Publications by authors named "Lewin S"

Background: Women with inflammatory bowel disease (IBD) face complexities of disease management during pregnancy and childbirth. Apprehension regarding vaginal delivery in pregnant individuals with IBD persists due to concern for perianal disease and perineal trauma. The incidence of poor wound healing after obstetric anal sphincter injury is approximately 4% in the general population.

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This target product profile (TPP) highlights the minimal and optimal characteristics for ex-vivo and in-vivo cell and gene therapy-based products aimed at achieving an HIV cure (ie, durable antiretroviral-free viral control). The need for an effective, safe, scalable, affordable, accessible, and acceptable cure for HIV infection remains a major global priority. The possibilities for cell and gene therapy-based products for an HIV cure are rapidly expanding.

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The impact of combined heat and drought stress was investigated in and compared to individual stresses to reveal additive effects and interactions. A combination of plant metabolomics and root and rhizosphere bacterial metabarcoding were used to unravel effects at the plant holobiont level. Hierarchical cluster analysis of metabolomics signatures pointed out two main clusters, one including heat and combined heat and drought, and the second cluster that included the control and drought treatments.

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Introduction: We designed the Informed Health Choices (IHC) secondary school intervention and evaluated whether it improves students' ability to assess the trustworthiness of claims about treatment effects in Uganda. We conducted a process evaluation alongside a randomized trial to identify factors that may affect the implementation, fidelity, and scaling up of the intervention in Uganda. We also explored the potential adverse and beneficial effects of the intervention.

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Introduction: We evaluated the Informed Health Choices secondary school intervention to help students in Kenya think critically about health choices. We conducted this process evaluation to explore if the intervention was implemented as planned, identify factors that facilitated or hindered implementation, potential benefits of the intervention, and how to scale up the intervention beyond the trial.

Methods: This was a mixed methods process evaluation nested in a cluster-randomized trial of the Informed Health Choices intervention.

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Introduction: We evaluated the Informed Health Choices secondary school intervention in a cluster randomized trial in Rwanda. The intervention was effective in helping students to think critically about health. In parallel to the trial, we conducted a process evaluation to assess factors affecting the implementation, impacts, and scale-up of the intervention.

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Background: Mirvetuximab soravtansine-gynx (MIRV) is a first-in-class, folate receptor alpha (FRα)-targeting antibody-drug conjugate with United States Food and Drug Administration approval for FRα-positive platinum-resistant ovarian cancer. PICCOLO is a phase II, global, open-label, single-arm trial of MIRV as third-line or greater (≥3L) treatment in patients with FRα-positive (≥75% of cells with ≥2+ staining intensity) recurrent platinum-sensitive ovarian cancer (PSOC).

Patients And Methods: Participants received MIRV (6 mg/kg adjusted ideal body weight every 3 weeks) until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death.

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Background: There is no guideline regarding whether patients treated with intravenous corticosteroids for acute severe ulcerative colitis (ASUC) should be monitored in the hospital after transitioning to oral steroids. Our study aimed to: (1) compare rates of oral steroid transition failure and 30-day readmission between ASUC hospitalizations with extended inpatient monitoring compared to accelerated inpatient monitoring, and (2) identify predictors of oral steroid transition failure.

Methods: A retrospective cohort study of ulcerative colitis (UC) related admissions at UCSF from 2014 to 2022 was conducted comparing rates of steroid transition failures in extended inpatient monitoring (≥ 24 h on oral steroids prior to discharge) to accelerated inpatient monitoring (< 24 h on oral steroids).

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Article Synopsis
  • Critical thinking about health choices is important for students to make informed decisions and avoid misinformation; this study evaluates a school-based intervention aimed at enhancing critical thinking in adolescents.
  • Conducted in Kenya, Rwanda, and Uganda, the intervention involved teacher training and digital resources, focusing on key health concepts, and included over 11,000 students across 244 schools.
  • After one year, results showed that students in the intervention schools had better test scores compared to baseline, with a significant improvement in passing rates, though retention decreased over time.
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The coronavirus disease 2019 (COVID-19) pandemic has highlighted that preparedness for and responsiveness to pandemics requires public health platforms and processes which are nimble and evidence-based and a research ecosystem which is rapidly responsive to the evolving needs of society and decision-makers. The national BEAT COVID-19 research consortium was funded in 2020 by the Snow Medical Research Foundation (Snow Medical). Its Expert Advisory Committee met with the consortium post-pandemic to summarise the research undertaken and to consider lessons learned through the research response to COVID-19 in Australia.

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  • Chronic infection with Hepatitis B Virus (HBV) leads to weak virus-specific T cell responses, complicating viral clearance while causing significant liver inflammation due to immune responses.
  • A new assay developed for detecting HBV Capsid-Antibody Complexes (CACs) showed high accuracy in measuring these complexes in serum and linked them to increased liver inflammation and damage in chronic hepatitis B patients.
  • The study provides strong evidence that CACs play a key role in complement-mediated liver injury, establishing a new factor to consider alongside existing clinical markers for monitoring inflammation in chronic hepatitis B.
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  • Many child health guidelines in Malawi, Nigeria, and South Africa are old and don’t involve enough people in making decisions.
  • The GELA project helped create better guidelines by getting groups together to discuss and prioritize the most important child health topics, using current evidence to adapt existing recommendations.
  • National teams in these countries created five new recommendations for child health, but they needed more evidence and training to make good decisions.
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  • Opioid use in hospitalized patients with inflammatory bowel disease doesn't help with pain and might keep them in the hospital longer.
  • A study tracked patients with acute severe ulcerative colitis and found that those using a lot of opioids had delays in getting other important treatments.
  • Patients who used high amounts of opioids were more likely to leave the hospital with opioids, while overall, the use of opioids didn't change their hospital stay length or costs.
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Long COVID occurs in a small but important minority of patients following COVID-19, reducing quality of life and contributing to healthcare burden. Although research into underlying mechanisms is evolving, immunity is understudied. SARS-CoV-2-specific T cell responses are of key importance for viral clearance and COVID-19 recovery.

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Following success in cancer immunotherapy, immune checkpoint blockade is emerging as an exciting potential treatment for some infectious diseases, specifically two chronic viral infections, HIV and hepatitis B. Here, we will discuss the function of immune checkpoints, their role in infectious disease pathology, and the ability of immune checkpoint blockade to reinvigorate the immune response. We focus on blockade of programmed cell death 1 (PD-1) to induce durable immune-mediated control of HIV, given that anti-PD-1 can restore function to exhausted HIV-specific T cells and also reverse HIV latency, a long-lived form of viral infection.

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Background: Learning to thinking critically about health information and choices can protect people from unnecessary suffering, harm, and resource waste. Earlier work revealed that children can learn these skills, but printing costs and curricula compatibility remain important barriers to school implementation. We aimed to develop a set of digital learning resources for students to think critically about health that were suitable for use in Kenyan, Rwandan, and Ugandan secondary schools.

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Background: Healthcare workers sometimes develop their own informal solutions to deliver services. One such solution is to use their personal mobile phones or other mobile devices in ways that are unregulated by their workplace. This can help them carry out their work when their workplace lacks functional formal communication and information systems, but it can also lead to new challenges.

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Persistence of the rebound-competent viral reservoir (RCVR) within the CD4+ T cell compartment of people living with HIV remains a major barrier to HIV cure. Here, we determined the effects of the pan-lymphocyte-depleting monoclonal antibody (mAb) alemtuzumab on the RCVR in SIVmac239-infected rhesus macaques (RM) receiving antiretroviral therapy (ART). Alemtuzumab administered during chronic ART or at the time of ART initiation induced >95% depletion of circulating CD4+ T cells in peripheral blood and substantial CD4+ T cell depletion in lymph nodes.

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Article Synopsis
  • Poverty-related diseases are a major cause of death in children under five in sub-Saharan Africa, highlighting the need for effective clinical practice guidelines (CPGs) to improve health outcomes.
  • The Global Evidence, Local Adaptation (GELA) project aims to enhance the development of CPGs by strengthening the capacity of researchers and decision-makers to utilize global research in Malawi, South Africa, and Nigeria over three years.
  • The project's monitoring and evaluation work package will assess the impact of various activities on local stakeholder engagement, capacity development, and the application of evidence in decision-making processes.
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Here, we present a protocol to evaluate the killing capacity and functional profile of human HIV-specific CD8 T cells. We describe steps for culturing peripheral blood mononuclear cells (PBMCs) from patients with HIV on antiretroviral therapy (ART) with HIV peptides ex vivo and quantifying HIV-specific CD8 T cell killing using flow cytometry. We then detail procedures for integrating the established killing assay with intracellular cytokine staining (ICS) and assessing CD8 T cell function.

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HIV persistence in the brain is a barrier to cure, and potentially contributes to HIV-associated neurocognitive disorders. Whether HIV transcription persists in the brain despite viral suppression with antiretroviral therapy (ART) and is subject to the same blocks to transcription seen in other tissues and blood, is unclear. Here, we quantified the level of HIV transcripts in frontal cortex tissue from virally suppressed or non-virally suppressed people with HIV (PWH).

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  • Platinum-sensitive ovarian cancer (PSOC) is commonly treated with platinum-based chemotherapy plus bevacizumab, but patients often face disease progression within a year, indicating a need for new treatment strategies.
  • Mirvetuximab soravtansine-gynx (MIRV), an antibody-drug conjugate targeting folate receptor alpha, has shown promising results when used with bevacizumab, particularly in patients with high levels of FRα.
  • The ongoing Phase III GLORIOSA trial aims to compare the effectiveness of MIRV plus bevacizumab against bevacizumab alone for patients with FRα-high PSOC after responding to previous treatment.
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Much anticipation surrounds artificial intelligence's (AI) emergence as a promising tool in health care. It offers potential to revolutionise clinical practice through assistive and autonomous operation. The high prevalence of cardiac disease globally provides an opportunity for AI technology to increase health care efficiency and improve patient outcomes.

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Background: Immunocompromised hosts (ICH) experience more breakthrough infections and worse clinical outcomes following infection with COVID-19 than immunocompetent people. Prophylactic monoclonal antibody therapies can be challenging to access, and escape variants emerge rapidly. Immunity conferred through vaccination remains a central prevention strategy for COVID-19.

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