MAVMET trial: maraviroc and/or metformin for metabolic dysfunction associated fatty liver disease in adults with suppressed HIV.

Objective: Metabolic dysfunction associated fatty liver disease (MAFLD) is over-represented in people with HIV (PWH). Maraviroc (MVC) and/or metformin (MET) may reduce MAFLD by influencing inflammatory pathways and fatty acid metabolism.

Design: Open-label, 48-week randomized trial with a 2 x 2 factorial design.

Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.

Accelerating clinical development of a live attenuated vaccine against Paratyphi A (VASP): study protocol for an observer-participant-blind randomised control trial of a novel oral vaccine using a human challenge model of Paratyphi A infection in healthy adult volunteers.

Introduction: This is the first efficacy study of an oral live attenuated vaccine against Paratyphi A using a human challenge model of paratyphoid infection. . Paratyphi A is responsible for 3.

Malaria patient spectrum representation in therapeutic clinical trials of uncomplicated malaria: a scoping review of the literature.

Background: For the results of clinical trials to have external validity, the patients included in the study must be representative of the population presenting in the general clinical settings. A scoping literature review was performed to evaluate how the eligibility criteria used in anti-malarial efficacy and safety trials translate into patient selection.

Methods: A search of the WorldWide Antimalarial Resistance Network (WWARN) Clinical Trials Publication Library, MEDLINE, The Cochrane Library, and clinicaltrials.

Mucosal-Associated Invariant T cells exhibit distinct functional signatures associated with protection against typhoid fever.

We have previously demonstrated that Mucosal-Associated Invariant T (MAIT) cells secrete multiple cytokines after exposure to Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever in humans. However, whether cytokine secreting MAIT cells can enhance or attenuate the clinical severity of bacterial infections remain debatable.

Neurochemical abnormalities in chronic fatigue syndrome: a pilot magnetic resonance spectroscopy study at 7 Tesla.

Rationale: Chronic fatigue syndrome (CFS) is a common and burdensome illness with a poorly understood pathophysiology, though many of the characteristic symptoms are likely to be of brain origin. The use of high-field proton magnetic resonance spectroscopy (MRS) enables the detection of a range of brain neurochemicals relevant to aetiological processes that have been linked to CFS, for example, oxidative stress and mitochondrial dysfunction.

Methods: We studied 22 CFS patients and 13 healthy controls who underwent MRS scanning at 7 T with a voxel placed in the anterior cingulate cortex.

Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 in the UK: a substudy of two randomised controlled trials (COV001 and COV002).

Background: COVID-19 vaccine supply shortages are causing concerns about compromised immunity in some countries as the interval between the first and second dose becomes longer. Conversely, countries with no supply constraints are considering administering a third dose. We assessed the persistence of immunogenicity after a single dose of ChAdOx1 nCoV-19 (AZD1222), immunity after an extended interval (44-45 weeks) between the first and second dose, and response to a third dose as a booster given 28-38 weeks after the second dose.

Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial.

Background: A new variant of SARS-CoV-2, B.1.1.

Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials.

Background: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4-12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses.

Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge.

Background: The medium-term effects of Coronavirus disease (COVID-19) on organ health, exercise capacity, cognition, quality of life and mental health are poorly understood.

Methods: Fifty-eight COVID-19 patients post-hospital discharge and 30 age, sex, body mass index comorbidity-matched controls were enrolled for multiorgan (brain, lungs, heart, liver and kidneys) magnetic resonance imaging (MRI), spirometry, six-minute walk test, cardiopulmonary exercise test (CPET), quality of life, cognitive and mental health assessments.

Findings: At 2-3 months from disease-onset, 64% of patients experienced breathlessness and 55% reported fatigue.

T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has caused a global pandemic, and safe, effective vaccines are urgently needed. Strong, Th1-skewed T cell responses can drive protective humoral and cell-mediated immune responses and might reduce the potential for disease enhancement. Cytotoxic T cells clear virus-infected host cells and contribute to control of infection.

Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses.

More than 190 vaccines are currently in development to prevent infection by the novel severe acute respiratory syndrome coronavirus 2. Animal studies suggest that while neutralizing antibodies against the viral spike protein may correlate with protection, additional antibody functions may also be important in preventing infection. Previously, we reported early immunogenicity and safety outcomes of a viral vector coronavirus vaccine, ChAdOx1 nCoV-19 (AZD1222), in a single-blinded phase 1/2 randomized controlled trial of healthy adults aged 18-55 years ( NCT04324606 ).

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

Background: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials.

Methods: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa.

Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial.

Background: Older adults (aged ≥70 years) are at increased risk of severe disease and death if they develop COVID-19 and are therefore a priority for immunisation should an efficacious vaccine be developed. Immunogenicity of vaccines is often worse in older adults as a result of immunosenescence. We have reported the immunogenicity of a novel chimpanzee adenovirus-vectored vaccine, ChAdOx1 nCoV-19 (AZD1222), in young adults, and now describe the safety and immunogenicity of this vaccine in a wider range of participants, including adults aged 70 years and older.

Homologous and heterologous re-challenge with Salmonella Typhi and Salmonella Paratyphi A in a randomised controlled human infection model.

Enteric fever is a systemic infection caused by Salmonella Typhi or Paratyphi A. In many endemic areas, these serovars co-circulate and can cause multiple infection-episodes in childhood. Prior exposure is thought to confer partial, but incomplete, protection against subsequent attacks of enteric fever.

Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial.

Background: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2.

Methods: We did a phase 1/2, single-blind, randomised controlled trial in five trial sites in the UK of a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal conjugate vaccine (MenACWY) as control.

An evaluation of rectal artesunate for the pre-hospital management of severe malaria.

Introduction: Severe falciparum malaria stills accounts for around half a million childhood deaths per year in sub-Saharan Africa. Prompt treatment of sick children close to home starting with artesunate given rectally by appropriately trained people can be lifesaving.

Areas Covered: Rectal artesunate (RAS) has been developed for use in the WHO approved strategy of pre-referral intervention.

Treatment responses to Azithromycin and Ciprofloxacin in uncomplicated Salmonella Typhi infection: A comparison of Clinical and Microbiological Data from a Controlled Human Infection Model.

Background: The treatment of enteric fever is complicated by the emergence of antimicrobial resistant Salmonella Typhi. Azithromycin is commonly used for first-line treatment of uncomplicated enteric fever, but the response to treatment may be sub-optimal in some patient groups when compared with fluoroquinolones.

Methods: We performed an analysis of responses to treatment with azithromycin (500mg once-daily, 14 days) or ciprofloxacin (500mg twice-daily, 14 days) in healthy UK volunteers (18-60 years) enrolled into two Salmonella controlled human infection studies.

Comparison of an ordinal endpoint to time-to-event, longitudinal, and binary endpoints for use in evaluating treatments for severe influenza requiring hospitalization.

Background/aims: The Food and Drug Administration recommends research into developing well-defined and reliable endpoints to evaluate treatments for severe influenza requiring hospitalization. A novel 6-category ordinal endpoint of patient health status after 7 days that ranges from death to hospital discharge with resumption of normal activities is being used in a randomized placebo-controlled trial of intravenous immunoglobulin (IVIG) for severe influenza (FLU-IVIG). We compare the power of the ordinal endpoint under a proportional odds model to other types of endpoints as a function of various trial parameters.

Novel genetically-modified chimpanzee adenovirus and MVA-vectored respiratory syncytial virus vaccine safely boosts humoral and cellular immunity in healthy older adults.

Objectives: Respiratory syncytial virus (RSV) causes respiratory infection across the world, with infants and the elderly at particular risk of developing severe disease and death. The replication-defective chimpanzee adenovirus (PanAd3-RSV) and modified vaccinia virus Ankara (MVA-RSV) vaccines were shown to be safe and immunogenic in young healthy adults. Here we report an extension to this first-in-man vaccine trial to include healthy older adults aged 60-75 years.

Oral versus Intravenous Antibiotics for Bone and Joint Infection.

Background: The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication.

Methods: We enrolled adults who were being treated for bone or joint infection at 26 U.