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Intraoperative frozen section (IFS) is used with the intention to improve functional and oncological outcomes for patients undergoing radical prostatectomy (RP). High resource requirements of IFS techniques such as NeuroSAFE may preclude widespread adoption, even if there are benefits to patients. Recent advances in fresh-tissue microscopic digital imaging technologies may offer an attractive alternative, and there is a growing body of evidence regarding these technologies. In this narrative review, we discuss some of the familiar limitations of IFS and compare these to the attractive counterpoints of modern digital imaging technologies such as the speed and ease of image generation, the locality of equipment within (or near) the operating room, the ability to maintain tissue integrity, and digital transfer of images. Confocal laser microscopy (CLM) is the modality most frequently reported in the literature for margin assessment during RP. We discuss several imitations and obstacles to widespread dissemination of digital imaging technologies. Among these, we consider how the 'en-face' margin perspective will challenge urologists and pathologists to understand afresh the meaning of positive margin significance. As a part of this, discussions on how to describe, categorize, react to, and evaluate these technologies are needed to improve patient outcomes. Limitations of this review include its narrative structure and that the evidence base in this field is relatively immature but developing at pace.
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OBJECTIVE: To compare biopsy recommendation rates and accuracy of the Prostate Imaging-Reporting and Data System, version 2 (PI-RADSv2) with the Likert scale for detection of clinically significant and insignificant prostate cancer in men screened within the Imperial Prostate 1 Prostate Cancer Screening Trial Using Imaging (IP1-PROSTAGRAM). PATIENTS AND METHODS: Men aged 50-69 years were screened with Prostagram MRI. Scans were prospectively reported using both PI-RADSv2 (excluding dynamic contrast-enhanced sequence score) and 5-point Likert scores by expert uro-radiologists. Systematic and targeted transperineal biopsy was recommended if the scan was scored ≥ 3, based on either reporting system. The proportion of patients recommended for biopsy and detection rates for Grade Groups (GGs) 1 and ≥ 2 were compared. Receiver operating characteristic (ROC) analysis was performed to compare performance. RESULTS: A total of 406 men underwent Prostagram MRI. The median (interquartile range) age and prostate-specific antigen level were 57 (53-61) years and 0.91 (0.56-1.74) ng/mL, respectively. At MRI score ≥ 3, more patients were recommended for biopsy based on Likert criteria (94/406; 23%, 95% confidence interval [CI] 19.2%-27.6%) compared to PI-RADSv2 (72/406; 18%, 95% CI 14.2%-21.9%; P = 0.03). For MRI scores ≥ 4, PI-RADSv2 and Likert scales led to 43/406 (11%, 95% CI 7.9%-14.1%) and 35/406 (9%, 95% CI 6.2%-11.9%) men recommended for biopsy (P = 0.40). For GG ≥ 2 detection, PIRADSv2 and Likert detected 22% (95% CI 11.4%-30.8%, 14/72) and 16% (95% CI 9.5%-25.3%, 15/94), respectively (P = 0.56). For GG1 cancers detection these were 11% (95% CI 4.3%-19.6%, seven of 72) vs 11% (95% CI 4.7%-17.8%, nine of 94; P = 1.00). The accuracy of PI-RADSv2 and Likert scale was similar (area under the ROC curve 0.64 vs 0.65, P = 0.95). CONCLUSIONS: In reporting non-contrast-enhanced Prostagram MRI in a screening population, the PI-RADSv2 and Likert scoring systems were equally accurate; however, Likert scale use led to more men undergoing biopsy without a subsequent increase in significant cancer detection rates. To improve reporting of Prostagram MRI, either the PI-RADSv2 or a modified Likert scale or a standalone scoring system should be developed.
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Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Neoplasias da Próstata/patologia , Sistemas de Dados , Detecção Precoce de Câncer , Antígeno Prostático Específico , Imageamento por Ressonância Magnética/métodos , Estudos RetrospectivosRESUMO
BackgroundPost-authorisation vaccine safety surveillance is well established for reporting common adverse events of interest (AEIs) following influenza vaccines, but not for COVID-19 vaccines.AimTo estimate the incidence of AEIs presenting to primary care following COVID-19 vaccination in England, and report safety profile differences between vaccine brands.MethodsWe used a self-controlled case series design to estimate relative incidence (RI) of AEIs reported to the national sentinel network, the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub. We compared AEIs (overall and by clinical category) 7 days pre- and post-vaccination to background levels between 1 October 2020 and 12 September 2021.ResultsWithin 7,952,861 records, 781,200 individuals (9.82%) presented to general practice with 1,482,273 AEIs, 4.85% within 7 days post-vaccination. Overall, medically attended AEIs decreased post-vaccination against background levels. There was a 3-7% decrease in incidence within 7 days after both doses of Comirnaty (RI: 0.93; 95% CI: 0.91-0.94 and RI: 0.96; 95% CI: 0.94-0.98, respectively) and Vaxzevria (RI: 0.97; 95% CI: 0.95-0.98). A 20% increase was observed after one dose of Spikevax (RI: 1.20; 95% CI: 1.00-1.44). Fewer AEIs were reported as age increased. Types of AEIs, e.g. increased neurological and psychiatric conditions, varied between brands following two doses of Comirnaty (RI: 1.41; 95% CI: 1.28-1.56) and Vaxzevria (RI: 1.07; 95% CI: 0.97-1.78).ConclusionCOVID-19 vaccines are associated with a small decrease in medically attended AEI incidence. Sentinel networks could routinely report common AEI rates, contributing to reporting vaccine safety.
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Vacinas contra COVID-19 , COVID-19 , Vacinas contra Influenza , Humanos , Vacina BNT162 , ChAdOx1 nCoV-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Inglaterra/epidemiologia , Vacinas contra Influenza/efeitos adversos , Vacinação/efeitos adversosRESUMO
PURPOSE: To investigate the technical success rate and 30-day complications of en-bloc resection of bladder tumour (ERBT) upon routine implementation regardless of tumour size. METHODS: This is a prospective, multi-centre, study on routine implementation of ERBT for patients with bladder tumours requiring transurethral surgery. Surgeons were allowed to cross over to conventional transurethral resection of bladder tumour (TURBT) when necessary. We performed an analysis for patients who had ERBT/TURBT as the definitive treatment. Study outcomes included the technical success rate of ERBT and 30-day complication rate. Multivariate logistic regression analysis was performed to investigate for predictors of a successful ERBT and factors associated with 30-day complications. RESULTS: A total of 135 patients were included in this study. The majority of the patients (80.0%) had bladder tumours of ≤ 3 cm. ERBT was successful in 99 patients, resulting in an overall technical success rate of 73.3%. When stratified according to tumour size, the technical success rates of ERBT were 94.3%, 82.2%, 75%, 84.3% and 29.6% for bladder tumour sizes of < 1 cm, 1.01-2 cm, 2.01-3 cm, ≤ 3 cm and > 3 cm respectively. Upon multivariate analysis, tumour size was the only significant factor predicting the success of ERBT (OR 0.920, 95% CI 0.882-0.960, p < 0.001). Moreover, ERBT was not a significant factor associated with 30-day complications. CONCLUSION: EBRT achieved a good technical success rate for the majority of patients with bladder tumours ≤ 3 cm. Regardless of tumour size, EBRT-first approach was safe to implement into routine clinical practice.
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Cistectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Prospectivos , Resultado do Tratamento , Uretra , Neoplasias da Bexiga Urinária/patologiaRESUMO
PURPOSE: The COVID-19 pandemic has led to the cancellation or deferment of many elective cancer surgeries. We performed a systematic review on the oncological effects of delayed surgery for patients with localised or metastatic renal cell carcinoma (RCC) in the targeted therapy (TT) era. METHOD: The protocol of this review is registered on PROSPERO(CRD42020190882). A comprehensive literature search was performed on Medline, Embase and Cochrane CENTRAL using MeSH terms and keywords for randomised controlled trials and observational studies on the topic. Risks of biases were assessed using the Cochrane RoB tool and the Newcastle-Ottawa Scale. For localised RCC, immediate surgery [including partial nephrectomy (PN) and radical nephrectomy (RN)] and delayed surgery [including active surveillance (AS) and delayed intervention (DI)] were compared. For metastatic RCC, upfront versus deferred cytoreductive nephrectomy (CN) were compared. RESULTS: Eleven studies were included for quantitative analysis. Delayed surgery was significantly associated with worse cancer-specific survival (HR 1.67, 95% CI 1.23-2.27, p < 0.01) in T1a RCC, but no significant difference was noted for overall survival. For localised ≥ T1b RCC, there were insufficient data for meta-analysis and the results from the individual reports were contradictory. For metastatic RCC, upfront TT followed by deferred CN was associated with better overall survival when compared to upfront CN followed by deferred TT (HR 0.61, 95% CI 0.43-0.86, p < 0.001). CONCLUSION: Noting potential selection bias, there is insufficient evidence to support the notion that delayed surgery is safe in localised RCC. For metastatic RCC, upfront TT followed by deferred CN should be considered.
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COVID-19/prevenção & controle , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/mortalidade , Neoplasias Renais/cirurgia , Tempo para o Tratamento , COVID-19/epidemiologia , COVID-19/transmissão , Carcinoma de Células Renais/patologia , Controle de Doenças Transmissíveis , Humanos , Neoplasias Renais/patologia , Nefrectomia , Taxa de SobrevidaRESUMO
OBJECTIVES: To review current data for the role of prostate specific membrane antigen (PSMA) radioligand therapy (RLT) for patients with advanced prostate cancer. This review provides an update for multidisciplinary teams on the current and potential future applications of theranostics in prostate cancer. METHODS: Narrative review focussing on PSMA as a target for RLT, and data using RESULTS: RLT with PSMA is an exciting therapeutic alternative to the existing management options already in use for patients with metastatic castrate-resistant prostate cancer (mCRPC). To date, most evidence exists regarding small-molecule PSMA inhibitors bound to beta-emitting radioisotopes such as 177Lu (Lu-PSMA). Prospective phase II data supports the safety and efficacy of Lu-PSMA in men with heavily pre-treated progressive mCRPC, and several late-phase randomised trials of Lu-PSMA are underway, with many more in the pipeline. Early results are encouraging, indicating that the theranostic approach may play a vital role in management of advanced prostate cancer and perhaps even in much earlier disease states. CONCLUSIONS: PSMA RLT is a promising new treatment option for men with mCPRC, and may also have utility in less advanced prostate cancer.
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Calicreínas/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Detecção Precoce de Câncer , Humanos , Masculino , Medicina de Precisão , Neoplasias da Próstata/terapia , RadioterapiaAssuntos
COVID-19/diagnóstico , Pulmão/fisiopatologia , Oximetria , Humanos , Pulmão/irrigação sanguínea , OxigênioRESUMO
BACKGROUND AND OBJECTIVE: Magnetic resonance imaging (MRI) can detect recurrences after focal therapy for prostate cancer but there is no robust guidance regarding its use. Our objective was to produce consensus recommendations on MRI acquisition, interpretation, and reporting after focal therapy. METHODS: A systematic review was performed in July 2022 to develop consensus statements. A two-round consensus exercise was then performed, with a consensus meeting in January 2023, during which 329 statements were scored by 23 panellists from Europe and North America spanning urology, radiology, and pathology with experience across eight focal therapy modalities. Using RAND Corporation/University of California-Los Angeles methodology, the Transatlantic Recommendations for Prostate Gland Evaluation with MRI after Focal Therapy (TARGET) were based on consensus for statements scored with agreement or disagreement. KEY FINDINGS AND LIMITATIONS: In total, 73 studies were included in the review. All 20 studies (100%) reporting suspicious imaging features cited focal contrast enhancement as suspicious for cancer recurrence. Of 31 studies reporting MRI assessment criteria, the Prostate Imaging-Reporting and Data System (PI-RADS) score was the scheme used most often (20 studies; 65%), followed by a 5-point Likert score (six studies; 19%). For the consensus exercise, consensus for statements scored with agreement or disagreement increased from 227 of 295 statements (76.9%) in round one to 270 of 329 statements (82.1%) in round two. Key recommendations include performing routine MRI at 12 mo using a multiparametric protocol compliant with PI-RADS version 2.1 standards. PI-RADS category scores for assessing recurrence within the ablation zone should be avoided. An alternative 5-point scoring system is presented that includes a major dynamic contrast enhancement (DCE) sequence and joint minor diffusion-weighted imaging and T2-weighted sequences. For the DCE sequence, focal nodular strong early enhancement was the most suspicious imaging finding. A structured minimum reporting data set and minimum reporting standards for studies detailing MRI data after focal therapy are presented. CONCLUSIONS AND CLINICAL IMPLICATIONS: The TARGET consensus recommendations may improve MRI acquisition, interpretation, and reporting after focal therapy for prostate cancer and provide minimum standards for study reporting. PATIENT SUMMARY: Magnetic resonance imaging (MRI) scans can detect recurrent of prostate cancer after focal treatments, but there is a lack of guidance on MRI use for this purpose. We report new expert recommendations that may improve practice.
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Imageamento por Ressonância Magnética , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Imageamento por Ressonância Magnética/normas , Próstata/diagnóstico por imagem , Próstata/patologia , Consenso , Internacionalidade , Recidiva Local de Neoplasia/diagnóstico por imagem , Guias de Prática Clínica como AssuntoRESUMO
Introduction: A prospective cohort study comparing peri- and postoperative outcomes for patients with predominantly anterior prostate cancer (APC) identified preoperatively against non-anterior prostate cancer (NAPC) treated via robotic-assisted radical prostatectomy (RARP). Patients and Methods: Of the 757 RARP's completed between January 2016 and April 2018, two comparative cohorts for anterior and an equivalent group of non-anterior prostate tumours each consisting of 152 patients were compared against each other. Data were collected on the following variables: patient age; operating consultant; preoperative PSA, ISUP grade, degree of nerve sparing; tumour staging; presence and location of positive surgical margins; PSA density, postoperative ISUP grade; treatment paradigm and postoperative PSA, erectile function, and continence outcomes with 2-year follow-up. Results: APCs were found to have significantly lower ISUP grading postoperatively; increased diagnosis via active surveillance over new diagnosis; more frequently undertaken bilateral nerve-sparing and long-term poorer continence outcomes at 18 and 24 months postoperatively (p < 0.05). Pre- and post-op PSA levels, erectile function, PSA density, positive surgical margins (PSM), age and tumour staging showed no significant differences between the APC and NAPC cohorts (p > 0.05). Conclusion: The lower ISUP grading could indicate APC as overall being less aggressive than NAPC, whereas the poorer long-term continence outcomes require further investigating. The non-significant differences amongst tumour staging, PSA density, preoperative PSA levels and PSM rates suggest that APC may not be as significant as predicted in diagnostic evaluation. Overall, this study provides useful information on the growing literature of anterior prostate cancer. Being the largest comparative cohort study to date on APC post-RARP, these results indicate the true characteristics of anterior tumours and their functional outcomes to help improve education, patient expectations and management.
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BACKGROUND: People with multiple health conditions are more likely to have poorer health outcomes and greater care and service needs; a reliable measure of multimorbidity would inform management strategies and resource allocation. AIM: To develop and validate a modified version of the Cambridge Multimorbidity Score in an extended age range, using clinical terms that are routinely used in electronic health records across the world (Systematized Nomenclature of Medicine - Clinical Terms, SNOMED CT). DESIGN AND SETTING: Observational study using diagnosis and prescriptions data from an English primary care sentinel surveillance network between 2014 and 2019. METHOD: In this study new variables describing 37 health conditions were curated and the associations modelled between these and 1-year mortality risk using the Cox proportional hazard model in a development dataset (n = 300 000). Two simplified models were then developed - a 20-condition model as per the original Cambridge Multimorbidity Score and a variable reduction model using backward elimination with Akaike information criterion as the stopping criterion. The results were compared and validated for 1-year mortality in a synchronous validation dataset (n = 150 000), and for 1-year and 5-year mortality in an asynchronous validation dataset (n = 150 000). RESULTS: The final variable reduction model retained 21 conditions, and the conditions mostly overlapped with those in the 20-condition model. The model performed similarly to the 37- and 20-condition models, showing high discrimination and good calibration following recalibration. CONCLUSION: This modified version of the Cambridge Multimorbidity Score allows reliable estimation using clinical terms that can be applied internationally across multiple healthcare settings.
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Multimorbidade , Systematized Nomenclature of Medicine , Humanos , Estudos Transversais , Registros Eletrônicos de Saúde , Atenção Primária à SaúdeRESUMO
OBJECTIVES: To estimate the incidence of adverse events of interest (AEIs) after receiving their first and second doses of coronavirus disease 2019 (COVID-19) vaccinations, and to report the safety profile differences between the different COVID-19 vaccines. DESIGN: We used a self-controlled case series design to estimate the relative incidence (RI) of AEIs reported to the Oxford-Royal College of General Practitioners national sentinel network. We compared the AEIs that occurred seven days before and after receiving the COVID-19 vaccinations to background levels between 1 October 2020 and 12 September 2021. SETTING: England, UK. PARTICIPANTS: Individuals experiencing AEIs after receiving first and second doses of COVID-19 vaccines. MAIN OUTCOME MEASURES: AEIs determined based on events reported in clinical trials and in primary care during post-license surveillance. RESULTS: A total of 7,952,861 individuals were vaccinated with COVID-19 vaccines within the study period. Among them, 781,200 individuals (9.82%) presented to general practice with 1,482,273 AEIs. Within the first seven days post-vaccination, 4.85% of all the AEIs were reported. There was a 3-7% decrease in the overall RI of AEIs in the seven days after receiving both doses of Pfizer-BioNTech BNT162b2 (RI = 0.93; 95% CI: 0.91-0.94) and 0.96; 95% CI: 0.94-0.98), respectively) and Oxford-AstraZeneca ChAdOx1 (RI = 0.97; 95% CI: 0.95-0.98) for both doses), but a 20% increase after receiving the first dose of Moderna mRNA-1273 (RI = 1.20; 95% CI: 1.00-1.44)). CONCLUSIONS: COVID-19 vaccines are associated with a small decrease in the incidence of medically attended AEIs. Sentinel networks could routinely report common AEI rates, which could contribute to reporting vaccine safety.
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Major vascular injuries during robotic renal surgery are rare, but the close proximity of the superior mesenteric artery (SMA) to the left renal artery means that it is liable to iatrogenic injury with potentially catastrophic implications. In this review, we present a case of accidental SMA ligation during a robot-assisted laparoscopic nephrectomy for a 12-cm upper pole renal mass. Prompt recognition and early vascular surgical assistance with conversion to open surgery allowed a primary vascular anastomosis to be made. A computed tomography angiogram at 6 wk was normal. On review of the imaging, the left renal artery take-off was higher than the SMA, which represents an anatomical variant and may have contributed to the injury. The risk of accidental SMA ligation is highest in left-sided tumours and in larger medial tumours that lead to significant distortion of the anatomy. The anatomy of the renal artery can also vary greatly. Surgeons must be knowledgeable of common variations and meticulously review preoperative imaging for the number and course of renal vessels as well as the location of the SMA. In cases of significant bleeding, rapid conversion to open surgery and urgent vascular consultation are critical. PATIENT SUMMARY: In this article, we describe an accidental injury to a major blood vessel (the superior mesenteric artery) during a left robotic radical nephrectomy (kidney removal) for a tumour. We discuss the anatomical relationships of the blood vessels of the small bowel and kidneys, and how to anticipate, recognise, and manage such accidental injuries.
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BACKGROUND: The recommended treatment for patients with Bacillus Calmette-Guérin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC) is radical cystectomy (RC). However, many patients refuse, or are unfit for RC. Therefore, alternative bladder-sparing treatment modalities are needed for BCG-unresponsive NMIBC. In this study we sought to assess the long-term efficacy of hyperthermic intravesical chemotherapy (HIVEC) as alternative to radical cystectomy in BCG-unresponsive non-muscle invasive bladder cancer patients. METHODS AND MATERIALS: Retrospectively collected data from 56 patients with BCG-unresponsive NMIBC who received ≥5 HIVEC instillations between October 2014 and March 2020 was analyzed. All patients met the BCG-unresponsive criteria according to the current EAU guideline on NMIBC 2020. Patients were followed-up with cystoscopy and/or bladder biopsies, urine cytology and annually CT-urography. The Primary outcome was the high grade (HG) recurrence-free survival (RFS), defined as the time from the first HIVEC instillation until histologically confirmed intravesical recurrence or last follow-up. The Kaplan Meier method was used to estimate survival outcomes. Secondary outcomes were: complete response rate (CR), adverse events (AE), assessed by the Common Terminology Criteria for Adverse Events v5.0 (CTCAE) and tumor progression to muscle invasive disease or distant metastases. RESULTS: The median follow-up was 32.2 months (IQR 13.7-44.8). The 1- and 2-year HG-RFS was 53% (SE:6.8) and 35% (SE:6.9), respectively. The CR for patients with CIS was 70% (21/30) at 6 months. Overall, 80% of the population developed an AE, only 1 was classified as CTCAE ≥3. Limitation of this study was the small sample size. CONCLUSION: HIVEC resulted in a 2-year HG-RFS of 35% for BCG-unresponsive NMIBC patients without severe side-effects and therefore HIVEC seems to be an alternative treatment option for patients who refuse or are unfit for RC.
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Administração Intravesical , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias da Bexiga Urinária/mortalidadeRESUMO
BACKGROUND: The pathophysiology of COVID-19 remains poorly understood. We aimed to estimate the contribution of intrapulmonary shunting and ventilation-to-perfusion (VA/Q) mismatch using a mathematical model to construct oxygen-haemoglobin dissociation curves (ODCs). METHODS: ODCs were constructed using transcutaneous pulse oximetry at two different fractions of inspired oxygen (FiO2). 199 patients were included from two large district general hospitals in the South East of England from 1st to 14th January 2021. The study was supported by the National Institute of Health Research (NIHR) Clinical Research Network. RESULTS: Overall mortality was 29%. Mean age was 68.2 years (SEM 1·2) with 46% female. Median shunt on admission was 17% (IQR 8-24.5); VA/Q was 0.61 (IQR 0.52-0.73). Shunt was 37.5% higher in deaths (median 22%, IQR 9-29) compared to survivors (16%, 8-21; p = 0.0088) and was a predictor of mortality (OR 1.04; 95% CI 1.01-1.07). Admission oxygen saturations were more strongly predictive of mortality (OR 0.91, 95% CI 0.87-0.96). There was no difference in VA/Q mismatch between deaths (0.60; IQR 0.50-0.73) and survivors (0.61; IQR 0.52-0.73; p = 0.63) and it was not predictive of mortality (OR 0.68; 95% CI 0.18-2.52; p = 0.55). Shunt negatively correlated with admission oxygen saturation (R -0.533; p<0.0001) whereas VA/Q was not (R 0.1137; p = 0.12). INTERPRETATION: Shunt, not VA/Q mismatch, was associated with worsening hypoxia, though calculating shunt was not of prognostic value. This study adds to our understanding of the pathophysiology of hypoxaemia in COVID-19. Our inexpensive and reliable technique may provide further insights into the pathophysiology of hypoxia in other respiratory diseases.
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COVID-19 , Pneumopatias , Humanos , Feminino , Idoso , Masculino , Relação Ventilação-Perfusão/fisiologia , Hipóxia , Oximetria/métodos , Oxigênio/fisiologiaRESUMO
BACKGROUND: Following COVID-19, up to 40% of people have ongoing health problems, referred to as postacute COVID-19 or long COVID (LC). LC varies from a single persisting symptom to a complex multisystem disease. Research has flagged that this condition is underrecorded in primary care records, and seeks to better define its clinical characteristics and management. Phenotypes provide a standard method for case definition and identification from routine data and are usually machine-processable. An LC phenotype can underpin research into this condition. OBJECTIVE: This study aims to develop a phenotype for LC to inform the epidemiology and future research into this condition. We compared clinical symptoms in people with LC before and after their index infection, recorded from March 1, 2020, to April 1, 2021. We also compared people recorded as having acute infection with those with LC who were hospitalized and those who were not. METHODS: We used data from the Primary Care Sentinel Cohort (PCSC) of the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database. This network was recruited to be nationally representative of the English population. We developed an LC phenotype using our established 3-step ontological method: (1) ontological step (defining the reasoning process underpinning the phenotype, (2) coding step (exploring what clinical terms are available, and (3) logical extract model (testing performance). We created a version of this phenotype using Protégé in the ontology web language for BioPortal and using PhenoFlow. Next, we used the phenotype to compare people with LC (1) with regard to their symptoms in the year prior to acquiring COVID-19 and (2) with people with acute COVID-19. We also compared hospitalized people with LC with those not hospitalized. We compared sociodemographic details, comorbidities, and Office of National Statistics-defined LC symptoms between groups. We used descriptive statistics and logistic regression. RESULTS: The long-COVID phenotype differentiated people hospitalized with LC from people who were not and where no index infection was identified. The PCSC (N=7.4 million) includes 428,479 patients with acute COVID-19 diagnosis confirmed by a laboratory test and 10,772 patients with clinically diagnosed COVID-19. A total of 7471 (1.74%, 95% CI 1.70-1.78) people were coded as having LC, 1009 (13.5%, 95% CI 12.7-14.3) had a hospital admission related to acute COVID-19, and 6462 (86.5%, 95% CI 85.7-87.3) were not hospitalized, of whom 2728 (42.2%) had no COVID-19 index date recorded. In addition, 1009 (13.5%, 95% CI 12.73-14.28) people with LC were hospitalized compared to 17,993 (4.5%, 95% CI 4.48-4.61; P<.001) with uncomplicated COVID-19. CONCLUSIONS: Our LC phenotype enables the identification of individuals with the condition in routine data sets, facilitating their comparison with unaffected people through retrospective research. This phenotype and study protocol to explore its face validity contributes to a better understanding of LC.
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COVID-19 , COVID-19/complicações , Teste para COVID-19 , Humanos , Fenótipo , Atenção Primária à Saúde , Estudos Retrospectivos , Síndrome de COVID-19 Pós-AgudaRESUMO
BACKGROUND: Most studies of long COVID (symptoms of COVID-19 infection beyond 4 weeks) have focused on people hospitalized in their initial illness. Long COVID is thought to be underrecorded in UK primary care electronic records. OBJECTIVE: We sought to determine which symptoms people present to primary care after COVID-19 infection and whether presentation differs in people who were not hospitalized, as well as post-long COVID mortality rates. METHODS: We used routine data from the nationally representative primary care sentinel cohort of the Oxford-Royal College of General Practitioners Research and Surveillance Centre (N=7,396,702), applying a predefined long COVID phenotype and grouped by whether the index infection occurred in hospital or in the community. We included COVID-19 infection cases from March 1, 2020, to April 1, 2021. We conducted a before-and-after analysis of long COVID symptoms prespecified by the Office of National Statistics, comparing symptoms presented between 1 and 6 months after the index infection matched with the same months 1 year previously. We conducted logistic regression analysis, quoting odds ratios (ORs) with 95% CIs. RESULTS: In total, 5.63% (416,505/7,396,702) and 1.83% (7623/416,505) of the patients had received a coded diagnosis of COVID-19 infection and diagnosis of, or referral for, long COVID, respectively. People with diagnosis or referral of long COVID had higher odds of presenting the prespecified symptoms after versus before COVID-19 infection (OR 2.66, 95% CI 2.46-2.88, for those with index community infection and OR 2.42, 95% CI 2.03-2.89, for those hospitalized). After an index community infection, patients were more likely to present with nonspecific symptoms (OR 3.44, 95% CI 3.00-3.95; P<.001) compared with after a hospital admission (OR 2.09, 95% CI 1.56-2.80; P<.001). Mental health sequelae were more strongly associated with index hospital infections (OR 2.21, 95% CI 1.64-2.96) than with index community infections (OR 1.36, 95% CI 1.21-1.53; P<.001). People presenting to primary care after hospital infection were more likely to be men (OR 1.43, 95% CI 1.25-1.64; P<.001), more socioeconomically deprived (OR 1.42, 95% CI 1.24-1.63; P<.001), and with higher multimorbidity scores (OR 1.41, 95% CI 1.26-1.57; P<.001) than those presenting after an index community infection. All-cause mortality in people with long COVID was associated with increasing age, male sex (OR 3.32, 95% CI 1.34-9.24; P=.01), and higher multimorbidity score (OR 2.11, 95% CI 1.34-3.29; P<.001). Vaccination was associated with reduced odds of mortality (OR 0.10, 95% CI 0.03-0.35; P<.001). CONCLUSIONS: The low percentage of people recorded as having long COVID after COVID-19 infection reflects either low prevalence or underrecording. The characteristics and comorbidities of those presenting with long COVID after a community infection are different from those hospitalized. This study provides insights into the presentation of long COVID in primary care and implications for workload.
Assuntos
COVID-19 , Infecções Comunitárias Adquiridas , Infecção Hospitalar , Síndrome de COVID-19 Pós-Aguda , Feminino , Humanos , Masculino , COVID-19/complicações , SARS-CoV-2RESUMO
BACKGROUND: This retrospective cohort study aims to define the clinical findings and outcomes of every patient admitted to a district general hospital in Surrey with COVID-19 in March 2020, providing a snapshot of the first wave of infection in the UK. This study is the first detailed insight into the impact of frailty markers on patient outcomes and provides the infection rate among healthcare workers. METHODS: Data were obtained from medical records. Outcome measures were level of oxygen therapy, discharge and death. Patients were followed up until 21 April 2020. RESULTS: 108 patients were included. 34 (31%) died in hospital or were discharged for palliative care. 43% of patients aged over 65 died. The commonest comorbidities were hypertension (49; 45%) and diabetes (25; 23%). Patients who died were older (mean difference ±SEM, 13.76±3.12 years; p<0.0001) with a higher NEWS2 score (median 6, IQR 2.5-7.5 vs median 2, IQR 2-6) and worse renal function (median differences: urea 2.7 mmol/L, p<0.01; creatinine 4 µmol/L, p<0.05; eGFR 14 mL/min, p<0.05) on admission compared with survivors. Frailty markers were identified as risk factors for death. Clinical Frailty Scale (CFS) was higher in patients over 65 who died than in survivors (median 5, IQR 4-6 vs 3.5, IQR 2-5; p<0.01). Troponin and creatine kinase levels were higher in patients who died than in those who recovered (p<0.0001). Lymphopenia was common (median 0.8, IQR 0.6-1.2; p<0.005). Every patient with heart failure died (8). 26 (24%) were treated with continuous positive airway pressure (CPAP; median 3 days, IQR 2-7.3) and 9 (8%) were intubated (median 14 days, IQR 7-21). All patients who died after discharge (4; 6%) were care home residents. 276 of 699 hospital staff tested were positive for COVID-19. CONCLUSIONS: This study identifies older patients with frailty as being particularly vulnerable and reinforces government policy to protect this group at all costs.