Notes

Paraneoplastic Erythema Annulare Centrifugum Eruption (Tranquility) Related to Metastatic Digestive tract Adenocarcinoma.
The magnitude of the association was higher for broad-spectrum antibiotics (HR, 1.27; 95% CI, 1.18-1.37), higher doses (HR, 1.32; 95% CI, 1.22-1.44), more frequent use (HR, 1.33; 95% CI, 1.21-1.46), and recent use (HR, 1.26; 95% CI, 1.17-1.35).

Use of antibiotics, especially of broad-spectrum type, of high dose and frequency, with recent use, was associated with an aggravated risk of psychiatric disorders, compared with no antibiotic use.

A better understanding of the microbiota-gut-brain axis may open up a wide avenue for the prevention and treatment of psychiatric disorders in cancer patients.
A better understanding of the microbiota-gut-brain axis may open up a wide avenue for the prevention and treatment of psychiatric disorders in cancer patients.
The impact of acute COVID-19 on people with asthma appears complex, being moderated by multiple interacting disease-specific, demographic and environmental factors. Research regarding longer-term effects in this group is limited. We aimed to assess impacts of COVID-19 and predictors of persistent symptoms, in people with asthma.

Using data from an online UK-wide survey of 4500 people with asthma (median age 50-59 years, 81% female), conducted in October 2020, we undertook a mixed methods analysis of the characteristics and experience of those reporting having had COVID-19.

The COVID-19 group (n=471, 10.5%) reported increased inhaler use and worse asthma management, compared with those not reporting COVID-19, but did not differ by gender, ethnicity or household income. Among the COVID-19 group, 56.1% reported having long COVID, 20.2% were 'unsure'. Those with long COVID were more likely than those without long COVID to describe their breathing as worse or much worse after their initial illness (73.7% vs 34.8%, p<0.001), increased inhaler use (67.8% vs 34.8%, p<0.001) and worse or much worse asthma management (59.6% vs 25.6%, p<0.001). Having long COVID was not associated with age, gender, ethnicity, UK nation or household income.Analysis of free text survey responses identified three key themes (1) variable COVID-19 severity, duration and recovery; (2) symptom overlap and interaction between COVID-19 and asthma; (3) barriers to accessing healthcare.

Persisting symptoms are common in people with asthma following COVID-19. Measures are needed to ensure appropriate healthcare access including clinical evaluation and investigation, to distinguish between COVID-19 symptoms and asthma.
Persisting symptoms are common in people with asthma following COVID-19. Measures are needed to ensure appropriate healthcare access including clinical evaluation and investigation, to distinguish between COVID-19 symptoms and asthma.
Adoptive T-cell transfer has become an attractive therapeutic approach for hematological malignancies but shows poor activity against large and heterogeneous solid tumors. Interleukin-12 (IL-12) exhibits potent antitumor efficacy against solid tumors, but its clinical application has been stalled because of toxicity. Here, we aimed to develop a safe approach to IL-12 T-cell therapy for eliminating large solid tumors.

We generated a cell membrane-anchored IL-12 (aIL12), a tumor-targeted IL-12 (ttIL12), and a cell membrane-anchored and ttIL-12 (attIL12) and a cell membrane-anchored and tumor-targeted ttIL-12 (attIL12) armed T cells, chimeric antigen receptor-T cells, and T cell receptor-T (TCR-T) cells with each. We compared the safety and efficacy of these armed T cells in treating osteosarcoma patient-derived xenograft tumors and mouse melanoma tumors after intravenous infusions of the armed T cells.

attIL12-T cell infusion showed remarkable antitumor efficacy in human and mouse large solid tumor models. Mechanistically, attIL12-T cells targeted tumor cells expressing cell-surface vimentin, enriching effector T cell and interferon γ production in tumors, which in turn stimulates dendritic cell maturation for activating secondary T-cell responses and tumor antigen spreading. Both attIL12- and aIL12-T-cell transfer eliminated peripheral cytokine release and the associated toxic effects.

This novel approach sheds light on the safe application of IL-12-based T-cell therapy for large and heterogeneous solid tumors.
This novel approach sheds light on the safe application of IL-12-based T-cell therapy for large and heterogeneous solid tumors.
Adoptive transfer of CD19-specific chimeric antigen receptor (CD19CAR) T cells can induce dramatic disease regression in patients with B cell malignancies. CD19CAR T cell therapy may be limited by insufficient engraftment and persistence, resulting in tumor relapse. We previously demonstrated a proof of principle that cytomegalovirus (CMV)-specific T cells can be isolated and enriched prior to CD19CAR transduction to produce CMV-CD19CAR T cells, and that these CMV-CD19CAR T cells can be expanded in vivo through CMV vaccination, resulting in better tumor control in a murine model. Here we developed a clinical platform for generating CMV-CD19CAR T cells.

Peripheral blood mononuclear cells (PBMCs) collected from CMV-seropositive healthy donors were stimulated with a good manufacturing practices-grade PepTivator overlapping CMVpp65 peptide pool and enriched for CMV-responsive interferon γ (IFNγ)+T cells using IFNγ Catchmatrix, within the CliniMACS Prodigy Cytokine Capture System (Miltenyi Biotec). Resulting Ceasibility of our large-scale platform for generating CMV-CD19CAR T cells for clinical application. We plan to initiate a clinical trial at City of Hope using CMV-CD19CAR T cells for patients with intermediate/high-grade B cell non-Hodgkin's lymphoma immediately after autologous hematopoietic cell transplantation followed by vaccination with a novel CMV vaccine based on Modified Vaccinia Ankara (Triplex) 28 days and 56 days post-T cell infusion.
We demonstrated the feasibility of our large-scale platform for generating CMV-CD19CAR T cells for clinical application. We plan to initiate a clinical trial at City of Hope using CMV-CD19CAR T cells for patients with intermediate/high-grade B cell non-Hodgkin's lymphoma immediately after autologous hematopoietic cell transplantation followed by vaccination with a novel CMV vaccine based on Modified Vaccinia Ankara (Triplex) 28 days and 56 days post-T cell infusion.
Information on emergency department (ED) visits for mental and substance use disorders (MSUDs) is important for planning services but has not been explored in British Columbia (BC), Canada. We describe all MSUD ED visits for people ages 15 and older in the province of BC in 2017/2018 and document trends in MSUD ED visits between 2007/2008 and 2017/2018 by disorder group.

Population-based linked administrative data comprised of ED records and physician billings capturing all MSUD ED visits in BC.

BC is Canada's westernmost province with a population of approximately 5 million. Permanent residents receive first-dollar coverage for all medically necessary services provided by licensed physicians or in hospitals, including ED services.

All people age >15 with MSUD ED visits during the study period.

All claims with a service location in the ED or corresponding to fee items billed only in the ED were examined alongside ED visits reported through a national reporting system. Patient characteristics (sexces and adequately resource and support EDs to manage growing patient populations.
Early identification of patients who may suffer from unexpected adverse events (eg, sepsis, sudden cardiac arrest) gives bedside staff valuable lead time to care for these patients appropriately. Consequently, many machine learning algorithms have been developed to predict adverse events. However, little research focuses on how these systems are implemented and how system design impacts clinicians' decisions or patient outcomes. IKK-16 This protocol outlines the steps to review the designs of these tools.

We will use scoping review methods to explore how tools that leverage machine learning algorithms in predicting adverse events are designed to integrate into clinical practice. We will explore the types of user interfaces deployed, what information is displayed, and how clinical workflows are supported. Electronic sources include Medline, Embase, CINAHL Complete, Cochrane Library (including CENTRAL), and IEEE Xplore from 1 January 2009 to present. We will only review primary research articles that report findin. Findings will be disseminated through peer-reviewed publications.
Countries in sub-Saharan Africa suffer the highest rates of child mortality worldwide. Urban areas tend to have lower mortality than rural areas, but these comparisons likely mask large within-city inequalities. We aimed to estimate rates of under-five mortality (U5M) at the neighbourhood level for Ghana's Greater Accra Metropolitan Area (GAMA) and measure the extent of intraurban inequalities.

We accessed data on >700 000 women aged 25-49 years living in GAMA using the most recent Ghana census (2010). We summarised counts of child births and deaths by five-year age group of women and neighbourhood (n=406) and applied indirect demographic methods to convert the summaries to yearly probabilities of death before age five years. We fitted a Bayesian spatiotemporal model to the neighbourhood U5M probabilities to obtain estimates for the year 2010 and examined their correlations with indicators of neighbourhood living and socioeconomic conditions.

U5M varied almost five-fold across neighbourhoods in GAMA hs.
Reducing child mortality in high-burden urban neighbourhoods in GAMA, where a substantial portion of the urban population resides, should be prioritised as part of continued efforts to meet the Sustainable Development Goal national target of less than 25 deaths per 1000 live births.
Stroke survivors can have a high disability rate with low quality of daily life, resulting in a heavy burden on family and society. Transcranial magnetic stimulation has been widely applied to brain injury repair, neurological disease treatment, cognition and emotion regulation and so on. However, there is still much to be desired in the theories of using these neuromodulation techniques to treat stroke-caused hemiplegia. It is generally recognised that synaptic plasticity is an important basis for functional repair after brain injury. This study protocol aims to examine the corticocortical paired associative stimulation (ccPAS) for inducing synaptic plasticity to rescue the paralysed after stroke.

The current study is designed as a 14-week double-blind randomised sham-controlled clinical trial, composed of 2-week intervention and 12-week follow-up. For the study, 42 patients who had a stroke aged 40-70 will be recruited, who are randomly assigned either to the ccPAS intervention group, or to the control th the Helsinki declaration. Written informed consent was obtained from all individual participants included in the study. Study findings will be disseminated in the printed media.

Chinese Clinical Trial Registry ChiCTR2000036685.
Chinese Clinical Trial Registry ChiCTR2000036685.
We explore the cost of care of type 2 diabetes mellitus (T2DM) using time-driven activity-based costing (TDABC) and connect that cost to resulting patient health outcomes.

We construct six care pathways varying from low-risk to high-risk patients over a 12-month cycle of care. We collect time, resource and cost data on activities in each care pathway and compute a time-driven estimate of cost. Use of patient outcome data highlights the health outcomes achieved.

Primary, secondary and tertiary care.

Medical staff involved in the care of patients with T2DM.

Primary resources consumed to provide T2DM care. Secondary health outcomes for representative patient within each patient category.

By computing cost of T2DM care and associated complications of chronic kidney disease, active foot disease, moderate risk of active foot disease and myocardial infarction, we show that when patients develop acute complications, significant costs are incurred, as compared with the cost of maintaining a patient at low or moderate risk.
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