Porcine-derived pancreatic enzyme replacement therapy: a cause of hepatitis E virus transmission?

Recently, in Canada, Thornton et al observed a higher proportion of anti-hepatitis E virus (HEV) IgG among persons with cystic fibrosis having received (20.7%) or not (19.3%) a lung transplantation compared with a non-cystic fibrosis population (10.7%).1 In order to understand the difference in the seropositivity rate between these populations, they focused their research on the use of pancreatic enzyme replacement therapy (PERT).1 Indeed, pancreatic insufficiency is quite common in patients with cystic fibrosis, requiring PERT. PERT is porcine derived. Pork is one of the main reservoirs of HEV.2 Zoonotic transmission of viruses through PERT was previously recognised.3 Thornton et al detected HEV RNA in 44% of PERT capsules obtained from different formulations and produced by four different manufacturers.1 In their study, 3 out of 29 lung transplant patients with cystic fibrosis have detectable HEV RNA and developed chronic…

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Porcine-derived pancreatic enzyme replacement therapy linking to chronic hepatitis E: broad implications

We read with interest the recent work by Thornton et al, which described three cases of chronic hepatitis E in persons with cystic fibrosis (pwCF) after lung transplantation.1 Because most pwCF took porcine-derived pancreatic enzyme replacement therapy (PERT), the authors suspected PERT as a plausible source of transmitting hepatitis E virus (HEV) to these patients. Alarmingly, the authors found that 44% of PERT capsules were positive for HEV viral RNA.1 Although there remains a knowledge gap whether the viral components presented in PERT are actually infectious, which can be further assessed for example by using experimental models, the intriguing findings from this study do bear broad implications (figure 1). Currently, PERT is indicated for treating exocrine pancreatic insufficiency due to cystic fibrosis or other conditions in both paediatric and adult patients, and thus the overall size of this patient population is substantial.

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First H5N1 Bird Flu Infections in Pigs Raises Concerns

The US Department of Agriculture (USDA) recently identified the nation’s first cases of avian influenza A(H5N1) virus, or H5N1 bird flu, in swine. The infected pigs were 2 of 5 on a noncommercial farm in Oregon that shared water, housing, and equipment with infected poultry, which likely facilitated the virus’ transmission.

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Identifying people with post-COVID condition using linked, population-based administrative health data from Manitoba, Canada: prevalence and predictors in a cohort of COVID-positive individuals

Objective
Many individuals exposed to SARS-CoV-2 experience long-term symptoms as part of a syndrome called post-COVID condition (PCC). Research on PCC is still emerging but is urgently needed to support diagnosis, clinical treatment guidelines and health system resource allocation. In this study, we developed a method to identify PCC cases using administrative health data and report PCC prevalence and predictive factors in Manitoba, Canada.

Design
Cohort study.

Setting
Manitoba, Canada.

Participants
All Manitobans who tested positive for SARS-CoV-2 during population-wide PCR testing from March 2020 to December 2021 (n=66 365) and were subsequently deemed to have PCC based on International Classification of Disease-9/10 diagnostic codes and prescription drug codes (n=11 316). Additional PCC cases were identified using predictive modelling to assess patterns of health service use, including physician visits, emergency department visits and hospitalisation for any reason (n=4155).

Outcomes
We measured PCC prevalence as % PCC cases among Manitobans with positive tests and identified predictive factors associated with PCC by calculating odds ratios with 95% confidence intervals, adjusted for sociodemographic and clinical characteristics (aOR).

Results
Among 66 365 Manitobans with positive tests, we identified 15 471 (23%) as having PCC. Being female (aOR 1.64, 95% CI 1.58 to 1.71), being age 60–79 (aOR 1.33, 95% CI 1.25 to 1.41) or age 80+ (aOR 1.62, 95% CI 1.46 to 1.80), being hospitalised within 14 days of COVID-19 infection (aOR 1.95, 95% CI 1.80 to 2.10) and having a Charlson Comorbidity Index of 1+ (aOR 1.95, 95% CI 1.78 to 2.14) were predictive of PCC. Receiving 1+ doses of the COVID-19 vaccine (one dose, aOR 0.80, 95% CI 0.74 to 0.86; two doses, aOR 0.29, 95% CI 0.22 to 0.31) decreased the odds of PCC.

Conclusions
This data-driven approach expands our understanding of the prevalence and epidemiology of PCC and may be applied in other jurisdictions with population-based data. The study provides additional insights into risk and protective factors for PCC to inform health system planning and service delivery.

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Enhancing Neuron Activity Promotes Functional Recovery by Inhibiting Microglia-Mediated Synapse Elimination After Stroke

Stroke, Ahead of Print. BACKGROUND:Activating glutamatergic neurons in the ipsilesional motor cortex can promote functional recovery after stroke. However, the underlying molecular mechanisms remain unclear. Clarifying key molecular mechanisms involved in recovery could help understand the development of neuromodulation strategies after stroke.METHODS:Adeno-associated virus 2/9-CamKIIa-hM3Dq-mCherry was injected into ipsilesional motor cortex by stereotaxic in the photothrombotic stroke model. Starting from the third day after the stroke, male mice were injected intraperitoneally with clozapine-N-oxide every day to activate excitatory neurons. C1q-blocking antibody and annexin V were used to inhibit C1q and exposed phosphatidylserine (EPS), respectively. The cylinder test and grid-walking test were performed to evaluate functional recovery. The potential molecular mechanisms of excitatory neuronal activation on microglia-mediated synaptic pruning after stroke by immunofluorescence, real-time polymerase chain reaction, Western blotting, and RNA sequencing.RESULTS:Activating excitatory neurons significantly promoted functional recovery and inhibited microglia-mediated synaptic pruning after stroke. Furthermore, it decreased EPS and C1q levels in synapses. On the contrary, inhibiting excitatory neurons aggravated functional defects, promoted microglia-mediated synaptic pruning, and increased EPS and C1q levels in synapses. Selective blocking of EPS repressed C1q tagging of synapses and microglia-mediated synaptic pruning and improved functional recovery. Meanwhile, blocking EPS markedly rescued synaptic density, and motor function deteriorated by chemogenetic inhibition. In addition, C1q-blocking antibody prevented phosphatidylserine engulfment by microglia.CONCLUSIONS:Together, these data provide mechanistic insight into microglia-mediated synapse pruning after neuronal activation after stroke and identify the role of C1q binding to EPS in stroke treatment during the repair phase.

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Post-COVID-19 conditions and health effects in Africa: a scoping review

Introduction
The SARS-CoV-2 pandemic has caused global devastations in social, economic and health systems of every nation, but disproportionately of nations in Africa. In addition to its grave effects on the global systems, there is continuation or development of new symptoms among individuals who have contracted the virus, with the potential to further stress the health systems on the continent. Therefore, the aim of this scoping review was to collate and summarise the existing research evidence on the prevalence and health effects of post–COVID-19 conditions in Africa.

Methods and analysis
Five main databases were thoroughly searched from 1 September 2023 to 10 May 2024 for eligible articles based on the pre-established inclusion and exclusion criteria. These databases included PubMed, Central, Scopus, Dimensions AI and JSTOR. A total of 17 papers were included in the review. The protocol for this review is already published in BMJ Open; doi:10.1136/bmjopen-2023-082519.

Results
The prevalence of post–COVID-19 conditions in Africa ranged from 2% to as high as 94.7%. Fatigue, dyspnoea and brain fog were among the commonly reported symptoms of post–COVID-19 conditions. Reduced functional status as well as physical and psychosocial disorders were the main health effects reported by the studies reviewed, but no study yet reported the effects of post–COVID-19 conditions on the health systems in Africa.

Conclusions
There is an evidence of high prevalence of post–COVID-19 conditions in the African setting. However, there is limited evidence of the health effects of the post–COVID-19 conditions on patients and health systems in Africa.

Ethics and dissemination
This scoping review involved analysis of secondary data; therefore, no ethical approval was needed. Dissemination of the result is being done through international journals and may also be presented at available research conferences.

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US Triplet and Higher-Order Birth Rate Down 62% Since 1998

Between 1980 and 1998, the triplet and higher-order multiple birth rate in the US soared from 37 to about 194 births per 100 000—a rise associated with older maternal age and a spike in the use of fertility treatments. But from 1998 to 2023, this rate dropped to 74 births per 100 000, a decline of 62%, according to a National Center for Health Statistics data brief.

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Impact of the SARS-CoV-2/COVID-19 pandemic on the patient journeys of those with a newly diagnosed paediatric brain tumour in the UK: a qualitative study

Objectives
To explore the impact of the SARS-CoV-2/COVID-19 pandemic on the diagnosis, management and patient journey for children and young people with a newly diagnosed brain tumour in the UK.

Design
Exploratory qualitative study focused on patient journeys from multiple perspectives, conducted as part of a wider mixed-methods study.

Setting
Three paediatric oncology tertiary centres in the UK.

Participants
10 children and young people with brain tumours (n=6 females, n=4 males), 20 caregivers (n=16 females, n=4 males) and 16 stakeholders (specialist nurses, consultant neurosurgeons and oncologists, and representatives from brain tumour charities) were interviewed between January 2022 and June 2023.

Results
The paper incorporates multiple perspectives, including those of children and young people, parents/caregivers, clinical staff and charity representatives, to explore the patient journey. Five themes describe the journey for new patients with paediatric brain tumour during the pandemic, focusing on (1) challenges getting into the healthcare system, (2) managing as a family during restrictions imposed by the pandemic, (3) complexities of building a cohesive and supportive healthcare team, (4) difficulties caregivers experienced in accessing practical and emotional support in hospital and (5) ongoing difficulties experienced by families in the community.

Conclusions
Findings from this study offer practical insights from children, parents/caregivers and relevant stakeholders to improve the healthcare system during future disruptions. Overall, this study not only sheds light on the challenges faced by families during the pandemic but also provides suggestions for improving healthcare services to ensure a more comprehensive and effective response in times of crisis.

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