RSS 1.0Cancer and Associated Specialties
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Sociodemographic variations in the uptake of faecal immunochemical tests in primary care: A retrospective studyAbstract Background Faecal immunochemical test (FIT) usage for symptomatic patients is increasing, but variations in use caused by sociodemographic factors are unknown. A clinical pathway for colorectal cancer (CRC) was introduced in primary care for symptomatic patients in November 2017. The pathway was commissioned to provide GPs with direct access to FITs. Aim To identify whether sociodemographic factors affect FIT return in symptomatic patients. Design and setting A retrospective study was undertaken in Nottingham, UK, following the introduction of FIT as triage tool in primary care. It was mandated for all colorectal referrals (except rectal bleeding or mass) to secondary care. FIT was used, alongside full blood count and ferritin, to stratify CRC risk. Method All referrals from November 2017 to December 2021 were retrospectively reviewed. Sociodemographic factors affecting FIT return were analysed by multivariate logistic regression. Results A total of 35 289 (90.7%) patients returned their index FIT, while 3631 (9.3%) did not. On multivariate analysis, males were less likely to return an FIT (odds ratio [OR] 1.11, 95% confidence interval [CI] = 1.03 to 1.19). Patients aged ≥65 years were more likely to return an FIT (OR 0.78 for non-return, 95% CI = 0.72 to 0.83). Unreturned FIT more than doubled in the most compared with the least deprived quintile (OR 2.20, 95% CI = 1.99 to 2.43). Patients from Asian (OR 1.82, 95% CI = 1.58 to 2.10), Black (OR 1.21, 95% CI = 0.98 to 1.49), and mixed or other ethnic groups (OR 1.29, 95% CI = 1.05 to 1.59) were more likely to not return an FIT compared with patients from a White ethnic group. A total of 599 (1.5%) CRCs were detected; 561 in those who returned a first FIT request. Conclusion FIT return in those suspected of having CRC varied by sex, age, ethnic group, and socioeconomic deprivation. Strategies to mitigate effects on FIT return and CRC detection should be considered as FIT usage expands.
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Understanding colorectal cancer risk for symptomatic patients in primary care: A cohort study utilising faecal immunochemical tests and blood results in EnglandSummary Background A faecal immunochemical tests (FIT) cut-off of ≥10 μg Hb/g faeces is now recommended in the UK as a gateway to urgent (suspected cancer) investigation for colorectal cancer (CRC), based on an expected CRC risk threshold of 3%. Aims To quantify the risk of CRC at FIT cut-offs by age, haemoglobin and platelet strata. Methods A cohort study of a symptomatic CRC pathway based on primary care FIT tests in Nottingham, UK (November 2017–2021) with 1-year follow-up. Heat maps showed the cumulative 1-year CRC risk using Kaplan–Meier estimates. Results In total, 514 (1.5%) CRCs were diagnosed following 33,694 index FIT requests. Individuals with a FIT ≥ 10 μg Hb/g faeces had a >3% risk of CRC, except patients under the age of 40 years (CRC risk 1.45% [95% CI: 0.03%–2.86%]). Non-anaemic patients with a FIT < 100 μg Hb/g faeces had a CRC risk of <3%, except those between the age of 70 and 85 years (5.26% 95% CI: 2.72%–7.73%). Using a ≥3% CRC threshold in patients <55 years calculated using FIT, age and anaemia might allow 160–220 colonoscopies per 10,000 FITs to be re-purposed, at a cost of missing 1–2 CRCs. Conclusions FIT alone with a single cut-off is unlikely to be a panacea for optimising CRC diagnosis, as risk varies by FIT, age and anaemia when faecal haemoglobin levels are below 100 μg Hb/g. Tailored FIT cut-offs for investigation on a CRC pathway could reduce the number of investigations needed at a 3% CRC risk threshold.
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Co-infection in critically ill patients with COVID-19: An observational cohort study from EnglandIntroduction. During previous viral pandemics, reported co-infection rates and implicated pathogens have varied. In the 1918 influenza pandemic, a large proportion of severe illness and death was complicated by bacterial co-infection, predominantly Streptococcus pneumoniae and Staphylococcus aureus. Gap statement. A better understanding of the incidence of co-infection in patients with COVID-19 infection and the pathogens involved is necessary for effective antimicrobial stewardship. Aim. To describe the incidence and nature of co-infection in critically ill adults with COVID-19 infection in England. Methodology. A retrospective cohort study of adults with COVID-19 admitted to seven intensive care units (ICUs) in England up to 18 May 2020, was performed. Patients with completed ICU stays were included. The proportion and type of organisms were determined at 48 h following hospital admission, corresponding to community and hospital-acquired co-infections. Results. Of 254 patients studied (median age 59 years (IQR 49-69); 64.6 % male), 139 clinically significant organisms were identified from 83 (32.7 %) patients. Bacterial co-infections/ co-colonisation were identified within 48 h of admission in 14 (5.5 %) patients; the commonest pathogens were Staphylococcus aureus (four patients) and Streptococcus pneumoniae (two patients). The proportion of pathogens detected increased with duration of ICU stay, consisting largely of Gram-negative bacteria, particularly Klebsiella pneumoniae and Escherichia coli. The co-infection/ co-colonisation rate >48 h after admission was 27/1000 person-days (95 % CI 21.3-34.1). Patients with co-infections/ co-colonisation were more likely to die in ICU (crude OR 1.78,95 % CI 1.03-3.08, P=0.04) compared to those without co-infections/ co-colonisation. Conclusion. We found limited evidence for community-acquired bacterial co-infection in hospitalised adults with COVID-19, but a high rate of Gram-negative infection acquired during ICU stay.
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Cost-effectiveness of adrenaline for out-of-hospital cardiac arrestBACKGROUND: The 'Prehospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug Administration In Cardiac Arrest' (PARAMEDIC2) trial showed that adrenaline improves overall survival, but not neurological outcomes. We sought to determine the within-trial and lifetime health and social care costs and benefits associated with adrenaline, including secondary benefits from organ donation. METHODS: We estimated the costs, benefits (quality-adjusted life years (QALYs)) and incremental cost-effectiveness ratios (ICERs) associated with adrenaline during the 6-month trial follow-up. Model-based analyses explored how results altered when the time horizon was extended beyond 6 months and the scope extended to include recipients of donated organs. RESULTS: The within-trial (6 months) and lifetime horizon economic evaluations focussed on the trial population produced ICERs of 1,693,003 (1,946,953) and 81,070 (93,231) per QALY gained in 2017 prices, respectively, reflecting significantly higher mean costs and only marginally higher mean QALYs in the adrenaline group. The probability that adrenaline is cost-effective was less than 1% across a range of cost-effectiveness thresholds. Combined direct economic effects over the lifetimes of survivors and indirect economic effects in organ recipients produced an ICER of 16,086 (18,499) per QALY gained for adrenaline with the probability that adrenaline is cost-effective increasing to 90% at a 30,000 (34,500) per QALY cost-effectiveness threshold. CONCLUSIONS: Adrenaline was not cost-effective when only directly related costs and consequences are considered. However, incorporating the indirect economic effects associated with transplanted organs substantially alters cost-effectiveness, suggesting decision-makers should consider the complexity of direct and indirect economic impacts of adrenaline. TRIAL REGISTRATION: ISRCTN73485024 . Registered on 13 March 2014.
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Resumption of cardiac activity after withdrawal of life-sustaining measuresBACKGROUND: The minimum duration of pulselessness required before organ donation after circulatory determination of death has not been well studied. METHODS: We conducted a prospective observational study of the incidence and timing of resumption of cardiac electrical and pulsatile activity in adults who died after planned withdrawal of life-sustaining measures in 20 intensive care units in three countries. Patients were intended to be monitored for 30 minutes after determination of death. Clinicians at the bedside reported resumption of cardiac activity prospectively. Continuous blood-pressure and electrocardiographic (ECG) waveforms were recorded and reviewed retrospectively to confirm bedside observations and to determine whether there were additional instances of resumption of cardiac activity. RESULTS: A total of 1999 patients were screened, and 631 were included in the study. Clinically reported resumption of cardiac activity, respiratory movement, or both that was confirmed by waveform analysis occurred in 5 patients (1%). Retrospective analysis of ECG and blood-pressure waveforms from 480 patients identified 67 instances (14%) with resumption of cardiac activity after a period of pulselessness, including the 5 reported by bedside clinicians. The longest duration after pulselessness before resumption of cardiac activity was 4 minutes 20 seconds. The last QRS complex coincided with the last arterial pulse in 19% of the patients. CONCLUSIONS: After withdrawal of life-sustaining measures, transient resumption of at least one cycle of cardiac activity after pulselessness occurred in 14% of patients according to retrospective analysis of waveforms; only 1% of such resumptions were identified at the bedside. These events occurred within 4 minutes 20 seconds after a period of pulselessness. (Funded by the Canadian Institutes for Health Research and others.). Copyright © 2021 Massachusetts Medical Society.
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Organ donation and transplantationAn ethical organ donation and transplantation program regarding deceased patients donors would balance the needs of the organ recipient with the needs of the organ donor and his or her family. The solution to achieve ethical balance is not easy. The donation community leans toward Kantian ethics to justify actions on the donor, while the transplant community tends toward utilitarian justifications that focus on recipient outcomes. Yet the responsibility to achieve balance lies with both communities (and their wider healthcare colleagues) to work together so that good end-of-life care for donors is achieved while simultaneously increasing the number and quality of deceased organ transplants. This chapter will use our personal knowledge of the British and Spanish organ donation and transplantation systems to ask if organ transplantation fosters or threatens end-of-life care in critical care and emergency medicine. Our conclusion is that by adopting a rule utilitarianism approach, ethical balance is more likely to be achieved. We propose three rules for any donation and transplantation program: (1) The exploration of organ donation for all patients dying in critical care and emergency medicine should be pursued, as organ donation might improve end-of-life care and can honor the ideal of a “good death”; (2) Organ donation must never compromise a “good death”; and (3) All parties should seek to build institutional trustworthiness.
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Maintaining the permanence principle for death during in situ normothermic regional perfusion for donation after circulatory death organ recovery: A United Kingdom and Canadian proposalThere is international variability in the determination of death. Death in donation after circulatory death (DCD) can be defined by the permanent cessation of brain circulation. Post-mortem interventions that restore brain perfusion should be prohibited as they invalidate the diagnosis of death. Retrieval teams should develop protocols that ensure the continued absence of brain perfusion during DCD organ recovery. In situ normothermic regional perfusion (NRP) or restarting the heart in the donor's body may interrupt the permanent cessation of brain perfusion because, theoretically, collateral circulations may restore it. We propose refinements to current protocols to monitor and exclude brain reperfusion during in situ NRP. In abdominal NRP, complete occlusion of the descending aorta prevents brain perfusion in most cases. Inserting a cannula in the ascending aorta identifies inadequate occlusion of the descending aorta or any collateral flow and diverts flow away from the brain. In thoracoabdominal NRP opening the aortic arch vessels to atmosphere allows collateral flow to be diverted away from the brain, maintaining the permanence standard for death and respecting the dead donor rule. We propose that these hypotheses are correct when using techniques that simultaneously occlude the descending aorta and open the aortic arch vessels to atmosphere. Copyright © 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.
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Expanding controlled donation after the circulatory determination of death: Statement from an international collaborativeA decision to withdraw life-sustaining treatment (WLST) is derived by a conclusion that further treatment will not enable a patient to survive or will not produce a functional outcome with acceptable quality of life that the patient and the treating team regard as beneficial. Although many hospitalized patients die under such circumstances, controlled donation after the circulatory determination of death (cDCDD) programs have been developed only in a reduced number of countries. This International Collaborative Statement aims at expanding cDCDD in the world to help countries progress towards self-sufficiency in transplantation and offer more patients the opportunity of organ donation. The Statement addresses three fundamental aspects of the cDCDD pathway. First, it describes the process of determining a prognosis that justifies the WLST, a decision that should be prior to and independent of any consideration of organ donation and in which transplant professionals must not participate. Second, the Statement establishes the permanent cessation of circulation to the brain as the standard to determine death by circulatory criteria. Death may be declared after an elapsed observation period of 5 min without circulation to the brain, which confirms that the absence of circulation to the brain is permanent. Finally, the Statement highlights the value of perfusion repair for increasing the success of cDCDD organ transplantation. cDCDD protocols may utilize either in situ or ex situ perfusion consistent with the practice of each country. Methods to accomplish the in situ normothermic reperfusion of organs must preclude the restoration of brain perfusion to not invalidate the determination of death.
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Oxygen saturation and haemodynamic changes prior to circulatory arrest: Implications for transplantation and resuscitationAIMS: To describe the progression of oxygen saturations and blood pressure observations prior to death. INTRODUCTION: The progression of physiological changes around death is unknown. This has important implications in organ donation and resuscitation. Donated organs have a maximal warm ischaemic threshold. In hypoxic cardiac arrest, an understanding of pre-cardiac arrest physiology is important in prognosticating and will allow earlier identification of terminal states. METHODS: Data were examined for all regional patients over a two-year period offering organ donation after circulatory death. Frequent observations were taken contemporaneously by the organ donation nurse at the time of and after withdrawal of intensive care. RESULTS: In all, 82 case notes were examined of patients aged 0 to 76 (median 52, 4 < 18 years). From withdrawal of intensive care to death took a mean of 28.5 min (range 4 to 185). A terminal deterioration in saturations (from an already low baseline) commenced 14 min prior to circulatory arrest, followed by a blood pressure fall commencing 8 min prior to circulatory arrest, and finally a rapid fall in heart rate commencing 4 min prior to circulatory arrest. Two patients had a warm ischaemic time of greater than 30 min; 15 patients had a warm ischaemia time of 10 min or greater; and 53 patients had a warm ischaemia time of 5 min or less. It was observed that 0/82 patients had saturations of less than 40% for more than 3 min prior to cardiac arrest and 74/82 for more than 2 min. CONCLUSIONS: There is a perimortem sequence of hypoxia, then hypotension, and then bradycardia. The heart is extremely resistant to hypoxia. A warm ischaemic time of over 30 min is rare.
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The rule of threes: Three factors that triple the likelihood of families overriding first person consent for organ donation in the UKBetween 1 April 2012 and 31 March 2015, 263 of the 2244 families in the UK whose loved ones had registered to donate organs for transplantation after their death on the NHS Organ Donor Register chose to override this decision; an override rate of 11.7%. Multivariable logistic regression analysis was applied to data relating to various aspects of the family approach in order to identify factors associated with such overrides. The factors associated with family overrides were failure to involve the Specialist Nurse for Organ Donation in the family approach (odds ratio 3.0), donation after circulatory death (odds ratio 2.7) and Black, Asian or Minority Ethnicity (odds ratio 2.7). This highlights the need to further engage with these groups in exploring donation as an end of life choice, and suggests that there may be, from the perspective of the family, fundamental differences between donation after brainstem death and circulatory death. It further adds to the body of data linking involvement of the Specialist Nurse for Organ Donation in the family approach to improved UK consent rates.
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Donation after the circulatory determination of death: Some responses to recent criticismsThis article defends the criterion of permanence as a valid criterion for declaring death against some well-known recent objections. We argue that it is reasonable to adopt the criterion of permanence for declaring death, given how difficult it is to know when the point of irreversibility is actually reached. We claim that this point applies in all contexts, including the donation after circulatory determination of death context. We also examine some of the potentially unpalatable ramifications, for current death declaration practices, of adopting the irreversibility criterion.
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Increasing organ donation rates by revealing recipient details to families of potential donorsMany families refuse to consent to donation from their deceased relatives or over-rule the consent given before death by the patient, but giving families more information about the potential recipients of organs could reduce refusal rates. In this paper, we analyse arguments for and against doing so, and conclude that this strategy should be attempted. While it would be impractical and possibly unethical to give details of actual potential recipients, generic, realistic information about the people who could benefit from organs should be provided to families before they make a decision about donation or attempt to over-rule it. Copyright © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
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Conscientious objection to deceased organ donation by healthcare professionalsIn this article, we analyse the potential benefits and disadvantages of permitting healthcare professionals to invoke conscientious objection to deceased organ donation. There is some evidence that permitting doctors and nurses to register objections can ultimately lead to attitudinal change and acceptance of organ donation. However, while there may be grounds for conscientious objection in other cases such as abortion and euthanasia, the life-saving nature of donation and transplantation renders objection in this context more difficult to justify. In general, dialogue between healthcare professionals is a more appropriate solution, and any objections must be justified with a strong rationale in hospitals where such policies are put in place.
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An international legal review of the relationship between brain death and organ transplantationThe "dead-donor rule" states that, in any case of vital organ donation, the potential donor should be determined to be dead before transplantation occurs. In many countries around the world, neurological criteria can be used to legally determine death (also referred to as brain death). Nevertheless, there is considerable controversy in the bioethics literature over whether brain death is the equivalent of biological death. This international legal review demonstrates that there is considerable variability in how different jurisdictions have evolved to justify the legal status of brain death and its relationship to the dead-donor rule. In this article, we chose to review approaches that are representative of many different jurisdictions-the United States takes an approach similar to that of many European countries; the United Kingdom's approach is followed by Canada, India, and influences many other Commonwealth countries; Islamic jurisprudence is applicable to several different national laws; the Israeli approach is similar to many Western countries, but incorporates noteworthy modifications; and Japan's relatively idiosyncratic approach has received some attention in the literature. Illuminating these different justifications may help develop respectful policies regarding organ donation within countries with diverse populations and allow for more informed debate about brain death and the dead-donor rule. Copyright 2018 The Journal of Clinical Ethics. All rights reserved.
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Circulatory arrest, brain arrest and death determinationTechnological advances, particularly in the capacity to support, replace or transplant failing organs, continue to challenge and refine our understanding of human death. Given the ability to reanimate organs before and after death, both inside and outside of the body, through reinstitution of oxygenated circulation, concepts related to death of organs (e.g. cardiac death) are no longer valid. This paper advances the rationale for a single conceptual determination of death related to permanent brain arrest, resulting from primary brain injury or secondary to circulatory arrest. The clinical characteristics of brain arrest are the permanent loss of capacity for consciousness and loss of all brainstem functions. In the setting of circulatory arrest, death occurs after the arrest of circulation to the brain rather than death of the heart. Correspondingly, any intervention that resumes oxygenated circulation to the brain after circulatory arrest would invalidate the determination of death.
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European vignettes in donation after circulatory deathDonation after circulatory death (DCD) is increasing in Europe, yet there is widespread variability in practice. Insight into actual practice is difficult to acquire simply by analyzing protocols and laws from each individual country. For this reason, the 3 DCD vignettes in this article have been constructed to outline routine and standard DCD practice in the United Kingdom, the Netherlands, and Spain. These imagined vignettes reflect a "typical" case, based on the authors' extensive experience with DCD but are not real patient cases. They are a resource aimed at stimulating discussion regarding European organ donation practice and provide a knowledge bank for those wanting to establish a DCD program in their country. It is our hope that by providing these vignettes, the wider organ donation and transplant community, as well as philosophers and the public, will have a better understanding of what DCD really is and what it really isn't.
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Critical care in the emergency department: Organ donationOrgan transplantation is associated with improved outcomes for some patients with end-stage organ failure; however, the number of patients awaiting a transplant exceeds the available organs. Recently, an extended role has been proposed for EDs in the recognition and management of potential donors. The present review presents an illustrative case report and considers current transplantation practice in the UK. Ethical and legal considerations, the classification of deceased donors and future developments promising greater numbers of organs are discussed. Copyright Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
