scholarly journals Use of high dose cyproterone acetate and risk of intracranial meningioma in women: cohort study

BMJ ◽  
2021 ◽  
pp. n37
Author(s):  
Alain Weill ◽  
Pierre Nguyen ◽  
Moujahed Labidi ◽  
Benjamin Cadier ◽  
Thibault Passeri ◽  
...  
Keyword(s):  
Cohort Study ◽  
Confidence Interval ◽  
Skull Base ◽  
Cumulative Dose ◽  
Cyproterone Acetate ◽  
Exposed Group ◽  
Additional Analysis ◽  
Control Group ◽  
High Dose

Abstract Objective To assess the risk of meningioma associated with use of high dose cyproterone acetate, a progestogen indicated for clinical hyperandrogenism. Design Observational cohort study. Setting Data from SNDS, the French administrative healthcare database, between 2007 and 2015. Participants 253 777 girls and women aged 7-70 years living in France who started cyproterone acetate between 2007 and 2014. Participants had at least one reimbursement for high dose cyproterone acetate and no history of meningioma or benign brain tumour, or long term disease status. Participants were considered to be exposed when they had received a cumulative dose of at least 3 g during the first six months (139 222 participants) and very slightly exposed (control group) when they had received a cumulative dose of less than 3 g (114 555 participants). 10 876 transgender participants (male to female) were included in an additional analysis. Main outcome measure Surgery (resection or decompression) or radiotherapy for one or more intracranial meningiomas. Results Overall, 69 meningiomas in the exposed group (during 289 544 person years of follow-up) and 20 meningiomas in the control group (during 439 949 person years of follow-up) were treated by surgery or radiotherapy. The incidence of meningioma in the two groups was 23.8 and 4.5 per 100 000 person years, respectively (crude relative risk 5.2, 95% confidence interval 3.2 to 8.6; adjusted hazard ratio 6.6, 95% confidence interval 4.0 to 11.1). The adjusted hazard ratio for a cumulative dose of cyproterone acetate of more than 60 g was 21.7 (10.8 to 43.5). After discontinuation of cyproterone acetate for one year, the risk of meningioma in the exposed group was 1.8-fold higher (1.0 to 3.2) than in the control group. In a complementary analysis, 463 women with meningioma were observed among 123 997 already using cyproterone acetate in 2006 (risk of 383 per 100 000 person years in the group with the highest exposure in terms of cumulative dose). Meningiomas located in the anterior skull base and middle skull base, particularly the medial third of the middle skull base, involving the spheno-orbital region, appeared to be specific to cyproterone acetate. An additional analysis of transgender participants showed a high risk of meningioma (three per 14 460 person years; 20.7 per 100 000 person years). Conclusions A strong dose-effect relation was observed between use of cyproterone acetate and risk of intracranial meningiomas. A noticeable reduction in risk was observed after discontinuation of treatment.

Impact of cochlear modiolus dose on hearing preservation following stereotactic radiosurgery for non–vestibular schwannoma neoplasms of the lateral skull base: a cohort study

2020 ◽  
Vol 133 (3) ◽  
pp. 736-741
Author(s):  
Lucas P. Carlstrom ◽  
Jeffrey T. Jacob ◽  
Christopher S. Graffeo ◽  
Avital Perry ◽  
Michael S. Oldenburg ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cohort Study ◽  
Skull Base ◽  
Stereotactic Radiosurgery ◽  
Vestibular Schwannoma ◽  
Hearing Preservation ◽  
Control Group ◽  
High Dose ◽  
Petroclival Meningiomas ◽  
Lateral Skull Base

OBJECTIVERadiation dose to the cochlea has been proposed as a key prognostic factor in hearing preservation following stereotactic radiosurgery (SRS) for vestibular schwannoma (VS). However, understanding of the predictive value of cochlear dose on hearing outcomes following SRS for patients with non-VS tumors of the lateral skull base (LSB) is incomplete. The authors investigated rates of hearing loss following high-dose SRS in patients with LSB non-VS lesions compared with patients with VS.METHODSPatients with LSB meningioma or jugular paraganglioma and serviceable pretreatment hearing who underwent SRS treatment during 2007–2016 and received a modiolus dose > 5 Gy were included in a retrospective cohort study, along with a similarly identified control group of consecutive patients with sporadic VS.RESULTSSixteen patients with non-VS tumors and a control group of 43 patients with VS met study criteria. Serviceable hearing, defined as American Academy of Otololaryngology–Head and Neck Surgery class A/B, was maintained in 13 non-VS versus 23 VS patients (81% vs 56%, p = 0.07). All 3 instances of hearing loss in non-VS patients were observed in cerebellopontine angle (CPA) meningiomas. Non-VS with preserved hearing had a median modiolus dose of 6.9 Gy (range 5.7–19.2 Gy), versus 7.4 Gy (range 5.4–7.6 Gy) in those patients with post-SRS hearing loss (p = 0.53). Sporadic VS patients received an overall median modiolus point-dose of 6.8 Gy (range 5.4–11.7 Gy).CONCLUSIONSThe modiolus dose threshold of 5 Gy does not predict hearing loss in patients with non-VS tumors undergoing SRS, suggesting that dosimetric parameters derived from VS may not be applicable to this population. Differential rates of hearing loss appear to vary by pathology, with paragangliomas and petroclival meningiomas demonstrating decreased risk of hearing loss compared to CPA meningiomas that may directly compress the cochlear nerve similarly to VS.

scholarly journals Do welfare benefit reassessments of people with mental health conditions lead to worse mental health? A prospective cohort study

2019 ◽  
Vol 66 (2) ◽  
pp. 136-149
Author(s):  
Ruth Stuart ◽  
Sanchika Campbell ◽  
Beatrice Osumili ◽  
Emily J Robinson ◽  
Mary Frost-Gaskin ◽  
...  
Keyword(s):  
Mental Health ◽  
Cohort Study ◽  
Health Service ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Exposed Group ◽  
Health Conditions ◽  
Control Group ◽  
Mental Health Conditions

Background: There have been cases of suicide following the Work Capability Assessment (WCA), a questionnaire and interview for those claiming benefits due to ill health or disability in the United Kingdom. Aims: To examine whether experiencing problems with welfare benefits, including WCA, among people with pre-existing mental health conditions was associated with poorer mental health and wellbeing and increased health service use and costs. Methods: A prospective cohort study of an exposed group ( n = 42) currently seeking help from a Benefits Advice Service in London and a control group ( n = 45) who had recently received advice from the same service. Questionnaires at baseline and 3-, 6- and 12-month follow-ups. Results: The exposed group had higher mean scores for anxiety ( p = .008) and depression ( p = .016) at baseline and the control group higher mean scores for wellbeing at baseline ( p = .034) and 12 months ( p = .035). However, loss to follow-up makes overall results difficult to interpret. The control group had higher incomes throughout the study, particularly at the 12-month follow-up ( p = .004), but the differences could have been accounted for by other factors. Health service costs were skewed by a few participants who used day-care services intensively or had inpatient stays. Over the study period the proportion of exposed participants engaged in benefits reassessment ranged from 50% to 88%, and 40% to 76% of controls. Conclusion: The hardship of living with financial insecurity and a mental health condition made it difficult for our participants to sustain involvement in a 12-month study and the frequency of benefit reviews meant that the experiences of our controls were similar to our exposed group. These limitations limit interpretation but confirm the relevance of our research. The control data raise the question of whether people with mental health conditions are being disproportionately reassessed.

Asthma and Immunoglobulin E Antibodies After Respiratory Syncytial Virus Bronchiolitis: A Prospective Cohort Study With Matched Controls

PEDIATRICS ◽  
1995 ◽  
Vol 95 (4) ◽  
pp. 500-505 ◽  
Author(s):  
N. Sigurs ◽  
R. Bjarnason ◽  
F. Sigurbergsson ◽  
B. Kjellman ◽  
B. Björkstén
Keyword(s):  
Risk Factor ◽  
Cohort Study ◽  
Respiratory Syncytial Virus ◽  
Prospective Cohort ◽  
Egg White ◽  
Control Group ◽  
Igg Antibodies ◽  
Ige Antibodies ◽  
Syncytial Virus

Objective. To study the occurrence of bronchial obstructive symptoms and immunoglobulin (Ig) E antibodies after respiratory syncytial virus (RSV) bronchiolitis in infancy. Previous studies of this subject have mostly been retrospective or without controls, or the controls have not been followed prospectively. Design. This was a prospective cohort study with matched controls. Participants. Forty-seven infants had experienced RSV bronchiolitis severe enough to cause hospitalization at a mean age of 3½ months. For each child with RSV infection, two controls were acquired from the local Child Health Center and matched for date of birth, sex, and residence. Only one control was obtained for one RSV child, and the control group thus contained 93 children. Methods. All the children underwent two follow-up examinations, the first one at a mean age of 1 year and the second at a mean age of 3 years. At the first follow-up, a skin-prick test against egg white was performed, and serum IgG antibodies against RSV were measured. At the second follow-up, serum IgE antibodies were measured using screening tests for common food and inhalant antibodies, and skin-prick tests against egg white, cat, birch, and mite allergen were performed. Hereditary and environmental factors (passive smoking, indoor furred animals) and duration of breast-feeding were recorded. Results. At the first follow-up, 89% in the RSV group and 27% in the control group had IgG antibodies against RSV (P < .001). At the second follow-up, asthma, defined as three episodes of bronchial obstruction verified by a physician, was found in 11 of 47 children (23%) in the RSV group and in 1 of 93 children (1%) in the control group (P < .001). A positive test for IgE antibodies was noted in 14 of 44 (32%) RSV children and in 8 of 92 (9%) children in the control group (P = .002). An analysis of risk factors for the development of asthma and IgE antibodies on the whole group of 140 children showed that RSV bronchiolitis was the most important risk factor, and a family history of atopy or asthma further increased the risk. Conclusions. Respiratory syncytial virus bronchiolitis during the first year of life apparently is an important risk factor for the development of asthma and sensitization to common allergens during the subsequent 2 years, particularly in children with heredity for atopy/asthma.

scholarly journals Follow-up of incidental pulmonary nodules and association with mortality in a safety-net cohort

Diagnosis ◽  
2019 ◽  
Vol 6 (4) ◽  
pp. 351-359 ◽  
Author(s):  
Jonathan S. Lee ◽  
Sarah Lisker ◽  
Eric Vittinghoff ◽  
Roy Cherian ◽  
David B. McCoy ◽  
...  
Keyword(s):  
Cohort Study ◽  
Confidence Interval ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Pulmonary Nodules ◽  
Safety Net ◽  
Mortality Rates ◽  
All Cause Mortality ◽  
Multivariable Models

Abstract Background Though incidental pulmonary nodules are common, rates of guideline-recommended surveillance and associations between surveillance and mortality are unclear. In this study, we describe adherence (categorized as complete, partial, late and none) to guideline-recommended surveillance among patients with incidental 5–8 mm pulmonary nodules and assess associations between adherence and mortality. Methods This was a retrospective cohort study of 551 patients (≥35 years) with incidental pulmonary nodules conducted from September 1, 2008 to December 31, 2016, in an integrated safety-net health network. Results Of the 551 patients, 156 (28%) had complete, 87 (16%) had partial, 93 (17%) had late and 215 (39%) had no documented surveillance. Patients were followed for a median of 5.2 years [interquartile range (IQR), 3.6–6.7 years] and 82 (15%) died during follow-up. Adjusted all-cause mortality rates ranged from 2.24 [95% confidence interval (CI), 1.24–3.25] deaths per 100 person-years for complete follow-up to 3.30 (95% CI, 2.36–4.23) for no follow-up. In multivariable models, there were no statistically significant associations between the levels of surveillance and mortality (p > 0.16 for each comparison with complete surveillance). Compared with complete surveillance, adjusted mortality rates were non-significantly increased by 0.45 deaths per 100 person-years (95% CI, −1.10 to 2.01) for partial, 0.55 (95% CI, −1.08 to 2.17) for late and 1.05 (95% CI, −0.35 to 2.45) for no surveillance. Conclusions Although guideline-recommended surveillance of small incidental pulmonary nodules was incomplete or absent in most patients, gaps in surveillance were not associated with statistically significant increases in mortality in a safety-net population.

Efficacy, toxicity, and applicability of high-dose sequential chemotherapy as adjuvant treatment in operable breast cancer with 10 or more involved axillary nodes: five-year results.

1997 ◽  
Vol 15 (6) ◽  
pp. 2312-2321 ◽  
Author(s):  
A M Gianni ◽  
S Siena ◽  
M Bregni ◽  
M Di Nicola ◽  
S Orefice ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Standard Dose ◽  
Treated Group ◽  
Multicenter Trial ◽  
Control Group ◽  
High Dose ◽  
Axillary Nodes ◽  
Major Toxicity ◽  
Nonhematologic Toxicity

PURPOSE To assess the efficacy, toxicity, and applicability of high-dose therapy administered as adjuvant initial treatment to women with breast cancer with extensive nodal involvement. PATIENTS AND METHODS Sixty-seven patients with stage II to III breast cancer involving > or = 10 axillary nodes received a novel high-dose sequential (HDS) regimen, including the high-dose administration of three non-cross-resistant drugs (cyclophosphamide, methotrexate, and melphalan) given within the shortest interval of time as possible with hematologic and nonhematologic toxicity. RESULTS Sixty-three patients completed the program as planned, one patient died of acute toxicity, and three patients were switched to standard-dose adjuvant therapy. After a median follow-up duration of 48.5 months and a lead follow-up of 78 months, actuarial relapse-free survival for all 67 registered patients is 57% and overall survival is 70%, respectively. Comparison with a historical control group of 58 consecutive patients showed a significantly superior rate of freedom from relapse for the HDS-treated group (57% v 41%, respectively), in particular when two subgroups of patients, more homogeneous for their number of involved nodes, were compared (65% v 42%). Overall, treatment was of short duration (median, 70 days), required a median of 32 days of hospital stay, and was associated with only a few severe side effects (the most distressing being oral mucositis after melphalan therapy). CONCLUSION HDS therapy emerges as an effective and applicable regimen, whose major toxicity was occasional. Final assessment of its value in a randomized, multicenter trial is presently underway.

scholarly journals Effect of high-dose vitamin C therapy on severe burn patients: a nationwide cohort study

Critical Care ◽  
2019 ◽  
Vol 23 (1) ◽  
Author(s):  
Mikio Nakajima ◽  
Morita Kojiro ◽  
Shotaro Aso ◽  
Hiroki Matsui ◽  
Kiyohide Fushimi ◽  
...  
Keyword(s):  
Propensity Score ◽  
Vitamin C ◽  
Confidence Interval ◽  
Hospital Mortality ◽  
Control Group ◽  
High Dose ◽  
Burn Patients ◽  
Severe Burn ◽  
Severe Burns ◽  
High Dose Vitamin

Abstract Background Vitamin C is a well-documented antioxidant that reduces oxidative stress and fluid infusion in high doses; however, the association between high-dose vitamin C and reduced mortality remains unclear. This study evaluates the effect of high-dose vitamin C in severe burn patients under two varying thresholds. Methods We enrolled adult patients with severe burns (burn index ≥ 15) who were registered in the Japanese Diagnosis Procedure Combination national inpatient database from 2010 to 2016. Propensity score matching was performed between patients who received high-dose vitamin C within 1 day of admission (vitamin C group) and those who did not (control group). High-dose vitamin C was defined as a dosage in excess of 10 g or 24 g within 2 days of admission. The primary outcome was in-hospital mortality. Results Eligible patients (n = 2713) were categorized into the vitamin C group (n = 157) or control group (n = 2556). After 1:4 propensity score matching, we compared 157 and 628 patients who were administered high-dose vitamin C (> 10-g threshold) and controls, respectively. Under this particular threshold, high-dose vitamin C therapy was associated with reduced in-hospital mortality (risk ratio, 0.79; 95% confidence interval, 0.66–0.95; p = 0.006). In contrast, in-hospital mortality did not differ between the control and high-dose vitamin C group under the > 24-g threshold (risk ratio, 0.83; 95% confidence interval, 0.68–1.02; p = 0.068). Conclusions High-dose vitamin C therapy was associated with reduced mortality in patients with severe burns when used under a minimum threshold of 10 g within the first 2 days of admission. While “high-dose” vitamin C therapy lacks a universal definition, the present study reveals that different “high-dose” regimens may yield improved outcomes.

scholarly journals Weight change over two years in people prescribed olanzapine, quetiapine and risperidone in UK primary care: Cohort study in THIN, a UK primary care database

2018 ◽  
Vol 32 (10) ◽  
pp. 1098-1103 ◽  
Author(s):  
David PJ Osborn ◽  
Irene Petersen ◽  
Nick Beckley ◽  
Kate Walters ◽  
Irwin Nazareth ◽  
...  
Keyword(s):  
Primary Care ◽  
Cohort Study ◽  
Weight Gain ◽  
Confidence Interval ◽  
Weight Change ◽  
Antipsychotic Treatment ◽  
Weight Changes ◽  
Baseline Weight ◽  
Care Database

Background: Follow-up studies of weight gain related to antipsychotic treatment beyond a year are limited in number. We compared weight change in the three most commonly prescribed antipsychotics in a representative UK General Practice database. Method: We conducted a cohort study in United Kingdom primary care records of people newly prescribed olanzapine, quetiapine or risperidone. The primary outcome was weight in each six month period for two years after treatment initiation. Weight changes were compared using linear regression, adjusted for age, baseline weight and diagnosis. Results: N = 6338 people received olanzapine, 12,984 quetiapine and 6556 risperidone. Baseline weight was lowest for men treated with olanzapine (80.8 kg versus 83.5 kg quetiapine, 82.0 kg risperidone) and women treated with olanzapine (67.7 kg versus 71.5 kg quetiapine 68.4 kg risperidone. Weight gain occurred during treatment with all three drugs. Compared with risperidone mean weight gain was higher with olanzapine (adjusted co-efficient +1.24 kg (95% confidence interval: 0.69–1.79 kg per six months) for men and +0.77 kg (95% confidence interval: 0.29–1.24 kg) for women). Weight gain with quetiapine was lower in unadjusted models compared with risperidone, but this difference was not significant after adjustment. Conclusion: Olanzapine is more commonly prescribed to people with lower weight. However, after accounting for baseline weight, age, sex and diagnosis, olanzapine is still associated with greater weight gain over two years than risperidone or quetiapine. Baseline weight does not ameliorate the risks of weight gain associated with antipsychotic medication. Weight gain should be assertively discussed and managed for people prescribed antipsychotics, especially olanzapine.

scholarly journals Common conditions associated with hereditary haemochromatosis genetic variants: cohort study in UK Biobank

BMJ ◽  
2019 ◽  
pp. k5222 ◽  
Author(s):  
Luke C Pilling ◽  
Jone Tamosauskaite ◽  
Garan Jones ◽  
Andrew R Wood ◽  
Lindsay Jones ◽  
...  
Keyword(s):  
Cohort Study ◽  
Confidence Interval ◽  
Community Sample ◽  
Hospital Inpatient ◽  
Uk Biobank ◽  
European Descent ◽  
Hereditary Haemochromatosis ◽  
Condition Versus ◽  
Early Case

Abstract Objective To compare prevalent and incident morbidity and mortality between those with the HFE p.C282Y genetic variant (responsible for most hereditary haemochromatosis type 1) and those with no p.C282Y mutations, in a large UK community sample of European descent. Design Cohort study. Setting 22 centres across England, Scotland, and Wales in UK Biobank (2006-10). Participants 451 243 volunteers of European descent aged 40 to 70 years, with a mean follow-up of seven years (maximum 9.4 years) through hospital inpatient diagnoses and death certification. Main outcome measure Odds ratios and Cox hazard ratios of disease rates between participants with and without the haemochromatosis mutations, adjusted for age, genotyping array type, and genetic principal components. The sexes were analysed separately as morbidity due to iron excess occurs later in women. Results Of 2890 participants homozygous for p.C282Y (0.6%, or 1 in 156), haemochromatosis was diagnosed in 21.7% (95% confidence interval 19.5% to 24.1%, 281/1294) of men and 9.8% (8.4% to 11.2%, 156/1596) of women by end of follow-up. p.C282Y homozygous men aged 40 to 70 had a higher prevalence of diagnosed haemochromatosis (odds ratio 411.1, 95% confidence interval 299.0 to 565.3, P<0.001), liver disease (4.30, 2.97 to 6.18, P<0.001), rheumatoid arthritis (2.23, 1.51 to 3.31, P<0.001), osteoarthritis (2.01, 1.71 to 2.36, P<0.001), and diabetes mellitus (1.53, 1.16 to 1.98, P=0.002), versus no p.C282Y mutations (n=175 539). During the seven year follow-up, 15.7% of homozygous men developed at least one incident associated condition versus 5.0% (P<0.001) with no p.C282Y mutations (women 10.1% v 3.4%, P<0.001). Haemochromatosis diagnoses were more common in p.C282Y/p.H63D heterozygotes, but excess morbidity was modest. Conclusions In a large community sample, HFE p.C282Y homozygosity was associated with substantial prevalent and incident clinically diagnosed morbidity in both men and women. As p.C282Y associated iron overload is preventable and treatable if intervention starts early, these findings justify re-examination of options for expanded early case ascertainment and screening.

scholarly journals Histomolecular characterization of intracranial meningiomas developed in patients exposed to high-dose cyproterone acetate: an antiandrogen treatment

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Sylvain Portet ◽  
Rania Naoufal ◽  
Gaëlle Tachon ◽  
Adrien Simonneau ◽  
Anaïs Chalant ◽  
...  
Keyword(s):  
Skull Base ◽  
Cyproterone Acetate ◽  
Comparative Genomic ◽  
High Dose ◽  
Low Grade ◽  
Pharmacological Interaction ◽  
Pik3ca Mutations ◽  
History Of ◽  
Underlying Mechanisms ◽  
Copy Number Changes

Abstract Background Meningiomas are the most common primary intracranial tumors in adults. The relationship between meningiomas and exogenous sex hormones such as cyproterone acetate (CPA) is well documented, yet the underlying mechanisms remain unknown. Defining the histomolecular status of meningiomas developed on CPA would help us to better understand the oncogenesis of these tumors. Methods We identified 30 patients operated for a meningioma after long-term high-dose CPA therapy and with a history of CPA discontinuation before establishing the indication for surgical intervention. We used array-comparative genomic hybridization (to characterize copy number changes in those 30 meningiomas and subsequently performed next-generation sequencing with the National Institute of Cancer (INCa) solid tumor panel, which is a targeted panel of clinically actionable genes. We also examined grade, type, and clinical features. Results We identified AKT1 mutations or PIK3CA mutations in 33.3% of CPA meningiomas. AKT1 and PIK3CA mutations were mutually exclusive. Enrichment in oncogenic PIK3CA mutations in the CPA cohort was detected. CPA meningiomas showed chromosomal stability and were located mainly in the skull base. Ninety percent of CPA meningiomas were low-grade meningiomas and 63.4% were meningotheliomas. Half of our CPA cohort had microcystic components. Conclusion Our study shows that low-grade meningothelial meningiomas of the skull base are predominant in CPA meningiomas. We identified PIK3CA/AKT1 pathway as a hypothetical actor in onco-pharmacological interaction between meningiomas and CPA. This signaling pathway could be an interesting target for precision medicine trials in meningioma patients who have been subjected to CPA. Our results could invite the scientific community to review the current classification of meningiomas and to evolve toward more specific histomolecular classification.

scholarly journals Observational cohort study to investigate the unmet need and time waiting for referral for specialist opinion in adult asthma in England (UNTWIST asthma)

BMJ Open ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. e031740
Author(s):  
John D Blakey ◽  
Alicia Gayle ◽  
Mariel G Slater ◽  
Gareth H Jones ◽  
Michael Baldwin
Keyword(s):  
Cohort Study ◽  
Waiting Time ◽  
Unmet Need ◽  
Observational Cohort Study ◽  
Clinical Practice Research Datalink ◽  
High Dose ◽  
Specialist Referral ◽  
Number Of Patients ◽  
Observational Cohort

ObjectivesThis study aimed to estimate how many patients with asthma in England met the referral eligibility criteria using national asthma guidelines, identify what proportion were referred and determine the average waiting time to referral.DesignThis is an observational cohort study.Setting/Data sourcesRoutinely collected healthcare data were provided by Clinical Practice Research Datalink records and Hospital Episode Statistics records from January 2007 to December 2015.ParticipantsPatients with asthma aged 18–80 years participated in this study.Main outcome measuresEligibility for referral by the British Thoracic Society/Scottish Intercollegiate Guidelines Network (BTS/SIGN) 2016 guidelines, determined after a 3-month pharmacological therapy exposure assessment, was classed by either ‘high-dose therapies’, ‘continuous or frequent use of oral steroids’ or ‘incident eligibility’ during follow-up (continuous oral corticosteroids for more than 3 months, or ≥800 µg/day inhaled corticosteroids/long-acting β2-agonist (or three controllers) and ≥2 asthma attacks/year).ResultsFrom the final cohort (n=23293), 19837 patients were eligible for specialist referral during follow-up based on the BTS/SIGN guideline recommendations. Among eligible patients without any previously recorded referral, 4% were referred during follow-up, with a median waiting time of 880 days (IQR=1428 days) between eligibility and referral.ConclusionsA large number of patients with asthma were eligible for specialist referral, of which a small proportion were referred, and many experienced a long waiting time before referral. The results indicate a major unmet need in asthma referral, which is a potential source of preventable harm and are likely to have implications regarding how services are organised to address this unmet need.

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