Characteristics and outcomes of COVID-19 patients presumed to be treated with sotrovimab in NHS hospitals in England.

BACKGROUND: The impact of the constantly evolving severe acute respiratory syndrome coronavirus 2 on the effectiveness of early coronavirus disease 2019 (COVID-19) treatments is unclear. Here, we report characteristics and acute clinical outcomes of patients with COVID-19 treated with a monoclonal antibody (mAb; presumed to be sotrovimab) across six distinct periods covering the emergence and predominance of Omicron subvariants (BA.1, BA.2, and BA.5) in England. METHODS: Retrospective cohort study using data from the Hospital Episode Statistics database from January 1-July 31, 2022. Included patients received a mAb delivered by a National Health Service (NHS) hospital as a day-case, for which the primary diagnosis was COVID-19. Patients were presumed to have received sotrovimab based on NHS data showing that 99.98% of COVID-19-mAb-treated individuals received sotrovimab during the study period. COVID-19-attributable hospitalizations were reported overall and across six distinct periods of Omicron subvariant prevalence. Subgroup analyses were conducted in patients with severe renal disease and active cancer. RESULTS: Among a total of 10,096 patients, 1.0% (n = 96) had a COVID-19-attributable hospitalization, 4.6% (n = 465) had a hospital visit due to any cause, and 0.3% (n = 27) died due to any cause during the acute period. COVID-19-attributable hospitalization rates were consistent among subgroups, and no significant differences were observed across periods of Omicron subvariant predominance. CONCLUSIONS: Levels of COVID-19-attributable hospitalizations and deaths were low in mAb-treated patients and among subgroups. Similar hospitalization rates were observed whilst Omicron BA.1, BA.2, and BA.5 were predominant, despite reported reductions in in vitro neutralization activity of sotrovimab against BA.2 and BA.5.

Comparative effectiveness of sotrovimab versus no treatment in non-hospitalised high-risk COVID-19 patients in north west London: a retrospective cohort study.

BACKGROUND: We assessed the effectiveness of sotrovimab vs no early COVID-19 treatment in highest-risk COVID-19 patients during Omicron predominance. METHODS: Retrospective cohort study using the Discover dataset in North West London. Included patients were non-hospitalised, aged ≥12 years and met ≥1 National Health Service highest-risk criterion for sotrovimab treatment. We used Cox proportional hazards models to compare HRs of 28-day COVID-19-related hospitalisation/death between highest-risk sotrovimab-treated and untreated patients. Age, renal disease and Omicron subvariant subgroup analyses were performed. RESULTS: We included 599 sotrovimab-treated patients and 5191 untreated patients. Compared with untreated patients, the risk of COVID-19 hospitalisation/death (HR 0.50, 95% CI 0.24, 1.06; p=0.07) and the risk of COVID-19 hospitalisation (HR 0.43, 95% CI 0.18, 1.00; p=0.051) were both lower in the sotrovimab-treated group; however, statistical significance was not reached. In the ≥65 years and renal disease subgroups, sotrovimab was associated with a significantly reduced risk of COVID-19 hospitalisation, by 89% (HR 0.11, 95% CI 0.02, 0.82; p=0.03) and 82% (HR 0.18, 95% CI 0.05, 0.62; p=0.007), respectively. CONCLUSIONS: Risk of COVID-19 hospitalisation in sotrovimab-treated patients aged ≥65 years and with renal disease was significantly lower compared with untreated patients. Overall, risk of hospitalisation was also lower for sotrovimab-treated patients, but statistical significance was not reached.

Assessment of bone-targeting agents use in patients with bone metastasis from breast, lung or prostate cancer using structured and unstructured electronic health records from a regional UK-based hospital.

ObjectiveTo assess use of bone-targeting agents (BTA) in patients with confirmed bone metastases (BM) from breast cancer (BC), non-small cell lung cancer (NSCLC) or prostate cancer (PC). DESIGN: Retrospective cohort study. SETTING: Regional hospital-based oncology database of approximately 2 million patients in England. PARTICIPANTS: Patients aged ≥18 years with a diagnosis of BC, NSCLC or PC as well as BM between 1 January 2007 and 31 December 2018, with follow-up to 30 June 2020 or death; BM diagnosis ascertained from recorded medical codes and unstructured data using natural language processing (NLP). MAIN OUTCOMES MEASURES: Initiation or non-initiation of BTA following BM diagnosis, time from BM diagnosis to BTA initiation, time from first to last BTA, time from last BTA to death. RESULTS: This study included 559 BC, 894 NSCLC and 1013 PC with BM; median age (Q1-Q3) was 65 (52-76), 69 (62-77) and 75 (62-77) years, respectively. NLP identified BM diagnosis from unstructured data for 92% patients with BC, 92% patients with NSCLC and 95% patients with PC. Among patients with BC, NSCLC and PC with BM, 47%, 87% and 88% did not receive a BTA, and 53%, 13% and 12% received at least one BTA, starting a median 65 (27-167), 60 (28-162) and 610 (295-980) days after BM, respectively. Median (Q1-Q3) duration of BTA treatment was 481 (188-816), 89 (49-195) and 115 (53-193) days for patients with BC, NSCLC and PC. For those with a death record, median time from last BTA to death was 54 (26-109) for BC, 38 (17-98) for NSCLC and 112 (44-218) days for PC. CONCLUSION: In this study identifying BM diagnosis from both structured and unstructured data, a high proportion of patients did not receive a BTA. Unstructured data provide new insights on the real-world use of BTA.

Ovarian Real-World International Consortium (ORWIC): A multicentre, real-world analysis of epithelial ovarian cancer treatment and outcomes.

Introduction: Much drug development and published analysis for epithelial ovarian cancer (EOC) focuses on early-line treatment. Full sequences of treatment from diagnosis to death and the impact of later lines of therapy are rarely studied. We describe the establishment of an international network of cancer centers configured to compare real-world treatment pathways in UK, Portugal, Germany, South Korea, France and Romania (the Ovarian Real-World International Consortium; ORWIC). Methods: 3344 patients diagnosed with EOC (2012-2018) were analysed using a common data model and hub and spoke programming approach applied to existing electronic medical records. Consistent definition of line of therapy between sites and an efficient approach to analysis within the limitations of local information governance was achieved. Results: Median age of participants was 53-67 years old and 5-29% were ECOG >1. Between 62% and 84% of patients were diagnosed with late-stage disease (FIGO III-IV). Sites treating younger and fitter patients had higher rates of debulking surgery for those diagnosed at late stage than sites with older, more frail patients. At least 21% of patients treated with systemic anti-cancer therapy (SACT) had recurrent disease following second-line therapy (2L); up to 11 lines of SACT treatment were recorded for some patients. Platinum-based SACT was consistently used across sites at 1L, but choices at 2L varied, with hormone therapies commonly used in the UK and Portugal. The use (and type) of maintenance therapy following 1L also varied. Beyond 2L, there was little consensus between sites on treatment choice: trial compounds and unspecified combinations of other agents were common. Discussion: Specific treatment sequences are reported up to 4L and the establishment of this network facilitates future analysis of comparative outcomes per line of treatment with the aim of optimizing available options for patients with recurrent EOC. In particular, this real-world network can be used to assess the growing use of PARP inhibitors. The real-world optimization of advanced line treatment will be especially important for patients not usually eligible for involvement with clinical trials. The resources to enable this analysis to be implemented elsewhere are supplied and the network will seek to grow in coverage of further sites.

High prevalence of epilepsy in onchocerciasis endemic regions in the Democratic Republic of the Congo.

BACKGROUND: An increased prevalence of epilepsy has been reported in many onchocerciasis endemic areas. The objective of this study was to determine the prevalence of epilepsy in onchocerciasis endemic areas in the Democratic Republic of the Congo (DRC) and investigate whether a higher annual intake of Ivermectin was associated with a lower prevalence of epilepsy. METHODOLOGY/PRINCIPLE FINDINGS: Between July 2014 and February 2016, house-to-house epilepsy prevalence surveys were carried out in areas with a high level of onchocerciasis endemicity: 3 localities in the Bas-Uele, 24 in the Tshopo and 21 in the Ituri province. Ivermectin uptake was recorded for every household member. This database allowed a matched case-control pair subset to be created that enabled putative risk factors for epilepsy to be tested using univariate logistic regression models. Risk factors relating to onchocerciasis were tested using a multivariate random effects model. To identify presence of clusters of epilepsy cases, the Kulldorff's scan statistic was used. Of 12, 408 people examined in the different health areas 407 (3.3%) were found to have a history of epilepsy. A high prevalence of epilepsy was observed in health areas in the 3 provinces: 6.8-8.5% in Bas-Uele, 0.8-7.4% in Tshopo and 3.6-6.2% in Ituri. Median age of epilepsy onset was 9 years, and the modal age 12 years. The case control analysis demonstrated that before the appearance of epilepsy, compared to the same life period in controls, persons with epilepsy were around two times less likely (OR: 0.52; 95%CI: (0.28, 0.98)) to have taken Ivermectin than controls. After the appearance of epilepsy, there was no difference of Ivermectin intake between cases and controls. Only in Ituri, a significant cluster (p-value = 0.0001) was identified located around the Draju sample site area. CONCLUSIONS: The prevalence of epilepsy in health areas in onchocerciasis endemic regions in the DRC was 2-10 times higher than in non-onchocerciasis endemic regions in Africa. Our data suggests that Ivermectin protects against epilepsy in an onchocerciasis endemic region. However, a prospective population based intervention study is needed to confirm this.

A Two-Locus Model of the Evolution of Insecticide Resistance to Inform and Optimise Public Health Insecticide Deployment Strategies.

We develop a flexible, two-locus model for the spread of insecticide resistance applicable to mosquito species that transmit human diseases such as malaria. The model allows differential exposure of males and females, allows them to encounter high or low concentrations of insecticide, and allows selection pressures and dominance values to differ depending on the concentration of insecticide encountered. We demonstrate its application by investigating the relative merits of sequential use of insecticides versus their deployment as a mixture to minimise the spread of resistance. We recover previously published results as subsets of this model and conduct a sensitivity analysis over an extensive parameter space to identify what circumstances favour mixtures over sequences. Both strategies lasted more than 500 mosquito generations (or about 40 years) in 24% of runs, while in those runs where resistance had spread to high levels by 500 generations, 56% favoured sequential use and 44% favoured mixtures. Mixtures are favoured when insecticide effectiveness (their ability to kill homozygous susceptible mosquitoes) is high and exposure (the proportion of mosquitoes that encounter the insecticide) is low. If insecticides do not reliably kill homozygous sensitive genotypes, it is likely that sequential deployment will be a more robust strategy. Resistance to an insecticide always spreads slower if that insecticide is used in a mixture although this may be insufficient to outperform sequential use: for example, a mixture may last 5 years while the two insecticides deployed individually may last 3 and 4 years giving an overall 'lifespan' of 7 years for sequential use. We emphasise that this paper is primarily about designing and implementing a flexible modelling strategy to investigate the spread of insecticide resistance in vector populations and demonstrate how our model can identify vector control strategies most likely to minimise the spread of insecticide resistance.

Prevalence of River Epilepsy in the Orientale Province in the Democratic Republic of the Congo.

BACKGROUND: An increased prevalence of epilepsy has been reported in many onchocerciasis endemic areas. OBJECTIVE: To determine the prevalence and distribution of epilepsy in an onchocerciasis endemic region in the Democratic Republic of the Congo (DRC). DESIGN/METHODS: An epilepsy prevalence study was carried out in 2014, in two localities of the Bas-Uélé district, an onchocerciasis endemic region in the Orientale Province of the DRC. Risk factors for epilepsy were identified using a random effects logistic regression model and the distribution of epilepsy cases was investigated using the Moran's I statistic of spatial auto-correlation. RESULTS: Among the 12,776 individuals of Dingila, 373 (2.9%) individuals with epilepsy were identified. In a house-to-house survey in Titule, 68 (2.3%) of the 2,908 people who participated in the survey were found to present episodes of epilepsy. Epilepsy showed a marked spatial pattern with clustering of cases occurring within and between adjacent households. Individual risk of epilepsy was found to be associated with living close to the nearest fast flowing river where blackflies (Diptera: Simuliidae)-the vector of Onchocerca volvulus-oviposit and breed. CONCLUSIONS: The prevalence of epilepsy in villages in the Bas-Uélé district in the DRC was higher than in non-onchocerciasis endemic regions in Africa. Living close to a blackflies infested river was found to be a risk factor for epilepsy.

The Perfect Burrow, but for What? Identifying Local Habitat Conditions Promoting the Presence of the Host and Vector Species in the Kazakh Plague System.

INTRODUCTION: The wildlife plague system in the Pre-Balkhash desert of Kazakhstan has been a subject of study for many years. Much progress has been made in generating a method of predicting outbreaks of the disease (infection by the gram negative bacterium Yersinia pestis) but existing methods are not yet accurate enough to inform public health planning. The present study aimed to identify characteristics of individual mammalian host (Rhombomys opimus) burrows related to and potentially predictive of the presence of R.opimus and the dominant flea vectors (Xenopsylla spp.). METHODS: Over four seasons, burrow characteristics, their current occupancy status, and flea and tick burden of the occupants were recorded in the field. A second data set was generated of long term occupancy trends by recording the occupancy status of specific burrows over multiple occasions. Generalised linear mixed models were constructed to identify potential burrow properties predictive of either occupancy or flea burden. RESULTS: At the burrow level, it was identified that a burrow being occupied by Rhombomys, and remaining occupied, were both related to the characteristics of the sediment in which the burrow was constructed. The flea burden of Rhombomys in a burrow was found to be related to the tick burden. Further larger scale properties were also identified as being related to both Rhombomys and flea presence, including latitudinal position and the season. CONCLUSIONS: Therefore, in advancing our current predictions of plague in Kazakhstan, we must consider the landscape at this local level to increase our accuracy in predicting the dynamics of gerbil and flea populations. Furthermore this demonstrates that in other zoonotic systems, it may be useful to consider the distribution and location of suitable habitat for both host and vector species at this fine scale to accurately predict future epizootics.