BRN2 suppresses apoptosis, reprograms DNA damage repair, and is associated with a high somatic mutation burden in melanoma.

Whether cell types exposed to a high level of environmental insults possess cell type-specific prosurvival mechanisms or enhanced DNA damage repair capacity is not well understood. BRN2 is a tissue-restricted POU domain transcription factor implicated in neural development and several cancers. In melanoma, BRN2 plays a key role in promoting invasion and regulating proliferation. Here we found, surprisingly, that rather than interacting with transcription cofactors, BRN2 is instead associated with DNA damage response proteins and directly binds PARP1 and Ku70/Ku80. Rapid PARP1-dependent BRN2 association with sites of DNA damage facilitates recruitment of Ku80 and reprograms DNA damage repair by promoting Ku-dependent nonhomologous end-joining (NHEJ) at the expense of homologous recombination. BRN2 also suppresses an apoptosis-associated gene expression program to protect against UVB-, chemotherapy- and vemurafenib-induced apoptosis. Remarkably, BRN2 expression also correlates with a high single-nucleotide variation prevalence in human melanomas. By promoting error-prone DNA damage repair via NHEJ and suppressing apoptosis of damaged cells, our results suggest that BRN2 contributes to the generation of melanomas with a high mutation burden. Our findings highlight a novel role for a key transcription factor in reprogramming DNA damage repair and suggest that BRN2 may impact the response to DNA-damaging agents in BRN2-expressing cancers.

Patterns of somatic structural variation in human cancer genomes.

A key mutational process in cancer is structural variation, in which rearrangements delete, amplify or reorder genomic segments that range in size from kilobases to whole chromosomes1-7. Here we develop methods to group, classify and describe somatic structural variants, using data from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumour types8. Sixteen signatures of structural variation emerged. Deletions have a multimodal size distribution, assort unevenly across tumour types and patients, are enriched in late-replicating regions and correlate with inversions. Tandem duplications also have a multimodal size distribution, but are enriched in early-replicating regions-as are unbalanced translocations. Replication-based mechanisms of rearrangement generate varied chromosomal structures with low-level copy-number gains and frequent inverted rearrangements. One prominent structure consists of 2-7 templates copied from distinct regions of the genome strung together within one locus. Such cycles of templated insertions correlate with tandem duplications, and-in liver cancer-frequently activate the telomerase gene TERT. A wide variety of rearrangement processes are active in cancer, which generate complex configurations of the genome upon which selection can act.

Somatic mutations and clonal dynamics in healthy and cirrhotic human liver.

The most common causes of chronic liver disease are excess alcohol intake, viral hepatitis and non-alcoholic fatty liver disease, with the clinical spectrum ranging in severity from hepatic inflammation to cirrhosis, liver failure or hepatocellular carcinoma (HCC). The genome of HCC exhibits diverse mutational signatures, resulting in recurrent mutations across more than 30 cancer genes1-7. Stem cells from normal livers have a low mutational burden and limited diversity of signatures8, which suggests that the complexity of HCC arises during the progression to chronic liver disease and subsequent malignant transformation. Here, by sequencing whole genomes of 482 microdissections of 100-500 hepatocytes from 5 normal and 9 cirrhotic livers, we show that cirrhotic liver has a higher mutational burden than normal liver. Although rare in normal hepatocytes, structural variants, including chromothripsis, were prominent in cirrhosis. Driver mutations, such as point mutations and structural variants, affected 1-5% of clones. Clonal expansions of millimetres in diameter occurred in cirrhosis, with clones sequestered by the bands of fibrosis that surround regenerative nodules. Some mutational signatures were universal and equally active in both non-malignant hepatocytes and HCCs; some were substantially more active in HCCs than chronic liver disease; and others-arising from exogenous exposures-were present in a subset of patients. The activity of exogenous signatures between adjacent cirrhotic nodules varied by up to tenfold within each patient, as a result of clone-specific and microenvironmental forces. Synchronous HCCs exhibited the same mutational signatures as background cirrhotic liver, but with higher burden. Somatic mutations chronicle the exposures, toxicity, regeneration and clonal structure of liver tissue as it progresses from health to disease.

NF2-related schwannomatosis and other schwannomatosis: an updated genetic and epidemiological study.

OBJECTIVES: New diagnostic criteria for NF2-related schwannomatosis (NF2) were published in 2022. An updated UK prevalence was generated in accordance with these, with an emphasis on the rate of de novo NF2 (a 50% frequency is widely quoted in genetic counselling). The distribution of variant types among de novo and familial NF2 cases was also assessed. METHODS: The UK National NF2 database identifies patients meeting updated NF2 criteria from a highly ascertained population cared for by England's specialised service. Diagnostic prevalence was assessed on 1 February 2023. Molecular analysis of blood and, where possible, tumour specimens for NF2, LZTR1 and SMARCB1 was performed. RESULTS: 1084 living NF2 patients were identified on prevalence day (equivalent to 1 in 61 332). The proportion with NF2 inherited from an affected parent was only 23% in England. If people without a confirmed molecular diagnosis or bilateral vestibular schwannoma are excluded, the frequency of de novo NF2 remains high (72%). Of the identified de novo cases, almost half were mosaic. The most common variant type was nonsense variants, accounting for 173/697 (24.8%) of people with an established variant, but only 18/235 (7.7%) with an inherited NF2 pathogenic variant (p<0.0001). Missense variants had the highest proportion of familial association (56%). The prevalence of LZTR1-related schwannomatosis and SMARCB1-related schwannomatosis was 1 in 527 000 and 1 in 1.1M, respectively, 8.4-18.4 times lower than NF2. CONCLUSIONS: This work confirms a much higher rate of de novo NF2 than previously reported and highlights the benefits of maintaining patient databases for accurate counselling.

The makings of an exclusive community: students' perceptions of dangerous others.

Contemporarily, universities are perceived as neoliberal entities, self-absorbed, driven by corporate interests, markets and economic goals, rather than perceived as providing a public good, concerned for the wider world (del Cerro Santamaria in Review of European Studies, 12(1), 22-38, 2020). This perception of universities as individualised communities rather than collective communities (Rousseau in Social Currents, 7(5), 395-401, 2020) accentuates the responsibilisation of individuals who are viewed as responsible for solving their own problems (Martinez and Garcia in What is neoliberalism, 2000), including ensuring their own safety (Garland in The British Journal of Criminology, 36(4), 445-471, 1996). Set against this social-political backdrop, this paper, using data from an online survey about students' perceptions of on-campus safety at a university in the north of England, shows how some students, particularly women students, view others as dangerous, rather than view them as vulnerable groups who are residing on the margins of an inequitable society. The porous borders of the university campuses amplify some students' perceptions of dangerous others and students' suggestions for campus security to keep out such others arguably serve to aggravate rather than relieve their perceptions of unsafety. Yet the porous borders of the campuses should be seen as advantageous because an ecological university can connect its students to the wider world to help facilitate care for the other (Barnett in The ecological university, 2018). In doing so, this may enhance students' own sense of well-being and safety in the urban environment. This is a timely argument amidst a global pandemic, where the university restricts access to unauthorised others and, in doing so, facilitates the makings of an exclusive community.

Re-evaluation of missense variant classifications in NF2.

Missense variants in the NF2 gene result in variable NF2 disease presentation. Clinical classification of missense variants often represents a challenge, due to lack of evidence for pathogenicity and function. This study provides a summary of NF2 missense variants, with variant classifications based on currently available evidence. NF2 missense variants were collated from pathology-associated databases and existing literature. Association for Clinical Genomic Sciences Best Practice Guidelines (2020) were followed in the application of evidence for variant interpretation and classification. The majority of NF2 missense variants remain classified as variants of uncertain significance. However, NF2 missense variants identified in gnomAD occurred at a consistent rate across the gene, while variants compiled from pathology-associated databases displayed differing rates of variation by exon of NF2. The highest rate of NF2 disease-associated variants was observed in exon 7, while lower rates were observed toward the C-terminus of the NF2 protein, merlin. Further phenotypic information associated with variants, alongside variant-specific functional analysis, is necessary for more definitive variant interpretation. Our data identified differences in frequency of NF2 missense variants by exon between gnomAD population data and NF2 disease-associated variants, suggesting a potential genotype-phenotype correlation; further work is necessary to substantiate this.

Factors influencing fatigue in UK nurses working in respiratory clinical areas during the second wave of the Covid-19 pandemic: An online survey.

AIMS AND OBJECTIVES: This study explores UK nurses' experiences of working in a respiratory clinical area during the COVID-19 pandemic over winter 2020. BACKGROUND: During the first wave of the pandemic, nurses working in respiratory clinical areas experienced significant levels of anxiety and depression. As the pandemic has progressed, levels of fatigue in nurses have not been assessed. METHODS: A cross-sectional e-survey was distributed via professional respiratory societies and social media. The survey included Generalised Anxiety Disorder Assessment (GAD7), Patient Health Questionnaire (PHQ9, depression), a resilience scale (RS-14) and Chalder mental and physical fatigue tools. The STROBE checklist was followed as guidance to write the manuscript. RESULTS: Despite reporting anxiety and depression, few nurses reported having time off work with stress, most were maintaining training and felt prepared for COVID challenges in their current role. Nurses reported concerns over safety and patient feedback was both positive and negative. A quarter of respondents reported wanting to leave nursing. Nurses experiencing greater physical fatigue reported higher levels of anxiety and depression. CONCLUSIONS: Nurses working in respiratory clinical areas were closely involved in caring for COVID-19 patients. Nurses continued to experience similar levels of anxiety and depression to those found in the first wave and reported symptoms of fatigue (physical and mental). A significant proportion of respondents reported considering leaving nursing. Retention of nurses is vital to ensure the safe functioning of already overstretched health services. Nurses would benefit from regular mental health check-ups to ensure they are fit to practice and receive the support they need to work effectively. RELEVANCE TO CLINICAL PRACTICE: A high proportion of nurses working in respiratory clinical areas have been identified as experiencing fatigue in addition to continued levels of anxiety, depression over winter 2020. Interventions need to be implemented to help provide mental health support and improve workplace conditions to minimise PTSD and burnout.

Pathogenic Variants in PIGG Cause Intellectual Disability with Seizures and Hypotonia.

Glycosylphosphatidylinositol (GPI) is a glycolipid that anchors >150 various proteins to the cell surface. At least 27 genes are involved in biosynthesis and transport of GPI-anchored proteins (GPI-APs). To date, mutations in 13 of these genes are known to cause inherited GPI deficiencies (IGDs), and all are inherited as recessive traits. IGDs mainly manifest as intellectual disability, epilepsy, coarse facial features, and multiple organ anomalies. These symptoms are caused by the decreased surface expression of GPI-APs or by structural abnormalities of GPI. Here, we present five affected individuals (from two consanguineous families from Egypt and Pakistan and one non-consanguineous family from Japan) who show intellectual disability, hypotonia, and early-onset seizures. We identified pathogenic variants in PIGG, a gene in the GPI pathway. In the consanguineous families, homozygous variants c.928C>T (p.Gln310(∗)) and c.2261+1G>C were found, whereas the Japanese individual was compound heterozygous for c.2005C>T (p.Arg669Cys) and a 2.4 Mb deletion involving PIGG. PIGG is the enzyme that modifies the second mannose with ethanolamine phosphate, which is removed soon after GPI is attached to the protein. Physiological significance of this transient modification has been unclear. Using B lymphoblasts from affected individuals of the Egyptian and Japanese families, we revealed that PIGG activity was almost completely abolished; however, the GPI-APs had normal surface levels and normal structure, indicating that the pathogenesis of PIGG deficiency is not yet fully understood. The discovery of pathogenic variants in PIGG expands the spectrum of IGDs and further enhances our understanding of this etiopathogenic class of intellectual disability.

Genomic Classification and Prognosis in Acute Myeloid Leukemia.

BACKGROUND: Recent studies have provided a detailed census of genes that are mutated in acute myeloid leukemia (AML). Our next challenge is to understand how this genetic diversity defines the pathophysiology of AML and informs clinical practice. METHODS: We enrolled a total of 1540 patients in three prospective trials of intensive therapy. Combining driver mutations in 111 cancer genes with cytogenetic and clinical data, we defined AML genomic subgroups and their relevance to clinical outcomes. RESULTS: We identified 5234 driver mutations across 76 genes or genomic regions, with 2 or more drivers identified in 86% of the patients. Patterns of co-mutation compartmentalized the cohort into 11 classes, each with distinct diagnostic features and clinical outcomes. In addition to currently defined AML subgroups, three heterogeneous genomic categories emerged: AML with mutations in genes encoding chromatin, RNA-splicing regulators, or both (in 18% of patients); AML with TP53 mutations, chromosomal aneuploidies, or both (in 13%); and, provisionally, AML with IDH2(R172) mutations (in 1%). Patients with chromatin-spliceosome and TP53-aneuploidy AML had poor outcomes, with the various class-defining mutations contributing independently and additively to the outcome. In addition to class-defining lesions, other co-occurring driver mutations also had a substantial effect on overall survival. The prognostic effects of individual mutations were often significantly altered by the presence or absence of other driver mutations. Such gene-gene interactions were especially pronounced for NPM1-mutated AML, in which patterns of co-mutation identified groups with a favorable or adverse prognosis. These predictions require validation in prospective clinical trials. CONCLUSIONS: The driver landscape in AML reveals distinct molecular subgroups that reflect discrete paths in the evolution of AML, informing disease classification and prognostic stratification. (Funded by the Wellcome Trust and others; ClinicalTrials.gov number, NCT00146120.).

Melatonin and health: an umbrella review of health outcomes and biological mechanisms of action.

BACKGROUND: Our aims were to evaluate critically the evidence from systematic reviews as well as narrative reviews of the effects of melatonin (MLT) on health and to identify the potential mechanisms of action involved. METHODS: An umbrella review of the evidence across systematic reviews and narrative reviews of endogenous and exogenous (supplementation) MLT was undertaken. The Oxman checklist for assessing the methodological quality of the included systematic reviews was utilised. The following databases were searched: MEDLINE, EMBASE, Web of Science, CENTRAL, PsycINFO and CINAHL. In addition, reference lists were screened. We included reviews of the effects of MLT on any type of health-related outcome measure. RESULTS: Altogether, 195 reviews met the inclusion criteria. Most were of low methodological quality (mean -4.5, standard deviation 6.7). Of those, 164 did not pool the data and were synthesised narratively (qualitatively) whereas the remaining 31 used meta-analytic techniques and were synthesised quantitatively. Seven meta-analyses were significant with P values less than 0.001 under the random-effects model. These pertained to sleep latency, pre-operative anxiety, prevention of agitation and risk of breast cancer. CONCLUSIONS: There is an abundance of reviews evaluating the effects of exogenous and endogenous MLT on health. In general, MLT has been shown to be associated with a wide variety of health outcomes in clinically and methodologically heterogeneous populations. Many reviews stressed the need for more high-quality randomised clinical trials to reduce the existing uncertainties.

Prognosis for patients with CML and >10% BCR-ABL1 after 3 months of imatinib depends on the rate of BCR-ABL1 decline.

In chronic myeloid leukemia (CML) patients, a breakpoint cluster region-Abelson (BCR-ABL1) value >10% at 3 months of therapy is statistically associated with poorer outcome, yet many of these patients still achieve satisfactory outcomes. We investigated 528 first-line imatinib-treated patients to determine whether patients with the poorest outcome can be better discriminated at 3 months. All outcomes were significantly superior for the 410 patients with BCR-ABL1 ≤10% at 3 months (P < .001). However, the poorest outcomes among the 95 evaluable patients with BCR-ABL1 >10% at 3 months were identified by the rate of BCR-ABL1 decline from baseline, assessed by estimating the number of days over which BCR-ABL1 halved. Patients with BCR-ABL1 halving time <76 days (n = 74) had significantly superior outcomes compared with patients whose BCR-ABL1 values did not halve by 76 days (n = 21; 4-year overall survival, 95% vs 58%, P = .0002; progression-free survival, 92% vs 63%, P = .008; failure-free survival, 59% vs 6%, P < .0001; and major molecular response, 54% vs 5%, P = .008). By multivariate analysis, the halving time was an independent predictor of outcome in this poor risk group. Our study highlighted that the rate of BCR-ABL1 decline may be a critical prognostic discriminator of the patients with very poor outcome among those >10% at 3 months. The International Randomized IFN vs STI571 (IRIS) trial was registered at http://www.clinicaltrials.gov as #NCT00006343. The Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) trial was registered at http://www.clinicaltrials.gov as #NCT00124748. The Therapeutic Intensification in DE-novo Leukaemia (TIDEL) I trial was registered at http://www.ANZCTR.org.au as #ACTRN12607000614493. The TIDEL II trial was registered at http://www.ANZCTR.org.au as #ACTRN12607000325404.

A comparative analysis of algorithms for somatic SNV detection in cancer.

MOTIVATION: With the advent of relatively affordable high-throughput technologies, DNA sequencing of cancers is now common practice in cancer research projects and will be increasingly used in clinical practice to inform diagnosis and treatment. Somatic (cancer-only) single nucleotide variants (SNVs) are the simplest class of mutation, yet their identification in DNA sequencing data is confounded by germline polymorphisms, tumour heterogeneity and sequencing and analysis errors. Four recently published algorithms for the detection of somatic SNV sites in matched cancer-normal sequencing datasets are VarScan, SomaticSniper, JointSNVMix and Strelka. In this analysis, we apply these four SNV calling algorithms to cancer-normal Illumina exome sequencing of a chronic myeloid leukaemia (CML) patient. The candidate SNV sites returned by each algorithm are filtered to remove likely false positives, then characterized and compared to investigate the strengths and weaknesses of each SNV calling algorithm. RESULTS: Comparing the candidate SNV sets returned by VarScan, SomaticSniper, JointSNVMix2 and Strelka revealed substantial differences with respect to the number and character of sites returned; the somatic probability scores assigned to the same sites; their susceptibility to various sources of noise; and their sensitivities to low-allelic-fraction candidates. AVAILABILITY: Data accession number SRA081939, code at http://code.google.com/p/snv-caller-review/ CONTACT: david.adelson@adelaide.edu.au SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A women-centred exploration of postpartum perineal pain when the perineum is diagnosed as intact: A French Gadamerian research study.

BACKGROUND: Postpartum perineal pain is a frequent symptom (90%) with consequences on postnatal health regardless of whether the perineum remains intact. The impact of that pain on both short and long-term health has been studied and literature suggests midwives have a role to play in addressing this issue. However, the determinants of perineal pain when no lesions are identified are under researched and there is little understanding of women's views on this topic. AIM AND OBJECTIVES: The aim of the study was to gain an understanding of postpartum perineal pain when the perineum is considered to be intact. The objectives were •To gain an understanding of postpartum pain and its consequences on health and well-being •To explore women's views and understanding of perineal pain postpartum •To gain an understanding of the determinants of postpartum perineal pain when no anatomic lesion is diagnosed. METHODS: A Gadamerian hermeneutic approach was used to achieve a shared understanding of the issue. Participants were recruited from two maternity hospitals in the French area of Vaucluse. All women aged 18 to 45 years old, having given birth vaginally to a single live child and diagnosed with an intact perineum, were invited to participate in face-to-face interviews. Eleven participants were interviewed once, six of whom agreed to a second interview which took place over the telephone due to Covid lockdown. FINDINGS: The findings identified three major themes 1. Can't honestly call it pain, 2. Reassurance in normality, 3. Managing the unexpected. The use of the word pain to describe perineal sensations in postpartum was questioned by the participants, who used inner resources to deal with these sensations. Fostering self-confidence, having the possibility to explain the sensations and qualifying them as normal were some approaches women usedto manage their postpartum perineal sensations in a positive manner.

Quality of life of children and young people with anterior chest wall deformity: a systematic review of the literature.

OBJECTIVE: The aim of this study was to evaluate the current evidence regarding the quality of life (QoL) of children and young people with anterior chest wall deformity (ACWD). METHODS: Using a defined search strategy, a systematic review of the literature was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. RESULTS: The search identified 305 articles, after refinement, the full text of 51 studies were reviewed and 10 included in the review. A total of eight studies described QoL associated with the correction of ACWD and two studies reported on QoL without correction. The surgical correction of ACWD was reported in six studies and non-surgical correction in two studies. A total of three disease-specific and 24 generic QoL measures were used. The variation in QoL outcome measures, together with a lack of consistency in the time scales of data collection, did not allow for direct comparison between studies. However, the improvement in psychosocial QoL following correction of ACWD is clear. The impact of ACWD on physical QoL is less defined and the influence of age, gender, severity and type of deformity is uncertain. The literature identified primarily surrounds QoL outcomes in relation to surgical correction and is therefore not representative of all children and young people with ACWD. CONCLUSIONS: Correction of ACWD is associated with significant improvement in the psychosocial QoL of children and young people. Further work is required to standardise QoL data collection for all children with ACWD to achieve a greater understanding of the impact and guide future management.

The management of symptomatic hyperostotic bilateral spheno-orbital meningiomas: patient series.

BACKGROUND: The occurrence of hyperostotic bilateral spheno-orbital meningiomas (BSOMs) is very rare. Patients present with bilateral symptoms and require bilateral treatment. This series describes 6 patients presenting to 2 UK neurosurgical units and includes a literature review. To the best of the authors' knowledge, this is the largest series documented. OBSERVATIONS: This is a retrospective review of patients with BSOMs presenting between 2006 and 2023. Six females, whose mean age was 43 (range: 36-64) years, presented with features of visual disturbance. Bilateral sphen-oorbital meningiomas were identified. All patients underwent bilateral staged resections. The patients had an initial improvement in their symptoms. Extensive genetic testing was performed in 4 patients, with no variants in the NF2, LZTR1, SMARCB1, SMARCE1, and SMARCA4 genes or other variants detected. The mean follow-up was 100.3 (range: 64-186) months. Sixty-seven percent of patients had good long-term visual acuity. The progression rate was 75% and was particularly aggressive in 1 patient. Four patients required radiation therapy, and 2 needed further surgery. LESSONS: Hyperostotic BSOMs are extensive, challenging tumors causing significant disability. They can recur, with significant patient impact. Multidisciplinary management and indefinite long-term follow-up are essential. The biology of these tumors remains unclear. As molecular testing expands, the understanding of BSOM oncogenesis and potential therapeutic targets is likely to improve.

Nurse led versus lay educators support for those with asthma in primary care: a costing study.

BACKGROUND: Regular review and support for asthma self-management is promoted in guidelines. A randomised controlled trial suggested that unscheduled health care usage was similar when patients were offered self management support by a lay-trainer or practice nurses. METHODS: Following the RCT, a costing study was undertaken using the trial data to account for the cost of delivery of the service under both strategies and the resulting impact on unscheduled healthcare (measure of effectiveness) in this trial. RESULTS: One year data (n = 418) showed that 29% (61/205) of the nurse group required unscheduled healthcare (177 events) compared with 30.5% (65/213) for lay-trainers (178 events).The training costs for the lay-trainers were greater than nurses (£36 versus £18 respectively per patient, p<0.001), however, the consultation cost for lay-trainers were lower than nurses (£6 per patient versus £24, p<0.001). If the cost of unscheduled healthcare are accounted for then the costs of nurses is £161, and £135 for lay-trainers (mean difference £25, [95% CI = -£97, £149, p = 0.681]). The total costs (delivery and unscheduled healthcare) were £202 per patient for nurses versus £178 for lay-trainers, (mean difference £24, [95%CI = -£100, £147, p = 0.707]). CONCLUSIONS: There were no significant differences in the cost of training and healthcare delivery between nurse and lay trainers, and no significant difference in the cost of unscheduled health care use.

A centralised respiratory diagnostic service for primary care: a 4-year audit.

BACKGROUND: The literature shows that delayed or erroneous diagnosis of respiratory conditions may be common in primary care due to underuse of spirometry or poor spirometric technique. The Community Respiratory Assessment Unit (CRAU) was established to optimise diagnosis and treatment of respiratory disease by providing focused history-taking, quality-assured spirometry, and evidence-based guideline-derived management advice. AIMS: To review the service provided by the CRAU to primary care health professionals. METHODS: Data from 1,156 consecutive GP referrals over 4 years were analysed. RESULTS: From the 1,156 referrals, 666 were referred for one of five common reasons: suspected asthma, confirmed asthma, suspected chronic obstructive pulmonary disease (COPD), confirmed COPD, or unexplained breathlessness. COPD was the most prevalent referral indication (445/666, 66.8%), but one-third of suggested diagnoses of COPD by the GP were found to be incorrect (161/445, 36%) with inappropriate prescribing of inhaled therapies resulting from this misdiagnosis. Restrictive pulmonary defects (56/666, 8% of referrals) were overlooked and often mistaken for obstructive conditions. The potential for obesity to cause breathlessness may not be fully appreciated. CONCLUSIONS: Misdiagnosis has significant financial, ethical, and safety implications. This risk may be minimised by better support for primary care physicians such as diagnostic centres (CRAU) or alternative peripatetic practice-based services operating to quality-controlled standards.

Self-management in chronic lung disease: what is missing?

Self-management, as a strategy to support those living with chronic respiratory conditions such as asthma and COPD, has been widely advocated in guidelines and adopted in practice. However, there can be a disconnect between the goals of patients and healthcare professionals. Goals and barriers to self-management are often compounded by the complex social, emotional and medical needs of patients. People living with chronic respiratory conditions also often have symptoms of anxiety and depression, which can impact on self-management. Self-management therefore requires patients and healthcare professionals to work together and it is essential to involve patients when designing, implementing and evaluating self-management interventions. Patient preferences are clearly important and goal setting needs an individual, flexible and responsive approach from healthcare professionals, which aligns to a more personalised approach to management of treatable traits and the burden of disease. To achieve these goals, healthcare professionals need education to support patients in self-management and behaviour change. This approach should lead to shared decision-making and partnership working that puts the patient right at the centre of their care.