The National COVID Cancer Antibody Survey: a hyper-accelerated study proof of principle for cancer research.

The COVID-19 pandemic has led to a range of novel and adaptive research designs. In this perspective, we use our experience coordinating the National COVID Cancer Antibody Survey to demonstrate how a balance between speed and integrity can be achieved within a hyper-accelerated study design. Using the COVID-19 pandemic as an example, we show this approach is necessary in the face of uncertain and evolving situations wherein reliable information is needed in a timely fashion to guide policy. We identify streamlined participant involvement, healthcare systems integration, data architecture and real-world real-time analytics as key areas that differentiate this design from traditional cancer trials, and enable rapid results. Caution needs to be taken to avoid the exclusion of patient subgroups without digital access or literacy. We summarise the merits and defining features of hyper-accelerated cancer studies.

Systematic review and meta-analysis of the clinical effectiveness of tixagevimab/cilgavimab for prophylaxis of COVID-19 in immunocompromised patients.

Immunocompromised patients, such as those with a haematological malignancy, are at higher risk of SARS-CoV-2 infection, severe outcomes and mortality. Tixagevimab/cilgavimab is a monoclonal antibody combination which binds to the SARS-CoV-2 spike protein. The PROVENT phase III clinical trial reported that tixagevimab/cilgavimab prophylaxis significantly reduced the risk of COVID-19 infection in immunocompromised participants. However, the trial was conducted before the Omicron variant became prevalent. This systematic review and meta-analysis provide an up-to-date summary of the real-world effectiveness of tixagevimab/cilgavimab in immunocompromised patients, including patients with haematological malignancies. Clinical studies from 1 January 2021 to 1 October 2022, which reported breakthrough COVID-19 infections after tixagevimab/cilgavimab, were included. COVID-19-related hospitalisations, intensive care admissions and mortality were also assessed. A meta-analysis was performed to ascertain overall clinical effectiveness. Eighteen studies, with 25 345 immunocompromised participants, including 5438 patients with haematological pathologies, were included in the review. The overall clinical effectiveness of tixagevimab/cilgavimab against COVID-19 breakthrough infection, hospitalisation, intensive care admission and COVID-19-specific mortality was 40.54%, 66.19%, 82.13% and 92.39%, respectively. This review highlights the clinical effectiveness of tixagevimab/cilgavimab at reducing COVID-19 infection and severe outcomes for immunosuppressed individuals, including patients with a haematological malignancy, during the Omicron-predominant era. Real-world studies are important to provide ongoing certainty of the clinical benefit for immunocompromised patients against new SARS-CoV-2 variants.

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.

Cyclostationarity-based joint monitoring of symbol-rate, frequency offset, CD and OSNR for Nyquist WDM superchannels.

Software-defined transceivers can be reconfigured based on demand and existing channel impairments, and as such, monitoring of both signal and channel parameters is necessary. We demonstrate a novel joint estimation method suitable for spectrally efficient Nyquist wavelength-division multiplexing (WDM), based on the cyclostationary property of linearly modulated signals, exploited both in the frequency and time domains. Using a Nyquist superchannel composed of three 10 GBaud channels, we experimentally demonstrate the simultaneous monitoring of symbol-rate with 100% accuracy, roll-off, frequency offset (FO), chromatic dispersion (CD) and optical signal-to-noise ratio (OSNR) with root-mean-square errors (RMSE) of 20%, 4 MHz, 200 ps/nm and 1.5 dB respectively, when the roll-off factor is larger than 0.06 for DP-QPSK and 0.3 for DP-16QAM.

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.

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.

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.

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.

Minute ventilation/carbon dioxide production in patients with dysfunctional breathing.

Dysfunctional breathing refers to a multi-dimensional condition that is characterised by pathological changes in an individual's breathing. These changes lead to a feeling of breathlessness and include alterations in the biomechanical, psychological and physiological aspects of breathing. This makes dysfunctional breathing a hard condition to diagnose, given the diversity of aspects that contribute to the feeling of breathlessness. The disorder can debilitate individuals without any health problems, but may also be present in those with underlying cardiopulmonary co-morbidities. The ventilatory equivalent for CO2 (V eqCO2 ) is a physiological parameter that can be measured using cardiopulmonary exercise testing. This review will explore how this single measurement can be used to aid the diagnosis of dysfunctional breathing. A background discussion about dysfunctional breathing will allow readers to comprehend its multidimensional aspects. This will then allow readers to understand how V eqCO2 can be used in the wider diagnosis of dysfunctional breathing. Whilst V eqCO2 cannot be used as a singular parameter in the diagnosis of dysfunctional breathing, this review supports its use within a broader algorithm to detect physiological abnormalities in patients with dysfunctional breathing. This will allow for more individuals to be accurately diagnosed and appropriately managed.

A long-reach ultra-dense 10 Gbit/s WDM-PON using a digital coherent receiver.

We investigate the impact of channel spacing and nonlinear transmission over 120 km of standard single mode fiber for a 10 Gbit/s long-reach wavelength division multiplexed passive optical network (WDM-PON). We employed polarization division multiplexed quadrature phase shift keying (PDM-QPSK), which allowed data transmission at 3.125 GBaud, including a 25% overhead for forward error correction. To receive this spectrally efficient modulation format, a digital coherent receiver was employed, allowing for both frequency selectivity and an increased sensitivity of -45 dBm (25 photons/bit).We investigated a channel spacing as low as 5 GHz, for which the loss budget was 48.6 dB, increasing to 54.0 dB for a 50 GHz grid.

Cardiopulmonary Exercise Testing in the Assessment of Dysfunctional Breathing.

Dysfunctional breathing (DB) is a disabling condition which affects the biomechanical breathing pattern and is challenging to diagnose. It affects individuals in many circumstances, including those without underlying disease who may even be athletic in nature. DB can also aggravate the symptoms of those with established heart or lung conditions. However, it is treatable and individuals have much to gain if it is recognized appropriately. Here we consider the role of cardiopulmonary exercise testing (CPET) in the identification and management of DB. Specifically, we have described the diagnostic criteria and presenting symptoms. We explored the physiology and pathophysiology of DB and physiological consequences in the context of exercise. We have provided examples of its interplay with co-morbidity in other chronic diseases such as asthma, pulmonary hypertension and left heart disease. We have discussed the problems with the current methods of diagnosis and proposed how CPET could improve this. We have provided guidance on how CPET can be used for diagnosis, including consideration of pattern recognition and use of specific data panels. We have considered categorization, e.g., predominant breathing pattern disorder or acute or chronic hyperventilation. We have explored the distinction from gas exchange or ventilation/perfusion abnormalities and described other potential pitfalls, such as false positives and periodic breathing. We have also illustrated an example of a clinical pathway utilizing CPET in the diagnosis and treatment of individuals with suspected DB.

Illness perception in tuberculosis by implementation of the Brief Illness Perception Questionnaire - a TBNET study.

How patients relate to the experience of their illness has a direct impact over their behavior. We aimed to assess illness perception in patients with pulmonary tuberculosis (TB) by means of the Brief Illness Perception Questionnaire (BIPQ) in correlation with patients' demographic features and clinical TB score. Our observational questionnaire based study included series of consecutive TB patients enrolled in several countries from October 2008 to January 2011 with 167 valid questionnaires analyzed. Each BIPQ item assessed one dimension of illness perceptions like the consequences, timeline, personal control, treatment control, identity, coherence, emotional representation and concern. An open question referred to the main causes of TB in each patient's opinion. The over-all BIPQ score (36.25 ± 11.054) was in concordance with the clinical TB score (p ≤ 0.001). TB patients believed in the treatment (the highest item-related score for treatment control) but were unsure about the illness identity. Illness understanding and the clinical TB score were negatively correlated (p < 0.01). Only 25% of the participants stated bacteria or TB contact as the first ranked cause of the illness. For routine clinical practice implementation of the BIPQ is convenient for obtaining fast and easy assessment of illness perception with potential utility in intervention design. This time saving effective personalized approach may improve communication with TB patients and contribute to better behavioral strategies in disease control.