiopathic pulmonary fibrosis but not with development of lung fibrosis in systemic sclerosis or sarcoidosis.

BACKGROUND: A polymorphism (rs35705950) 3 kb upstream of MUC5B, the gene encoding Mucin 5 subtype B, has been shown to be associated with familial and sporadic idiopathic pulmonary fibrosis (IPF). We set out to verify whether this variant is also a risk factor for fibrotic lung disease in other settings and to confirm the published findings in a UK Caucasian IPF population. METHODS: Caucasian UK healthy controls (n=416) and patients with IPF (n=110), sarcoidosis (n=180) and systemic sclerosis (SSc) (n=440) were genotyped to test for association. The SSc and sarcoidosis cohorts were subdivided according to the presence or absence of fibrotic lung disease. To assess correlation with disease progression, time to decline in forced vital capacity and/or lung carbon monoxide transfer factor was used in the IPF and SSc groups, while a persistent decline at 4 years since baseline was evaluated in patients with sarcoidosis. RESULTS: A significant association of the MUC5B promoter single nucleotide polymorphism with IPF (p=2.04 × 10(-17); OR 4.90, 95% CI 3.42 to 7.03) was confirmed in this UK population. The MUC5B variant was not a risk factor for lung fibrosis in patients with SSc or sarcoidosis and did not predict more rapidly progressive lung disease in any of the groups. Rather, a trend for a longer time to decline in forced vital capacity was observed in patients with IPF. CONCLUSIONS: We confirm the MUC5B variant association with IPF. We did not observe an association with lung fibrosis in the context of SSc or sarcoidosis, potentially highlighting fundamental differences in genetic susceptibility, although the limited subgroup numbers do not allow a definitive exclusion of an association.

Macrophage migration inhibitory factor enzymatic activity, lung inflammation, and cystic fibrosis.

RATIONALE: Macrophage migration inhibitory factor (MIF) is a proinflammatory mediator with unique tautomerase enzymatic activity; the precise function has not been clearly defined. We previously demonstrated that individual patients with cystic fibrosis (CF) who are genetically predisposed to be high MIF producers develop accelerated end-organ injury. OBJECTIVES: To characterize the effects of the MIF-CATT polymorphism in patients with CF ex vivo. To investigate the role of MIF's tautomerase activity in a murine model of Pseudomonas aeruginosa infection. METHODS: MIF and tumor necrosis factor (TNF)-α protein levels were assessed in plasma or peripheral blood mononuclear cell (PBMC) supernatants by ELISA. A murine pulmonary model of chronic Pseudomonas infection was used in MIF wild-type mice (mif(+/+)) and in tautomerase-null, MIF gene knockin mice (mif (P1G/P1G)). MEASUREMENTS AND MAIN RESULTS: MIF protein was measured in plasma and PBMCs from 5- and 6-CATT patients with CF; LPS-induced TNF-α production from PBMCs was also assessed. The effect of a specific inhibitor of MIF-tautomerase activity, ISO-1, was investigated in PBMCs. In the murine infection model, total weight loss, differential cell counts, bacterial load, and intraacinar airspace/tissue volume were measured. MIF and TNF-α levels were increased in 6-CATT compared with 5-CATT patients with CF. LPS-induced TNF-α production from PBMCs was attenuated in the presence of ISO-1. In a murine model of Pseudomonas infection, significantly less pulmonary inflammation and bacterial load was observed in mif(P1G/P1G) compared with mif(+/+) mice. CONCLUSIONS: MIF-tautomerase activity may provide a novel therapeutic target in patients with chronic inflammatory diseases such as CF, particularly those patients who are genetically predisposed to produce increased levels of this cytokine.

Pharmacological management of systemic sclerosis associated interstitial lung disease.

INTRODUCTION: Interstitial lung disease (ILD) is a major cause of disease-related morbidity and one of the leading causes of mortality in patients with systemic sclerosis (SSc). Many patients will be diagnosed with SSc before the emergence of clinically meaningful ILD. Screening and early recognition of SSc-ILD allows prompt intervention and improved clinical outcomes. In recent years, clinical trial data from large well-designed randomized controlled trials have greatly enhanced our understanding of the natural history of SSc-ILD and risk factors for progressive disease. These advances have led to the emergence of treatment paradigms designed to address the management of both established and subclinical disease. AREAS COVERED: The present review shall consider the findings of recent trials and implications for modern pharmacological management of SSc-ILD. Where relevant, knowledge gaps shall be highlighted to outline the potential focus of additional research in this field. EXPERT OPINION: Recent clinical trial data have confirmed beyond doubt the value of immunomodulatory treatment in SSc-ILD, and it is expected this shall translate into improved clinical outcomes in SSc-ILD. We need better methods of cohort enrichment for SSc-ILD clinical trials, and biomarker discovery may establish molecular signatures allowing more personalized approaches to SSc-ILD prevention and management.

Animal-derived medicinal products: community representatives' views of their use.

In the UK, there are a variety of religious or cultural beliefs and preferences that guide people in a range of lifestyle decisions. This qualitative study aimed to better understand the views of the public around prescribing animal-derived products, in particular low-molecular-weight heparin (LMWH), from a potential patient perspective. A series of quality improvement focus groups with stakeholders were undertaken to understand perceptions and to evaluate and inform an established treatment pathway. Stakeholders discussed finding out about the porcine nature of LMWH asking 'Why don't they tell us?', suggesting that they 'shouldn't have to give out clues' about their personal preferences. Participants' thoughts about 'how' information be provided, by 'whom' and 'when' were gained. The stakeholders indicated that current practice is unacceptable for patients. They require greater knowledge and transparency regarding product components and recommend that healthcare professionals provide more dialogue and choice to patients.