Humoral and cellular immune responses after 6 months of a heterologous SARS-CoV-2 booster with the protein-based PHH-1V vaccine in a phase IIb trial.

The HIPRA-HH-2 was a multicentre, randomized, active-controlled, double-blind, non-inferiority phase IIb clinical trial comparing the immunogenicity and safety of the PHH-1V adjuvanted recombinant vaccine as a heterologous booster against homologous booster with BNT162b2. Interim results demonstrated strong humoral and cellular immune response against the SARS-CoV-2 Wuhan-Hu-1 strain and the Beta, Delta, and Omicron BA.1 variants up to day 98 post-dosing.

Real-world effects of antidepressants for depressive disorder in primary care: population-based cohort study.

Background: Antidepressants' effects are established in randomised controlled trials (RCTs), but not in the real world.

Aims: To investigate real-world comparative effects of antidepressants for depression and compare them with RCTs.

Method: We performed a cohort study based on the QResearch database.

Identification of methodological issues regarding direct impact indicators of COVID-19: a rapid scoping review on morbidity, severity and mortality.

Background: During the first epidemic wave, COVID-19 surveillance focused on quantifying the magnitude and the escalation of a growing global health crisis. The scientific community first assessed risk through basic indicators, such as the number of cases or rates of new cases and deaths, and later began using other direct impact indicators to conduct more detailed analyses. We aimed at synthesizing the scientific community's contribution to assessing the direct impact of the COVID-19 pandemic on population health through indicators reported in research papers.

Safety and immunogenicity of a recombinant protein RBD fusion heterodimer vaccine against SARS-CoV-2.

In response to COVID-19 pandemic, we have launched a vaccine development program against SARS-CoV-2. Here we report the safety, tolerability, and immunogenicity of a recombinant protein RBD fusion heterodimeric vaccine against SARS-CoV-2 (PHH-1V) evaluated in a phase 1-2a dose-escalation, randomized clinical trial conducted in Catalonia, Spain. 30 young healthy adults were enrolled and received two intramuscular doses, 21 days apart of PHH-1V vaccine formulations [10 µg (n = 5), 20 µg (n = 10), 40 µg (n = 10)] or control [BNT162b2 (n = 5)].

Preclinical evaluation of PHH-1V vaccine candidate against SARS-CoV-2 in non-human primates.

SARS-CoV-2 emerged in December 2019 and quickly spread worldwide, continuously striking with an unpredictable evolution. Despite the success in vaccine production and mass vaccination programs, the situation is not still completely controlled, and therefore accessible second-generation vaccines are required to mitigate the pandemic. We previously developed an adjuvanted vaccine candidate coded PHH-1V, based on a heterodimer fusion protein comprising the RBD domain of two SARS-CoV-2 variants.

Immunogenicity and safety in pigs of PHH-1V, a SARS-CoV-2 RBD fusion heterodimer vaccine candidate.

The continuing high global incidence of COVID-19 and the undervaccinated status of billions of persons strongly motivate the development of a new generation of efficacious vaccines. We have developed an adjuvanted vaccine candidate, PHH-1V, based on a protein comprising the receptor binding domain (RBD) of the Beta variant of SARS-CoV-2 fused in tandem with the equivalent domain of the Alpha variant, with its immunogenicity, safety and efficacy previously demonstrated in mouse models. In the present study, we immunized pigs with different doses of PHH-1V in a prime-and-boost scheme showing PHH-1V to exhibit an excellent safety profile in pigs and to produce a solid RBD-specific humoral response with neutralising antibodies to 7 distinct SARS-CoV-2 variants of concern, with the induction of a significant IFNγ T-cell response.

Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial.

Background: A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration.

Methods: The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine-either heterologous (PHH-1V group) or homologous (BNT162b2 group)-in 10 centres in Spain.

Factors influencing influenza, pneumococcal and shingles vaccine uptake and refusal in older adults: a population-based cross-sectional study in England.

Objectives: Uptake of influenza, pneumococcal and shingles vaccines in older adults vary across regions and socioeconomic backgrounds. In this study, we study the coverage and factors associated with vaccination uptake, as well as refusal in the unvaccinated population and their associations with ethnicity, deprivation, household size and health conditions.

Design, Setting And Participants: This is a cross-sectional study of adults aged 65 years or older in England, using a large primary care database.

Preclinical evaluation of a COVID-19 vaccine candidate based on a recombinant RBD fusion heterodimer of SARS-CoV-2.

Current COVID-19 vaccines have been associated with a decline in infection rates, prevention of severe disease, and a decrease in mortality rates. However, SARS-CoV-2 variants are continuously evolving, and development of new accessible COVID-19 vaccines is essential to mitigate the pandemic. Here, we present data on preclinical studies in mice of a receptor-binding domain (RBD)-based recombinant protein vaccine (PHH-1V) consisting of an RBD fusion heterodimer comprising the B.

Temporality of body mass index, blood tests, comorbidities and medication use as early markers for pancreatic ductal adenocarcinoma (PDAC): a nested case-control study.

Objective: Prior studies identified clinical factors associated with increased risk of pancreatic ductal adenocarcinoma (PDAC). However, little is known regarding their time-varying nature, which could inform earlier diagnosis. This study assessed temporality of body mass index (BMI), blood-based markers, comorbidities and medication use with PDAC risk .

UK poSt Arthroplasty Follow-up rEcommendations (UK SAFE): what does analysis of linked, routinely collected national data sets tell us about mid-late term revision risk after hip replacement? Retrospective cohort study.

Objective: To identify patients at risk of mid-late term revision of hip replacement to inform targeted follow-up.

Design: Analysis of linked national data sets from primary and secondary care (Clinical Practice Research Datalink (CPRD-GOLD); National Joint Registry (NJR); English Hospital Episode Statistics (HES); Patient-Reported Outcome Measures (PROMs)).

Participants: Primary elective total hip replacement (THR) aged≥18.

UK poSt Arthroplasty Follow-up rEcommendations (UK SAFE): what does analysis of linked, routinely collected national datasets tell us about mid-late term revision risk after knee replacement?

Objective: To identify patients at risk of mid-late term revision of knee replacement (KR) to inform targeted follow-up.

Design: Analysis of linked national datasets from primary and secondary care (Clinical Practice Research Datalink (CPRD GOLD), National Joint Registry (NJR), English Hospital Episode Statistics (HES) and Patient Reported Outcome Measures (PROMs)).

Participants: Primary elective KRs aged ≥18 years.

Lifestyle advice for hypertension or diabetes: trend analysis from 2002 to 2017 in England.

Background: Guidelines recommend that GPs give patients lifestyle advice to manage hypertension and diabetes. Increasing evidence shows that this is an effective and practical treatment for these conditions, but it is unclear whether GPs offer this support.

Aim: To investigate trends in the percentage of patients with hypertension/diabetes receiving lifestyle advice versus medication.

Risk factors associated with poor pain outcomes following primary knee replacement surgery: Analysis of data from the clinical practice research datalink, hospital episode statistics and patient reported outcomes as part of the STAR research programme.

Objective: Identify risk factors for poor pain outcomes six months after primary knee replacement surgery.

Methods: Observational cohort study on patients receiving primary knee replacement from the UK Clinical Practice Research Datalink, Hospital Episode Statistics and Patient Reported Outcomes. A wide range of variables routinely collected in primary and secondary care were identified as potential predictors of worsening or only minor improvement in pain, based on the Oxford Knee Score pain subscale.

Clinical and molecular associations with outcomes at 2 years after acute knee injury: a longitudinal study in the Knee Injury Cohort at the Kennedy (KICK).

Background: Joint injury is a major risk factor for osteoarthritis and provides an opportunity to prospectively examine early processes associated with osteoarthritis. We investigated whether predefined baseline demographic and clinical factors, and protein analytes in knee synovial fluid and in plasma or serum, were associated with clinically relevant outcomes at 2 years after knee injury.

Methods: This longitudinal cohort study recruited individuals aged 16-50 years between Nov 1, 2010, and Nov 28, 2014, across six hospitals and clinics in London, UK.

Association Between Race and COVID-19 Outcomes Among 2.6 Million Children in England.

Importance: Although children mainly experience mild COVID-19 disease, hospitalization rates are increasing, with limited understanding of underlying factors. There is an established association between race and severe COVID-19 outcomes in adults in England; however, whether a similar association exists in children is unclear.

Objective: To investigate the association between race and childhood COVID-19 testing and hospital outcomes.

NHS Health Checks: an observational study of equity and outcomes 2009-2017.

Background: The NHS Health Check cardiovascular prevention programme is now 10 years old.

Aim: To describe NHS Heath Check attendance, new diagnoses, and treatment in relation to equity indicators.

Design And Setting: A nationally representative database derived from 1500 general practices from 2009-2017.

Post-operative determinants of chronic pain after primary knee replacement surgery: Analysis of data on 258,386 patients from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man (NJR).

Objective: To identify post-operative risk factors for the development of chronic pain after knee replacement.

Design: Primary knee replacements in persons aged ≥18 years between April 2008 and December 2016 from the National Joint Registry, linked with English Hospital Episode Statistics data, and Patient Reported Outcome Measures. The outcome was chronic pain 6-months after surgery (Oxford Knee pain score).

NHS Health Checks for people with mental ill-health 2013-2017: an observational study.

Aims: People living with serious mental ill-health experience adverse cardiovascular outcomes causing some of the greatest health inequality gaps in England, UK. We describe uptake of the NHS Health Check programme in people with mental ill-health, and rates of new diagnoses and management of cardiovascular risk factors in those who attend NHS Health Checks in comparison to those people without mental ill-health.

Methods: We used a large nationally representative database of people registered with general practitioners in England (QResearch).

Occupation and risk of knee osteoarthritis and knee replacement: A longitudinal, multiple-cohort study.

Objectives: To examine the effect of occupation on knee osteoarthritis (OA) and total knee replacement (TKR) in working-aged adults.

Methods: We used longitudinal data from the Chingford, Osteoarthritis Initiative (OAI) and Multicentre Osteoarthritis (MOST) studies. Participants with musculoskeletal disorders and/or a history of knee-related surgery were excluded.

Costs of Joint Replacement in Osteoarthritis: A Study Using the National Joint Registry and Clinical Practice Research Datalink Data Sets.

Objective: To estimate the costs of primary hip and knee replacement in individuals with osteoarthritis up to 2 years postsurgery, compare costs before and after the surgery, and identify predictors of hospital costs.

Methods: Patients age ≥18 years with primary planned hip or knee replacements and osteoarthritis in England between 2008 and 2016 were identified from the National Joint Registry and linked with Hospital Episode Statistics data containing inpatient episodes. Primary care data linked with hospital outpatient records were also used to identify patients age ≥18 years with primary hip or knee replacements between 2008 and 2016.

Psychological distress in women and men living with HIV in Spain: a cross-sectional telephone survey.

Background: Psychological distress includes a broader range of experiences, varying from less severe symptoms of depression and anxiety to severe psychiatric disease. Global estimates for depression and anxiety in 2017 were 3.4% and 3.

Real-world effect of antidepressants for depressive disorder in primary care: protocol of a population-based cohort study.

Introduction: Clinical guidelines recommend antidepressants as the first line of treatment for adults with moderate-to-severe depression. Randomised trials provide the best evidence on the comparative effectiveness of antidepressants for depression, but are limited by a short follow-up and a highly selected population. We aim to conduct a cohort study on a large database to assess acceptability, efficacy, safety and tolerability of antidepressant monotherapy in people with depressive disorder in primary care.

Is Aspirin as Effective as the Newer Direct Oral Anticoagulants for Venous Thromboembolism Prophylaxis After Total Hip and Knee Arthroplasty? An Analysis From the National Joint Registry for England, Wales, Northern Ireland, and the Isle of Man.

Background: Few studies have compared aspirin with direct oral anticoagulants (DOACs) (DOACs = direct thrombin inhibitors and factor Xa inhibitors) for venous thromboembolism (VTE) prophylaxis after total hip arthroplasty (THA) and total knee arthroplasty (TKA). We assessed the efficacy and safety of aspirin compared with DOACs for VTE prophylaxis after THA and TKA using the world's largest joint arthroplasty registry.

Methods: We studied the National Joint Registry linked to English hospital inpatient episodes for 218,650 THA and TKA patients.