Long-term outcomes (beyond 5 years) of liver transplant recipients-A transatlantic multicenter study.

The long-term (>5 y) outcomes following liver transplantation (LT) have not been extensively reported. The aim was to evaluate outcomes of LT recipients who have survived the first 5 years. A multicenter retrospective analysis of prospectively collected data from 3 high volume LT centers (Dallas-USA, Birmingham-UK, and Barcelona-Spain) was undertaken. All adult patients, who underwent LT since the inception of the program to December 31, 2010, and survived at least 5 years since their LT were included. Patient survival was the primary outcome. A total of 3682 patients who survived at least 5 years following LT (long-term survivors) were included. Overall, median age at LT was 52 years (IQR 44-58); 53.1% were males; and 84.6% were Caucasians. A total of 49.4% (n=1820) died during a follow-up period of 36,828 person-years (mean follow-up 10 y). A total of 80.2% (n=1460) of all deaths were premature deaths. Age-standardized all-cause mortality as compared to general population was 3 times higher for males and 5 times higher for females. On adjusted analysis, besides older recipients and older donors, predictors of long-term mortality were malignancy, cardiovascular disease, and dialysis. Implementation of strategies such as noninvasive cancer screening, minimizing immunosuppression, and intensive primary/secondary cardiovascular prevention could further improve survival.

Creative Mental Health Literacy Practices: A Qualitative Study Exploring How Students Use Literacy to Promote Wellbeing and Manage Mental Health Conditions While at University.

Understanding how students manage their mental health while at university is more important than ever, given the increasing number of undergraduate students experiencing poor mental health and seeking support from their universities. This paper reports on an exploratory qualitative study and discusses how students with mental-health conditions use literacy (reading, writing, and the use of texts) to manage their mental health, focusing on reading for pleasure, creative writing, and bullet journaling. Through in-depth qualitative interviews across the academic year of 2018-2019, 11 students' reflective accounts of their practices in managing their mental health were collected and then thematically analysed. This paper focusses on the experiences of three students as case studies of how students use literacy to manage times of mental health distress and promote wellbeing through relaxation, the expression of emotions, and the recording of their mental health. These practices enabled the processing of emotions, engagement in supportive relationships, development of a sense of self, and reflection of mental health progress. These findings demonstrate that supporting students to engage in self-directed creative literacy practices could help students to manage their mental health and develop on-going positive strategies while helping universities manage the increased demand for help from students.

Patient Management and Clinical Outcomes Associated with a Recorded Diagnosis of Stage 3 Chronic Kidney Disease: The REVEAL-CKD Study.

INTRODUCTION: Guidelines for the treatment of chronic kidney disease (CKD) recommend early intervention and management to slow disease progression. However, associations between diagnosis and CKD progression are not fully understood. METHODS: REVEAL-CKD (NCT04847531) is a retrospective observational study of patients with stage 3 CKD. Data were extracted from the US TriNetX database. Eligible patients had two consecutive estimated glomerular filtration rate (eGFR) measurements indicative of stage 3 CKD (≥ 30 and < 60 ml/min/1.73 m2) recorded 91-730 days apart from 2015 to 2020. Diagnosed patients were included if their first CKD diagnosis code was recorded at least 6 months after their second qualifying eGFR measurement. We assessed CKD management and monitoring practices for the 180 days before and after CKD diagnosis, annual eGFR decline in the 2 years before and after CKD diagnosis, and associations between diagnostic delay and post-diagnosis event rates. RESULTS: The study included 26,851 patients. After diagnosis, we observed significant increases in the prescribing rate of guideline-recommended medications such as angiotensin-converting enzyme inhibitors (rate ratio [95% confidence interval]: 1.87 [1.82, 1.93]), angiotensin receptor blockers (1.91 [1.85, 1.97]) and mineralocorticoid receptor antagonists (2.23 [2.13, 2.34]). Annual eGFR decline was significantly reduced following a CKD diagnosis, from 3.20 ml/min/1.73 m2 before diagnosis to 0.74 ml/min/1.73 m2 after diagnosis. Delayed diagnosis (by 1-year increments) was associated with elevated risk of CKD progression to stage 4/5 (1.40 [1.31-1.49]), kidney failure (hazard ratio [95% confidence interval]: 1.63 [1.23-2.18]) and the composite of myocardial infarction, stroke and hospitalization for heart failure (1.08 [1.04-1.13]). CONCLUSIONS: A recorded CKD diagnosis was associated with significant improvements in CKD management and monitoring practices and attenuated eGFR decline. Recorded diagnosis of stage 3 CKD is an important first step to reduce the risk of disease progression and minimize adverse clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04847531.

Chronic kidney disease (CKD) is a long-term condition in which the function of the kidneys is reduced. Kidney function is monitored using a measurement called the estimated glomerular filtration rate. CKD can be separated into stages of severity, ranging from 1 (mild) to 5 (severe), using estimated glomerular filtration rate. Mild to moderate CKD (stages 1­3) is difficult to diagnose because there are usually no symptoms. In this study from the REVEAL-CKD programme, we looked at the effects of having undiagnosed stage 3 (moderate) CKD and examined how a CKD diagnosis affects disease management and worsening of the condition. Using a database of medical records for patients in the USA called TriNetX, we looked at data from over 26,000 patients with stage 3 CKD who were identified using estimated glomerular filtration rate measurements. We found that healthcare teams prescribed significantly more guideline-recommended medications and did more clinical monitoring in the 180 days after a CKD diagnosis than they did before the diagnosis. Additionally, the rate of decline in kidney function slowed after a CKD diagnosis. Delaying diagnosis by 1 year increased the risk of deterioration of the condition by 40%, the risk of needing a kidney transplant or long-term dialysis treatment by 63% and the risk of major heart and blood vessel diseases (known as cardiovascular events) by 8%. Our findings suggest that diagnosis of stage 3 CKD is an important first step to reduce the risk of the disease worsening and other complications. Video Abstract (MP4 82773 KB).

Prevalence of undiagnosed stage 3 chronic kidney disease in France, Germany, Italy, Japan and the USA: results from the multinational observational REVEAL-CKD study.

OBJECTIVES: REVEAL-CKD aims to estimate the prevalence of, and factors associated with, undiagnosed stage 3 chronic kidney disease (CKD). DESIGN: Multinational, observational study. SETTING: Data from six country-specific electronic medical records and/or insurance claims databases from five countries (France, Germany, Italy, Japan and the USA [two databases]). PARTICIPANTS: Eligible participants (≥18 years old) had ≥2 consecutive estimated glomerular filtration rate (eGFR) measurements (calculated from serum creatinine values, sex and age) taken from 2015 onwards that were indicative of stage 3 CKD (≥30 and <60 mL/min/1.73 m2). Undiagnosed cases lacked an International Classification of Diseases 9/10 diagnosis code for CKD (any stage) any time before, and up to 6 months after, the second qualifying eGFR measurement (study index). MAIN OUTCOME MEASURES: The primary outcome was point prevalence of undiagnosed stage 3 CKD. Time to diagnosis was assessed using the Kaplan-Meier approach. Factors associated with lacking a CKD diagnosis and risk of diagnostic delay were assessed using logistic regression adjusted for baseline covariates. RESULTS: The prevalence of undiagnosed stage 3 CKD was 95.5% (19 120/20 012 patients) in France, 84.3% (22 557/26 767) in Germany, 77.0% (50 547/65 676) in Italy, 92.1% (83 693/90 902) in Japan, 61.6% (13 845/22 470) in the US Explorys Linked Claims and Electronic Medical Records Data database and 64.3% (161 254/250 879) in the US TriNetX database. The prevalence of undiagnosed CKD increased with age. Factors associated with undiagnosed CKD were female sex (vs male, range of odds ratios across countries: 1.29-1.77), stage 3a CKD (vs 3b, 1.81-3.66), no medical history (vs a history) of diabetes (1.26-2.77) or hypertension (1.35-1.78). CONCLUSIONS: There are substantial opportunities to improve stage 3 CKD diagnosis, particularly in female patients and older patients. The low diagnosis rates in patients with comorbidities that put them at risk of disease progression and complications require attention. TRIAL REGISTRATION: NCT04847531.

The incidence of Kawasaki disease using hospital admissions data for England 2006-2021.

OBJECTIVE: To describe the incidence of Kawasaki Disease (kDa) between 2006 and 2021 in England. METHODS: We identified all cases in hospital episode statistics with an ICD-10 diagnostic code M303 (for kDa) between 1 April 2006 and 31 March 2021. We validated 83 diagnoses using hospital medical records and found >97% accuracy. We calculated incidence rate ratios (IRRs) using Poisson regression and assessed the influence of age, sex, ethnicity and index of multiple deprivation (IMD). We used Office for National Statistics population estimates for England as the denominator. RESULTS: We identified a total of 5908 cases of kDa in all children under the age of 16 (mean age 3.8, s.d.=3.2, 95% CI: 3.7, 3.9). Incidence in children aged <5 years was 8.9 (95% CI: 8.6, 9.2)/100 000 person-years; in children aged 5-9, 2.4 (95% CI: 2.3, 2.6)/100 000 person-years; and in children aged 10-15, 0.6 (95% CI: 0.6, 0.7). Male : female ratio was 1.5 : 1. Incidence was higher among non-White than White ethnicities [adjusted IRR 2.1 (2.0-2.2) for Asian, 3.0 (2.8-3.3) for Black and 4.5 (4.2-4.8) for other ethnicities]. The incidence increased with socioeconomic deprivation; the adjusted IRR of the least deprived IMD quintile compared with the most deprived quintile was 0.81 (0.77-0.84). CONCLUSIONS: Incidence rates of kDa derived from hospital admission data in England were higher than in studies relying on clinician reporting. We confirm previous findings on the influence of sex and ethnicity on kDa incidence and observe that there was a higher incidence of kDa within more deprived socioeconomic groups.

Validation of methods to identify people with idiopathic inflammatory myopathies using hospital episode statistics.

Objective: Hospital episode statistics (HES) are routinely recorded at every hospital admission within the National Health Service (NHS) in England. This study validates diagnostic ICD-10 codes within HES as a method of identifying cases of idiopathic inflammatory myopathies (IIMs). Methods: All inpatient admissions at one NHS Trust between 2010 and 2020 with relevant diagnostic ICD-10 codes were extracted from HES. Hospital databases were used to identify all outpatients with IIM, and electronic care records were reviewed to confirm coding accuracy. Total hospital admissions were calculated from NHS Digital reports. The sensitivity and specificity of each code and code combinations were calculated to develop an optimal algorithm. The optimal algorithm was tested in a sample of admissions at another NHS Trust. Results: Of the 672 individuals identified by HES, 510 were confirmed to have IIM. Overall, the positive predictive value (PPV) was 76% and sensitivity 89%. Combination algorithms achieved PPVs between 89 and 94%. HES can also predict the presence of IIM-associated interstitial lung disease (ILD) with a PPV of 79% and sensitivity of 71%. The optimal algorithm excluded children (except JDM code M33.0), combined M33.0, M33.1, M33.9, M36.0, G72.4, M60.8 and M33.2, and included M60.9 only if it occurred alongside an ILD code (J84.1, J84.9 or J99.1). This produced a PPV of 88.9% and sensitivity of 84.2%. Retesting this algorithm at another NHS Trust confirmed a high PPV (94.4%). Conclusion: IIM ICD-10 code combinations in HES have high PPVs and sensitivities. Algorithms tested in this study could be applied across all NHS Trusts to enable robust and cost-effective whole-population research into the epidemiology of IIM.

Investigating the global prevalence and consequences of undiagnosed stage 3 chronic kidney disease: methods and rationale for the REVEAL-CKD study.

Background: Timely diagnosis and treatment of stage 3 chronic kidney disease (CKD) can prevent further loss of kidney function and progression to kidney failure. However, contemporary data on the global prevalence of undiagnosed stage 3 CKD are scarce. REVEAL-CKD is a multinational, multifocal and observational study aiming to provide insights into undiagnosed stage 3 CKD in a large population. Methods: Patients (aged ≥18 years) with data in selected secondary databases from 11 countries will be included if they have at least two estimated glomerular filtration rate (eGFR) measurements from 2015 onwards that are ≥30 and <60 mL/min/1.73 m2, recorded >90 and ≤730 days apart. Undiagnosed cases are those without an International Classification of Diseases 9/10 diagnosis code for CKD (any stage) any time before and up to 6 months after the second qualifying eGFR measurement. Time to diagnosis will be assessed using a Kaplan-Meier approach; patient characteristics associated with undiagnosed CKD will be assessed using adjusted logistical regression analyses. Results: REVEAL-CKD will assess the point prevalence of undiagnosed stage 3 CKD and time to CKD diagnosis in initially undiagnosed cases overall and in individual countries. Trends in undiagnosed CKD prevalence by calendar year will be assessed. Patient characteristics, healthcare resource utilization, adverse clinical outcomes, and CKD management and monitoring practices in patients with versus without a CKD diagnosis will be compared. Conclusions: REVEAL-CKD will increase awareness of the global clinical and economic burden of undiagnosed stage 3 CKD and provide valuable insights to inform clinical practice and policy changes.

COVID-19 infection, admission and death among people with rare autoimmune rheumatic disease in England: results from the RECORDER project.

OBJECTIVES: To calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the first wave of the COVID-19 pandemic in England compared with the general population. METHODS: We used Hospital Episode Statistics to identify all people alive on 1 March 2020 with ICD-10 codes for RAIRD from the whole population of England. We used linked national health records (demographic, death certificate, admissions and PCR testing data) to calculate rates of COVID-19 infection and death up to 31 July 2020. Our primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. General population data from Public Health England and the Office for National Statistics were used for comparison. We also describe COVID-19-related hospital admissions and all-cause deaths. RESULTS: We identified a cohort of 168 680 people with RAIRD, of whom 1874 (1.11%) had a positive COVID-19 PCR test. The age-standardized infection rate was 1.54 (95% CI: 1.50, 1.59) times higher than in the general population. A total of 713 (0.42%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardized mortality rate for COVID-19-related death was 2.41 (2.30-2.53) times higher than in the general population. There was no evidence of an increase in deaths from other causes in the RAIRD population. CONCLUSIONS: During the first wave of COVID-19 in England, people with RAIRD had a 54% increased risk of COVID-19 infection and more than twice the risk of COVID-19-related death compared with the general population. These increases were seen despite shielding policies.

Biomarker Testing for People With Advanced Lung Cancer in England.

INTRODUCTION: Optimal management of people with advanced NSCLC depends on accurate identification of predictive markers. Yet, real-world data in this setting are limited. We describe the impact, timeliness, and outcomes of molecular testing for patients with advanced NSCLC and good performance status in England. METHODS: In collaboration with Public Health England, patients with stages IIIB to IV NSCLC, with an Eastern Cooperative Oncology Group performance status of 0 to 2, in England, between June 2017 and December 2017, were identified. All English hospitals were invited to record information. RESULTS: A total of 60 of 142 invited hospitals in England participated in this study and submitted data on 1157 patients. During the study period, 83% of patients with advanced adenocarcinoma underwent molecular testing for three recommended predictive biomarkers (EGFR, ALK, and programmed death-ligand 1). A total of 80% of patients with nonsquamous carcinomas on whom biomarker testing was performed had adequate tissue for analysis on initial sampling. First-line treatment with a tyrosine kinase inhibitor was received by 71% of patients with adenocarcinoma and a sensitizing EGFR mutation and by 59% of those with an ALK translocation. Of patients with no driver mutation and a programmed death-ligand 1 expression of greater than or equal to 50%, 47% received immunotherapy. CONCLUSIONS: We present a comprehensive data set for molecular testing in England. Although molecular testing is well established in England, timeliness and uptake of targeted therapies should be improved.

Opioids and the Risk of Fracture: A Self-Controlled Case Series Study in the Clinical Practice Research Datalink.

Self-controlled study designs can be used to assess the association between exposures and acute outcomes while controlling for important confounders. Using routinely collected health data, a self-controlled case series design was used to investigate the association between opioid use and bone fractures in 2008-2017 among adults registered in the United Kingdom Clinical Practice Research Datalink. The relative incidence of fracture was estimated, comparing periods when these adults were exposed and unexposed to opioids, adjusted for time-varying confounders. Of 539,369 people prescribed opioids, 67,622 sustained fractures and were included in this study. The risk of fracture was significantly increased when the patient was exposed to opioids, with an adjusted incidence rate ratio of 3.93 (95% confidence interval (CI): 3.82, 4.04). Fracture risk was greatest in the first week of starting opioid use (adjusted incidence rate ratio: 7.81, 95% CI: 7.40, 8.25) and declined with increasing duration of use. Restarting opioid use after a gap in exposure significantly increased fracture risk (adjusted incidence rate ratio: 5.05, 95% CI: 4.83, 5.29) when compared with nonuse. These findings highlight the importance of raising awareness of fractures among patients at opioid initiation and demonstrate the utility of self-controlled methods for pharmacoepidemiologic research.

Risk of death among people with rare autoimmune diseases compared with the general population in England during the 2020 COVID-19 pandemic.

OBJECTIVES: To quantify the risk of death among people with rare autoimmune rheumatic diseases (RAIRD) during the UK 2020 COVID-19 pandemic compared with the general population, and compared with their pre-COVID risk. METHODS: We conducted a cohort study in Hospital Episode Statistics for England from 2003 onwards, and linked data from the NHS Personal Demographics Service. We used ONS published data for general population mortality rates. RESULTS: We included 168 691 people with a recorded diagnosis of RAIRD alive on 1 March 2020. Their median age was 61.7 (IQR 41.5-75.4) years, and 118 379 (70.2%) were female. Our case ascertainment methods had a positive predictive value of 85%. A total of 1815 (1.1%) participants died during March and April 2020. The age-standardized mortality rate (ASMR) among people with RAIRD (3669.3; 95% CI: 3500.4, 3838.1 per 100 000 person-years) was 1.44 (95% CI: 1.42, 1.45) times higher than the average ASMR during the same months of the previous 5 years, whereas in the general population of England it was 1.38 times higher. Age-specific mortality rates in people with RAIRD compared with the pre-COVID rates were higher from the age of 35 upwards, whereas in the general population the increased risk began from age 55 upwards. Women had a greater increase in mortality rates during COVID-19 compared with men. CONCLUSION: The risk of all-cause death is more prominently raised during COVID-19 among people with RAIRD than among the general population. We urgently need to quantify how much risk is due to COVID-19 infection and how much is due to disruption to health-care services.

Prospective Study of Psychological Morbidity and Illness Perceptions in Young People With Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Psychological morbidity is increased in young people with inflammatory bowel disease [IBD]. Illness perceptions may be an important factor. This study aimed to describe the prevalence and severity of psychological morbidity and to examine relationships between baseline illness perceptions and anxiety, depression, and health-related quality of life [HRQoL], at baseline and 12 months later, in 16-21 year olds with IBD. METHODS: IBD patients [n = 121] completed measures of anxiety, depression, HRQoL, and illness perceptions [IPQ-R] at baseline and follow-up [n = 100, 83%]. RESULTS: Among the 121 patients at baseline [median age 19.3 years, 40% female, 62% Crohn's disease, 73% in clinical remission], 55% reported elevated symptoms of anxiety/depression and 83% reported low HRQoL. Negative illness perceptions at baseline were significantly correlated with greater anxiety, depression, and lower HRQoL at baseline and follow-up. In regression analysis at baseline, the IPQ-R domain of greater perception of a cyclical nature of IBD was an independent predictor of anxiety, and a greater perceived emotional impact of IBD was an independent predictor of anxiety, depression, and HRQoL. Female gender and clinical relapse were also independent predictors of lower HRQoL. After controlling for baseline measures, clinical risk factors and illness perceptions did not explain additional variance in psychological morbidity at follow-up. CONCLUSIONS: A high prevalence of psychological morbidity, stable over 1 year, was demonstrated in young people with IBD. Having negative illness perceptions, being female, and having active disease predicted those at greatest risk of psychological morbidity. Illness perceptions may be an appropriate target for psychological interventions.