Abstract
Background
Surgical resection remains the best option for long-term survival in many solid tumors. Surgery can, however, lead to tumor cell release into the circulation. Data have suggested ...differential effects of anesthetic agents on cancer cell growth. This retrospective analysis investigated the association of anesthetic technique with long-term survival in patients presenting for elective surgery in a comprehensive cancer center over 3 yr.
Methods
All patients undergoing elective surgery between June 2010 and May 2013 were included. Patients were grouped according to whether they had received volatile inhalational (INHA) or total IV anesthesia (TIVA). After excluding those who received both forms of anesthesia during the study period, Kaplan–Meier survival curves were constructed from the date of surgery to death. After propensity matching, univariate and multivariable regression models were used to compare hazard ratios for death.
Results
A total of 11,395 anesthetics using INHA or TIVA were delivered in the study period. After exclusions, 3,316 patients (796 deaths, 24%) remained in the INHA group and 3,714 (504 deaths, 13.5%) in the TIVA group. After propensity matching, 2,607 patients remained in each group (597 deaths, 22.8%, in INHA group vs. 407, 15.6%, in TIVA group). Volatile inhalational anesthesia was associated with a hazard ratio of 1.59 (1.30 to 1.95) for death on univariate analysis and 1.46 (1.29 to 1.66) after multivariable analysis of known confounders in the matched group.
Conclusions
This retrospective analysis demonstrates an association between type of anesthetic delivered and survival. This analysis alongside biological plausibility should lead to urgent prospective work exploring the effect of anesthetic technique on survival.
During the COVID-19 lockdown, referrals via the 2-week-wait urgent pathway for suspected cancer in England, UK, are reported to have decreased by up to 84%. We aimed to examine the impact of ...different scenarios of lockdown-accumulated backlog in cancer referrals on cancer survival, and the impact on survival per referred patient due to delayed referral versus risk of death from nosocomial infection with severe acute respiratory syndrome coronavirus 2.
In this modelling study, we used age-stratified and stage-stratified 10-year cancer survival estimates for patients in England, UK, for 20 common tumour types diagnosed in 2008–17 at age 30 years and older from Public Health England. We also used data for cancer diagnoses made via the 2-week-wait referral pathway in 2013–16 from the Cancer Waiting Times system from NHS Digital. We applied per-day hazard ratios (HRs) for cancer progression that we generated from observational studies of delay to treatment. We quantified the annual numbers of cancers at stage I–III diagnosed via the 2-week-wait pathway using 2-week-wait age-specific and stage-specific breakdowns. From these numbers, we estimated the aggregate number of lives and life-years lost in England for per-patient delays of 1–6 months in presentation, diagnosis, or cancer treatment, or a combination of these. We assessed three scenarios of a 3-month period of lockdown during which 25%, 50%, and 75% of the normal monthly volumes of symptomatic patients delayed their presentation until after lockdown. Using referral-to-diagnosis conversion rates and COVID-19 case-fatality rates, we also estimated the survival increment per patient referred.
Across England in 2013–16, an average of 6281 patients with stage I–III cancer were diagnosed via the 2-week-wait pathway per month, of whom 1691 (27%) would be predicted to die within 10 years from their disease. Delays in presentation via the 2-week-wait pathway over a 3-month lockdown period (with an average presentational delay of 2 months per patient) would result in 181 additional lives and 3316 life-years lost as a result of a backlog of referrals of 25%, 361 additional lives and 6632 life-years lost for a 50% backlog of referrals, and 542 additional lives and 9948 life-years lost for a 75% backlog in referrals. Compared with all diagnostics for the backlog being done in month 1 after lockdown, additional capacity across months 1–3 would result in 90 additional lives and 1662 live-years lost due to diagnostic delays for the 25% backlog scenario, 183 additional lives and 3362 life-years lost under the 50% backlog scenario, and 276 additional lives and 5075 life-years lost under the 75% backlog scenario. However, a delay in additional diagnostic capacity with provision spread across months 3–8 after lockdown would result in 401 additional lives and 7332 life-years lost due to diagnostic delays under the 25% backlog scenario, 811 additional lives and 14 873 life-years lost under the 50% backlog scenario, and 1231 additional lives and 22 635 life-years lost under the 75% backlog scenario. A 2-month delay in 2-week-wait investigatory referrals results in an estimated loss of between 0·0 and 0·7 life-years per referred patient, depending on age and tumour type.
Prompt provision of additional capacity to address the backlog of diagnostics will minimise deaths as a result of diagnostic delays that could add to those predicted due to expected presentational delays. Prioritisation of patient groups for whom delay would result in most life-years lost warrants consideration as an option for mitigating the aggregate burden of mortality in patients with cancer.
None.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Introduction
Palliative care within intensive care units (ICU) benefits decision-making, symptom control, and end-of-life care. It has been shown to reduce the length of ICU stay and the use of ...non-beneficial and unwanted life-sustaining therapies. However, it is often initiated late or not at all. There is increasing evidence to support screening ICU patients using palliative care referral criteria or “triggers”. The aim of the project was to assess the need for palliative care referral during ICU admission using “trigger” tools.
Methods
Electronic record review of cancer patients who died in or within 30 days of discharge from oncology ICU, between 2016 and 2018. Patients referred to palliative care before or during ICU admission were identified. Three sets of palliative care referral “triggers” were applied: one that is being tested locally and two internationally derived tools. The proportion of patients who met any of these triggers during their final ICU admission was calculated.
Results
Records of 149 patients were reviewed: median age 65 (range 20–83). Most admissions (89%) were unplanned, with the most common diagnoses being haemato-oncology (31%) and gastrointestinal (16%) cancers. Most (73%) were unknown to palliative care pre-ICU admission; 44% were referred between admission and death. The median time from referral to death was 0 day (range 0–19). On ICU admission, 97–99% warranted referral to palliative care using locally and internationally derived triggers.
Conclusion
All “trigger” tools identified a high proportion of patients who may have warranted a palliative care referral either before or during admission to ICU. The routine use of trigger tools could help streamline referral pathways and underpin the development of an effective consultative model of palliative care within the ICU setting to enhance decision-making about appropriate treatment and patient-centred care.
To evaluate the impact of faecal immunochemical testing (FIT) prioritisation to mitigate the impact of delays in the colorectal cancer (CRC) urgent diagnostic (2-week-wait (2WW)) pathway consequent ...from the COVID-19 pandemic.
We modelled the reduction in CRC survival and life years lost resultant from per-patient delays of 2-6 months in the 2WW pathway. We stratified by age group, individual-level benefit in CRC survival versus age-specific nosocomial COVID-19-related fatality per referred patient undergoing colonoscopy. We modelled mitigation strategies using thresholds of FIT triage of 2, 10 and 150 µg Hb/g to prioritise 2WW referrals for colonoscopy. To construct the underlying models, we employed 10-year net CRC survival for England 2008-2017, 2WW pathway CRC case and referral volumes and per-day-delay HRs generated from observational studies of diagnosis-to-treatment interval.
Delay of 2/4/6 months across all 11 266 patients with CRC diagnosed per typical year via the 2WW pathway were estimated to result in 653/1419/2250 attributable deaths and loss of 9214/20 315/32 799 life years. Risk-benefit from urgent investigatory referral is particularly sensitive to nosocomial COVID-19 rates for patients aged >60. Prioritisation out of delay for the 18% of symptomatic referrals with FIT >10 µg Hb/g would avoid 89% of these deaths attributable to presentational/diagnostic delay while reducing immediate requirement for colonoscopy by >80%.
Delays in the pathway to CRC diagnosis and treatment have potential to cause significant mortality and loss of life years. FIT triage of symptomatic patients in primary care could streamline access to colonoscopy, reduce delays for true-positive CRC cases and reduce nosocomial COVID-19 mortality in older true-negative 2WW referrals. However, this strategy offers benefit only in short-term rationalisation of limited endoscopy services: the appreciable false-negative rate of FIT in symptomatic patients means most colonoscopies will still be required.
...we evaluated omicron nAbT in four patients with a history of breakthrough delta infection after two vaccine doses. The exact correlates of immune protection against VOC remain undefined; however, ...multiple studies have shown that higher nAbT correlate with reduced risk of symptomatic infection.10,11 Finally, we did not evaluate vaccine-induced cellular responses to omicron as we had for other VOCs.2 We note that emerging reports suggest T-cell responses against omicron remain comparable to ancestral variants in the general population without cancer.12,13 In conclusion, we show that most of the patients with cancer in the CAPTURE cohort lacked detectable nAbT against omicron following two vaccine doses, independent of the vaccine type. CS is funded by CRUK (TRACERx, PEACE and CRUK Cancer Immunotherapy Catalyst Network), the CRUK Lung Cancer Centre of Excellence (C11496/A30025), the Rosetrees Trust, Butterfield and Stoneygate Trusts, the Novo Nordisk Foundation (ID16584), a Royal Society Professorship Enhancement award (RP/EA/180007), the National Institute of Health Research (NIHR) Biomedical Research Centre at University College London Hospitals, the CRUK University College London Centre, the Experimental Cancer Medicine Centre and the Breast Cancer Research Foundation (BCRF 20-157). ST is funded by Cancer Research UK (A29911); the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC10988), the UK Medical Research Council (FC10988), and the Wellcome Trust (FC10988); the NIHR Biomedical Research Centre at the Royal Marsden Hospital and Institute of Cancer Research (grant reference number A109), the Royal Marsden Cancer Charity, The Rosetrees Trust (A2204), Ventana Medical Systems (grant reference numbers 10467 and 10530), the National Institute of Health (U01 CA247439) and Melanoma Research Alliance (686061).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Post-operative outcomes may be improved by the use of flow related end-points for intra-venous fluid and/or low dose inotropic therapy. The mechanisms underlying this benefit remain uncertain. The ...objective of this study was to assess the effects of stroke volume guided intra-venous fluid and low dose dopexamine on tissue microvascular flow and oxygenation and inflammatory markers in patients undergoing major gastrointestinal surgery.
Randomised, controlled, single blind study of patients admitted to a university hospital critical care unit following major gastrointestinal surgery. For eight hours after surgery, intra-venous fluid therapy was guided by measurements of central venous pressure (CVP group), or stroke volume (SV group). In a third group stroke volume guided fluid therapy was combined with dopexamine (0.5 mcg/kg/min) (SV & DPX group).
135 patients were recruited (n = 45 per group). In the SV & DPX group, increased global oxygen delivery was associated with improved sublingual (P < 0.05) and cutaneous microvascular flow (P < 0.005) (sublingual microscopy and laser Doppler flowmetry). Microvascular flow remained constant in the SV group but deteriorated in the CVP group (P < 0.05). Cutaneous tissue oxygen partial pressure (PtO2) (Clark electrode) improved only in the SV & DPX group (P < 0.001). There were no differences in serum inflammatory markers. There were no differences in overall complication rates between the groups although acute kidney injury was more frequent in the CVP group (CVP group ten patients (22%); pooled SV and SV & DPX groups seven patients (8%); P = 0.03) (post hoc analysis).
Stroke volume guided fluid and low dose inotropic therapy was associated with improved global oxygen delivery, microvascular flow and tissue oxygenation but no differences in the inflammatory response to surgery. These observations may explain improved clinical outcomes associated with this treatment in previous trials.
ISRCTN 94850719.
Abstract Background Improving outcomes after surgery is a major public health research priority for patients, clinicians and the NHS. The greatest burden of perioperative complications, mortality and ...healthcare costs lies amongst the population of patients aged over 50 years who undergo major non-cardiac surgery. The Volatile vs Total Intravenous Anaesthesia for major non-cardiac surgery (VITAL) trial specifically examines the effect of anaesthetic technique on key patient outcomes: quality of recovery after surgery (quality of recovery after anaesthesia, patient satisfaction and major post-operative complications), survival and patient safety. Methods A multi-centre pragmatic efficient randomised trial with health economic evaluation comparing total intravenous anaesthesia with volatile-based anaesthesia in adults (aged 50 and over) undergoing elective major non-cardiac surgery under general anaesthesia. Discussion Given the very large number of patients exposed to general anaesthesia every year, even small differences in outcome between the two techniques could result in substantial excess harm. Results from the VITAL trial will ensure patients can benefit from the very safest anaesthesia care, promoting an early return home, reducing healthcare costs and maximising the health benefits of surgical treatments. Trial registration ISRCTN62903453. September 09, 2021.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
During the on‐going COVID‐19 pandemic a number of key public health services have been severely impacted. These include elective surgical services due to the synergetic resources required to provide ...both perioperative surgical care whilst also treating acute COVID‐19 patients and also the poor outcomes associated with surgical patients who develop COVID‐19 in the perioperative period. This article discusses the important principles and concepts for providing important surgical services during the COVID‐19 pandemic based on the model of the RMCancerSurgHub which is providing surgical cancer services for a population of approximately 2 million people across London during the pandemic. The model focusses on creating local and regional hub centres which provide urgent treatment for surgical patients in an environment that is relatively protected from the burden of COVID‐19 illness. The model extensively utilises the extended multidisciplinary team to allow for a flexible approach with core services delivered in ‘clean’ sites which can adapt to viral surges. A key requirement is that of a clinical prioritisation process which allows for equity in access within and between specialties ensuring that patients are treated on the basis of greatest need, while at the same time protecting those whose conditions can safely wait from exposure to the virus. Importantly, this model has the ability to scale‐up activity and lead units and networks into the recovery phase. The model discussed is also broadly applicable to providing surgical services during any viral pandemic.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
BACKGROUND:Surgical resection remains the best option for long-term survival in many solid tumors. Surgery can, however, lead to tumor cell release into the circulation. Data have suggested ...differential effects of anesthetic agents on cancer cell growth. This retrospective analysis investigated the association of anesthetic technique with long-term survival in patients presenting for elective surgery in a comprehensive cancer center over 3 yr.
METHODS:All patients undergoing elective surgery between June 2010 and May 2013 were included. Patients were grouped according to whether they had received volatile inhalational (INHA) or total IV anesthesia (TIVA). After excluding those who received both forms of anesthesia during the study period, Kaplan–Meier survival curves were constructed from the date of surgery to death. After propensity matching, univariate and multivariable regression models were used to compare hazard ratios for death.
RESULTS:A total of 11,395 anesthetics using INHA or TIVA were delivered in the study period. After exclusions, 3,316 patients (796 deaths, 24%) remained in the INHA group and 3,714 (504 deaths, 13.5%) in the TIVA group. After propensity matching, 2,607 patients remained in each group (597 deaths, 22.8%, in INHA group vs. 407, 15.6%, in TIVA group). Volatile inhalational anesthesia was associated with a hazard ratio of 1.59 (1.30 to 1.95) for death on univariate analysis and 1.46 (1.29 to 1.66) after multivariable analysis of known confounders in the matched group.
CONCLUSIONS:This retrospective analysis demonstrates an association between type of anesthetic delivered and survival. This analysis alongside biological plausibility should lead to urgent prospective work exploring the effect of anesthetic technique on survival.
Impaired vagal function in older individuals, quantified by the ‘gold standard’ delayed heart rate recovery after maximal exercise (HRRexercise), is an independent predictor of cardiorespiratory ...capacity and mortality (particularly when HRR ≤12 beats min−1). Heart rate also often declines after orthostatic challenge (HRRorthostatic), but the mechanism remains unclear. We tested whether HRRorthostatic reflects similar vagal autonomic characteristics as HRRexercise.
Prospective multicentre cohort study of subjects scheduled for cardiopulmonary exercise testing (CPET) as part of routine care. Before undergoing CPET, heart rate was measured with participants seated for 3 min, before standing for 3 min (HRRorthostatic). HRRexercise 1 min after the end of CPET was recorded. The primary outcome was the correlation between mean heart rate change every 10 s for 1 min after peak heart rate was attained on standing and after exercise for each participant. Secondary outcomes were HRRorthostatic and peak VO2 compared between individuals with HRRexercise <12 beats min−1.
A total of 87 participants (mean age: 64 yr 61–66; 48 (55%) females) completed both tests. Mean heart rate change every 10 s for 1 min after peak heart rate after standing and exercise was significantly correlated (R2=0.81; P<0.0001). HRRorthostatic was unchanged in individuals with HRRexercise ≤12 beats min−1 (n=27), but was lower when HRRexercise >12 beats min−1 (n=60; mean difference: 3 beats min−1 95% confidence interval 1–5 beats min−1; P<0.0001). Slower HRRorthostatic was associated with lower peak VO2 (mean difference: 3.7 ml kg min−1 95% confidence interval 0.7–6.8 ml kg min−1; P=0.039).
Prognostically significant heart rate recovery after exhaustive exercise is characterised by quantitative differences in heart rate recovery after orthostatic challenge. These data suggest that orthostatic challenge is a valid, simple test indicating vagal impairment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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