Lavanya Diwakar

Diagnosis and management of hymenoptera venom allergy: British Society for Allergy and Clinical Immunology (BSACI) guidelines

This guidance for the management of patients with hymenoptera venom allergy has been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). The guideline is based on evidence as well as on expert opinion and is for use by both adult physicians and pediatricians practising allergy. During the development of these guidelines, all BSACI members were included in the consultation process using a web‐based system. Their comments and suggestions were carefully considered by the SOCC. Where evidence was lacking, consensus was reached by the experts on the committee. Included in this guideline are epidemiology, risk factors, clinical features, diagnostic tests, natural history of hymenoptera venom allergy and guidance on undertaking venom immunotherapy (VIT). There are also separate sections on children, elevated baseline tryptase and mastocytosis and mechanisms underlying VIT. Finally, we have made recommendations for potential areas of future research.

Does rituximab aggravate pre-existing hypogammaglobulinaemia?

Rituximab, an anti-CD20 chimeric antibody, is the first monoclonal agent to be used in the therapy of cancer. It has been hailed as one of the most important therapeutic developments of the decade. While transient peripheral B cell depletion is common after rituximab therapy, immunoglobulin levels are generally not affected. This is because CD20 is expressed on pre-B and mature B lymphocytes but not on stem cells or plasma cells. Two adult patients with pre-existing primary antibody deficiency who presented with recurrent infections immediately following rituximab use for the treatment of refractory idiopathic thrombocytopenic purpura (ITP) are described. Both were previously treated with various immunosuppressive agents without any notable infective problems. However, a few weeks after treatment with rituximab, these patients presented with clinically significant immunodeficiency requiring intravenous immunoglobulin replacement therapy. This striking temporal relationship between rituximab administration and onset of infections suggests that rituximab has accelerated the presentation of immune deficiency in these patients. Increased vigilance around the use of newer immunomodulatory agents such as rituximab is recommended.

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.

Practice of venom immunotherapy in the United Kingdom: a national audit and review of literature.

Background Venom immunotherapy (VIT) is the only effective treatment for prevention of serious allergic reactions to bee and wasp stings in sensitized individuals. However, controversies exist relating to diagnosis, indications for treatment and treatment schedules. We audited current practice of VIT in the United Kingdom to evaluate adherence to international guidelines.

The Percutaneous shunting in Lower Urinary Tract Obstruction (PLUTO) study and randomised controlled trial: evaluation of the effectiveness, cost-effectiveness and acceptability of percutaneous vesicoamniotic shunting for lower urinary tract obstruction.

BACKGROUND Congenital lower urinary tract obstruction (LUTO) is a disease associated with high perinatal mortality and childhood morbidity. Fetal vesicoamniotic shunting (VAS) bypasses the obstruction with the potential to improve outcome. OBJECTIVE To determine the effectiveness, cost-effectiveness and patient acceptability of VAS for fetal LUTO. DESIGN A multicentre, randomised controlled trial incorporating a prospective registry, decision-analytic health economic model and preplanned Bayesian analysis using elicited opinions. Patient acceptability was evaluated by interview in a qualitative study. SETTING Fetal medicine departments in the UK, Ireland and the Netherlands. PARTICIPANTS Pregnant women with a male singleton fetus with LUTO. INTERVENTIONS In utero percutaneous VAS compared with conservative care. MAIN OUTCOME MEASURES The primary outcome was survival to 28 days. Secondary outcome measures were survival and renal function at 1 year of age, cost of care and cost per additional life-year and per disability-free survival at the end of 1 year. RESULTS The trial stopped early with 31 women randomised because of difficulties in recruitment. Of those randomised to VAS and conservative management, 3/16 (19%) and 2/15 (13%), respectively, did not receive their allocated intervention. Based on intention-to-treat analysis, survival at 28 days was higher if allocated VAS (50%) than conservative management (27%) [relative risk (RR) 1.88, 95% confidence interval (CI) 0.71 to 4.96, p = 0.27]. At 12 months survival was 44% in the VAS arm and 20% in the conservative arm (RR 2.19, 95% CI 0.69 to 6.94, p = 0.25). Neither difference was statistically significant. Of survivors at 1 year, two in the VAS arm had no evidence of renal impairment and four in the VAS arm and two in the conservative arm required medical management. One baby in the conservative arm had end-stage renal failure at 1 year. VAS was more expensive because of additional surgery and intensive care. VAS cost £15,500 per survivor at 1 year and £43,900 per disability-free year. Elicited expert opinions showed uncertainty in the effect of VAS at 28 days. In a Bayesian analysis combining elicited opinion with the results, uncertainty of the benefit of VAS remained (RR 1.31, 95% credible interval 0.84 to 2.18). The acceptability study identified visualisation of the fetus during ultrasound scanning, perceiving a personal benefit, and altruism as positive influences on recruitment. Fear of the VAS procedure and the perceived severity of LUTO influenced non-participation. The need for more detailed information about the condition and its implications during pregnancy and following delivery was a further important finding of this research. Recruitment was hampered by logistical and regulatory difficulties, a lower incidence of LUTO and lower antenatal diagnosis rate [estimated to be 3.34 (95% CI 2.95 to 3.72) per 10,000 total births and 47%, respectively, in an associated epidemiological study] and high termination of pregnancy rates. In the registry women also demonstrated a clear preference for conservative management. CONCLUSIONS Survival to 28 days and 1 year appears to be higher with VAS than with conservative management, but it is not possible to prove benefit beyond reasonable doubt. Notably, prognosis in both arms for survival and renal function is poor. VAS was substantially more costly and unlikely to be regarded as cost-effective based on the 1-year data. Parents should be counselled about the risks of pregnancy loss with or without VAS insertion. The National Institute for Health and Care Excellence interventional procedures guidance (IPG 202) should be updated to reflect this new evidence. Babies in the PLUTO trial should be followed up long term for the different outcomes. TRIAL REGISTRATION ISRCTN53328556. FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 17, No. 59. See the NIHR Journals Library website for further project information.

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 womans 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.

Retrospective case series analysis of penicillin allergy testing in a UK specialist regional allergy clinic

Introduction Penicillin allergy is the most common drug allergy. Skin testing for the major (PPL) and minor determinants (MDMs) of penicillin offers increased sensitivity and specificity over in vitro testing alone. Following a worldwide absence of reagents, a new kit was licensed in the UK in 2008 (Diater, Spain) and this report evaluates its use in a UK specialist allergy clinic. Methods Prospective data on 50 consecutive patients tested with the new reagents were collected. The departmental protocol is adapted from the 2003 EAACI position paper. Results 14% (7/50) and 12% (6/50) of patients were diagnosed with immediate and non-immediate reactions respectively. The negative predictive value of the PPL and MDM reagents at the neat concentration for an immediate reaction was 93% (true negatives 37, false negatives 3). Two patients experienced systemic reactions to DPT in the absence of demonstrable specific IgE. None of the patients were diagnosed using skin prick testing alone or at lower concentrations of IDT. Five patients were diagnosed at the IDT stage and two at the DPT stage in the absence of demonstrable specific IgE. Six patients were diagnosed with non-immediate reactions, two on IDT alone and four following IDT and DPT. Conclusion The new PPL and MDM determinants offer enhanced sensitivity when evaluating β-lactam hypersensitivity; however, there are limitations to the current testing regimens. The UK would benefit from local guidelines, which incorporate the new reagents and acknowledge the high amoxicillin prescription rate and the relatively lower specialist-to-patient ratio in this country.

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.

An economic evaluation of outpatient versus inpatient polyp treatment for abnormal uterine bleeding

To undertake a cost‐effectiveness analysis of outpatient uterine polypectomy compared with standard inpatient treatment under general anaesthesia.

Evaluation of the Cost Effectiveness of Vesico-Amniotic Shunting in the Management of Congenital Lower Urinary Tract Obstruction (Based on Data from the PLUTO Trial)

Objective To determine the cost-effectiveness of in-utero percutaneous Vesico Amniotic Shunt (VAS) in the management of fetal lower urinary tract obstruction (LUTO) Design Model based economic analysis using data from the randomised controlled arm of the PLUTO (percutaneous vesico-amniotic shunting for lower urinary tract obstruction) trial. Setting Fetal medicine departments in United Kingdom, Ireland and Netherlands. Population or Sample Pregnant women with a male, singleton fetus with LUTO. Methods Costs and outcomes were prospectively collected in the trial; three separate base case analyses were performed using the intention to treat (ITT), per protocol and uniform prior methods. Deterministic and probabilistic sensitivity analyses were performed to explore data uncertainty. Main Outcome Measures Survival at 28 days, 1 year and disease free survival at 1 year. Results VAS was more expensive but appeared to result in higher rates of survival compared with conservative management in patients with LUTO. Using ITT analysis the incremental cost effectiveness ratios based on outcomes of survival at 28 days, 1 year, or 1 morbidity-free year on the VAS arm were £15,506, £15,545, and £43,932, respectively. Conclusions VAS is a more expensive option compared to the conservative approach in the management of individuals with LUTO. Data from the RCT suggest that VAS improves neonatal survival but does not result in significant improvements in morbidity. Our analysis concludes that VAS is not likely to be cost effective in the management of these patients given the NICE (National Institute of Health and Clinical Excellence) cost threshold of £20,000 per QALY.