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Ovarian cancer symptoms in pre-clinical invasive epithelial ovarian cancer – an exploratory analysis nested within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)
ObjectiveUKCTOCS provides an opportunity to explore symptoms in preclinical invasive epithelial ovarian cancer (iEOC). We report on symptoms in women with pre-clinical (screen-detected) cancers (PC) compared to clinically diagnosed (CD) cancers.MethodsIn UKCTOCS, 202638 postmenopausal women, aged 50–74 were randomly allocated (April 17, 2001-September 29, 2005) 2:1:1 to no screening or annual screening till Dec 31,2011, using a multimodal or ultrasound strategy. Follow-up was through national registries. An outcomes committee adjudicated on OC diagnosis, histotype, stage. Eligible women were those diagnosed with iEOC at primary censorship (Dec 31, 2014). Symptom details were extracted from trial clinical-assessment forms and medical records. Descriptive statistics were used to compare symptoms in PC versus CD women with early (I/II) and advanced (III/IV/unable to stage) stage high-grade-serous (HGSC) cancer. ISRCTN-22488978; ClinicalTrials.gov-NCT00058032.Results1133 (286PC; 847CD) women developed iEOC. Median age (years) at diagnosis was earlier in PC compared to CD (66.8PC, 68.7CD, p = 0.0001) group. In the PC group, 48% (112/234; 90%, 660/730CD) reported symptoms when questioned. Half PC (50%, 13/26PC; 36%, 29/80CD; p = 0.213) women with symptomatic HGSC had >1symptom, with abdominal symptoms most common, both in early (62%, 16/26, PC; 53% 42/80, CD; p = 0.421) and advanced (57%, 49/86, PC; 74%, 431/580, CD; p = 0.001) stages. In symptomatic early-stage HGSC, compared to CD, PC women reported more gastrointestinal (change in bowel habits and dyspepsia) (35%, 9/26PC; 9%, 7/80CD; p = 0.001) and systemic (mostly lethargy/tiredness) (27%, 7/26PC; 9%, 7/80CD; p = 0.017) symptoms.ConclusionsOur findings, add to the growing evidence, that we should reconsider what constitutes alert symptoms for early tubo-ovarian cancer. We need a more nuanced complex of key symptoms which is then evaluated and refined in a prospective trial.</p
Elevated preoperative heart rate is associated with cardiopulmonary and autonomic impairment in high-risk surgical patients
Background: Elevated preoperative heart rate (HR) is associated with perioperative myocardial injury and death. In apparently healthy individuals, high resting HR is associated with development of cardiac failure. Given that patients with overt cardiac failure have poor perioperative outcomes, we hypothesized that subclinical cardiac failure, identified by cardiopulmonary exercise testing, was associated with elevated preoperative HR > 87 beats min-1(HR > 87). Methods: This was a secondary analysis of an observational cohort study of surgical patients aged ≥45 yr. The exposure of interest was HR > 87, recorded at rest before preoperative cardiopulmonary exercise testing. The predefined outcome measures were the following established predictors of mortality in patients with overt cardiac failure in the general population: ventilatory equivalent for carbon dioxide (V E/V co2) ratio ≥34, heart rate recovery ≤6 and peak oxygen uptake (V o2) ≤14 ml kg-1min-1. We used logistic regression analysis to test for association between HR > 87 and markers of cardiac failure. We also examined the relationship between HR > 87 and preoperative left ventricular stroke volume in a separate cohort of patients. Results: HR > 87 was present in 399/1250 (32%) patients, of whom 438/1250 (35%) had V E/V co2ratio ≥34, 200/1250 (16%) had heart rate recovery ≤6, and 396/1250 (32%) had peak V o2≤14 ml kg-1min-1. HR > 87 was independently associated with peak V o2≤14 ml kg-1min-1{odds ratio (OR) 1.69 [1.12-3.55]; P=0.01} and heart rate recovery ≤6 (OR 2.02 [1.30-3.14]; P 87 was not associated with V E/V co2ratio ≥34 (OR 1.31 [0.92-1.87]; P=0.14). In a separate cohort, HR > 87 (33/181; 18.5%) was associated with impaired preoperative stroke volume (OR 3.21 [1.26-8.20]; P=0.01). Conclusions: Elevated preoperative heart rate is associated with impaired cardiopulmonary performance consistent with clinically unsuspected, subclinical cardiac failure. Clinical trial registration. ISRCTN88456378