In the UK, additional COVID-19 vaccine booster doses and treatments are offered to people who are immunosuppressed to protect against severe COVID-19, but how best to choose the individuals that ...receive these vaccine booster doses and treatments is unclear. We investigated the association between seropositivity to SARS-CoV-2 spike protein with demographic, disease, and treatment-related characteristics after at least three COVID-19 vaccines in three cohorts of people who are immunosuppressed.
In a cross-sectional study using UK national disease registries, we identified, contacted, and recruited recipients of solid organ transplants, participants with rare autoimmune rheumatic diseases, and participants with lymphoid malignancies who were 18 years or older, resident in the UK, and who had received at least three doses of a COVID-19 vaccine. The study was open to recruitment from Dec 7, 2021, to June 26, 2022. Participants received a lateral flow immunoassay test for SARS-CoV-2 spike antibodies to complete at home, and an online questionnaire. Multivariable logistic regression was used to estimate the mutually adjusted odds of seropositivity against each characteristic.
Between Feb 14 and June 26, 2022, we screened 101 972 people (98 725 invited, 3247 self-enrolled) and recruited 28 411 (27·9%) to the study. 23 036 (81·1%) recruited individuals provided serological data. Of these, 9927 (43·1%) were recipients of solid organ transplants, 6516 (28·3%) had rare autoimmune rheumatic diseases, and 6593 (28·6%) had lymphoid malignancies. 10 485 (45·5%) participants were men and 12 535 (54·4%) were women (gender was not reported for 16 <0·1% participants), and 21661 (94·0%) participants were of White ethnicity. The median age of participants with solid organ transplants was 60 years (SD 50–67), with rare autoimmune rheumatic diseases was 65 years (54–73), and with lymphoid malignancy was 69 years (61–75). Of the 23 036 participants with serological data, 6583 (28·6%) had received three vaccine doses, 14 234 (61·8%) had received four vaccine doses, and 2219 (9·6%) had received five or more vaccine doses. IgG anti-spike antibodies were undetectable in 2310 (23·3%) of 9927 patients with solid organ transplants, 922 (14·1%) of 6516 patients with rare autoimmune rheumatic diseases, and 1366 (20·7%) of 6593 patients with lymphoid malignancies. In all groups, seropositivity was associated with younger age, higher number of vaccine doses (ie, five vs three), and previous COVID-19. Immunosuppressive medication reduced the likelihood of seropositivity: the lowest odds of seropositivity were found in recipients of solid organ transplants receiving a combination of an anti-proliferative agent, a calcineurin inhibitor, and steroids, and those with rare autoimmune rheumatic diseases or lymphoid malignancies treated with anti-CD20 therapies.
Approximately one in five recipients of solid organ transplants, individuals with rare autoimmune rheumatic diseases, and individuals with lymphoid malignancies have no detectable IgG anti-spike antibodies despite three or more vaccine doses, but this proportion decreases with sequential booster doses. Choice of immunosuppressant and disease type is strongly associated with serological response. Antibody testing using lateral flow immunoassay tests could enable rapid identification of individuals who are most likely to benefit from additional COVID-19 interventions.
UK Research and Innovation, Kidney Research UK, Blood Cancer UK, Vasculitis UK and the Cystic Fibrosis Trust.
Sudden out-of-hospital cardiac arrest is the third leading cause of death in industrialized nations. Many of these lives could be saved if bystander cardiopulmonary resuscitation rates were better. ..."All citizens of the world can save a life-CHECK-CALL-COMPRESS." With these words, the International Liaison Committee on Resuscitation launched the 2019 global "World Restart a Heart" initiative to increase public awareness and improve the rates of bystander cardiopulmonary resuscitation and overall survival for millions of victims of cardiac arrest globally. All participating organizations were asked to train and to report the numbers of people trained and reached. Overall, social media impact and awareness reached up to 206 million people, and >5.4 million people were trained in cardiopulmonary resuscitation worldwide in 2019. Tool kits and information packs were circulated to 194 countries worldwide. Our simple and unified global message, "CHECK-CALL-COMPRESS," will save hundreds of thousands of lives worldwide and will further enable many policy makers around the world to take immediate and sustainable action in this most important healthcare issue and initiative.
To benchmark the dosimetric quality assessment of prostate intensity-modulated radiotherapy and determine whether the quality is influenced by disease or treatment factors.
We retrospectively ...analyzed the data from 155 consecutive men treated radically for prostate cancer using intensity-modulated radiotherapy to 78 Gy between January 2007 and March 2009 across six radiotherapy treatment centers. The plan quality was determined by the measures of coverage, homogeneity, and conformity. Tumor coverage was measured using the planning target volume (PTV) receiving 95% and 100% of the prescribed dose (V(95%) and V(100%), respectively) and the clinical target volume (CTV) receiving 95% and 100% of the prescribed dose. Homogeneity was measured using the sigma index of the PTV and CTV. Conformity was measured using the lesion coverage factor, healthy tissue conformity index, and the conformity number. Multivariate regression models were created to determine the relationship between these and T stage, risk status, androgen deprivation therapy use, treatment center, planning system, and treatment date.
The largest discriminatory measurements of coverage, homogeneity, and conformity were the PTV V(95%), PTV sigma index, and conformity number. The mean PTV V(95%) was 92.5% (95% confidence interval, 91.3-93.7%). The mean PTV sigma index was 2.10 Gy (95% confidence interval, 1.90-2.20). The mean conformity number was 0.78 (95% confidence interval, 0.76-0.79). The treatment center independently influenced the coverage, homogeneity, and conformity (all p < .0001). The planning system independently influenced homogeneity (p = .038) and conformity (p = .021). The treatment date independently influenced the PTV V(95%) only, with it being better at the start (p = .013). Risk status, T stage, and the use of androgen deprivation therapy did not influence any aspect of plan quality.
Our study has benchmarked measures of coverage, homogeneity, and conformity for the treatment of prostate cancer using IMRT. The differences seen between centers and planning systems and the coverage deterioration over time highlight the need for every center to determine their own benchmarks and apply clinical vigilance with respect to maintaining these through quality assurance.
•The COVID-19 pandemic saw an improvement in adherence to BOAST guidelines for fracture clinic review within 72 h, demonstrating successful nationwide integration of VFC practices.•Despite a ...significant increase in direct discharge rates from VFC during the COVID-19 pandemic, there was no change in unplanned reattendance, complications or patient satisfaction.•Several variables such as unplanned reattendance and missed injuries were consistently associated with patient dissatisfaction – this calls for targeted interventions to improve patient experiences and outcomes in a VFC setting.
Virtual fracture clinics (VFCs) are advocated by the British Orthopaedic Association Standards for Trauma (BOAST). We aimed to assess the impact of the transition from face-to-face fracture clinic review and identify any change in clinical outcome and patient satisfaction.
A national, cross-sectional cohort study of VFCs across the UK over two separate two-week periods pre- and during the first UK COVID-19 lockdown was undertaken. Data comprising patient and injury characteristics, unplanned reattendance and complications within three months following discharge from VFC were collected by local collaborators. Telephone questionnaires were conducted to determine patient satisfaction and patient-reported outcome for patients discharged without face-to-face consultation. The primary outcome measure was the percentage of unplanned reattendances after direct discharge from VFC.
Data was analysed for 51 UK VFCs comprising 6134 patients from the pre-pandemic group (06/05/2019–19/05/2019) and 4366 patients from the first UK lockdown (04/05/2020–17/05/2020). During lockdown, the rate of direct discharge from VFC increased significantly (odds ratio (OR) 2.01, p<0.001) from 30 % (n = 1856/6134) to 46 % (n = 2021/4366). The rate of compliance with BOAST guidance recommending fracture clinic review within three days increased (OR 1.93, p<0.001) from 82 % (n = 5003/6134) to 89 % (n = 3883/4366). There were no differences in the rates of unplanned reattendance (6 % pre- and 7 % during lockdown, p = 0.281) or complications (0.2 % for both, p = 0.815). There were 1527/3877 patients discharged without face-to-face review from VFC who completed telephone questionnaires (mean follow-up 18-months in pre-pandemic group and 6-months in lockdown group). Satisfaction was high in both cohorts (80 % pre- and 76 % lockdown, p = 0.093). Dissatisfaction was associated with an unplanned reattendance (p<0.001) or a missed injury (p<0.05).
Despite a significant rise in direct discharge from VFC, there was no significant change in unplanned attendances, complications, or patient satisfaction. However, there are factors associated with dissatisfaction and these should be considered in the evolution of VFC.
Abstract Background Few studies have assessed regional variation in the organisation of stroke services, particularly health care resourcing, presence of protocols and discharge planning. Our aim was ...to compare stroke care organisation within middle- (MIC) and high-income country (HIC) hospitals participating in the Head Positioning in Stroke Trial (HeadPoST). Methods HeadPoST is an on-going international multicenter crossover cluster-randomized trial of ‘sitting-up’ versus ‘lying-flat’ head positioning in acute stroke. As part of the start-up phase, one stroke care organisation questionnaire was completed at each hospital. The World Bank gross national income per capita criteria
were
used for classification. Results 94 hospitals from 9 countries completed the questionnaire, 51 corresponding to MIC and 43 to HIC. Most participating hospitals had a dedicated stroke care unit/ward, with access to diagnostic services and expert stroke physicians, and offering intravenous thrombolysis. There was a no difference for the presence of a dedicated multidisciplinary stroke team, although greater access to a broad spectrum of rehabilitation therapists in HIC compared to MIC hospitals was observed. Significantly more patients arrived within a 4-
h
window of symptoms onset in HIC hospitals (41 vs. 13%; P < 0.001), and a significantly higher proportion of acute ischemic stroke patients received intravenous thrombolysis (10 vs. 5%; P = 0.002) compared to MIC hospitals. Conclusions Although all hospitals provided advanced care for people with stroke, differences were found in stroke care organisation and treatment. Future multilevel analyses aims to determine the influence of specific organisational factors on patient outcomes.
Diarrhoeal disease is responsible for 8.6% of global child mortality. Recent epidemiological studies found the protozoan parasite Cryptosporidium to be a leading cause of paediatric diarrhoea, with ...particularly grave impact on infants and immunocompromised individuals. There is neither a vaccine nor an effective treatment. Here we establish a drug discovery process built on scalable phenotypic assays and mouse models that take advantage of transgenic parasites. Screening a library of compounds with anti-parasitic activity, we identify pyrazolopyridines as inhibitors of Cryptosporidium parvum and Cryptosporidium hominis. Oral treatment with the pyrazolopyridine KDU731 results in a potent reduction in intestinal infection of immunocompromised mice. Treatment also leads to rapid resolution of diarrhoea and dehydration in neonatal calves, a clinical model of cryptosporidiosis that closely resembles human infection. Our results suggest that the Cryptosporidium lipid kinase PI(4)K (phosphatidylinositol-4-OH kinase) is a target for pyrazolopyridines and that KDU731 warrants further preclinical evaluation as a drug candidate for the treatment of cryptosporidiosis.
West Nile virus (WNV) causes severe neurological disease in less than 1% of infections. However, meningoencephalitis may be more common in immunosuppressed transplant patients. In 2002, a WNV ...outbreak occurred in our region. To determine the spectrum of disease of community acquired WNV infection and assess public health behavior patterns in transplant recipients, we carried out a seroprevalence study. Patients were enrolled from outpatient transplant clinics in October 2002 and sera were screened for WNV. Questionnaires about WNV were provided to patients. Eight hundred sixteen organ transplant patients were enrolled. The seroprevalence of WNV IgM was 2/816 (0.25%; 95% CI 0.03–0.88%). By extrapolation to our entire transplant population of 2360 patients, and using data from hospital‐based surveillance, the risk of meningoencephalitis in a transplant patient infected with WNV is estimated to be 40% (95% CI 16–80%). With regards to knowledge and behavior, 56% patients knew of and 47% used at least one protective measure against WNV. Only 33% used insect repellent. The risk of meningoencephalitis in transplant recipients is much higher than in the general population. There is incomplete knowledge and poor rates of compliance amongst patients with regards to WNV prevention.
Abstract only Background and Purpose: There is limited evidence on head positioning in acute ischemic stroke (AIS) or intracerebral hemorrhage (ICH). Potential benefits for lying flat (0°) include ...improved collateral blood flow in AIS and for head up (30°) reduced cerebral oedema in ICH. The Head Positioning in Stroke Trial (HeadPoST) aims to provide reliable evidence on the optimum head position in acute stroke. Methods: HeadPoST is a prospective, cluster randomised, crossover, blinded outcome assessed, clinical trial with consecutive patient recruitment who were positioned within 24 hours of admission. Hospitals were randomised to service organisation to compare lying flat vs. sitting up (≥30°) head positioning of stroke patients. An innovative centralized remote monitoring system was used to assess data quality across participating countries. Results: Over a 30 month study period, 10,000+ patients were recruited across 114 hospitals in 9 countries. A web-based monitoring system provided alerts for cross-over time points and achievement of cluster balance. Centralised reports included serious adverse events, protocol deviations, forms completion, data queries, entry delays and data validation, which were distributed to regional co-ordinating centres for action. Details of these procedures are outlined. Conclusions: Reliable, complete, and high quality data were required for this pragmatic international nursing care clinical trial, which used a novel cluster cross-over design.
Hepatocellular carcinoma (HCC) is the 6th most common cancer in the world, but the second most common cause of cancer death. There is no universally accepted consensus practice guidelines for HCC ...owing to rapid developments in new treatment modalities, the heterogeneous epidemiology and clinical presentation of HCC worldwide. However, a number of regional and national guidelines currently exist which reflect practice relevant to the epidemiology and collective experience of the consensus group. In 2014, clinicians at the multidisciplinary Comprehensive Liver Cancer Clinic (CLCC) at the National Cancer Centre Singapore (NCCS) reviewed the latest published scientific data and existing international and regional practice guidelines, such as those of the National Comprehensive Cancer Network, American Association for the Study of Liver Diseases and the Asian Pacific Association for the Study of the Liver, and modified them to reflect local practice. These would serve as a template by which treatment outcomes can be collated and benchmarked against international data. The NCCS Consensus Guidelines for HCC have been successfully implemented in the CLCC since their publication online on 26th September 2014, and the guidelines allow outcomes of treatment to be compared to international data. These guidelines will be reviewed periodically to incorporate new data.
Objectives
To test the hypothesis that observation with early salvage radiotherapy (
SRT
) is not inferior to ‘standard’ treatment with adjuvant
RT
(
ART
) with respect to biochemical failure in ...patients with
pT3
disease and/or positive surgical margins (
SMs
) after radical prostatectomy (
RP
).
To compare the following secondary endpoints between the two arms: patient‐reported outcomes, adverse events, biochemical failure‐free survival, overall survival, disease‐specific survival, time to distant failure, time to local failure, cost utility analysis, quality adjusted life years and time to androgen deprivation.
Patients and Methods
The
R
adiotherapy –
A
djuvant Versus
E
arly
S
alvage (
RAVES
) trial is a phase
III
multicentre randomised controlled trial led by the
T
rans
T
asman
R
adiation
O
ncology
G
roup (
TROG
), in collaboration with the
U
rological
S
ociety of
A
ustralia and
N
ew
Z
ealand (
USANZ
), and the
A
ustralian and
N
ew
Z
ealand
U
rogenital and
P
rostate
C
ancer
T
rials
G
roup (
ANZUP
).
In all, 470 patients are planned to be randomised 1:1 to either
ART
commenced at ≤4 months of
RP
(standard of care) or close observation with early
SRT
triggered by a
PSA
level of >0.20 ng/mL (experimental arm).
Eligible patients have had a
RP
for adenocarcinoma of the prostate with at least one of the following risk factors: positive
SMs
± extraprostatic extension ± seminal vesicle involvement. The postoperative
PSA
level must be ≤0.10 ng/mL.
Rigorous investigator credentialing and a quality assurance programme are designed to promote consistent
RT
delivery among patients.
Results
Trial is currently underway, with 258 patients randomised as of 31
O
ctober 2013.
International collaborations have developed, including a planned meta‐analysis to be undertaken with the
UK M
edical
R
esearch
C
ouncil/National Cancer Institute of Canada Clinical Trials Group
RADICALS
(Radiotherapy and Androgen Deprivation In Combination with Local Surgery) trial and an innovative psycho‐oncology sub‐study to investigate a patient decision aid resource.
Conclusion
On the current evidence available, it remains unclear if
ART
is equivalent or superior to observation with early
SRT
.
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