Prophylaxis in hereditary angioedema: a United Kingdom Delphi consensus.

Hereditary angioedema (HAE) is a rare inherited disorder causing recurrent episodes of swelling that can be potentially life threatening. Treatment of HAE can be divided into on-demand treatment for swelling, and prophylaxis. The last UK consensus on HAE was in 2014 and since then, new medications for prophylaxis have been developed, with more drugs in the pipeline. International guidelines currently recommend the use of long-term prophylaxis (LTP) as the only way of achieving disease control and normalizing patient lives. Modern prophylactic medications are available in the UK, although access is restricted primarily by HAE attack frequency. To establish an updated view of UK clinicians and patients, a Delphi process was used to develop statements regarding LTP as well as other aspects of HAE management. There was consensus that UK access criteria for modern LTP agents based on numerical frequency of attacks alone are too simplistic and potentially disadvantage a cohort of patients who may benefit from LTP. Additionally, there was agreement that patients should be seen in expert centres, remote monitoring of patients is popular post-pandemic, and that the use of patient-reported outcome measures has the potential to improve patient care. Psychological health is an area in which patients may benefit, and recognition of this is important for future research and development.

Outcomes following SARS-CoV-2 infection in patients with primary and secondary immunodeficiency in the UK.

In March 2020, the United Kingdom Primary Immunodeficiency Network (UKPIN) established a registry of cases to collate the outcomes of individuals with PID and SID following SARS-CoV-2 infection and treatment. A total of 310 cases of SARS-CoV-2 infection in individuals with PID or SID have now been reported in the UK. The overall mortality within the cohort was 17.7% (n = 55/310). Individuals with CVID demonstrated an infection fatality rate (IFR) of 18.3% (n = 17/93), individuals with PID receiving IgRT had an IFR of 16.3% (n = 26/159) and individuals with SID, an IFR of 27.2% (n = 25/92). Individuals with PID and SID had higher inpatient mortality and died at a younger age than the general population. Increasing age, low pre-SARS-CoV-2 infection lymphocyte count and the presence of common co-morbidities increased the risk of mortality in PID. Access to specific COVID-19 treatments in this cohort was limited: only 22.9% (n = 33/144) of patients admitted to the hospital received dexamethasone, remdesivir, an anti-SARS-CoV-2 antibody-based therapeutic (e.g. REGN-COV2 or convalescent plasma) or tocilizumab as a monotherapy or in combination. Dexamethasone, remdesivir, and anti-SARS-CoV-2 antibody-based therapeutics appeared efficacious in PID and SID. Compared to the general population, individuals with PID or SID are at high risk of mortality following SARS-CoV-2 infection. Increasing age, low baseline lymphocyte count, and the presence of co-morbidities are additional risk factors for poor outcome in this cohort.

National Survey of United Kingdom Paediatric Allergy Services.

BACKGROUND: Comprehensive national assessments of paediatric allergy services are rarely undertaken, and have never been undertaken in the United Kingdom. A 2006 survey estimated national capacity at 30,000 adult or paediatric new allergy appointments per year and identified 58 hospital clinics offering a paediatric allergy service. OBJECTIVE: The UK Paediatric Allergy Services Survey was the first comprehensive assessment of UK paediatric allergy service provision. METHODS: All 450 UK hospitals responded to a survey. Paediatric allergy services are provided in 154 lead hospitals with 75 further linked hospitals. All 154 lead paediatric allergy services completed a detailed questionnaire between February 2019 and May 2020. RESULTS: The 154 paediatric allergy services self-define as secondary (126/154, 82%) or tertiary (28/154, 18%) level services. The annual capacity is 85,600 new and 111,400 follow-up appointments. Fifty-eight percent (85/146) of services offer ≤10 new appointments per week (no data provided from 8 services-2 no response, 6 unknown) and 50% (70/139) of the services undertaking challenges undertake ≤2 food or drug challenges per week (no data from 3 challenge services). Intramuscular adrenaline is rarely used during challenges-median annual frequency 0 in secondary services and 2 in tertiary services. Allergen-specific immunotherapy is offered in 39% (60/154) of services, with 71% (41/58) of these centres treating ≤10 patients per annum (no data from 2 immunotherapy services). The 12 largest services see 31% of all new paediatric allergy appointments, undertake 51% of new immunotherapy patient provision and 33% of food or drug challenges. Seventy percent (97/126) of secondary and all tertiary services are part of a regional paediatric allergy network. Only nine services offer immunotherapy for any food (3 for peanut), 10 drug desensitization and 18 insect venom immunotherapy. CONCLUSIONS: There has been a fourfold increase in paediatric allergy clinics and an approximately sevenfold increase in new patient appointment numbers in the United Kingdom over the past 15 years. Most services are small, with significant regional variation in availability of specific services such as allergen immunotherapy. Our findings emphasize the need for national standards, local networks and simulation training to ensure consistent and safe service provision.

Understanding parent preferences for NHS paediatric allergy services.

OBJECTIVES: To understand parent preferences for NHS paediatric allergy services. DESIGN: A stated preference study (discrete choice experiment). SETTING: West Midlands, UK. PARTICIPANTS: A sample of parents of children aged 16 years or younger recruited from the general population through a third party company approved by the University of Birmingham. INTERVENTION: An online questionnaire with 18 choice questions describing two hypothetical paediatric allergy specialist clinics described in terms of the clinician, information provision, additional facilities, waiting times and out of pocket expenses. Main outcome measures Preference and willingness to pay estimates for each of the specified attributes. RESULTS: Parents strongly preferred that their children be reviewed by consultants or specialist nurses formally trained in allergy compared with consultants with no formal allergy training [Willingness to pay (WTP) estimates for nurse specialist £150.9 (138.8-163.2), trained allergy consultants £218.7 (205.7-231.9), compared with consultants without formal training]. They were willing to wait longer to see trained practitioners. Parents also expressed a strong preference for improving online information regarding allergies [WTP for written information £18.4 (6.1-30.6) and £72.6 for improved online information (59.9-85.3), compared with verbal information]. Specialist clinics with additional dietician and eczema support were also preferred [WTP £29.9 (19.8-40.1), compared with no additional support]. CONCLUSIONS: Parents showed strong preference for formally trained practitioners in specialist allergy clinics. Access to improved online allergy information and additional facilities within allergy clinics were also preferred. These findings have implications for future commissioning of paediatric allergy services in the UK.

Parent experiences with paediatric allergy pathways in the West Midlands: A qualitative study.

BACKGROUND: The prevalence, severity and complexity of allergic diseases have been increasing steadily in the United Kingdom over the last few decades. Primary care physicians are often not adequately trained in allergy management while specialist services for allergy are scarce and heterogeneous. Services, therefore, have been unable to meet the rising demand. This is particularly true for paediatric allergy services in the United Kingdom. OBJECTIVE: To understand parent experiences with paediatric allergy pathways in the West Midlands (WM) region of the United Kingdom. METHODS: Parents of children aged between 0 and 16 years from the WM region were recruited opportunistically until thematic saturation was achieved. Eighteen semi-structured interviews were carried out and transcribed verbatim. Data were analysed on NVivo software using the framework method. Themes were identified from the transcripts as well as from existing literature. RESULTS: Parents highlighted numerous issues related to allergy services in the region including difficulties with being taken seriously by their physicians, problems with accessing health care and issues with information and the need for additional supportive care for allergies. CONCLUSIONS AND CLINICAL RELEVANCE: Primary care for children with allergies in the WM is disparate. Parents experience difficulties in accessing primary and secondary care services and also obtaining timely and appropriate information regarding their child's allergies. Most parents were happy to be reviewed by either specialist nurses or by consultants in the hospital. Improving accessibility and availability of reliable information as well as provision of additional services (such as psychologists and dietetics) were highlighted by parents as being important to allergy services in the region. These findings can help inform future planning and commissioning of allergy services.

Methods Used in Economic Evaluations of Tuberculin Skin Tests and Interferon Gamma Release Assays for the Screening of Latent Tuberculosis Infection: A Systematic Review.

BACKGROUND: Latent tuberculosis infection (LTBI) provides a constant pool of new active tuberculosis cases; a third of the earth's population is estimated to be infected with LTBI. OBJECTIVE: The objective of this systematic review was to assess the quality and summarize the available evidence from published economic evaluations reporting on the cost-effectiveness of tuberculin skin tests (TSTs) compared with interferon gamma release assays (IGRAs) for the screening of LTBI. METHODS: An extensive systematic review of the published literature was conducted. A two-step process was adopted to identify relevant articles: information was extracted into evidence tables and then analyzed. The quality of the publications was assessed using a 10-item checklist specific for economic evaluations. RESULTS: Twenty-eight studies were identified for inclusion in this review. Most of the studies found IGRAs to be more cost-effective than TSTs; however, the conclusions from the studies varied significantly. Most studies scored highly on the checklist although only one fulfilled all the stipulated criteria. A wide variety of methodological approaches were documented; identified differences included the type of economic evaluation and model, time horizon, perspective, and outcomes measures. CONCLUSIONS: The lack of consistent methods across studies makes it difficult to draw any firm conclusions about the most cost-effective option between TSTs and IGRAs. This problem can be solved by improving the quality of economic evaluation studies in the field of LTBI screening, through adherence to quality checklists.

Hereditary Angioedema patient experiences of medication use and emergency care.

BACKGROUND: Hereditary angioedema (HAE) is a rare inherited illness characterised by recurrent swellings. Four percent of HAE attacks are life threatening throat swellings requiring urgent medical intervention. The aim of this study was to gain an in depth understanding of patient experiences of use of treatment and emergency care. METHODS: 65 participants completed an online survey including open ended questions about their experiences and/or completed an in-depth interview. Interview participants were asked to share and talk about up to five images that they felt best represented their life experiences with HAE. Data were analysed using reflexive thematic analysis. RESULTS: Treatment experiences highlighted the life changing nature of new treatments and benefits for quality of life, but also illustrated common barriers to treatment administration. Emergency care experiences illustrated how throat attacks and fear of their future occurrence could be traumatic. DISCUSSION: Findings indicate that HAE patients need psychological support to process fears and negative experiences. In addition, psychological barriers to treatment administration must be addressed to ensure treatment is used effectively. Education for emergency practitioners is also needed to improve emergency treatment and reduce the psychological burden of delayed emergency care.

Provision of Food Allergy Care in the United Kingdom and United States: Current Issues and Future Directions.

Food allergy (FA) is a growing issue worldwide. The United Kingdom and United States are high-income, industrialized countries with reported increases in FA prevalence over the past few decades. This review compares delivery of FA care in the United Kingdom and United States and each country's response to the heightened demand and disparities for FA services. In the United Kingdom, allergy specialists are scarce and general practitioners (GPs) provide most allergy care. Whereas the United States has more allergists per capita than the United Kingdom, there is still a shortage of allergy services owing to the greater reliance on specialist care for FA in America and wide geographic variation in access to allergist services. Currently, generalists in these countries lack the specialty training and equipment to diagnose and manage FA optimally. Moving forward, the United Kingdom aims to enhance training for GPs so they may provide better quality frontline allergy care. In addition, the United Kingdom is implementing a new tier of semi-specialized GPs and increasing cross-center collaboration through clinical networks. The United Kingdom and United States aim to increase the number of FA specialists, which is critical at a time of rapidly expanding management options for allergic and immunologic diseases requiring clinical expertise and shared decision-making to select appropriate therapies. While these countries aim to grow their supply of quality FA services actively, further efforts to build clinical networks and perhaps recruit international medical graduates and expand telehealth services are necessary to reduce disparities in access to care. For the United Kingdom in particular, increasing quality services will require additional support from the leadership of the centralized National Health Service, which remains challenging.

A multicenter chart review of patient characteristics, treatment, and outcomes in hereditary angioedema: unmet need for more effective long-term prophylaxis.

BACKGROUND: Hereditary angioedema (HAE) is a rare disease characterized by unpredictable, recurring subcutaneous or submucosal swelling. Without effective therapy, HAE can negatively impact patients' quality of life. Management of HAE includes on-demand treatment of attacks and short- and long-term prophylaxis (LTP) to prevent attacks. Newer therapies may be more tolerable and effective in managing HAE; however, therapies such as androgens are still widely used in some countries owing to their relative ease of access and adequate disease control for some patients. This study evaluated the characteristics, treatment patterns, clinical outcomes, and healthcare resource utilization of a multinational cohort of patients with HAE, with a focus on understanding reasons for recommending or discontinuing available therapies. METHODS: A retrospective chart review was conducted at 12 centers in six countries and included data from patients with HAE type 1 or 2 who were ≥ 12 years of age at their first clinical visit. The relationship between LTP use and attack rates was evaluated using a multivariable Poisson regression model. Data were collected between March 2018 and July 2019. RESULTS: Data from 225 patients were collected (62.7% female, 86.2% White, 90.2% type 1); 64.4% of patients had their first HAE-related visit to the center prior to or during 2014. Treatment patterns varied between countries. Overall, 85.8% of patients were prescribed on-demand treatment and 53.8% were prescribed LTP, most commonly the androgen danazol (53.7% of patients who used LTP). Plasma-derived C1 inhibitor (Cinryze®) was used by 29.8% of patients for LTP. Patients who received LTP had a significantly lower rate of HAE attacks than patients who did not receive any LTP (incidence rate ratio (95% confidence interval) 0.90 (0.84-0.96)). Androgens were the most commonly discontinued therapy (51.3%), with low tolerability cited as the most frequent reason for discontinuation (50.0%). CONCLUSIONS: Overall, findings from this study support the use of LTP in the prevention of HAE attacks; a lower rate of attacks was observed with LTP compared with no LTP. However, the type of LTP used varied between countries, with tolerability and accessibility to specific treatments playing important roles in management decision-making.

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial.

BACKGROUND: Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. METHODS: In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. FINDINGS: Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57-0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. INTERPRETATION: Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19. FUNDING: Sponsored by the University of Dundee and supported through an Investigator Initiated Research award from Insmed, Bridgewater, NJ; STOP-COVID19 trial.

Atraumatic splenic rupture due to covid-19 infection.

BACKGROUND: Covid-19 is a novel disease caused by the severe acute respiratory coronavirus (SARS-CoV2). We discuss a gentleman who presented with an atraumatic rupture of the spleen secondary to this infection. BRIEF SUMMARY OF PRESENTATION: A 57-year-old service engineer was brought into the emergency department after having collapsed at home. RT-PCR was positive for covid-19 infection. CT scan showed evidence of haemoperitoneum and splenic rupture. He underwent splenic artery embolisation and required ventilatory and circulatory support on ITU. He made a full recovery and was discharged home 3 weeks later. DISCUSSION AND RELEVANCE: Atraumatic splenic rupture is a rare, potentially fatal condition which has been described as a complication of haematological and non-haematological malignancies, inflammatory disorders and infections. There is emerging evidence to suggest that covid-19 has a direct destructive impact on the spleen, causing lymphoid follicle attrition and nodular atrophy in addition to microvascular thrombosis and necrosis. This is the first report of atraumatic splenic rupture secondary to covid-19 infection, to our knowledge.

Cycle threshold values are inversely associated with poorer outcomes in hospitalized patients with COVID-19: a prospective, observational cohort study conducted at a UK tertiary hospital.

This single-centre observational study demonstrated that lower cycle threshold (Ct) values (indicating higher viral loads) on admission to hospital were associated with poorer outcomes in unvaccinated, hospitalized patients with coronavirus disease 2019 (COVID-19). Demographic and outcome data were collected prospectively for all adult patients who tested positive for severe acute respiratory syndrome coronavirus-2 on admission to the University Hospitals North Midlands NHS Trust between 1 February and 1 July 2020. Nasopharyngeal swab samples were obtained, and a valid Ct value was determined for all patients using the Viasure reverse transcription polymerase chain reaction assay, validated by Public Health England, on admission to hospital. Multi-variable logistic regression results based on data from 618 individuals demonstrated a significant inverse relationship between the odds of death and Ct values (adjusted odds ratio 0.95, 95% confidence interval 0.92-0.98, P=0.001). The association remained highly significant after adjusting for known clinical risk factors for COVID-19.

Clinical, immunological, and epidemiological importance of antituberculosis T cell responses in HIV-infected Africans.

BACKGROUND: Human immunodeficiency virus (HIV)-associated tuberculosis is a major cause of mortality in Africa. The assay of T cell interferon- gamma released in response to antigens of greater specificity than purified protein derivative is a useful improvement over the Mantoux tuberculin skin test, but few studies have evaluated interferon-gamma secretion in HIV-infected individuals. METHODS: Mycobacterium tuberculosis antigen-specific interferon-gamma secretion was assessed by whole blood assay and enzyme-linked immunospot, which were compared with the Mantoux tuberculin skin test in HIV-infected and HIV-uninfected individuals without active tuberculosis and HIV-infected patients with pulmonary tuberculosis in Khayelitsha, South Africa. RESULTS: The skin test and whole blood assay responses to purified protein derivative in HIV-positive subjects were decreased, compared with responses in HIV-negative subjects (P < .001). By contrast, the responses to M. tuberculosis antigens (early secreted antigenic target 6, culture filtrate protein 10, TB10.3, and alpha-crystallin 2) were less affected, indicating a high prevalence of latent tuberculosis (approximately 80%) in both HIV-negative and HIV-positive subject groups. Whole blood assay responses did not differ between the HIV-positive subjects without tuberculosis and HIV-positive subjects with tuberculosis, but the enzyme-linked immunospot method response to early secreted antigenic target 6 and culture filtrate protein 10 was higher in the group of HIV-infected subjects with tuberculosis (P < or = .04), although this group had lower CD4+ cell counts. A ratio of the combined enzyme-linked immunospot method response divided by the CD4+ cell count of > 1.0 had 88% sensitivity and 80% specificity for active pulmonary tuberculosis in HIV-infected individuals. CONCLUSIONS: Interferon-gamma release appears to be less impaired than skin testing by HIV coinfection. The novel potential to relate the enzyme-linked immunospot method and CD4+ cell count to assist diagnosis of active tuberculosis in patients with HIV infection is important and deserves further evaluation.

Systematic review of pathways for the delivery of allergy services.

OBJECTIVES: The incidence and prevalence of allergies worldwide has been increasing and allergy services globally are unable to keep up with this increase in demand. This systematic review aims to understand the delivery of allergy services worldwide, challenges faced and future directions for service delivery. METHODS: A systematic scoping review of Ovid, EMBASE, HMIC, CINAHL, Cochrane, DARE, NHS EED and INAHTA databases was carried out using predefined inclusion and exclusion criteria. Data on the geographical region, study design and treatment pathways described were collected, and the findings were narratively reported. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. RESULTS: 205 publications were screened and 27 selected for review. Only 3 were prospective studies, and none included a control group. There were no eligible publications identified from North America, Africa, Australia and most parts of Asia. Most publications relate to allergy services in the UK. In general, allergy services globally appear not to have kept pace with increasing demand. The review suggests that primary care practitioners are not being adequately trained in allergy and that there is a paucity of appropriately trained specialists, especially in paediatric allergy. There appear to be considerable barriers to service improvement, including lack of political will and reluctance to allocate funds from local budgets. CONCLUSIONS: Demand for allergy services appears to have significantly outpaced supply. Primary and secondary care pathways in allergy seem inadequate leading to poor referral practices, delays in patient management and consequently poor outcomes. Improvement of services requires strong public and political engagement. There is a need for well-planned, prospective studies in this area and a few are currently underway. There is no evidence to suggest that any given pathway of service provision is better than another although data from a few long-term, prospective studies look very promising.

Prescription rates of adrenaline auto-injectors for children in UK general practice: a retrospective cohort study.

BACKGROUND: Adrenaline auto-injectors (AAI) should be provided to individuals considered to be at high risk of anaphylaxis. There is some evidence that the rate of AAI prescription is increasing, but the true extent has not been previously quantified. AIM: To estimate the trends in annual GP-issued prescriptions for AAI among UK children between 2000 and 2012. DESIGN AND SETTING: Retrospective cohort study using data from primary care practices that contributed to The Health Improvement Network (THIN) database. METHOD: Children and young people aged between 0-17 years of age with a prescription for AAIs were identified, and annual AAI device prescription rates were estimated using Stata (version 12). RESULTS: A total of 1.06 million UK children were identified, providing 5.1 million person years of follow-up data. Overall, 23 837 children were deemed high risk by their GPs, and were prescribed 98 737 AAI devices. This equates to 4.67 children (95% confidence interval [CI] = 4.66 to 4.69), and 19.4 (95% CI = 19.2 to 19.5) devices per 1000 person years. Between 2000 and 2012, there has been a 355% increase in the number of children prescribed devices, and a 506% increase in the total number of AAI devices prescribed per 1000 person years in the UK. The number of devices issued per high-risk child during this period has also increased by 33%. CONCLUSION: The number of children being prescribed AAI devices and the number of devices being prescribed in UK primary care between 2000 and 2012 has significantly increased. A discussion to promote rational prescribing of AAIs in the NHS is needed.

Evaluation of AllergiSense Smartphone Tools for Adrenaline Injection Training.

Anaphylaxis is an increasingly prevalent life-threatening allergic condition that requires people with anaphylaxis and their caregivers to be trained in the avoidance of allergen triggers and in the administration of adrenaline autoinjectors. The prompt and correct administration of autoinjectors in the event of an anaphylactic reaction is a significant challenge in the management of anaphylaxis. Unfortunately, many people do not know how to use autoinjectors and either fail to use them or fail to use them correctly. This is due in part to deficiencies in training and also to the lack of a system encouraging continuous practice with feedback. Assistive smartphone healthcare technologies have demonstrated potential to support the management of chronic conditions such as diabetes and cardiovascular disease, but there have been deficiencies in their evaluation and there has been a lack of application to anaphylaxis. This paper describes AllergiSense, a smartphone app and sensing system for anaphylaxis management, and presents the results of a randomized, controlled, prepost evaluation of AllergiSense injection training and feedback tools with healthy participants. Participants whose training was supplemented with AllergiSense injection feedback achieved significantly better practiced injections with 90.5% performing correct injections compared to only 28.6% in the paper-only control group. In addition, the results provide insights into possible self-efficacy failings in traditional training and the benefits of embedding self-efficacy theory into the technology design process.

Outpatient versus inpatient uterine polyp treatment for abnormal uterine bleeding: randomised controlled non-inferiority study.

OBJECTIVE: To compare the effectiveness and acceptability of outpatient polypectomy with inpatient polypectomy. DESIGN: Pragmatic multicentre randomised controlled non-inferiority study. SETTING: Outpatient hysteroscopy clinics in 31 UK National Health Service hospitals. PARTICIPANTS: 507 women who attended as outpatients for diagnostic hysteroscopy because of abnormal uterine bleeding and were found to have uterine polyps. INTERVENTIONS: Participants were randomly assigned to either outpatient uterine polypectomy under local anaesthetic or inpatient uterine polypectomy under general anaesthesia. Data were collected on women's self reported bleeding symptoms at baseline and at 6, 12, and 24 months. Data were also collected on pain and acceptability of the procedure at the time of polypectomy. MAIN OUTCOME MEASURES: The primary outcome was successful treatment, determined by the women's assessment of bleeding at six months, with a prespecified non-inferiority margin of 25%. Secondary outcomes included generic (EQ-5D) and disease specific (menorrhagia multi-attribute scale) quality of life, and feasibility and acceptability of the procedure. RESULTS: 73% (166/228) of women in the outpatient group and 80% (168/211) in the inpatient group reported successful treatment at six months (intention to treat relative risk 0.91, 95% confidence interval 0.82 to 1.02; per protocol relative risk 0.92, 0.82 to 1.02). Failure to remove polyps was higher (19% v 7%; relative risk 2.5, 1.5 to 4.1) and acceptability of the procedure was lower (83% v 92%; 0.90, 0.84 to 0.97) in the outpatient group Quality of life did not differ significantly between the groups. Four uterine perforations, one of which necessitated bowel resection, all occurred in the inpatient group. CONCLUSIONS: Outpatient polypectomy was non-inferior to inpatient polypectomy. Failure to remove a uterine polyp was, however, more likely with outpatient polypectomy and acceptability of the procedure was slightly lower. TRIAL REGISTRATION: International Clinical Trials Registry 65868569.

A randomised controlled trial of Outpatient versus inpatient Polyp Treatment (OPT) for abnormal uterine bleeding.

BACKGROUND: Uterine polyps cause abnormal bleeding in women and conventional practice is to remove them in hospital under general anaesthetic. Advances in technology make it possible to perform polypectomy in an outpatient setting, yet evidence of effectiveness is limited. OBJECTIVES: To test the hypothesis that in women with abnormal uterine bleeding (AUB) associated with benign uterine polyp(s), outpatient polyp treatment achieved as good, or no more than 25% worse, alleviation of bleeding symptoms at 6 months compared with standard inpatient treatment. The hypothesis that response to uterine polyp treatment differed according to the pattern of AUB, menopausal status and longer-term follow-up was tested. The cost-effectiveness and acceptability of outpatient polypectomy was examined. DESIGN: A multicentre, non-inferiority, randomised controlled trial, incorporating a cost-effectiveness analysis and supplemented by a parallel patient preference study. Patient acceptability was evaluated by interview in a qualitative study. SETTING: Outpatient hysteroscopy clinics and inpatient gynaecology departments within UK NHS hospitals. PARTICIPANTS: Women with AUB - defined as heavy menstrual bleeding (formerly known as menorrhagia) (HMB), intermenstrual bleeding or postmenopausal bleeding - and hysteroscopically diagnosed uterine polyps. INTERVENTIONS: We randomly assigned 507 women, using a minimisation algorithm, to outpatient polypectomy compared with conventional inpatient polypectomy as a day case in hospital under general anaesthesia. MAIN OUTCOME MEASURES: The primary outcome was successful treatment at 6 months, determined by the woman's assessment of her bleeding. Secondary outcomes included quality of life, procedure feasibility, acceptability and cost per quality-adjusted life-year (QALY) gained. RESULTS: At 6 months, 73% (166/228) of women who underwent outpatient polypectomy were successfully treated compared with 80% (168/211) following inpatient polypectomy [relative risk (RR) 0.91, 95% confidence interval (CI) 0.82 to 1.02]. The lower end of the CIs showed that outpatient polypectomy was at most 18% worse, in relative terms, than inpatient treatment, within the 25% margin of non-inferiority set at the outset of the study. By 1 and 2 years the corresponding proportions were similar producing RRs close to unity. There was no evidence that the treatment effect differed according to any of the predefined subgroups when treatments by variable interaction parameters were examined. Failure to completely remove polyps was higher (19% vs. 7%; RR 2.5, 95% CI 1.5 to 4.1) with outpatient polypectomy. Procedure acceptability was reduced with outpatient compared with inpatient polyp treatment (83% vs. 92%; RR 0.90, 95% CI 0.84 to 0.97). There were no significant differences in quality of life. The incremental cost-effectiveness ratios at 6 and 12 months for inpatient treatment were £1,099,167 and £668,800 per additional QALY, respectively. CONCLUSIONS: When treating women with AUB associated with uterine polyps, outpatient polypectomy was non-inferior to inpatient polypectomy at 6 and 12 months, and relatively cost-effective. However, patients need to be aware that failure to remove a polyp is more likely with outpatient polypectomy and procedure acceptability lower. TRIAL REGISTRATION: Current Controlled Trials ISRCTN 65868569. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 61. See the NIHR Journals Library website for further project information.

Icatibant in the treatment of Angiotensin-converting enzyme inhibitor-induced angioedema.

We describe the case of a 75-year-old woman who presented with massive tongue and lip swelling secondary to angiotensin-converting enzyme inhibitor-induced angioedema. An awake fibre-optic intubation was performed because of impending airway obstruction. As there was no improvement in symptoms after 72 hours, the selective bradykinin B2 receptor antagonist icatibant (Firazyr) was administered and the patient's trachea was successfully extubated 36 hours later. To our knowledge this is the first documented case of icatibant being used for the treatment of angiotensin-converting enzyme inhibitor-induced angioedema in the United Kingdom and represents a novel therapeutic option in its management.