Auckland District Health Board

BACKGROUND: Oral propranolol has been used to treat complicated infantile hemangiomas, although data from randomized, controlled trials to inform its use are limited. METHODS: We performed a multicenter, randomized, double-blind, adaptive, phase 2-3 trial assessing the efficacy and safety of a pediatric-specific oral propranolol solution in infants 1 to 5 months of age with proliferating infantile hemangioma requiring systemic therapy. Infants were randomly assigned to receive placebo or one of four propranolol regimens (1 or 3 mg of propranolol base per kilogram of body weight per day for 3 or 6 months). A preplanned interim analysis was conducted to identify the regimen to study for the final efficacy analysis. The primary end point was success (complete or nearly complete resolution of the target hemangioma) or failure of trial treatment at week 24, as assessed by independent, centralized, blinded evaluations of standardized photographs. RESULTS: Of 460 infants who underwent randomization, 456 received treatment. On the basis of an interim analysis of the first 188 patients who completed 24 weeks of trial treatment, the regimen of 3 mg of propranolol per kilogram per day for 6 months was selected for the final efficacy analysis. The frequency of successful treatment was higher with this regimen than with placebo (60% vs. 4%, P<0.001). A total of 88% of patients who received the selected propranolol regimen showed improvement by week 5, versus 5% of patients who received placebo. A total of 10% of patients in whom treatment with propranolol was successful required systemic retreatment during follow-up. Known adverse events associated with propranolol (hypoglycemia, hypotension, bradycardia, and bronchospasm) occurred infrequently, with no significant difference in frequency between the placebo group and the groups receiving propranolol. CONCLUSIONS: This trial showed that propranolol was effective at a dose of 3 mg per kilogram per day for 6 months in the treatment of infantile hemangioma. (Funded by Pierre Fabre Dermatologie; ClinicalTrials.gov number, NCT01056341.).

Analyzing the type and frequency of patient-specific mutations that give rise to Duchenne muscular dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning, and improved clinical care. Locus-specific databases allow for the collection, organization, storage, and analysis of genetic variants of disease. Here, we describe the development and analysis of the TREAT-NMD DMD Global database (http://umd.be/TREAT_DMD/). We analyzed genetic data for 7,149 DMD mutations held within the database. A total of 5,682 large mutations were observed (80% of total mutations), of which 4,894 (86%) were deletions (1 exon or larger) and 784 (14%) were duplications (1 exon or larger). There were 1,445 small mutations (smaller than 1 exon, 20% of all mutations), of which 358 (25%) were small deletions and 132 (9%) small insertions and 199 (14%) affected the splice sites. Point mutations totalled 756 (52% of small mutations) with 726 (50%) nonsense mutations and 30 (2%) missense mutations. Finally, 22 (0.3%) mid-intronic mutations were observed. In addition, mutations were identified within the database that would potentially benefit from novel genetic therapies for DMD including stop codon read-through therapies (10% of total mutations) and exon skipping therapy (80% of deletions and 55% of total mutations).

Background In laboratory animals, exposure to most general anaesthetics leads to neurotoxicity manifested by neuronal cell death and abnormal behaviour and cognition. Some large human cohort studies have shown an association between general anaesthesia at a young age and subsequent neurodevelopmental deficits, but these studies are prone to bias. Others have found no evidence for an association. We aimed to establish whether general anaesthesia in early infancy affects neurodevelopmental outcomes. Methods In this international, assessor-masked, equivalence, randomised, controlled trial conducted at 28 hospitals in Australia, Italy, the USA, the UK, Canada, the Netherlands, and New Zealand, we recruited infants of less than 60 weeks' postmenstrual age who were born at more than 26 weeks' gestation and were undergoing inguinal herniorrhaphy, without previous exposure to general anaesthesia or risk factors for neurological injury. Patients were randomly assigned (1:1) by use of a web-based randomisation service to receive either awake-regional anaesthetic or sevoflurane-based general anaesthetic. Anaesthetists were aware of group allocation, but individuals administering the neurodevelopmental assessments were not. Parents were informed of their infants group allocation upon request, but were told to mask this information from assessors. The primary outcome measure was full-scale intelligence quotient (FSIQ) on the Wechsler Preschool and Primary Scale of Intelligence, third edition (WPPSI-III), at 5 years of age. The primary analysis was done on a per-protocol basis, adjusted for gestational age at birth and country, with multiple imputation used to account for missing data. An intention-to-treat analysis was also done. A difference in means of 5 points was predefined as the clinical equivalence margin. This completed trial is registered with ANZCTR, number ACTRN12606000441516, and ClinicalTrials.gov, number NCT00756600. Findings Between Feb 9, 2007, and Jan 31, 2013, 4023 infants were screened and 722 were randomly allocated: 363 (50%) to the awake-regional anaesthesia group and 359 (50%) to the general anaesthesia group. There were 74 protocol violations in the awake-regional anaesthesia group and two in the general anaesthesia group. Primary outcome data for the per-protocol analysis were obtained from 205 children in the awake-regional anaesthesia group and 242 in the general anaesthesia group. The median duration of general anaesthesia was 54 min (IQR 41–70). The mean FSIQ score was 99·08 (SD 18·35) in the awake-regional anaesthesia group and 98·97 (19·66) in the general anaesthesia group, with a difference in means (awake-regional anaesthesia minus general anaesthesia) of 0·23 (95% CI −2·59 to 3·06), providing strong evidence of equivalence. The results of the intention-to-treat analysis were similar to those of the per-protocol analysis. Interpretation Slightly less than 1 h of general anaesthesia in early infancy does not alter neurodevelopmental outcome at age 5 years compared with awake-regional anaesthesia in a predominantly male study population.

Stroke is a leading cause of adult disability and the recovery of motor function is important for independence in activities of daily living. Predicting motor recovery after stroke in individual patients is difficult. Accurate prognosis would enable realistic rehabilitation goal-setting and more efficient allocation of resources. The aim of this study was to test and refine an algorithm for predicting the potential for recovery of upper limb function after stroke. Forty participants were prospectively enrolled within 3 days of ischaemic stroke. First, shoulder abduction and finger extension strength were graded 72 h after stroke onset to compute a shoulder abduction and finger extension score. Secondly, transcranial magnetic stimulation was used to assess the functional integrity of descending motor pathways to the affected upper limb. Third, diffusion-weighted magnetic resonance imaging was used to assess the structural integrity of the posterior limbs of the internal capsules. Finally, these measures were combined in the PREP algorithm for predicting an individual's potential for upper limb recovery at 12 weeks, measured with the Action Research Arm Test. A cluster analysis was used to independently group patients according to Action Research Arm Test score at 12 weeks, for comparison with predictions from the PREP algorithm. There was excellent correspondence between the cluster analysis of Action Research Arm Test score at 12 weeks and predictions made with the PREP algorithm. The algorithm had positive predictive power of 88%, negative predictive power of 83%, specificity of 88% and sensitivity of 73%. This study provides preliminary data in support of the PREP algorithm for the prognosis of upper limb recovery in individual patients. PREP may enable tailored planning of rehabilitation and more accurate stratification of patients in clinical trials.

BACKGROUND: Ovarian failure is a common toxic effect of chemotherapy. Studies of the use of gonadotropin-releasing hormone (GnRH) agonists to protect ovarian function have shown mixed results and lack data on pregnancy outcomes. METHODS: We randomly assigned 257 premenopausal women with operable hormone-receptor-negative breast cancer to receive standard chemotherapy with the GnRH agonist goserelin (goserelin group) or standard chemotherapy without goserelin (chemotherapy-alone group). The primary study end point was the rate of ovarian failure at 2 years, with ovarian failure defined as the absence of menses in the preceding 6 months and levels of follicle-stimulating hormone (FSH) in the postmenopausal range. Rates were compared with the use of conditional logistic regression. Secondary end points included pregnancy outcomes and disease-free and overall survival. RESULTS: At baseline, 218 patients were eligible and could be evaluated. Among 135 with complete primary end-point data, the ovarian failure rate was 8% in the goserelin group and 22% in the chemotherapy-alone group (odds ratio, 0.30; 95% confidence interval [CI], 0.09 to 0.97; two-sided P=0.04). Owing to missing primary end-point data, sensitivity analyses were performed, and the results were consistent with the main findings. Missing data did not differ according to treatment group or according to the stratification factors of age and planned chemotherapy regimen. Among the 218 patients who could be evaluated, pregnancy occurred in more women in the goserelin group than in the chemotherapy-alone group (21% vs. 11%, P=0.03); women in the goserelin group also had improved disease-free survival (P=0.04) and overall survival (P=0.05). CONCLUSIONS: Although missing data weaken interpretation of the findings, administration of goserelin with chemotherapy appeared to protect against ovarian failure, reducing the risk of early menopause and improving prospects for fertility. (Funded by the National Cancer Institute and others; POEMS/S0230 ClinicalTrials.gov number, NCT00068601.).

Hereditary angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1 inhibitor (type 1) and HAE with dysfunctional C1 inhibitor (type 2), by providing guidance on common and important clinical issues, such as: (1) How should HAE be diagnosed? (2) When should HAE patients receive prophylactic on top of on-demand treatment and what treatments should be used? (3) What are the goals of treatment? (4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast-feeding women? and (5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients.

Stringent nonpharmaceutical interventions (NPIs) such as lockdowns and border closures are not currently recommended for pandemic influenza control. New Zealand used these NPIs to eliminate coronavirus disease 2019 during its first wave. Using multiple surveillance systems, we observed a parallel and unprecedented reduction of influenza and other respiratory viral infections in 2020. This finding supports the use of these NPIs for controlling pandemic influenza and other severe respiratory viral threats.

BACKGROUND: Asthma is the most common chronic disease in children globally. The Global Asthma Network (GAN) Phase I study aimed to determine if the worldwide burden of asthma symptoms is changing. METHODS: This updated cross-sectional study used the same methods as the International study of Asthma and Allergies in Childhood (ISAAC) Phase III. Asthma symptoms were assessed from centres that completed GAN Phase I and ISAAC Phase I (1993-95), ISAAC Phase III (2001-03), or both. We included individuals from two age groups (children aged 6-7 years and adolescents aged 13-14 years) who self-completed written questionnaires at school. We estimated the 10-year rate of change in prevalence of current wheeze, severe asthma symptoms, ever having asthma, exercise wheeze, and night cough (defined by core questions in the questionnaire) for each centre, and we estimated trends across world regions and income levels using mixed-effects linear regression models with region and country income level as confounders. FINDINGS: Overall, 119 795 participants from 27 centres in 14 countries were included: 74 361 adolescents (response rate 90%) and 45 434 children (response rate 79%). About one in ten individuals of both age groups had wheeze in the preceding year, of whom almost half had severe symptoms. Most centres showed a change in prevalence of 2 SE or more between ISAAC Phase III to GAN Phase I. Over the 27-year period (1993-2020), adolescents showed a significant decrease in percentage point prevalence per decade in severe asthma symptoms (-0·37, 95% CI -0·69 to -0·04) and an increase in ever having asthma (1·25, 0·67 to 1·83) and night cough (4·25, 3·06 to 5·44), which was also found in children (3·21, 1·80 to 4·62). The prevalence of current wheeze decreased in low-income countries (-1·37, -2·47 to -0·27], in children and -1·67, -2·70 to -0·64, in adolescents) and increased in lower-middle-income countries (1·99, 0·33 to 3·66, in children and 1·69, 0·13 to 3·25, in adolescents), but it was stable in upper-middle-income and high-income countries. INTERPRETATION: Trends in prevalence and severity of asthma symptoms over the past three decades varied by age group, country income, region, and centre. The high worldwide burden of severe asthma symptoms would be mitigated by enabling access to effective therapies for asthma. FUNDING: International Union Against Tuberculosis and Lung Disease, Boehringer Ingelheim New Zealand, AstraZeneca Educational Grant, National Institute for Health Research, UK Medical Research Council, European Research Council, and Instituto de Salud Carlos III.

OBJECTIVE: Magnetic resonance imaging (MRI) is capable of revealing synovitis and tendinitis in early rheumatoid arthritis (RA), as well as bone edema and erosion. These features are visible before radiographic joint damage occurs. We sought to examine whether MRI of one body region (the wrist) can be used to predict whole-body radiography scores reflecting joint damage at 6 years. METHODS: We conducted a 6-year prospective study of a cohort of patients who fulfilled the criteria for RA at presentation, using clinical parameters, radiographs, and MRI scans of the dominant wrist. Of the 42 patients enrolled at baseline, full MRI, radiographic, and clinical data were available for 31 at 6-year followup. MRI scans were scored by 2 radiologists, using a validated scoring system. Radiographs of the hands and feet were graded using the modified Sharp scoring method. MRI and radiography scores obtained at baseline and 6 years were compared, and baseline MRI scores were examined for their ability to predict radiographic outcome at 6 years. RESULTS: At 6 years, the total Sharp score correlated significantly with the total MRI score and the MRI erosion score (r = 0.81, P < 0.0001 and r = 0.79, P < 0.0001, respectively). The 6-year Sharp score also correlated with the baseline total MRI and MRI erosion scores (r = 0.56, P < 0.0001 and r = 0.33, P = 0.03, respectively). MRI synovitis and bone edema scores remained constant for the group as a whole over 6 years, but bone erosion scores progressed (P = 0.0001), consistent with radiographic deterioration. Erosions on 6-year MRI scans were frequently preceded by MRI bone edema at baseline (odds ratio 6.5, 95% confidence interval 2.78-18.1). Regression models indicated that the baseline MRI bone edema score was predictive of the 6-year total Sharp score (P = 0.01), as was the C-reactive protein (CRP) level (P = 0.0002). Neither shared epitope status nor swollen or tender joint counts predicted radiographic outcome in this cohort. A model incorporating baseline MRI scores for erosion, bone edema, synovitis, and tendinitis plus the CRP level and the erythrocyte sedimentation rate explained 59% of the variance in the 6-year total Sharp score (R(2) = 0.59, adjusted R(2) = 0.44). CONCLUSION: MRI scans performed at the first presentation of RA can be used to help predict future radiographic damage, allowing disease-modifying therapy to be targeted to patients with aggressive disease.

BACKGROUND: Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously. RESULTS: We analyzed DNA from the largest reported international cohort of patients with DSD (278 patients with 46,XY DSD and 48 with 46,XX DSD). Our targeted gene panel compares favorably with other sequencing platforms. We found a total of 28 diagnostic genes that are implicated in DSD, highlighting the genetic spectrum of this disorder. Sequencing revealed 93 previously unreported DSD gene variants. Overall, we identified a likely genetic diagnosis in 43% of patients with 46,XY DSD. In patients with 46,XY disorders of androgen synthesis and action the genetic diagnosis rate reached 60%. Surprisingly, little difference in diagnostic rate was observed between singletons and trios. In many cases our findings are informative as to the likely cause of the DSD, which will facilitate clinical management. CONCLUSIONS: Our massively parallel sequencing targeted DSD gene panel represents an economical means of improving the genetic diagnostic capability for patients affected by DSD. Implementation of this panel in a large cohort of patients has expanded our understanding of the underlying genetic etiology of DSD. The inclusion of research candidate genes also provides an invaluable resource for future identification of novel genes.

BACKGROUND: Bisphosphonates prevent fractures in patients with osteoporosis, but their efficacy in women with osteopenia is unknown. Most fractures in postmenopausal women occur in those with osteopenia, so therapies that are effective in women with osteopenia are needed. METHODS: We conducted a 6-year, double-blind trial involving 2000 women with osteopenia (defined by a T score of -1.0 to -2.5 at either the total hip or the femoral neck on either side) who were 65 years of age or older. Participants were randomly assigned to receive four infusions of either zoledronate at a dose of 5 mg (zoledronate group) or normal saline (placebo group) at 18-month intervals. A dietary calcium intake of 1 g per day was advised, but calcium supplements were not provided. Participants who were not already taking vitamin D supplements received cholecalciferol before the trial began (a single dose of 2.5 mg) and during the trial (1.25 mg per month). The primary end point was the time to first occurrence of a nonvertebral or vertebral fragility fracture. RESULTS: At baseline, the mean (±SD) age was 71±5 years, the T score at the femoral neck was -1.6±0.5, and the median 10-year risk of hip fracture was 2.3%. A fragility fracture occurred in 190 women in the placebo group and in 122 women in the zoledronate group (hazard ratio with zoledronate, 0.63; 95% confidence interval, 0.50 to 0.79; P<0.001). The number of women that would need to be treated to prevent the occurrence of a fracture in 1 woman was 15. As compared with the placebo group, women who received zoledronate had a lower risk of nonvertebral fragility fractures (hazard ratio, 0.66; P=0.001), symptomatic fractures (hazard ratio, 0.73; P=0.003), vertebral fractures (odds ratio, 0.45; P=0.002), and height loss (P<0.001). CONCLUSIONS: The risk of nonvertebral or vertebral fragility fractures was significantly lower in women with osteopenia who received zoledronate than in women who received placebo. (Funded by the Health Research Council of New Zealand; Australian New Zealand Clinical Trials Registry number, ACTRN12609000593235 .).

Healthcare systems redesign and service improvement approaches are adopting participatory tools, techniques and mindsets. Participatory methods increasingly used in healthcare improvement coalesce around the concept of coproduction, and related practices of cocreation, codesign and coinnovation. These participatory methods have become the new Zeitgeist-the spirit of our times in quality improvement. The rationale for this new spirit of participation relates to voice and engagement (those with lived experience should be engaged in processes of development, redesign and improvements), empowerment (engagement in codesign and coproduction has positive individual and societal benefits) and advancement (quality of life and other health outcomes and experiences of services for everyone involved should improve as a result). This paper introduces Mental Health Experience Co-design (MH ECO), a peer designed and led adapted form of Experience-based Co-design (EBCD) developed in Australia. MH ECO is said to facilitate empowerment, foster trust, develop autonomy, self-determination and choice for people living with mental illnesses and their carers, including staff at mental health services. Little information exists about the underlying mechanisms of change; the entities, processes and structures that underpin MH ECO and similar EBCD studies. To address this, we identified eight possible mechanisms from an assessment of the activities and outcomes of MH ECO and a review of existing published evaluations. The eight mechanisms, recognition, dialogue, cooperation, accountability, mobilisation, enactment, creativity and attainment, are discussed within an 'explanatory theoretical model of change' that details these and ideal relational transitions that might be observed or not with MH ECO or other EBCD studies. We critically appraise the sociocultural and political movement in coproduction and draw on interdisciplinary theories from the humanities-narrative theory, dialogical ethics, cooperative and empowerment theory. The model advances theoretical thinking in coproduction beyond motivations and towards identifying underlying processes and entities that might impact on process and outcome. TRIAL REGISTRATION NUMBER: The Australian and New Zealand Clinical Trials Registry, ACTRN12614000457640 (results).

Pregnant women and newborns are at increased risk of vitamin D deficiency. Our objective was to create a global summary of maternal and newborn vitamin D status. We completed a systematic review (1959-2014) and meta-analysis of studies reporting serum 25-hydroxyvitamin D [25(OH)D] concentration in maternal and newborn populations. The 95 identified studies were unevenly distributed by World Health Organization (WHO) region: Americas (24), European (33), Eastern Mediterranean (13), South-East Asian (7), Western Pacific (16) and African (2). Average maternal 25(OH)D concentrations (nmol L(-1) ) by region were 47-65 (Americas), 15-72 (European), 13-60 (Eastern Mediterranean), 20-52 (South-East Asian), 42-72 (Western Pacific) and 92 (African). Average newborn 25(OH)D concentrations (nmol L(-1) ) were 35-77 (Americas), 20-50 (European), 5-50 (Eastern Mediterranean), 20-22 (South-East Asian), 32-67 (Western Pacific) and 27-35 (African). The prevalences of 25(OH)D <50 and <25 nmol L(-1) by WHO region in pregnant women were: Americas (64%, 9%), European (57%, 23%), Eastern Mediterranean (46%, 79%), South-East Asian (87%, not available) and Western Pacific (83%, 13%). Among newborns these values were: Americas (30%, 14%), European (73%, 39%), Eastern Mediterranean (60%, not available), South-East Asian (96%, 45%) and Western Pacific (54%, 14%). By global region, average 25(OH)D concentration varies threefold in pregnant women and newborns, and prevalence of 25(OH)D <25 nmol L(-1) varies eightfold in pregnant women and threefold in newborns. Maternal and newborn 25(OH)D concentrations are highly correlated. Addressing vitamin D deficiency in pregnant women and newborns should be a global priority. To protect children from the adverse effects of vitamin D deficiency requires appropriate interventions during both pregnancy and childhood.

Objective: Recovery of motor function is important for regaining independence after stroke, but difficult to predict for individual patients. Our aim was to develop an efficient, accurate, and accessible algorithm for use in clinical settings. Clinical, neurophysiological, and neuroimaging biomarkers of corticospinal integrity obtained within days of stroke were combined to predict likely upper limb motor outcomes 3 months after stroke. Methods: Data from 207 patients recruited within 3 days of stroke [103 females (50%), median age 72 (range 18-98) years] were included in a Classification and Regression Tree analysis to predict upper limb function 3 months poststroke. Results: The analysis produced an algorithm that sequentially combined a measure of upper limb impairment; age; the presence or absence of upper limb motor evoked potentials elicited with transcranial magnetic stimulation; and stroke lesion load obtained from MRI or stroke severity assessed with the NIHSS score. The algorithm makes correct predictions for 75% of patients. A key biomarker obtained with transcranial magnetic stimulation is required for one third of patients. This biomarker combined with NIHSS score can be used in place of more costly magnetic resonance imaging, with no loss of prediction accuracy. Interpretation: The new algorithm is more accurate, efficient, and accessible than its predecessors, which may support its use in clinical practice. While further work is needed to potentially incorporate sensory and cognitive factors, the algorithm can be used within days of stroke to provide accurate predictions of upper limb functional outcomes at 3 months after stroke. www.presto.auckland.ac.nz.

BACKGROUND: Implementation science research, especially when using participatory and co-design approaches, raises unique challenges for research ethics committees. Such challenges may be poorly addressed by approval and governance mechanisms that were developed for more traditional research approaches such as randomised controlled trials. DISCUSSION: Implementation science commonly involves the partnership of researchers and stakeholders, attempting to understand and encourage uptake of completed or piloted research. A co-creation approach involves collaboration between researchers and end users from the onset, in question framing, research design and delivery, and influencing strategy, with implementation and broader dissemination strategies part of its design from gestation. A defining feature of co-creation is its emergent and adaptive nature, making detailed pre-specification of interventions and outcome measures impossible. This methodology sits oddly with ethics committee protocols that require precise pre-definition of interventions, mode of delivery, outcome measurements, and the role of study participants. But the strict (and, some would say, inflexible) requirements of ethics committees were developed for a purpose - to protect participants from harm and help ensure the rigour and transparency of studies. We propose some guiding principles to help square this circle. First, ethics committees should acknowledge and celebrate the diversity of research approaches, both formally (through training) and informally (by promoting debate and discussion); without active support, their members may not understand or value participatory designs. Second, ground rules should be established for co-design applications (e.g. how to judge when 'consultation' or 'engagement' becomes research) and communicated to committee members and stakeholders. Third, the benefits of power-sharing should be recognised and credit given to measures likely to support this important goal, especially in research with vulnerable communities. Co-design is considered best practice, for example, in research involving indigenous peoples in New Zealand, Australia and Canada.

According to autobiographical memory theorists, past event conversations provide children with a framework for evaluating and connecting past events into a coherent autobiography (R. Fivush, 1994; K. Nelson, 1993; M. K. Welch-Ross, 1995). Two studies were conducted to empirically examine the association between past event conversation style and an independent measure of children's self-concept consistency. In Study 1, 50 New Zealand mothers discussed everyday past events with their children at 51 and 65 months of age. In Study 2, 51 New Zealand parents discussed 1 positive and 3 negative past events with their 5- and 6-year-old children. The consistency of children's self-views was assessed in both studies using the Children's Self-View Questionnaire (R. Eder, 1990). Children's self-concept consistency was moderately associated with greater explanation of the causes and consequences of children's negative emotions, resolution through social contact, and evaluation of positive events but not with simple attributions of emotion. These findings implicate parent-child conversations as a medium through which children can begin to understand the personal meaning of past experiences.

BACKGROUND: It is increasingly understood that voice-hearing is neither a rare phenomenon experienced only by 'psychiatric patients' nor a meaningless symptom of a 'mental illness'. AIMS: To estimate the prevalence of voice-hearing in the adult general population. METHODS: PsycINFO and relevant literature reviews were searched for studies of the prevalence of verbal auditory hallucinations among adults. RESULTS: Seventeen surveys, from nine countries, were identified. Comparisons across studies were problematic due to differences in definitions, methodologies, and cultural factors. Prevalence ranged from 0.6% to 84%, with an interquartile range (excluding the highest and lowest quartiles) of 3.1%-19.5%, and a median of 13.2%. CONCLUSIONS: Differences in prevalence can be attributed in part to differences in definitions and methodologies, but also to true variations based on gender, ethnicity and environmental context. The findings support the current movement away from pathological models of unusual experiences and towards understanding voice-hearing as occurring on a continuum in the general population, and having meaning in relation to the voice-hearer's life experiences.

Objective To develop and validate revised classification criteria for granulomatosis with polyangiitis (GPA). Methods Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate criteria items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data‐driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points‐based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. Results The development set for GPA consisted of 578 cases of GPA and 652 comparators. The validation set consisted of an additional 146 cases of GPA and 161 comparators. From 91 candidate items, regression analysis identified 26 items for GPA, 10 of which were retained. The final criteria and their weights were as follows: bloody nasal discharge, nasal crusting, or sino‐nasal congestion (+3); cartilaginous involvement (+2); conductive or sensorineural hearing loss (+1); cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or anti–proteinase 3 ANCA positivity (+5); pulmonary nodules, mass, or cavitation on chest imaging (+2); granuloma or giant cells on biopsy (+2); inflammation or consolidation of the nasal/paranasal sinuses on imaging (+1); pauci‐immune glomerulonephritis (+1); perinuclear ANCA or antimyeloperoxidase ANCA positivity (−1); and eosinophil count ≥1 × 10 9 /liter (−4). After excluding mimics of vasculitis, a patient with a diagnosis of small‐ or medium‐vessel vasculitis could be classified as having GPA if the cumulative score was ≥5 points. When these criteria were tested in the validation data set, the sensitivity was 93% (95% confidence interval [95% CI] 87–96%) and the specificity was 94% (95% CI 89–97%). Conclusion The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for GPA demonstrate strong performance characteristics and are validated for use in research.

AIM: This paper describes how co-design methods can be used to improve patient experiences and services within healthcare organisations. Using the Patient Co-design of Breast Service Project as an example, we describe how patient experiences were captured and understood, the improvements made and implications for future work. METHOD: We used a six-step process: engage, plan, explore, develop, decide and change. Tools and techniques employed were based on service design approaches. These included patient journey mapping, experience-based surveys and co-design workshops. RESULTS: Information, communication, navigation and co-ordination, and environment emerged as key themes for the Breast Service. And as a result, a suite of improvements were made. Key methodological learnings included using co-design alongside traditional quality improvement methodologies, engaging with patients early, the importance of staff buy-in and the necessity of trying things outside one's comfort zone. CONCLUSION: Use of co-design within the Breast Service has resulted in tangible improvements and has demonstrated the value of engaging patients and focussing on their experiences. It is recommended that: evaluation phases are factored into future co-design work, further research is conducted on sustainability and funding and support is given to allow co-design to become more widespread throughout New Zealand.

Around the world, innovative genomic-medicine programs capitalize on singular capabilities arising from local health care systems, cultural or political milieus, and unusual selected risk alleles or disease burdens. Such individual efforts might benefit from the sharing of approaches and lessons learned in other locales. The U.S. National Human Genome Research Institute and the National Academy of Medicine recently brought together 25 of these groups to compare projects, to examine the current state of implementation and desired near-term capabilities, and to identify opportunities for collaboration that promote the responsible practice of genomic medicine. Efforts to coalesce these groups around concrete but compelling signature projects should accelerate the responsible implementation of genomic medicine in efforts to improve clinical care worldwide.