Primary ciliary dyskinesia: An update on contemporary diagnosis.

KEY POINTS: Primary ciliary dyskinesia (PCD) is a complex diagnosis without a universal diagnostic test Clinicians must have some skepticism of historic diagnoses of PCD Clinicians should consider a diagnosis of PCD in patients with recalcitrant disease.

Disseminated tuberculosis, CMV viraemia & haemophagocytic-lymphohistiocystosis syndrome in an adult patient with anti- IFNγ autoantibodies - case report and brief review.

We report a case of an adult female with disseminated tuberculosis, cytomegalovirus viraemia and haemophagocytic-lymphohistiocystosis syndrome associated with neutralizing anti- interferon gamma (IFNγ) autoantibodies demonstrated by absent IFNγ stimulated STAT1 phosphorylation in the presence of patient sera. A brief review of immunodeficiency caused by anti-IFNγ autoantibodies is also described.

Noninvasive Monitoring of Mantle Cell Lymphoma by Immunoglobulin Gene Next-Generation Sequencing in a Phase 2 Study of Sequential Chemoradioimmunotherapy Followed by Autologous Stem-Cell Rescue.

BACKGROUND: Minimal residual disease (MRD) monitoring has been used to identify early molecular relapse and predict clinical relapse in mantle cell lymphoma (MCL). Few published data exist in MCL on the performance of next-generation sequencing-based assay of immunoglobulin gene rearrangements for MRD assessment. PATIENTS AND METHODS: In a prospective clinical trial (NCT01484093) with intensive induction chemotherapy and autologous stem-cell transplantation, posttreatment peripheral blood samples were collected from 16 MCL patients and analyzed with an earlier version of the Adaptive Biotechnologies MRD assay. RESULTS: Of the 7 patients whose disease remained in remission, the MRD test remained negative in 5 (71%). Of the 9 patients who experienced relapse, the MRD test was positive at least 3 months before relapse in 6 patients (67%) and positive at the time of relapse in 1 patient (11%). All patients with at least 2 positive MRD tests experienced relapse. CONCLUSION: The next-generation sequencing-based MRD assay identified early molecular relapse, and we observed more sensitivity in the cellular (circulating leukocytes) versus acellular (plasma cell-free DNA) compartment. This observation may be due to availability of tumor target or a limitation of the assay.

Simultaneous cochlear implantation and removal of acoustic neuroma: implications for hearing.

OBJECTIVE: To present our data evaluating the feasibility of simultaneous cochlear implantation with resection of acoustic neuroma. METHODS: This paper describes a case series of eight adult patients with a radiologically suspected acoustic neuroma, treated at a tertiary referral centre in Newcastle, Australia, between 2012 and 2015. Patients underwent cochlear implantation concurrently with removal of an acoustic neuroma. The approach was translabyrinthine, with facial nerve monitoring and electrically evoked auditory brainstem response testing. Standard post-implant rehabilitation was employed, with three and six months' follow-up data collected. The main outcome measures were: hearing, subjective benefit of implant, operative complications and tumour recurrence. RESULTS: Eight patients underwent simultaneous cochlear implantation with resection of acoustic neuroma over a 3-year period, and had 25-63 months' follow up. There were no major complications. All patients except one gained usable hearing and were daily implant users. CONCLUSION: Simultaneous cochlear implantation with resection of acoustic neuroma has been shown to be a safe treatment option, which will be applicable in a wide range of clinical scenarios as the indications for cochlear implantation continue to expand.

Patient-reported outcomes after surgery or radiotherapy for localised prostate cancer: a retrospective study.

INTRODUCTION: To compare the intermediate-term outcomes and patient-reported outcomes of robot-assisted laparoscopic prostatectomy (RALP) and radical external beam radiotherapy (RT) in Chinese patients with localised prostate cancer. METHODS: This was a retrospective study of patients with localised prostate cancer diagnosed between 2010 and 2011 and treated with either RALP or RT. Baseline patient and disease characteristics, post-treatment complications, and latest disease status were retrospectively collected from hospital records. For assessment of patient-reported outcomes, the Chinese version of the Expanded Prostate Cancer Index Composite (EPIC) questionnaire was completed by the patients. RESULTS: Ninety three patients aged 58 to 84 years were recruited. Thirty patients were treated by RALP (32.3%), whereas 63 received RT (67.7%). The RALP group had significantly lower baseline prostate-specific antigen levels than the RT group (P<0.001). More patients who underwent RALP reported urinary incontinence (70.0% vs 3.2%, P<0.001), whereas more patients who underwent RT reported other voiding symptoms (87.3% vs 50.0%, P<0.001) and perirectal bleeding (36.5% vs 0%, P<0.001) during follow-up. Of the 85 patients who were still alive at the time of the study, 52 (61.2%) returned completed questionnaires. Patients who underwent RALP had poorer median (interquartile range) EPIC urinary summary scores than patients who underwent RT [81.5 (18.3) vs 88.9 (17.9), P=0.016]. Urinary function [75.9 (20.4) vs 93.6 (16.2), P<0.001] and incontinence [60.5 (31.8) vs 91.8 (14.5), P<0.001] were also significantly worse in the RALP group. The bowel and sexual domain scores were similar between the two groups. CONCLUSIONS: We found that RALP and RT were associated with different patterns of complications and patient-reported outcomes. Urinary incontinence was much more prevalent in the patients treated surgically. This may significantly affect patients' quality of life.

Hepatic late adverse effects after antineoplastic treatment for childhood cancer.

BACKGROUND: Survival rates have greatly improved as a result of more effective treatments for childhood cancer. Unfortunately, the improved prognosis has been accompanied by the occurrence of late, treatment-related complications. Liver complications are common during and soon after treatment for childhood cancer. However, among long-term childhood cancer survivors, the risk of hepatic late adverse effects is largely unknown. To make informed decisions about future cancer treatment and follow-up policies, it is important to know the risk of, and associated risk factors for, hepatic late adverse effects. This review is an update of a previously published Cochrane review. OBJECTIVES: To evaluate all the existing evidence on the association between antineoplastic treatment (that is, chemotherapy, radiotherapy involving the liver, surgery involving the liver and BMT) for childhood cancer and hepatic late adverse effects. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2018, Issue 1), MEDLINE (1966 to January 2018) and Embase (1980 to January 2018). In addition, we searched reference lists of relevant articles and scanned the conference proceedings of the International Society of Paediatric Oncology (SIOP) (from 2005 to 2017) and American Society of Pediatric Hematology/Oncology (ASPHO) (from 2013 to 2018) electronically. SELECTION CRITERIA: All studies, except case reports, case series, and studies including fewer than 10 patients that examined the association between antineoplastic treatment for childhood cancer (aged 18 years or less at diagnosis) and hepatic late adverse effects (one year or more after the end of treatment). DATA COLLECTION AND ANALYSIS: Two review authors independently performed the study selection and 'risk of bias' assessment. The 'risk of bias' assessment was based on earlier checklists for observational studies. For the original version of the review, two review authors independently performed data extraction. For the update of the review, the data extraction was performed by one reviewer and checked by another reviewer. MAIN RESULTS: Thirteen new studies were identified for the update of this review. In total, we included 33 cohort studies including 7876 participants investigating hepatic late adverse effects after antineoplastic treatment (especially chemotherapy and radiotherapy) for different types of childhood cancer, both haematological and solid malignancies. All studies had methodological limitations. The prevalence of hepatic late adverse effects, all defined in a biochemical way, varied widely, between 0% and 84.2%. Selecting studies where the outcome of hepatic late adverse effects was well-defined as alanine aminotransferase (ALT) above the upper limit of normal, indicating cellular liver injury, resulted in eight studies. In this subgroup, the prevalence of hepatic late adverse effects ranged from 5.8% to 52.8%, with median follow-up durations varying from three to 23 years since cancer diagnosis in studies that reported the median follow-up duration. A more stringent selection process using the outcome definition of ALT as above twice the upper limit of normal, resulted in five studies, with a prevalence ranging from 0.9% to 44.8%. One study investigated biliary tract injury, defined as gamma-glutamyltransferase (γGT) above the upper limit of normal and above twice the upper limit of normal and reported a prevalence of 5.3% and 0.9%, respectively. Three studies investigated disturbance in biliary function, defined as bilirubin above the upper limit of normal and reported prevalences ranging from 0% to 8.7%. Two studies showed that treatment with radiotherapy involving the liver (especially after a high percentage of the liver irradiated), higher BMI, and longer follow-up time or older age at evaluation increased the risk of cellular liver injury in multivariable analyses. In addition, there was some suggestion that busulfan, thioguanine, hepatic surgery, chronic viral hepatitis C, metabolic syndrome, use of statins, non-Hispanic white ethnicity, and higher alcohol intake (> 14 units per week) increase the risk of cellular liver injury in multivariable analyses. Chronic viral hepatitis was shown to increase the risk of cellular liver injury in six univariable analyses as well. Moreover, one study showed that treatment with radiotherapy involving the liver, higher BMI, higher alcohol intake (> 14 units per week), longer follow-up time, and older age at cancer diagnosis increased the risk of biliary tract injury in a multivariable analysis. AUTHORS' CONCLUSIONS: The prevalence of hepatic late adverse effects among studies with an adequate outcome definition varied considerably from 1% to 53%. Evidence suggests that radiotherapy involving the liver, higher BMI, chronic viral hepatitis and longer follow-up time or older age at follow-up increase the risk of hepatic late adverse effects. In addition, there may be a suggestion that busulfan, thioguanine, hepatic surgery, higher alcohol intake (>14 units per week), metabolic syndrome, use of statins, non-Hispanic white ethnicity, and older age at cancer diagnosis increase the risk of hepatic late adverse effects. High-quality studies are needed to evaluate the effects of different therapy doses, time trends, and associated risk factors after antineoplastic treatment for childhood cancer.

Anaesthesia, surgery, and life-threatening allergic reactions: protocol and methods of the 6th National Audit Project (NAP6) of the Royal College of Anaesthetists.

BACKGROUND: Anaphylaxis during anaesthesia is a serious complication for patients and anaesthetists. METHODS: The Sixth National Audit Project (NAP6) of the Royal College of Anaesthetists examined the incidence, predisposing factors, management, and impact of life-threatening perioperative anaphylaxis in the UK. NAP6 included: a national survey of anaesthetists' experiences and perceptions; a national survey of allergy clinics; a registry collecting detailed reports of all Grade 3-5 perioperative anaphylaxis cases for 1 yr; and a national survey of anaesthetic workload and perioperative allergen exposure. NHS and independent sector (IS) hospitals were approached to participate. Cases were reviewed by a multi-disciplinary expert panel (anaesthetists, intensivists, allergists, immunologists, patient representatives, and stakeholders) using a structured process designed to minimise bias. Clinical management and investigation were compared with published guidelines. This paper describes detailed study methods and reports on project engagement by NHS and IS hospitals. The methodology includes a new classification of perioperative anaphylaxis and a new structured method for classifying suspected anaphylactic events including the degree of certainty with which a causal trigger agent can be attributed. RESULTS: NHS engagement was complete (100% of hospitals). Independent sector engagement was limited (13% of approached hospitals). We received >500 reports of Grade 3-5 perioperative anaphylaxis, with 266 suitable for analysis. We identified 199 definite or probable culprit agents in 192 cases. CONCLUSIONS: The methods of NAP6 were robust in identifying causative agents of anaphylaxis, and support the accompanying analytical papers.

Anaesthesia, surgery, and life-threatening allergic reactions: epidemiology and clinical features of perioperative anaphylaxis in the 6th National Audit Project (NAP6).

BACKGROUND: Anaphylaxis during anaesthesia is a serious complication for patients and anaesthetists. METHODS: The 6th National Audit Project (NAP6) on perioperative anaphylaxis collected and reviewed 266 reports of Grades 3-5 anaphylaxis over 1 yr from all NHS hospitals in the UK. RESULTS: The estimated incidence was ≈1:10 000 anaesthetics. Case exclusion because of reporting delays or incomplete data means true incidence might be ≈70% higher. The distribution of 199 identified culprit agents included antibiotics (94), neuromuscular blocking agents (65), chlorhexidine (18), and Patent Blue dye (9). Teicoplanin comprised 12% of antibiotic exposures, but caused 38% of antibiotic-induced anaphylaxis. Eighteen patients reacted to an antibiotic test dose. Succinylcholine-induced anaphylaxis, mainly presenting with bronchospasm, was two-fold more likely than other neuromuscular blocking agents. Atracurium-induced anaphylaxis mainly presented with hypotension. Non-depolarising neuromuscular blocking agents had similar incidences to each other. There were no reports of local anaesthetic or latex-induced anaphylaxis. The commonest presenting features were hypotension (46%), bronchospasm (18%), tachycardia (9.8%), oxygen desaturation (4.7%), bradycardia (3%), and reduced/absent capnography trace (2.3%). All patients were hypotensive during the episode. Onset was rapid for neuromuscular blocking agents and antibiotics, but delayed with chlorhexidine and Patent Blue dye. There were 10 deaths and 40 cardiac arrests. Pulseless electrical activity was the usual type of cardiac arrest, often with bradycardia. Poor outcomes were associated with increased ASA, obesity, beta blocker, and angiotensin-converting enzyme inhibitor medication. Seventy per cent of cases were reported to the hospital incident reporting system, and only 24% to Medicines and Healthcare products Regulatory Agency via the Yellow Card Scheme. CONCLUSIONS: The overall incidence of perioperative anaphylaxis was estimated to be 1 in 10 000 anaesthetics.

Cross-sectional study of perioperative drug and allergen exposure in UK practice in 2016: the 6th National Audit Project (NAP6) Allergen Survey.

BACKGROUND: Details of the current UK drug and allergen exposure were needed for interpretation of reports of perioperative anaphylaxis to the 6th National Audit Project (NAP6). METHODS: We performed a cross-sectional survey of 356 NHS hospitals determining anaesthetic drug usage in October 2016. All cases cared for by an anaesthetist were included. RESULTS: Responses were received from 342 (96%) hospitals. Within-hospital return rates were 96%. We collected 15 942 forms, equating to an annual caseload of 3.1 million, including 2.4 million general anaesthetics. Propofol was used in 74% of all cases and 90% of general anaesthetics. Maintenance included a volatile agent in 95% and propofol in 8.7%. Neuromuscular blocking agents were used in 47% of general anaesthetics. Analgesics were used in 88% of cases: opioids, 82%; paracetamol, 56%; and non-steroidal anti-inflammatory drugs, 28%. Antibiotics were administered in 57% of cases, including 2.5 million annual perioperative administrations; gentamicin, co-amoxiclav, and cefuroxime were most commonly used. Local anaesthetics were used in 74% cases and 70% of general anaesthetics. Anti-emetics were used in 73% of cases: during general anaesthesia, ondansetron in 78% and dexamethasone in 60%. Blood products were used in ≈3% of cases, gelatin <2%, starch very rarely, and tranexamic acid in ≈6%. Chlorhexidine and povidone-iodine exposures were 74% and 40% of cases, and 21% reported a latex-free environment. Exposures to bone cement, blue dyes, and radiographic contrast dye were each reported in 2-3% of cases. CONCLUSIONS: This survey provides insights into allergen exposures in perioperative care, which is important as denominator data for the NAP6 registry.

Anaesthesia, surgery, and life-threatening allergic reactions: management and outcomes in the 6th National Audit Project (NAP6).

BACKGROUND: Anaphylaxis during anaesthesia is a serious complication for patients and anaesthetists. There is little published information on management and outcomes of perioperative anaphylaxis in the UK. METHODS: The 6th National Audit Project of the Royal College of Anaesthetists (NAP6) collected and reviewed 266 reports of Grade 3-5 anaphylaxis from all UK NHS hospitals over 1 yr. Quality of management was assessed against published guidelines. RESULTS: Appropriately senior anaesthetists resuscitated all patients. Immediate management was 'good' in 46% and 'poor' in 15%. Recognition and treatment of anaphylaxis were prompt in 97% and 83% of cases, respectively. Epinephrine was administered i.v. in 76%, i.m. in 14%, both in 6%, and not at all in 11% of cases. A catecholamine infusion was administered in half of cases. Cardiac arrests (40 cases; 15%) were promptly treated but cardiac compressions were omitted in half of patients with unrecordable BP. The surgical procedure was abandoned in most cases, including 10% where surgery was urgent. Of 54% admitted to critical care, 70% were level 3, with most requiring catecholamine infusions. Ten (3.8%) patents (mostly elderly with cardiovascular disease) died from anaphylaxis. Corticosteroids and antihistamines were generally administered early. We found no clear evidence of harm or benefit from chlorphenamine. Two patients received vasopressin and one glucagon. Fluid administration was inadequate in 19% of cases. Treatment included sugammadex in 19 cases, including one when rocuronium had not been administered. Adverse sequelae (psychological, cognitive, or physical) were reported in one-third of cases. CONCLUSIONS: Management of perioperative anaphylaxis could be improved, especially with respect to administration of epinephrine, cardiac compressions, and i.v. fluid. Sequelae were common.

An observational national study of anaesthetic workload and seniority across the working week and weekend in the UK in 2016: the 6th National Audit Project (NAP6) Activity Survey.

BACKGROUND: UK national anaesthetic activity was studied in 2013 but weekend working was not examined. Understanding changes since 2013 in workload and manpower distribution, including weekends, would be of value in workforce planning. METHODS: We performed an observational survey of NHS hospitals' anaesthetic practice in October 2016 as part of the 6th National Audit Project of the Royal College of Anaesthetists (NAP6). All cases cared for by an anaesthetist during the study period were included. Patient characteristics and details of anaesthetic conduct were collected by local anaesthetists. RESULTS: Responses were received from 342/356 (96%) hospitals. In total, 15 942 cases were reported, equating to an annual anaesthetic workload of ≈3.13 million cases. Approximately 95% (9888/10 452) of elective and 72% (3184/4392) of emergency work was performed on weekdays and 89% (14 145/15 942) of activity was led by senior (consultant or career grade) anaesthetists and 1.1% (180/15942) by those with <2 yr anaesthetic experience. During weekends case urgency increased, the proportion of healthy patients reduced and case mix changed. Cases led by senior anaesthetists fell to 80% (947/1177) on Saturday and 66% (342/791) on Sunday. Senior involvement in obstetric anaesthetic activity was 69% (628/911) during the week and 45% (182/402) at weekends, compared with 93% (791/847) in emergency orthopaedic procedures during the week and 89% (285/321) at weekends. Since 2013, the proportion of obese patients, elective weekend working, and depth of anaesthesia monitoring has increased [12% (1464/12 213) vs 2.8%], but neuromuscular monitoring has not [37% (2032/5532) vs 38% of paralysed cases]. CONCLUSIONS: Senior clinicians deliver most UK anaesthesia care, including at weekends. Our findings are important for any planned workforce reorganisation to rationalise 7-day working.

Specialist perioperative allergy clinic services in the UK 2018: Results from the Royal College of Anaesthetists Sixth National Audit Project (NAP6) investigation of perioperative anaphylaxis.

BACKGROUND: The Royal College of Anaesthetists 6th National Audit Project examined Grade 3-5 perioperative anaphylaxis for 1 year in the UK. OBJECTIVE: To describe the causes and investigation of anaphylaxis in the NAP6 cohort, in relation to published guidance and previous baseline survey results. METHODS: We used a secure registry to gather details of Grade 3-5 perioperative anaphylaxis. Anonymous reports were aggregated for analysis and reviewed in detail. Panel consensus diagnosis, reaction grade, review of investigations and clinic assessment are reported and compared to the prior NAP6 baseline clinic survey. RESULTS: A total of 266 cases met inclusion criteria between November 2015 and 2016, detailing reactions and investigations. One hundred and ninety-two of 266 (72%) had anaphylaxis with a trigger identified, of which 140/192 (75%) met NAP6 criteria for IgE-mediated allergic anaphylaxis, 13% lacking evidence of positive IgE tests were labelled "non-allergic anaphylaxis". 3% were non-IgE-mediated anaphylaxis. Adherence to guidance was similar to the baseline survey for waiting time for clinic assessment. However, lack of testing for chlorhexidine and latex, non-harmonized testing practices and poor coverage of all possible culprits was confirmed. Challenge testing may be underused and many have unacceptably delayed assessments, even in urgent cases. Communication or information provision for patients was insufficient, especially for avoidance advice and communication of test results. Insufficient detail regarding skin test methods was available to draw conclusions regarding techniques. CONCLUSION AND CLINICAL RELEVANCE: Current clinical assessment in the UK is effective but harmonization of approach to testing, access to services and MHRA reporting is needed. Expert anaesthetist involvement should increase to optimize diagnostic yield and advice for future anaesthesia. Dynamic tryptase evaluation improves detection of tryptase release where peak tryptase is <14 µg/L and should be adopted. Standardized clinic reports containing appropriate details of tests, conclusions, avoidance, cross-reactivity and suitable alternatives are required to ensure effective, safe future management options.

Effect of the duration of hospice and palliative care on the quality of dying and death in patients with terminal cancer: A nationwide multicentre study.

Early referral to hospice and palliative care (HPC) has significant benefits, but little is known about the appropriate time for referral. The purpose of this study of terminal cancer patients was to identify the most appropriate time for referral to HPC. Cross-sectional correlation study design was used. Participants were the bereaved relatives, who were the adult primary caregivers of the 1,829 terminal cancer patients who died 2-6 months previously in nationwide centres that provide HPC in Korea. A post-bereavement survey (Good Death Inventory, GDI) of family caregivers was used to assess patients' quality of dying and death. Relative to patients who were in HPC for 3-7 days and HPC for 8-21 days, those in HPC for 22-84 days had significantly higher quality of dying. Propensity score matched comparison between the group hospitalised for 22-84 days (n = 65) and the group hospitalised for 85 days or longer (n = 65) showed no significant differences in all the items on quality of dying and death. Our results suggest that terminal cancer patients who stay in HPC at least for 22 days have improved quality of dying and death.

Prognostic value of sequencing-based minimal residual disease detection in patients with multiple myeloma who underwent autologous stem-cell transplantation.

BACKGROUND: Most patients with multiple myeloma (MM) are considered to be incurable, and relapse owing to minimal residual disease (MRD) is the main cause of death among these patients. Therefore, new technologies to assess deeper response are required. PATIENTS AND METHODS: We retrospectively analyzed 125 patients with MM who underwent high-dose melphalan plus autologous stem-cell transplantation (ASCT) to detect MRD in autograft/bone marrow (BM) cells using a next-generation sequencing (NGS)-based method and allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR). RESULTS: NGS-based method was applicable to 90% and this method had at least one to two logs greater sensitivity compared to ASO-PCR. MRD negative by NGS [MRDNGS(-)] (defined as <10-6) in post-ASCT BM cases (n = 26) showed a significantly better progression-free survival (PFS) (96% at 4 years, P < 0.001) and overall survival (OS) (100% at 4 years, P =0.04) than MRDNGS(+) in post-ASCT BM cases (n = 25). When restricting the analysis to the 39 complete response cases, patients who were MRDNGS(-) (n = 24) showed a significantly better PFS than those that were MRDNGS(+) (n = 15) (P =0.02). Moreover, MRDNGS(-) in post-ASCT BM cases (n = 12) showed significantly a better PFS than MRDNGS(+) cases (n = 7) where MRD was not detected by ASO-PCR (P = 0.001). Patients whose autografts were negative by NGS-based MRD assessment (<10-7) (n = 19) had 92% PFS and 100% OS at 4 years post-ASCT. Conversely, the NGS-based MRD positive patients who received post-ASCT treatment using novel agents (n = 49) had a significantly better PFS (P = 0.001) and tended to have a better OS (P= 0.214) than those that were untreated (n = 33). CONCLUSIONS: Low level MRD detected by NGS-based platform but not ASO-PCR has significant prognostic value when assessing either the autograft product or BM cells post-ASCT.

Specialist perioperative allergy clinic services in the UK 2016: Results from the Royal College of Anaesthetists Sixth National Audit Project.

BACKGROUND: Guidelines for investigation of perioperative drug allergy exist, but the quality of services is unknown. Specialist perioperative anaphylaxis services were surveyed through the Royal College of Anaesthetists 6th National Audit Project. OBJECTIVES: We compare self-declared UK practice in specialist perioperative allergy services with national recommendations. METHODS: A SurveyMonkey™ questionnaire was distributed to providers of allergy services in the UK. Responses were assessed for adherence to the best practice recommendations of the British Society for Allergy and Clinical Immunology (BSACI), the Association of Anaesthetists of Great Britain and Ireland and the National Institute for Health and Care Excellence (NICE) Guidance on Drug Allergy-CG183. RESULTS: Over 1200 patients were evaluated in 44 centres annually. Variation in workload, waiting times, access, staffing and diagnostic approach was noted. Paediatric centres had the longest routine waiting times (most wait >13 weeks) in contrast to adult centres (most wait <12 weeks). Service leads are allergists/immunologists (91%) or anaesthetists (7%). Potentially important differences were seen in: testing repertoire [10/44 (23%) lacked BSACI compliant neuromuscular blocking agent (NMBA) panels and 17/44 (39%) lacked a NAP6-defined extended panel; many failed to screen all cases for chlorhexidine 19/44 (43%) or latex 21/44 (48%)], staffing [only 26/44 (59%) had specialist nurses and 18/44 (41%) an anaesthetist] and provision of information [18/44 (41%) gave immediate information in clinic and 5/44 (11%) sign-posted support groups]. Most centres were able to provide diagnostic challenges to antibiotics [40/44 (91%]) and local anaesthetics [41/44 (93%)]. CONCLUSIONS AND CLINICAL RELEVANCE: Diagnostic testing is not harmonized, with marked variability in the NMBA panels used to identify safe alternatives. Chlorhexidine and latex are not part of routine testing in many centres. Poor access to services and patient information provision require attention. Harmonization of diagnostic approach is desirable, particularly with regard to a minimum NMBA panel for identification of safe alternatives.

Associations of B cell-activating factor (BAFF) and anti-BAFF autoantibodies with disease activity in multi-ethnic Asian systemic lupus erythematosus patients in Singapore.

To measure the levels of B cell-activating factor (BAFF) and endogenous anti-BAFF autoantibodies in a cohort of multi-ethnic Asian systemic lupus erythematosus (SLE) patients in Singapore, to determine their correlation with disease activity. Serum samples from 121 SLE patients and 24 age- and sex-matched healthy controls were assayed for BAFF and anti-BAFF immunoglobulin (Ig)G antibody levels by enzyme-linked immunosorbent assay (ELISA). The lowest reliable detection limit for anti-BAFF-IgG antibody levels was defined as 2 standard deviations (s.d.) from blank. Correlation of serum BAFF and anti-BAFF IgG levels with disease activity [scored by SLE Activity Measure revised (SLAM-R)], and disease manifestations were determined in these 121 patients. SLE patients had elevated BAFF levels compared to controls; mean 820 ± 40 pg/ml and 152 pg ± 45/ml, respectively [mean ± standard error of the mean (s.e.m.), P < 0·01], which were correlated positively with anti-dsDNA antibody levels (r = 0·253, P < 0·03), and SLAM-R scores (r = 0·627, P < 0·01). In addition, SLE patients had significantly higher levels of anti-BAFF IgG, which were correlated negatively with disease activity (r = -0·436, P < 0·01), levels of anti-dsDNA antibody (r = -0·347, P < 0·02) and BAFF (r = -0·459, P < 0·01). The majority of patients in this multi-ethnic Asian SLE cohort had elevated levels of BAFF and anti-BAFF antibodies. Anti-BAFF autoantibody levels correlated negatively with clinical disease activity, anti-dsDNA and BAFF levels, suggesting that they may be disease-modifying. Our results provide further information about the complexity of BAFF pathophysiology in different SLE disease populations and phenotypes, and suggest that studies of the influence of anti-cytokine antibodies in different SLE populations will be required when selecting patients for trials using targeted anti-cytokine therapies.

A Controlled Randomized Preliminary Trial of a Modified Dissonance-Based Eating Disorder Intervention Program.

OBJECTIVE: We conducted a controlled randomized preliminary trial of a modified dissonance-based eating disorder program (n = 24) compared to an assessment-only control condition (n = 23) via a longitudinal design (baseline, postintervention, 2-month follow-up) in a community sample of women (N = 47) with clinical (n = 22) and subclinical (n = 25) eating disorder symptoms. METHOD: The traditional content of the Body Project, a dissonance-based eating disorder prevention program, was modified to include verbal, written, and behavioral exercises designed to dissuade self-objectification and maladaptive social comparison. Women with clinical and subclinical symptoms were included in the target audience to investigate both the treatment and the indicated prevention utility of the modified dissonance program. Body dissatisfaction, self-esteem, self-objectification, thin-ideal internalization, maladaptive social comparison, trait anxiety, and eating disorder symptoms were evaluated in the control and the modified dissonance condition at baseline, postintervention, and 2-month follow-up. RESULTS: We predicted a statistically significant 2 (condition: control, modified dissonance) x 3 (time: baseline, postintervention, 2-month follow-up) interaction in the mixed factorial multivariate analyses of variance results. Results confirmed this hypothesis. Eating disorder risk factors and symptoms decreased significantly among participants in the modified dissonance condition at postintervention and 2-month follow-up compared to baseline; symptom improvement was greater among participants in the modified compared to the control condition. A secondary analysis indicated symptom improvement did not vary as a function of symptom status (clinical, subclinical), suggesting the program is efficacious in both indicated prevention and treatment applications. CONCLUSION: Results provide preliminary support for the modified dissonance program.

Anaesthesia-associated hypersensitivity reactions: seven years' data from a British bi-specialty clinic.

Our bi-specialty clinic was established to systematically investigate patients with suspected peri-operative hypersensitivity reactions. Four hundred and ten patients were studied; 316 following an intra-operative reaction ('postoperative' group) and 94 with a previous history of reaction, referred before undergoing anaesthesia ('pre-operative' group). In the postoperative group, 173 (54.7%) were diagnosed with IgE-mediated reactions: 65 (37.6%) to neuromuscular blocking drugs; 54 (31.2%) antibiotics; 15 (8.7%) chlorhexidine and 12 (6.9%) patent blue dye. Reactions were severe in 114 patients (65.9%). All reactions to patent blue dye were severe. We identified IgE sensitisation in 22 (13.2%) cases with isolated mucocutaneous reactions. Only 173 (54.7%) patients had serum tryptase samples taken. Referrers' suspected causal agent was confirmed in only 37.2% of patients. Of 94 patients reviewed 'pre-operatively', 29 (30.8%) were diagnosed with IgE-mediated hypersensitivity reactions, reinforcing the importance of investigating this group of patients. Knowledge of the range of causative agents identified in our study should guide the investigation of suspected peri-operative hypersensitivity reactions.

Leisure time physical activity before and during mid-pregnancy and offspring adiposity in mid-childhood.

BACKGROUND: Effects of maternal leisure time physical activity (LTPA) on paediatric obesity are unknown. The objective of this study was to examine associations of maternal LTPA with offspring overall and central adiposity in mid-childhood. METHODS: We analysed data from 802 mother-child dyads from Project Viva, a prospective pre-birth cohort study. Women reported average weekly LTPA before and during mid-pregnancy. At age 7-10 years, we measured fat, truncal fat and lean mass with dual-energy X-ray absorptiometry. Using multivariable linear regression, we examined associations of maternal LTPA with offspring adiposity, adjusting for child age and sex, maternal race/ethnicity, education, age, pre-pregnancy body mass index, marital status and smoking status. RESULTS: Mean (standard deviation) of LTPA before and during mid-pregnancy were 9.5 (8.1) and 7.1 (7.0) h week(-1) . At mean age 7.8 (0.8) years, childhood fat, truncal fat and lean mass indices were 4.3 (1.8), 1.4 (0.8) and 12.9 (1.4) kg m(-2) . We did not find that higher maternal LTPA was associated with lower child adiposity outcomes. For example, compared with 0-3 h week(-1) of LTPA during mid-pregnancy, children of mothers with +8 h week(-1) had fat mass index 0.07 kg m(-2) (95% confidence interval: -0.22, 0.36). In analyses of within-person LTPA change from before to mid-pregnancy, compared with +2 h week(-1) decrease in LTPA, increased LTPA (2 ± h week(-1) ) was associated with a 0.09 kg m(-2) fat mass index (-0.25, 0.43). CONCLUSIONS: Contrary to our hypothesis, higher LTPA before and during mid-pregnancy, and the change between them, were not associated with lower adiposity in mid-childhood.