Vaccine effectiveness against COVID-19 breakthrough infections in patients with cancer (UKCCEP): a population-based test-negative case-control study.

BACKGROUND: People with cancer are at increased risk of hospitalisation and death following infection with SARS-CoV-2. Therefore, we aimed to conduct one of the first evaluations of vaccine effectiveness against breakthrough SARS-CoV-2 infections in patients with cancer at a population level. METHODS: In this population-based test-negative case-control study of the UK Coronavirus Cancer Evaluation Project (UKCCEP), we extracted data from the UKCCEP registry on all SARS-CoV-2 PCR test results (from the Second Generation Surveillance System), vaccination records (from the National Immunisation Management Service), patient demographics, and cancer records from England, UK, from Dec 8, 2020, to Oct 15, 2021. Adults (aged ≥18 years) with cancer in the UKCCEP registry were identified via Public Health England's Rapid Cancer Registration Dataset between Jan 1, 2018, and April 30, 2021, and comprised the cancer cohort. We constructed a control population cohort from adults with PCR tests in the UKCCEP registry who were not contained within the Rapid Cancer Registration Dataset. The coprimary endpoints were overall vaccine effectiveness against breakthrough infections after the second dose (positive PCR COVID-19 test) and vaccine effectiveness against breakthrough infections at 3-6 months after the second dose in the cancer cohort and control population. FINDINGS: The cancer cohort comprised 377 194 individuals, of whom 42 882 had breakthrough SARS-CoV-2 infections. The control population consisted of 28 010 955 individuals, of whom 5 748 708 had SARS-CoV-2 breakthrough infections. Overall vaccine effectiveness was 69·8% (95% CI 69·8-69·9) in the control population and 65·5% (65·1-65·9) in the cancer cohort. Vaccine effectiveness at 3-6 months was lower in the cancer cohort (47·0%, 46·3-47·6) than in the control population (61·4%, 61·4-61·5). INTERPRETATION: COVID-19 vaccination is effective for individuals with cancer, conferring varying levels of protection against breakthrough infections. However, vaccine effectiveness is lower in patients with cancer than in the general population. COVID-19 vaccination for patients with cancer should be used in conjunction with non-pharmacological strategies and community-based antiviral treatment programmes to reduce the risk that COVID-19 poses to patients with cancer. FUNDING: University of Oxford, University of Southampton, University of Birmingham, Department of Health and Social Care, and Blood Cancer UK.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infectivity by Viral Load, S Gene Variants and Demographic Factors, and the Utility of Lateral Flow Devices to Prevent Transmission.

BACKGROUND: How severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity varies with viral load is incompletely understood. Whether rapid point-of-care antigen lateral flow devices (LFDs) detect most potential transmission sources despite imperfect clinical sensitivity is unknown. METHODS: We combined SARS-CoV-2 testing and contact tracing data from England between 1 September 2020 and 28 February 2021. We used multivariable logistic regression to investigate relationships between polymerase chain reaction (PCR)-confirmed infection in contacts of community-diagnosed cases and index case viral load, S gene target failure (proxy for B.1.1.7 infection), demographics, SARS-CoV-2 incidence, social deprivation, and contact event type. We used LFD performance to simulate the proportion of cases with a PCR-positive contact expected to be detected using 1 of 4 LFDs. RESULTS: In total, 231 498/2 474 066 (9%) contacts of 1 064 004 index cases tested PCR-positive. PCR-positive results in contacts independently increased with higher case viral loads (lower cycle threshold [Ct] values), for example, 11.7% (95% confidence interval [CI] 11.5-12.0%) at Ct = 15 and 4.5% (95% CI 4.4-4.6%) at Ct = 30. B.1.1.7 infection increased PCR-positive results by ~50%, (eg, 1.55-fold, 95% CI 1.49-1.61, at Ct = 20). PCR-positive results were most common in household contacts (at Ct = 20.1, 8.7% [95% CI 8.6-8.9%]), followed by household visitors (7.1% [95% CI 6.8-7.3%]), contacts at events/activities (5.2% [95% CI 4.9-5.4%]), work/education (4.6% [95% CI 4.4-4.8%]), and least common after outdoor contact (2.9% [95% CI 2.3-3.8%]). Contacts of children were the least likely to test positive, particularly following contact outdoors or at work/education. The most and least sensitive LFDs would detect 89.5% (95% CI 89.4-89.6%) and 83.0% (95% CI 82.8-83.1%) of cases with PCR-positive contacts, respectively. CONCLUSIONS: SARS-CoV-2 infectivity varies by case viral load, contact event type, and age. Those with high viral loads are the most infectious. B.1.1.7 increased transmission by ~50%. The best performing LFDs detect most infectious cases.

Conservative versus Surgical Management of Iatrogenic Tracheal Rupture.

Iatrogenic tracheal rupture (ITR) represents a life-threatening condition requiring prompt diagnosis, management, and treatment. The management of ITR is challenging, and treatment options depend on tear location, size, injury extent, and the patient's respiratory status. Although this complication has been extensively reported in published literature, the best evidence practice, for the management, requires clarification. In this review, the authors focused on the establishment of a differential diagnosis and the potential mechanism of the injury, the decision-making process, and the therapeutic approaches. It is suggested that for small lacerations or stable patients, conservative management could be considered sufficient, whereas invasive surgical therapy would be more appropriate in cases of large defects with significant air leak and patient instability.

A randomized controlled trial of the impact of support visits on self-isolation compliance: The Havering winter/spring support trial.

OBJECTIVES: Limited evidence exists on the policies to increase self-isolation compliance, with no experimental evidence. This trial aimed to evaluate the effect of a home visiting intervention in the London Borough of Havering on compliance with self-isolation guidance, relative to positive COVID-19 cases who received no home visits. DESIGN: Mixed method evaluation involving a two-arm randomized controlled trial (RCT) with an implementation and process evaluation. METHODS: A total of 3878 cases who tested positive for COVID-19 were randomly allocated with equal probability to receive home visits from Havering outreach team staff (n = 1946) or to a control group (n = 1932) who did not receive home visits. Randomization was implemented through a spreadsheet consisting of random numbers generated online that was used to randomly allocate cases to treatment and control. Check-in calls were conducted by a separate blinded contact tracing team on day six of isolation to measure successful self-isolation compliance. The primary intention-to-treat (ITT) analysis was conducted on 3860 cases as 18 patients were excluded from analysis because of the missing outcome data. For the implementation and process evaluation, qualitative, semi-structured, one-to-one interviews were conducted with trial participants in the treatment arm of the RCT (n = 15) and stakeholders within the London Borough of Havering's Adult Social Care and Health Team (n = 8). Qualitative data was analysed thematically using a framework approach. RESULTS: Positive cases who were allocated to receive the home visiting intervention (n = 1933) were more likely to report successful self-isolation compared to those allocated to the control group (n = 1927), an effect that was statistically significant (odds ratio 1.204 [95% CI: 1.052, 1.377]; absolute probability difference: 4.1 percentage points [95% CI: 1.2-6.9]). The implementation and process evaluation found that a key driver of compliance was altruistic motivation based on its perceived importance for protecting the community with some participants also reporting the potential of being caught not complying as a driving factor. Participants also reported that the intervention helped them 'feel supported', provided them with information about practical and financial support, and clarified their understanding or increased their awareness of self-isolation and COVID-19 guidance. No harms were reported from this trial. The trial was registered at the ISRCTN registry, number ISRCTN10030612. CONCLUSIONS: A home-visiting intervention conducted between January and March 2022 increased the self-isolation compliance of positive COVID-19 cases allocated to receive home visits. The implementation and process evaluation highlighted that the intervention increased individuals' motivation to comply with guidance, and addressed some barriers associated with opportunity and capability to comply. This trial provides much-needed evidence to inform the policy and intervention design to support public health and social measures in future outbreak scenarios.

A population-scale temporal case-control evaluation of COVID-19 disease phenotype and related outcome rates in patients with cancer in England (UKCCP).

Patients with cancer are at increased risk of hospitalisation and mortality following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the SARS-CoV-2 phenotype evolution in patients with cancer since 2020 has not previously been described. We therefore evaluated SARS-CoV-2 on a UK populationscale from 01/11/2020-31/08/2022, assessing case-outcome rates of hospital assessment(s), intensive care admission and mortality. We observed that the SARS-CoV-2 disease phenotype has become less severe in patients with cancer and the non-cancer population. Case-hospitalisation rates for patients with cancer dropped from 30.58% in early 2021 to 7.45% in 2022 while case-mortality rates decreased from 20.53% to 3.25%. However, the risk of hospitalisation and mortality remains 2.10x and 2.54x higher in patients with cancer, respectively. Overall, the SARS-CoV-2 disease phenotype is less severe in 2022 compared to 2020 but patients with cancer remain at higher risk than the non-cancer population. Patients with cancer must therefore be empowered to live more normal lives, to see loved ones and families, while also being safeguarded with expanded measures to reduce the risk of transmission.

Association of SARS-CoV-2 Spike Protein Antibody Vaccine Response With Infection Severity in Patients With Cancer: A National COVID Cancer Cross-sectional Evaluation.

Importance: Accurate identification of patient groups with the lowest level of protection following COVID-19 vaccination is important to better target resources and interventions for the most vulnerable populations. It is not known whether SARS-CoV-2 antibody testing has clinical utility for high-risk groups, such as people with cancer. Objective: To evaluate whether spike protein antibody vaccine response (COV-S) following COVID-19 vaccination is associated with the risk of SARS-CoV-2 breakthrough infection or hospitalization among patients with cancer. Design, Setting, and Participants: This was a population-based cross-sectional study of patients with cancer from the UK as part of the National COVID Cancer Antibody Survey. Adults with a known or reported cancer diagnosis who had completed their primary SARS-CoV-2 vaccination schedule were included. This analysis ran from September 1, 2021, to March 4, 2022, a period covering the expansion of the UK's third-dose vaccination booster program. Interventions: Anti-SARS-CoV-2 COV-S antibody test (Elecsys; Roche). Main Outcomes and Measures: Odds of SARS-CoV-2 breakthrough infection and COVID-19 hospitalization. Results: The evaluation comprised 4249 antibody test results from 3555 patients with cancer and 294 230 test results from 225 272 individuals in the noncancer population. The overall cohort of 228 827 individuals (patients with cancer and the noncancer population) comprised 298 479 antibody tests. The median age of the cohort was in the age band of 40 and 49 years and included 182 741 test results (61.22%) from women and 115 737 (38.78%) from men. There were 279 721 tests (93.72%) taken by individuals identifying as White or White British. Patients with cancer were more likely to have undetectable anti-S antibody responses than the general population (199 of 4249 test results [4.68%] vs 376 of 294 230 [0.13%]; P < .001). Patients with leukemia or lymphoma had the lowest antibody titers. In the cancer cohort, following multivariable correction, patients who had an undetectable antibody response were at much greater risk for SARS-CoV-2 breakthrough infection (odds ratio [OR], 3.05; 95% CI, 1.96-4.72; P < .001) and SARS-CoV-2-related hospitalization (OR, 6.48; 95% CI, 3.31-12.67; P < .001) than individuals who had a positive antibody response. Conclusions and Relevance: The findings of this cross-sectional study suggest that COV-S antibody testing allows the identification of patients with cancer who have the lowest level of antibody-derived protection from COVID-19. This study supports larger evaluations of SARS-CoV-2 antibody testing. Prevention of SARS-CoV-2 transmission to patients with cancer should be prioritized to minimize impact on cancer treatments and maximize quality of life for individuals with cancer during the ongoing pandemic.

What are orthognathic patients' expectations of treatment outcome--a qualitative study.

PURPOSE: Patient's expectations of treatment outcome are one of the key determinants of satisfaction. The aim of this study was to evaluate orthognathic patients' expectations of the outcome of orthognathic treatment. METHODS: This study was a cross-sectional qualitative study involving in-depth interviews with patients with dentofacial deformities. Patients who were about to commence orthognathic treatment were recruited from new-patient clinics. Inclusion criterion were patients of any ethnicity 16 years or older who were about to commence orthognathic treatment to correct a dentofacial deformity. Exclusion criteria were patients who had previously received orthognathic treatment, who were younger than 16 years, and those with congenital craniofacial anomalies or acquired defects. The data were analyzed using a framework approach to management and critical qualitative theory, which involved identifying the main themes and subthemes. RESULTS: Eighteen adult patients 18 to 40 years old were interviewed; 9 were women and 9 were men. Most were Caucasian and 6 were from the black and minority ethnic group. Participants' expectations could be divided broadly into 2 main categories: expectations of actual physical changes and expectations of the effects that these physical changes would indirectly have on them (nonphysical changes). In addition, a typology of patients, based on expectations, was identified, whereby patients could be classified as metamorphosizers, pragmatists, shedders, or evolvers, together with implications and suggestions for practice. CONCLUSIONS: These findings represent a new insight into the complex issues of managing patient expectations and satisfaction. The clinical relevance of identifying expectations is not just to ration treatment or identify those who will make good or bad candidates for treatment, but to be able to offer them additional support to enhance satisfaction with the outcome. This highlights the need for a qualitative methodology to complete the full circle of evidence-based practice.

Impact of dentofacial deformity and motivation for treatment: a qualitative study.

INTRODUCTION: Satisfaction with the outcome of orthognathic treatment is generally high; however, an important minority remains dissatisfied with the results. The reasons for this could be inadequate patient understanding and preparation, external motivation, and unrealistic expectations. In-depth appreciation of these issues can be obtained using qualitative research methods, but there is a paucity of qualitative research in this field. METHODS: This was a cross-sectional qualitative study of orthognathic patients conducted at a teaching hospital. In-depth interviews were conducted with 18 prospective orthognathic patients. The data were managed by using the framework approach and analyzed by using the critical qualitative theory. RESULTS: Two main themes were explored in the interviews: the impact of the dentofacial deformity and the motivation for treatment. Both the everyday problems of living with a dentofacial deformity and the motivation for seeking treatment could be classified either as exclusively practical (including functional and structural), exclusively psychological (including psychosocial and esthetic), or a combination. Different coping strategies were also described. The sources of motivation ranged between purely external to purely internal, with most subjects between these 2 extremes. CONCLUSIONS: In this article, we present a classification of the impact of dentofacial deformity that is a refinement of the traditional one that includes esthetic, functional, and psychosocial factors. The motivating factors, together with the triggers for accessing treatment and the source of motivation, are generally linked directly or indirectly to the problem and the impact of the condition. However, in a few patients, the motivation might not relate to the impact of the problem but to a complex array of other factors such as personality, upbringing, and relationships. Therefore, clinicians should not make assumptions but explore these factors on an individual basis without preconceived ideas.

COVID-19: Third dose booster vaccine effectiveness against breakthrough coronavirus infection, hospitalisations and death in patients with cancer: A population-based study.

PURPOSE: People living with cancer and haematological malignancies are at an increased risk of hospitalisation and death following infection with acute respiratory syndrome coronavirus 2. Coronavirus third dose vaccine boosters are proposed to boost waning immune responses in immunocompromised individuals and increase coronavirus protection; however, their effectiveness has not yet been systematically evaluated. METHODS: This study is a population-scale real-world evaluation of the United Kingdom's third dose vaccine booster programme for cancer patients from 8th December 2020 to 7th December 2021. The cancer cohort comprises individuals from Public Health England's national cancer dataset, excluding individuals less than 18 years. A test-negative case-control design was used to assess the third dose booster vaccine effectiveness. Multivariable logistic regression models were fitted to compare risk in the cancer cohort relative to the general population. RESULTS: The cancer cohort comprised of 2,258,553 tests from 361,098 individuals. Third dose boosters were evaluated by reference to 87,039,743 polymerase chain reaction coronavirus tests. Vaccine effectiveness against breakthrough infections, symptomatic infections, coronavirus hospitalisation and death in cancer patients were 59.1%, 62.8%, 80.5% and 94.5%, respectively. Lower vaccine effectiveness was associated with a cancer diagnosis within 12 months, lymphoma, recent systemic anti-cancer therapy (SACT) or radiotherapy. Patients with lymphoma had low levels of protection from symptomatic disease. In spite of third dose boosters, following multivariable adjustment, individuals with cancer remain at an increased risk of coronavirus hospitalisation and death compared to the population control (OR 3.38, 3.01, respectively. p < 0.001 for both). CONCLUSIONS: Third dose boosters are effective for most individuals with cancer, increasing protection from coronavirus. However, their effectiveness is heterogenous and lower than the general population. Many patients with cancer will remain at the increased risk of coronavirus infections even after 3 doses. In the case of patients with lymphoma, there is a particularly strong disparity of vaccine effectiveness against breakthrough infection and severe disease. Breakthrough infections will disrupt cancer care and treatment with potentially adverse consequences on survival outcomes. The data support the role of vaccine boosters in preventing severe disease, and further pharmacological intervention to prevent transmission and aid viral clearance to limit the disruption of cancer care as the delivery of care continues to evolve during the coronavirus pandemic.

Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial.

BACKGROUND: Whether remote ischaemic preconditioning, an intervention in which brief ischaemia of one tissue or organ protects remote organs from a sustained episode of ischaemia, is beneficial for patients undergoing coronary artery bypass graft surgery is unknown. We did a single-blinded randomised controlled study to establish whether remote ischaemic preconditioning reduces myocardial injury in these patients. METHODS: 57 adult patients undergoing elective coronary artery bypass graft surgery were randomly assigned to either a remote ischaemic preconditioning group (n=27) or to a control group (n=30) after induction of anaesthesia. Remote ischaemic preconditioning consisted of three 5-min cycles of right upper limb ischaemia, induced by an automated cuff-inflator placed on the upper arm and inflated to 200 mm Hg, with an intervening 5 min of reperfusion during which the cuff was deflated. Serum troponin-T concentration was measured before surgery and at 6, 12, 24, 48, and 72 h after surgery. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00397163. FINDINGS: Remote ischaemic preconditioning significantly reduced overall serum troponin-T release at 6, 12, 24, and 48 h after surgery. The total area under the curve was reduced by 43%, from 36.12 microg/L (SD 26.08) in the control group to 20.58 microg/L (9.58) in the remote ischaemic preconditioning group (mean difference 15.55 [SD 5.32]; 95% CI 4.88-26.21; p=0.005). INTERPRETATION: We have shown that adult patients undergoing elective coronary artery bypass graft surgery at a single tertiary centre could benefit from remote ischaemic preconditioning, using transient upper limb ischaemia.

Effect of remote ischaemic preconditioning on clinical outcomes in patients undergoing cardiac bypass surgery: a randomised controlled clinical trial.

OBJECTIVES: Remote ischaemic preconditioning (RIPC), using brief cycles of limb ischaemia/reperfusion, is a non-invasive, low-cost intervention that may reduce perioperative myocardial injury (PMI) in patients undergoing cardiac surgery. We investigated whether RIPC can also improve short-term clinical outcomes. METHODS: One hundred and eighty patients undergoing elective coronary artery bypass graft (CABG) surgery and/or valve surgery were randomised to receive either RIPC (2-5 min cycles of simultaneous upper arm and thigh cuff inflation/deflation; N=90) or control (uninflated cuffs placed on the upper arm and thigh; N=90). The study primary end point was PMI, measured by 72 h area under the curve (AUC) serum high-sensitive troponin-T (hsTnT); secondary end point included short-term clinical outcomes. RESULTS: RIPC reduced PMI magnitude by 26% (-9.303 difference (CI -15.618 to -2.987) 72 h hsTnT-AUC; p=0.003) compared with control. There was also evidence that RIPC reduced the incidence of postoperative atrial fibrillation by 54% (11% RIPC vs 24% control; p=0.031) and decreased the incidence of acute kidney injury by 48% (10.0% RIPC vs 21.0% control; p=0.063), and intensive care unit stay by 1 day (2.0 days RIPC (CI 1.0 to 4.0) vs 3.0 days control (CI 2.0 to 4.5); p=0.043). In a post hoc analysis, we found that control patients administered intravenous glyceryl trinitrate (GTN) intraoperatively sustained 39% less PMI compared with those not receiving GTN, and RIPC did not appear to reduce PMI in patients given GTN. CONCLUSIONS: RIPC reduced the extent of PMI in patients undergoing CABG and/or valve surgery. RIPC may also have beneficial effects on short-term clinical outcomes, although this will need to be confirmed in future studies. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov ID: NCT00397163.

A retrospective analysis of myocardial preservation techniques during coronary artery bypass graft surgery: are we protecting the heart?

BACKGROUND: Retrograde perfusion into coronary sinus during coronary artery bypass graft (CABG) surgery reduces the need for cardioplegic interruptions and ensures the distribution of cardioplegia to stenosed vessel territories, therefore enhancing the delivery of cardioplegia to the subendocardium. Peri-operative myocardial injury (PMI), as measured by the rise of serum level of cardiac biomarkers, has been associated with short and long-term clinical outcomes. We conducted a retrospective analysis to investigate whether the combination of antegrade and retrograde techniques of cardioplegia delivery is associated with a reduced PMI than that observed with the traditional methods of myocardial preservation. METHODS: Fifty-four consecutive patients underwent CABG surgery using either antegrade cold blood cardioplegia (group 1, n = 28) or cross-clamp fibrillation (group 2, n = 16) or antegrade retrograde warm blood cardioplegia (group 3, n = 10). The study primary end-point was PMI, evaluated with total area under the curve (AUC) of high-sensitivity Troponin-T (hsTnT), measured pre-operatively and at 6, 12, 24, 48 and 72 hours post-surgery. Secondary endpoints were acute kidney injury (AKI) and inotrope scores, length of intensive care unit (ICU) and hospital stay, new onset atrial fibrillation (AF) and clinical outcomes at 6 weeks (death, non-fatal myocardial infarction, coronary artery revascularization, stroke). RESULTS: There was evidence that mean total AUC of hsTnT was different among the three groups (P = 0.050). In particular mean total AUC of hsTnT was significantly lower in group 3 compared to both group 1 (-16.55; 95% CI: -30.08, -3.01; P = 0.018) with slightly weaker evidence of a lower mean hsTnT in group 3 when compared to group 2 (-15.13; 95% CI -29.87, -0.39; P = 0.044). There was no evidence of a difference when comparing group 2 to group 1 (-1.42,; 95% CI: -12.95, 10.12, P = 0.806). CONCLUSIONS: Our retrospective analysis suggests that, compared to traditional methods of myocardial preservation, antegrade retrograde cardioplegia may reduce PMI in patients undergoing first time CABG surgery.

Are coronary angiograms of value in the risk stratification of patients undergoing coronary artery bypass surgery?

INTRODUCTION: There are currently more than 20 risk-scoring systems that attempt to predict peri-operative mortality following coronary artery bypass surgery (CABG). All these scoring systems use objective criteria to assess operative risk. Angiographic data are currently not included in any of these systems. This pilot study assessed the value of coronary angiography in predicting peri-operative mortality following CABG. PATIENTS AND METHODS: Fourteen patients who died following first-time isolated CABG surgery were identified. These were matched with 14 patients of similar age, sex, left ventricle function and European System for Cardiac Operative Risk Evaluation (EuroSCORE). A panel of 25 clinicians were given details of the patients' age, sex, diabetic status, family history, smoking history, hypertensive status, lipid status, pre-operative symptoms, left ventricle ejection fraction and weight and shown the coronary angiograms of the patient. They were asked to predict the outcome following CABG for each patient. RESULTS: Receiver operator characteristic curves were constructed and the area under the curves calculated and analysed using a commercially available statistical package (PRISM). The area under the curve for the group was 0.6820 for the group. Consultant clinicians achieved an area of 0.6789 versus their trainees 0.6844 (P = NS). The cardiologists achieved an area of 0.7063 versus the cardiothoracic surgeons 0.6491 (P = NS). CONCLUSIONS: Despite the EuroSCORE predicting equal risk for the two groups of patients, it would appear that clinicians are able to identify individual higher risk patients by assessing pre-operatively the quality of the patient's coronary vasculature. Although the clinicians were able to predict individual patient mortality better than the EuroSCORE, the area under the curve indicates that it is not a robust method and clinicians, with all the clinical information to hand, are only moderately good at predicting the outcome following coronary artery bypass surgery.