Background/Aims Gout is associated with physical co-morbidities and a reduction in physical health-related quality of life. However, the association between gout and psychological comorbidity (depression and anxiety) has received less attention. A secondary analysis of data from a five-year prospective cohort study was performed to determine the prevalence and incidence of anxiety and depression in people with gout, and gout characteristics associated with psychological co-morbidity. Methods Adults aged ≥18 years with gout were identified via Read codes or allopurinol prescriptions from 20 general practices across the West Midlands. Questionnaires were mailed at baseline and at 12-, 36- and 60-months. Questionnaire data included socio-demographics, gout-related characteristics (flare frequency, oligo- or poly-articular gout, gout duration and allopurinol use) and validated anxiety (GAD-7) and depression (PHQ-9) questionnaires. Current anxiety and depression were defined as scores>10 on the GAD-7 and PHQ-9 respectively. The prevalence and incidence of new-onset anxiety or depression were described at 12, 36 and 60 months in those without anxiety and depression at baseline. Binary logistic regression used to determine baseline gout characteristics associated with developing new-onset anxiety or depression at each time point (odds ratios (OR), 95% confidence intervals (CI), adjusted for age, gender and deprivation). Results Of 1184 baseline responders, 721, 605 and 411 responded at 12-, 36- and 60-months, respectively. The peak prevalence of both depression and anxiety was at baseline at 12.6% and 10.0%, respectively. Responders with anxiety (GAD-7 ≥10) or depression (PHQ-9 ≥10) at baseline were excluded from new-onset analysis. Over five years, one in thirteen (7.5%) developed new-onset anxiety, and one in eleven (9.2%) developed new-onset depression at any future time point. Developing anxiety was associated with a history of oligo- or poly-articular gout flares at baseline (OR 2.31, 95% CI:1.26 to 4.23) but not flare frequency, gout duration, or allopurinol use. New-onset depression was associated with allopurinol use at baseline (OR 1.93, 95% CI: 1.01 to 3.69) but not flare frequency, gout duration, or oligo- or poly-articular gout flares. Conclusion Psychological co-morbidity is common in people living with gout; clinicians should be aware of this when assessing and treating people with gout. Disclosure J.J.R. Higgs: None. L. Clarson: None. R. Bajpai: None. S. Muller: None. E. Roddy: None.
Background/Aims Initiating urate-lowering therapy for gout commonly triggers a gout flare and hence co-prescription of colchicine or non-steroidal anti-inflammatory drug (NSAID) prophylaxis is recommended. However, little is known about the incidence of adverse events associated with prophylaxis. We aimed to determine the risk of adverse events severe enough to warrant seeking healthcare associated with colchicine or NSAID prophylaxis when initiating allopurinol for gout. Methods We conducted two matched retrospective cohort studies, using linked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) datasets. Adults aged ≥18 years with a Read code for gout and a new allopurinol prescription between 1997 and 2016 were identified. We compared those prescribed (1) colchicine or (2) NSAID prophylaxis with those prescribed no prophylaxis, individually matched by age, sex and propensity to receive prophylaxis, to reduce the impact of confounding by indication. Adverse events were identified in CPRD and HES using Read and ICD10 codes respectively. Associations between colchicine or NSAID prophylaxis and the first occurrence of each outcome were investigated using weighted Cox proportional hazards models. CPRD Gold and Aurum datasets were analysed separately and then combined using 2-stage individual patient data meta-analysis. Results 13,945 individuals who initiated allopurinol with colchicine prophylaxis were matched to 13,945 who initiated without prophylaxis (mean age 63.62 years [95%CI 63.54, 63.70]; 78% male). Diarrhoea was the most common adverse event in the colchicine group, followed by nausea/vomiting, myocardial infarction (MI), neuropathy, myalgia, and bone marrow suppression (Table). Diarrhoea, MI, neuropathy, myalgia, and bone marrow suppression were significantly more common with colchicine prophylaxis compared with no prophylaxis. 22,880 individuals who initiated allopurinol with NSAID prophylaxis were matched to 22,880 who initiated without prophylaxis (mean age 63.34 years [95%CI 63.26, 63.42]; 78% male). Angina, acute kidney injury, MI, and peptic ulcer disease were significantly more common with NSAID prophylaxis than without (Table). Conclusion Gastrointestinal, cardiorenal, myoneuropathic, and haematological adverse events were associated with prophylaxis, although absolute event rates were low. This information can inform treatment decisions and choice of colchicine or NSAID for prophylaxis when initiating allopurinol. Disclosure E. Roddy: None. R. Bajpai: None. H. Forrester: None. R. Partington: None. C.D. Mallen: Grants/research support; Keele University School Of Medicine has received funding from BMS to support a non-pharmacological atrial fibrillation screening study. L. Clarson: None. N. Padmanabhan: None. R. Whittle: None. S. Muller: None.
Background Children and young people (CYP) may experience prolonged symptoms following COVID-19, commonly termed "Long-COVID". The nature of this in CYP is unclear, as are the sequalae of acute COVID-19. We aimed to systematically synthesise evidence of the long-term outcomes of COVID-19 in CYP. Methods 13 databases were searched until January 2022. Inclusion criteria: Observational studies reporting outcomes occurring four-weeks or more after COVID-19 in children <18 years old. Exclusion criteria: Outcomes of Paediatric Inflammatory Multisystem Syndrome. Title, abstract and full text screening were conducted independently by two reviewers. Data extraction and risk of bias assessment was by one reviewer with independent verification. Critical appraisal tools appropriate for study type were employed. Results were narratively synthesised with meta-analysis to generate summary estimates of risk of prolonged symptoms in CYP. Findings 94 studies were included. 66 recruited from hospital settings, 8 recruited solely from community settings. >100 symptoms were reported, the most common being fatigue, headache and cognitive symptoms. Summary estimates of risk of prolonged symptoms were higher for hospital samples (31.2%, 95% CI 20.3% to 43.2%) than for community samples (4.6%, 95% CI 3.4% to 5.8). Sequalae including stroke, type-1 diabetes, Guillan-Barre syndrome, and persistent radiological or blood test abnormalities have been reported in CYP following COVID-19. Most studies reporting these are case reports / case series and quality of evidence is low. Interpretation Prolonged symptoms following COVID-19 in children are variable and multi-system. Rates in community samples are lower than hospital. There is limited data on other sequalae in CYP. Heterogeneity in diagnosis of COVID-19, symptom classification, assessment method and duration of follow-up made synthesis less secure. Funding HT, CB and GS have National Institute for Health and Care Research fellowships. RB, CM and VW are supported by the NIHR West Midlands Applied Research Collaboration. CM Is supported by the NIHR School for Primary Care Research Research in context panel Evidence before this study At the time of writing and to the best of our knowledge, the protocol for this systematic review was a novel endeavour to summarise the longer-term effects of COVID-19 in children and young people (CYP). At least three systematic reviews have since been published, summarising the symptom profile and prevalence of Long-COVID in CYP, but prevalence estimates vary widely and the evidence base remains uncertain. In addition, there is very limited information on other sequalae of COVID-19 in this population group. We searched thirteen electronic databases (MEDLINE, EMBASE, AMED, HMIC, CINAHLPlus, PsycINFO, Web of Science (Science Citation and Social Science Citation indicies), ASSIA, WHO COVID-19: Global literature on coronavirus disease, Cochrane COVID-19 study register, ProQuest Coronavirus research database, NDLTD and OpenGrey) up to January 2022 for any empirical study including search terms pertaining to longer term symptoms of COVID-19 in CYP (<18 years old). The quality of the studies was mixed. Results were analysed narratively for each objective, and random effects meta-analyses conducted to estimate risk of prolonged symptoms in CYP who have had COVID-19. Added value of this study This review adds to the evidence of the heterogeneity of prolonged symptoms following COVID-19 in CYP but importantly, stratifies risk of this by recruitment setting. We also synthesise evidence on broader sequalae of the acute infection in this CYP and longer-term effects in CYP with pre-existing conditions, which have not been considered in previous reviews. We purposefully included case studies and case series, to capture emerging patterns of outcomes, which may well be important in a novel condition with a rapidly increasing volume of publications. To our knowledge, this systematic review and meta-analysis is the most comprehensive to date. Implications of all the available evidence This review adds to the evidence that a substantial proportion of CYP do experience effects of COVID-19 that last longer than four-weeks, with the most frequently reported prolonged symptoms being fatigue, headache and cognitive symptoms. The proportion of CYP developing prolonged symptoms in children recruited from community setting was low, although this may translate to a large number of affected CYP at population level. There is a paucity of controlled studies and this limits confidence that prolonged symptoms are attributable to COVID-19. Sequalae including stroke, type-1 diabetes, Guillan-Barre syndrome, and persistent radiological or blood test abnormalities have been reported in CYP following COVID-19 but most studies reporting these are case reports / case series and quality of evidence is low. To develop treatment plans and interventions for affected CYP, further studies are needed to better characterise this condition and understand its impact on the lives of CYP and their families and communities. These should ideally recruit from community settings, include population-based control groups and consider using standardised definitions and outcome measures where possible.
Objectives: To evaluate treatment outcomes in patients from a low-middle income country (LMIC) with esophageal carcinoma who underwent esophagectomy after neoadjuvant chemoradiation (NACRT/S). Methods: Between 2010 and 2020, 254 patients (median follow-up: 53 months) met our inclusion criteria. Out-of-Field nodal regions were determined by reviewing individual radiotherapy plans. Cox regression modelling was performed to analyze overall survival (OS) and recurrence-free survival (RFS), while pathological complete response (pCR) prediction utilized Poisson regression. Results: The median OS was 71.4 months (IQR: 19.6-∞), RFS did not reach the median and pCR rate was 46%. On multivariable Cox regression, BMI [0.93 (0.89–0.98); 0.94 (0.89–0.99)] and absence of out-of-field node with extranodal extension (ENE)[0.22 (0.09–0.53); 0.30 (0.12–0.75)] influenced OS and RFS, respectively. Age [1.03 (1.01–1.06)], nodal stage [cN2-3 vs cN0: 2.67 (1.08–6.57)] and adventitial involvement [2.54 (1.36–4.72)] also influenced OS, while involved margins [3.12 (1.24–7.81)] influenced RFS. On multivariable Poisson regression, non-CROSS-chemotherapy regimens [0.65 (0.44–0.95)] and residual primary disease on pre-surgical imaging [0.73 (0.57–0.93)] were significantly associated with pCR. The most frequently involved in-field and out-of-field nodal regions were the peri-esophageal and peri-gastric (greater and lesser curvature) regions, respectively. Conclusions: NACRT/S is feasible and effective in patients from LMIC. Out-of-field ENE merits further investigation as a prognostic factor since it significantly influenced both OS and RFS. Advances in knowledge: The results of clinical trials are replicable in LMICs. Out-of-field ENE is an independent prognostic factor for OS and RFS.
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