Global mortality and readmission rates following COPD exacerbation-related hospitalisation: a meta-analysis of 65 945 individual patients.

Background: Exacerbations of COPD (ECOPD) have a major impact on patients and healthcare systems across the world. Precise estimates of the global burden of ECOPD on mortality and hospital readmission are needed to inform policy makers and aid preventive strategies to mitigate this burden. The aims of the present study were to explore global in-hospital mortality, post-discharge mortality and hospital readmission rates after ECOPD-related hospitalisation using an individual patient data meta-analysis (IPDMA) design. Methods: A systematic review was performed identifying studies that reported in-hospital mortality, post-discharge mortality and hospital readmission rates following ECOPD-related hospitalisation. Data analyses were conducted using a one-stage random-effects meta-analysis model. This study was conducted and reported in accordance with the PRISMA-IPD statement. Results: Data of 65 945 individual patients with COPD were analysed. The pooled in-hospital mortality rate was 6.2%, pooled 30-, 90- and 365-day post-discharge mortality rates were 1.8%, 5.5% and 10.9%, respectively, and pooled 30-, 90- and 365-day hospital readmission rates were 7.1%, 12.6% and 32.1%, respectively, with noticeable variability between studies and countries. Strongest predictors of mortality and hospital readmission included noninvasive mechanical ventilation and a history of two or more ECOPD-related hospitalisations <12 months prior to the index event. Conclusions: This IPDMA stresses the poor outcomes and high heterogeneity of ECOPD-related hospitalisation across the world. Whilst global standardisation of the management and follow-up of ECOPD-related hospitalisation should be at the heart of future implementation research, policy makers should focus on reimbursing evidence-based therapies that decrease (recurrent) ECOPD.

Recommendations for surveillance of pulmonary dysfunction among childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Childhood, adolescent, and young adult (CAYA) cancer survivors are at risk of pulmonary dysfunction. Current follow-up care guidelines are discordant. Therefore, the International Late Effects of Childhood Cancer Guideline Harmonization Group established and convened a panel of 33 experts to develop evidence-based surveillance guidelines. We critically reviewed available evidence regarding risk factors for pulmonary dysfunction, types of pulmonary function testing, and timings of surveillance, then we formulated our recommendations. We recommend that CAYA cancer survivors and healthcare providers are aware of reduced pulmonary function risks and pay vigilant attention to potential symptoms of pulmonary dysfunction, especially among survivors treated with allogeneic haematopoietic stem cell transplantation, thoracic radiotherapy, and thoracic surgery. Based on existing limited evidence and current lack of interventions, our panel recommends pulmonary function testing only for symptomatic survivors. Since scarce existing evidence informs our recommendation, we highlight the need for prospective collaborative studies to address pulmonary function knowledge gaps among CAYA cancer survivors.

Monitoring of ECFS quality standards for the clinical management of adults with cystic fibrosis.

BACKGROUND: Although cystic fibrosis (CF) standards of care have been produced and regularly updated, they are not specifically targeting at the adult population. The ECFS Standards of Care Project established an international task force of experts to identify quality standards for adults with CF and assess their adherence. METHODS: This study was composed of two phases. In the first one, a task force of international experts derived from published guidelines and graded ten quality standards for adult CF care using a modified Delphi methodology. In the second phase, an international audit was conducted among adult CF centers to retrospectively validate the quality statements and monitor adherence. RESULTS: The task force identified 10 quality standards specific to the care of adults with CF, mainly based on the 2018 ECFS standards of care. 14 adult CF centers participated in the audit, which showed that most quality standards for the management of CF in adults are met across Europe. Heterogeneity in adherence to standards was found across centers according to geographical setting and centers' characteristics. CONCLUSIONS: The identification of quality standards is a valuable resource for the standardization and monitoring of care delivery across centers taking care of adults with CF.

Systematic review and meta-analysis of prevalence of undiagnosed major cardiac comorbidities in COPD.

Background: It is often stated that heart disease is underdiagnosed in COPD. Evidence for this statement comes from primary studies, but these have not been synthesised to provide a robust estimate of the burden of undiagnosed heart disease. Methods: A systematic review of studies using active diagnostic techniques to establish the prevalence of undiagnosed major cardiac comorbidities in patients with COPD was carried out. MEDLINE, Embase, Scopus and Web of Science were searched for terms relating to heart failure (specifically, left ventricular systolic dysfunction (LVSD), coronary artery disease (CAD) and atrial fibrillation), relevant diagnostic techniques and COPD. Studies published since 1980, reporting diagnosis rates using recognised diagnostic criteria in representative COPD populations not known to have heart disease were included. Studies were classified by condition diagnosed, diagnostic threshold used and whether participants had stable or exacerbated COPD. Random-effects meta-analysis of prevalence was conducted where appropriate. Results: In general, prevalence estimates for undiagnosed cardiac comorbidities in COPD had broad confidence intervals, with significant study heterogeneity. Most notably, a prevalence of undiagnosed LVSD of 15.8% (11.1-21.1%) was obtained when defined as left ventricular ejection fraction <50%. Undiagnosed CAD was found in 2.3-18.0% of COPD patients and atrial fibrillation in 1.4% (0.3-3.5%). Conclusion: Further studies using recent diagnostic advances, and investigating therapeutic interventions for patients with COPD and heart disease are needed.

Admission blood eosinophil count, inpatient death and death at 1 year in exacerbating patients with COPD.

BACKGROUND: Blood eosinophil counts have been studied in patients with stable chronic obstructive pulmonary disease (COPD) and are a useful biomarker to guide inhaled corticosteroid use. Less is known about eosinophil counts during severe exacerbation. METHODS: In this retrospective study, 2645 patients admitted consecutively with COPD exacerbation across six UK hospitals were included in the study, and the clinical diagnosis was confirmed by a respiratory specialist. The relationship between admission eosinophil count, inpatient death and 1-year death was assessed. In a backward elimination, Poisson regression analysis using the log-link function with robust estimates, patients' markers of acute illness and stable-state characteristics were assessed in terms of their association with eosinopenia. RESULTS: 1369 of 2645 (52%) patients had eosinopenia at admission. Those with eosinopenia had a 2.5-fold increased risk of inpatient death compared with those without eosinopenia (12.1% vs 4.9%, RR=2.50, 95% CI 1.88 to 3.31, p<0.001). The same mortality risk with eosinopenia was seen among the subgroup with pneumonic exacerbation (n=788, 21.3% vs 8.5%, RR=2.5, 95% CI 1.67 to 2.24, p<0.001). In a regression analysis, eosinopenia was significantly associated with: older age and male sex; a higher pulse rate, temperature, neutrophil count, urea and C reactive protein level; a higher proportion of patients with chest X-ray consolidation and a reduced Glasgow Coma Score; and lower systolic and diastolic blood pressure measurements and lower oxygen saturation, albumin, platelet and previous admission counts. DISCUSSION: During severe COPD exacerbation, eosinopenia is common and associated with inpatient death and several markers of acute illness. Clinicians should be cautious about using eosinophil results obtained during severe exacerbation to guide treatment decisions regarding inhaled corticosteroid use.

Characterisation of key genotypic and phenotypic traits of clinical cystic fibrosis Staphylococcus aureus isolates.

Introduction. One third of people with CF in the UK are co-infected by both Staphylococcus aureus and Pseudomonas aeruginosa. Chronic bacterial infection in CF contributes to the gradual destruction of lung tissue, and eventually respiratory failure in this group.Gap Statement. The contribution of S. aureus to cystic fibrosis (CF) lung decline in the presence or absence of P. aeruginosa is unclear. Defining the molecular and phenotypic characteristics of a range of S. aureus clinical isolates will help further understand its pathogenic capabilities.Aim. Our objective was to use molecular and phenotypic tools to characterise twenty-five clinical S. aureus isolates collected from mono- and coinfection with P. aeruginosa from people with CF at the Royal Victoria Infirmary, Newcastle upon Tyne.Methodology. Genomic DNA was extracted and sequenced. Multilocus sequence typing was used to construct phylogeny from the seven housekeeping genes. A pangenome was calculated using Roary, and cluster of Orthologous groups were assigned using eggNOG-mapper which were used to determine differences within core, accessory, and unique genomes. Characterisation of sequence type, clonal complex, agr and spa types was carried out using PubMLST, eBURST, AgrVATE and spaTyper, respectively. Antibiotic resistance was determined using Kirby-Bauer disc diffusion tests. Phenotypic testing of haemolysis was carried out using ovine red blood cell agar plates and mucoid phenotypes visualised using Congo red agar.Results. Clinical strains clustered closely based on agr type, sequence type and clonal complex. COG analysis revealed statistically significant enrichment of COG families between core, accessory and unique pangenome groups. The unique genome was significantly enriched for replication, recombination and repair, and defence mechanisms. The presence of known virulence genes and toxins were high within this group, and unique genes were identified in 11 strains. Strains which were isolated from the same patient all surpassed average nucleotide identity thresholds, however, differed in phenotypic traits. Antimicrobial resistance to macrolides was significantly higher in the coinfection group.Conclusion. There is huge variation in genetic and phenotypic capabilities of S. aureus strains. Further studies on how these may differ in relation to other species in the CF lung may give insight into inter-species interactions.

Elexacaftor-Tezacaftor-Ivacaftor improve Gastro-Oesophageal reflux and Sinonasal symptoms in advanced cystic fibrosis.

Upper gastrointestinal and upper airway disease are common in cystic fibrosis (CF) and may contribute to lower airway infection and inflammation. In a longitudinal cohort study of 32 patients (23 men; median age 32.5 years) with advanced CF lung disease (median FEV1 24.8% predicted) starting elexacaftor-tezacaftor-ivacaftor, the reflux symptom index score fell from a pre-treatment median (IQR) of 15 (11-23) to 5 (2.8-7.3) (p<0.001), the Hull airway reflux score fell from a median of 26.5 (16.3-39) to 7.5 (4-12) (p<0.001), and the sinonasal outcome score from a median of 36.5 (22-24) to 20 (10-32) (p<0.001) at 6 months on treatment. Mean FEV1% predicted rose by 9.2 points, the median respiratory domain score of the CF Questionnaire-Revised rose by 27.8 points and mean body mass index rose by 2.6 kg/m2. In addition to improving lung function and weight, CFTR modulators improve upper airway and gastro-oesophageal reflux symptoms in advanced CF.

Exposure to bile and gastric juice can impact the aerodigestive microbiome in people with cystic fibrosis.

Studies of microbiota reveal inter-relationships between the microbiomes of the gut and lungs. This relationship may influence the progression of lung disease, particularly in patients with cystic fibrosis (CF), who often experience extraoesophageal reflux (EOR). Despite identifying this relationship, it is not well characterised. Our hypothesis is that the gastric and lung microbiomes in CF are related, with the potential for aerodigestive pathophysiology. We evaluated gastric and sputum bacterial communities by culture and 16S rRNA gene sequencing in 13 CF patients. Impacts of varying levels of bile acids, pepsin and pH on patient isolates of Pseudomonas aeruginosa (Pa) were evaluated. Clonally related strains of Pa and NTM were identified in gastric and sputum samples from patients with symptoms of EOR. Bacterial diversity was more pronounced in sputa compared to gastric juice. Gastric and lung bile and pepsin levels were associated with Pa biofilm formation. Analysis of the aerodigestive microbiomes of CF patients with negative sputa indicates that the gut can be a reservoir of Pa and NTM. This combined with the CF patient's symptoms of reflux and potential aspiration, highlights the possibility of communication between microorganisms of the gut and the lungs. This phenomenon merits further research.

Heart failure in patients with COPD exacerbations: Looking below the tip of the iceberg.

BACKGROUND: Patients surviving hospitalization for exacerbations of chronic obstructive pulmonary disease (ECOPD) are at heightened risk of cardiovascular events. Heart failure is often underdiagnosed and undertreated in COPD; better care could improve outcome. We aimed to capture contemporary investigation and management of heart failure (HF) in patients hospitalized with ECOPD. METHODS: In two UK hospitals, patients admitted with ECOPD between 2017 and 2020 were retrospectively identified. Baseline characteristics between known, newly diagnosed and no HF were compared using analysis of variance and chi-squared test. Impact of HF on mortality was assessed by Kaplan-Meier analysis and Cox proportional-hazards regression. Sensitivity and specificity of NT-proBNP for diagnosing HF at recognized thresholds were reported. RESULTS: On admission, 94/476 (19.7%) patients had known HF. Among remaining patients, 89/382 (23.3%) were investigated within 100 days of admission, confirming HF in 38. Of 33 patients with heart failure with reduced ejection fraction (HFrEF), 18 (54.5%) were prescribed ACE-inhibitor and B-blocker. 77/132 patients (58.3%) with HF and 108/344 patients (31.4%) without HF died (adjusted HR 2.03, 95% CI 1.46-2.82, p < 0.001) during follow up (median 11.7 months). At ≥400 pg/mL, NPV and PPV of NT-proBNP for the diagnosis of HF were 77.8% and 82.8%. CONCLUSIONS: A new diagnosis of HF was made in over 40% investigated. In patients with coexistent HF, undertreatment was common and 1-year mortality exceeded 50%. NT-proBNP may help identify patients who need cardiovascular functional imaging. Research to improve HF diagnosis and treatment in hospitalized ECOPD is urgently needed.

Impact of COVID-19 on Hospital Admissions for COPD Exacerbation: Lessons for Future Care.

Background and Objectives: Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. Acute exacerbations (AECOPD) are common and often triggered by viral infection. During the COVID-19 pandemic social restrictions, including 'shielding' and 'lockdowns', were mandated. Multiple, worldwide studies report a reduction in AECOPD admissions during this period. This study aims to assess the effect of the pandemic and Lockdown on the rates of admission with AECOPD and severity of hospitalised exacerbations in the North-East of England. Materials and Methods: Data were extracted for patients presenting with a diagnosis of AECOPD or respiratory failure secondary to AECOPD during the 'COVID-19 period' (26/3/20-31/12/20) and a date-matched control period from the year previous. We present descriptive statistics and regression analysis of the effects of the COVID-19 period on the rates of hospital admission. Results: Compared to the matched control period, the COVID-19 period was associated with fewer AECOPD admissions (COVID-19 = 719, control = 1257; rate ratio 0.57, p < 0.001) and shorter length of stay (COVID-19 = 3.9 ± 0.2, control = 4.78 ± 0.2 days; p = 0.002), with similar in-hospital plus 30-day post-discharge mortality. Demographics were similar between periods. Only six patients had a positive COVID-19 PCR test. Conclusion: During the COVID-19 period there was a substantial reduction in AECOPD admissions, but no increase in overall severity of exacerbations or mortality. Rather than fear driving delayed hospital presentation, physical and behavioural measures taken during this period to limit transmission of COVID-19 are likely to have reduced transmission of other respiratory viruses. This has important implications for control of future AECOPD.

How good is end of life care for patients dying with cystic fibrosis?

BACKGROUND: Cystic Fibrosis (CF) is a life-limiting illness. Audit of the care of patients dying of CF has not been published to date. METHODS: Newcastle and Oxford teams adapted the National Audit of Care at the End of Life and agreed additional questions that were particularly pertinent for patients dying as a consequence of their CF. Data were extracted and analysed for 15 patients. RESULTS: On recognition that the patient was dying, the CF teams were less good at reviewing the need for physiological observations (50% vs national 70%) but better at reviewing the need for capillary blood glucose monitoring, oxygen support and intravenous antibiotics compared with the national average for all patients.On recognition that the patient was dying, the CF teams were better at assessing pain (87% vs national 80%) and breathlessness (93% vs national 73%), but less good at assessing nausea and vomiting (47% vs national 74%).There was documented evidence that 100% of families and 64% of patients were aware that the patient was at risk of dying. CONCLUSION: Comparing care of this sample of patients dying with CF against the national data is a useful first step in understanding that many aspects of care are of high quality. This audit identifies the need to offer earlier conversations to patients as their voices may be missing from the conversation. Undertaking a national audit would provide a more reliable and a fuller picture.

Using a learning health system to understand the mismatch between medicines supply and actual medicines use among adults with cystic fibrosis.

BACKGROUND: Studies in separate cohorts suggest possible discrepancies between inhaled medicines supplied (median 50-60%) and medicines used (median 30-40%). We performed the first study that directly compares CF medicine supply against use to identify the cost of excess medicines supply. METHODS: This cross-sectional study included participants from 12 UK adult centres with ≥1 year of continuous adherence data from data-logging nebulisers. Medicine supply was measured as medication possession ratio (MPR) for a 1-year period from the first suitable supply date. Medicine use was measured as electronic data capture (EDC) adherence over the same period. The cost of excess medicines was calculated as whole excess box(es) supplied after accounting for the discrepancy between EDC adherence and MPR with 20% contingency. RESULTS: Among 275 participants, 133 (48.4%) were females and mean age was 30 years (95% CI 29-31 years). Median EDC adherence was 57% (IQR 23-86%), median MPR was 74% (IQR 46-96%) and the discrepancy between measures was median 14% (IQR 2-29%). Even with 20% contingency, mean potential cost of excess medicines was £1,124 (95% CI £855-1,394), ranging from £183 (95% CI £29-338) for EDC adherence ≥80% to £2,017 (95% CI £1,507-2,526) for EDC adherence <50%. CONCLUSIONS: This study provides a conservative estimate of excess inhaled medicines supply cost among adults with CF in the UK. The excess supply cost was highest among those with lowest EDC adherence, highlighting the importance of adherence support and supplying medicine according to actual use. MPR provides information about medicine supply but over-estimates actual medicine use.

Uptake of Clinical Prognostic Tools in COPD Exacerbations Requiring Hospitalisation.

Clinical prognostic tools are used to objectively predict outcomes in many fields of medicine. Whilst over 400 have been developed for use in chronic obstructive pulmonary disease (COPD), only a minority have undergone full external validation and just one, the DECAF score, has undergone an implementation study supporting use in clinical practice. Little is known about how such tools are used in the UK. We distributed surveys at two time points, in 2017 and 2019, to hospitals included in the Royal College of Physicians of London national COPD secondary care audit program. The survey assessed the use of prognostic tools in routine care of hospitalized COPD patients. Hospital response rates were 71/196 in 2017 and 72/196 in 2019. The use of the DECAF and PEARL scores more than doubled in decisions about unsupported discharge (7%-15.3%), admission avoidance (8.1%-17%) and readmission avoidance (4.8%-13.1%); it more than tripled (8.8%-27.8%) in decisions around hospital-at-home or early supported discharge schemes. In other areas, routine use of clinical prognostic tools was uncommon. In palliative care decisions, the use of the Gold Standards Framework Prognostic Indicator Guidance fell (5.6%-1.4%). In 2017, 43.7% of hospitals used at least one clinical prognostic tool in routine COPD care, increasing to 52.1% in 2019. Such tools can help challenge prognostic pessimism and improve care. To integrate these further into routine clinical care, future research should explore current barriers to their use and focus on implementation studies.Supplemental data for this article is available online at https://dx.doi.org/10.1080/15412555.2021.1959540.

Decontamination Strategies Used for AFB Culture Significantly Reduce the Viability of Mycobacterium abscessus Complex in Sputum Samples from Patients with Cystic Fibrosis.

Nontuberculous mycobacteria are important respiratory pathogens in patients with cystic fibrosis (CF). For diagnosis, international guidelines recommend culture of sputum that has been decontaminated via chemical treatment. Fifty-six sputum samples from 32 patients known to be previously colonized or infected with NTM were subdivided, and the aliquots were subjected to six different decontamination strategies, followed by quantitative culture for NTM. Thirty sputum samples contained Mycobacterium abscessus complex (MABSC) and 11 contained Mycobacterium avium complex (MAC). Decontamination strategies included treatment with N-acetyl L-cysteine with 2% sodium hydroxide (NALC-NaOH), 4% NaOH, 1% chlorhexidine, 0.5 N sulfuric acid, 5% oxalic acid, double decontamination with NALC-NaOH, followed by 5% oxalic acid, and saline (0.85%) as a control. The samples were also cultured directly with no treatment. Treatment with NALC-NaOH resulted in an average reduction in colony count of 87% for MABSC when compared with direct culture. NaOH at 4% caused a 98.3% average reduction in colony count. All treatments that included NaOH resulted in colony counts that were statistically lower than those obtained from direct culture or the saline-treated control (p < 0.05). Standard treatments using sulfuric or oxalic acids were less deleterious, but still resulted in an average reduction in colony count of at least 30%. The viability of MAC was much less affected by most decontamination treatments. In conclusion, the viability of MABSC was severely compromised by standard decontamination regimens. This supports recent evidence showing that optimal recovery of MABSC is achieved by culture on an appropriate selective agar without decontamination of sputum samples.

The influence of HLA genotype on the severity of COVID-19 infection.

The impact of COVID-19 varies markedly, not only between individual patients but also between different populations. We hypothesised that differences in human leukocyte antigen (HLA) genes might influence this variation. Using next generation sequencing, we analysed the class I and class II classical HLA genes of 147 individuals of European descent experiencing variable clinical outcomes following COVID-19 infection. Forty-nine of these patients were admitted to hospital with severe respiratory disease. They had no significant pre-existing comorbidities. We compared the results to those obtained from a group of 69 asymptomatic hospital workers who evidence of COVID exposure based on blood antibody testing. Allele frequencies in both the severe and asymptomatic groups were compared to local and national healthy controls with adjustments made for age and sex. With the inclusion of hospital staff who had reported localised symptoms only (limited to loss of smell/taste, n = 13) or systemic symptoms not requiring hospital treatment (n = 16), we carried out ordinal logistic regression modelling to determine the relative influence of age, BMI, sex and the presence of specific HLA genes on symptomatology. We found a significant difference in the allele frequency of HLA-DRB1*04:01 in the severe patient compared to the asymptomatic staff group (5.1% vs. 16.7%, P = .003 after adjustment for age and sex). There was a significantly lower frequency of the haplotype DQA1*01:01-DQB1*05:01-DRB1*01:01 in the asymptomatic group compared to the background population (P = .007). Ordinal logistic regression modelling confirmed the significant influence of DRB1*04:01 on the clinical severity of COVID-19 observed in the cohorts. These alleles are found in greater frequencies in the North Western European population. This regional study provides evidence that HLA genotype influences clinical outcome in COVID-19 infection. Validation studies must take account of the complex genetic architecture of the immune system across different geographies and ethnicities.

The impact of COVID-19 shielding on the wellbeing, mental health and treatment adherence of adults with cystic fibrosis.

People with cystic fibrosis (CF) were advised to undertake 'shielding' at home during the COVID-19 pandemic to reduce their risk of infection. We studied the impact shielding had on their wellbeing, mental health (GAD-7 and PHQ-9 scores) and adherence to treatment. 63 (46%) of 137 people surveyed responded (19 anonymously; 44 gave their identity). Most (94%) adhered to shielding advice 'all the time/often' but many (76%) found this difficult with disruption of their routines, relationships and exercise habits. Treatment adherence rates were high and continued during COVID-19. Depression scores were low and remained stable. Clinically significant anxiety rates rose from 27% pre-COVID-19 to 54% during COVID-19 and seven patients requested a psychology consultation from this study. There is a need to monitor the wellbeing of people with CF during the ongoing COVID-19 pandemic.

The Noninvasive Ventilation Outcomes (NIVO) score: prediction of in-hospital mortality in exacerbations of COPD requiring assisted ventilation.

INTRODUCTION: Acute exacerbations of COPD (AECOPD) complicated by acute (acidaemic) hypercapnic respiratory failure (AHRF) requiring ventilation are common. When applied appropriately, ventilation substantially reduces mortality. Despite this, there is evidence of poor practice and prognostic pessimism. A clinical prediction tool could improve decision making regarding ventilation, but none is routinely used. METHODS: Consecutive patients admitted with AECOPD and AHRF treated with assisted ventilation (principally noninvasive ventilation) were identified in two hospitals serving differing populations. Known and potential prognostic indices were identified a priori. A prediction tool for in-hospital death was derived using multivariable regression analysis. Prospective, external validation was performed in a temporally separate, geographically diverse 10-centre study. The trial methodology adhered to TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) recommendations. RESULTS: Derivation cohort: n=489, in-hospital mortality 25.4%; validation cohort: n=733, in-hospital mortality 20.1%. Using six simple categorised variables (extended Medical Research Council Dyspnoea score 1-4/5a/5b, time from admission to acidaemia >12 h, pH <7.25, presence of atrial fibrillation, Glasgow coma scale ≤14 and chest radiograph consolidation), a simple scoring system with strong prediction of in-hospital mortality is achieved. The resultant Noninvasive Ventilation Outcomes (NIVO) score had area under the receiver operating curve of 0.79 and offers good calibration and discrimination across stratified risk groups in its validation cohort. DISCUSSION: The NIVO score outperformed pre-specified comparator scores. It is validated in a generalisable cohort and works despite the heterogeneity inherent to both this patient group and this intervention. Potential applications include informing discussions with patients and their families, aiding treatment escalation decisions, challenging pessimism and comparing risk-adjusted outcomes across centres.

Current status of fertility and family formation in men with cystic fibrosis.

Men with cystic fibrosis are nearly always infertile due to congenital bilateral absence of the vas deferens, but can undergo assisted reproduction. Ill health may influence reproductive choices. This paper reports data on fertility and family formation in CF including the use of assisted reproduction in a total cohort of 205 men (mean age 30.9, range 16.6-64.3 years) studied over a 10-year period. Overall 102 (49.5%) were single, 52 (25.7%) were married, 48 (23.3%) were in long-term heterosexual relationships, and 3 (1.5%) were in same-sex relationships. One (0.5%) was fertile naturally. In total, 30 children were born to 23 (11%) men by assisted reproduction: 4 used donor sperm and 19 had sperm retrieval and intracytoplasmic sperm injection (ICSI). Two men each adopted two children; 15 (7.3%) men were acting as step-fathers to 20 children from their partners' previous relationships. Overall 41 (20%) men had fatherhood roles. ICSI was unsuccessful in 4 men. A further 16 men were referred for fertility treatment but did not proceed. Of the 19 men having children by ICSI, 3 died leaving 4 children. Men with CF face complex decisions when considering their relationships, fertility and fatherhood.