The oral microbiome is associated with HPA axis response to a psychosocial stressor.

Intense psychosocial stress during early life has a detrimental effect on health-disease balance in later life. Simultaneously, despite its sensitivity to stress, the developing microbiome contributes to long-term health. Following stress exposure, HPA-axis activation regulates the "fight or flight" response with the release of glucose and cortisol.

Use of drugs for hyperlipidaemia and diabetes and risk of primary and secondary brain tumours: nested case-control studies using the UK Clinical Practice Research Datalink (CPRD).

Objectives: Previous studies have suggested that fibrates and glitazones may have a role in brain tumour prevention. We examined if there is support for these observations using primary care records from the UK Clinical Practice Research Datalink (CPRD).

Design: We conducted two nested case-control studies using primary and secondary brain tumours identified within CPRD between 2000 and 2016.

Systematic review and meta-analysis of the accuracy of McIsaac and Centor score in patients presenting to secondary care with pharyngitis.

Background: Centor and McIsaac scores are clinical prediction rules for diagnosing group A streptococcus (GAS) infection in patients with pharyngitis. Their recommended thresholds vary between guidelines.

Objectives: To estimate the sensitivity and specificity of the McIsaac and Centor scores to diagnose GAS pharyngitis and evaluate their impact on antibiotic prescribing at each threshold in patients presenting to secondary care.

Identifying the Optimum Strategy for Identifying Adults and Children With Celiac Disease: A Cost-Effectiveness and Value of Information Analysis.

Objectives: Celiac disease (CD) is thought to affect around 1% of people in the United Kingdom, but only approximately 30% are diagnosed. The aim of this work was to assess the cost-effectiveness of strategies for identifying adults and children with CD in terms of who to test and which tests to use.

Methods: A decision tree and Markov model were used to describe testing strategies and model long-term consequences of CD.

Implementing Germ Defence digital behaviour change intervention via all primary care practices in England to reduce respiratory infections during the COVID-19 pandemic: an efficient cluster randomised controlled trial using the OpenSAFELY platform.

Background: Germ Defence ( www.germdefence.org ) is an evidence-based interactive website that promotes behaviour change for infection control within households.

Variation in laboratory testing for patients with long-term conditions: a longitudinal cohort study in UK primary care.

Background: Use of laboratory testing has increased in the UK over the past few decades, with considerable geographical variation.

Aim: To evaluate what laboratory tests are used to monitor people with hypertension, type 2 (T2) diabetes, or chronic kidney disease (CKD) and assess variation in test use in UK primary care.

Design & Setting: Longitudinal cohort study of people registered with UK general practices between June 2013 and May 2018 and previously diagnosed with hypertension, T2 diabetes, or CKD.

Development and external validation of a clinical prediction model to aid coeliac disease diagnosis in primary care: An observational study.

Background: Coeliac disease (CD) affects approximately 1% of the population, although only a fraction of patients are diagnosed. Our objective was to develop diagnostic prediction models to help decide who should be offered testing for CD in primary care.

Methods: Logistic regression models were developed in Clinical Practice Research Datalink (CPRD) GOLD (between Sep 9, 1987 and Apr 4, 2021, n=107,075) and externally validated in CPRD Aurum (between Jan 1, 1995 and Jan 15, 2021, n=227,915), two UK primary care databases, using (and controlling for) 1:4 nested case-control designs.

Early-Life Adversity Leaves Its Imprint on the Oral Microbiome for More Than 20 Years and Is Associated with Long-Term Immune Changes.

The early-life microbiome (ELM) interacts with the psychosocial environment, in particular during early-life adversity (ELA), defining life-long health trajectories. The ELM also plays a significant role in the maturation of the immune system. We hypothesised that, in this context, the resilience of the oral microbiomes, despite being composed of diverse and distinct communities, allows them to retain an imprint of the early environment.

The accuracy of diagnostic indicators for coeliac disease: A systematic review and meta-analysis.

Background: The prevalence of coeliac disease (CD) is around 1%, but diagnosis is challenged by varied presentation and non-specific symptoms and signs. This study aimed to identify diagnostic indicators that may help identify patients at a higher risk of CD in whom further testing is warranted.

Methods: International guidance for systematic review methods were followed and the review was registered at PROSPERO (CRD42020170766).

Unbiased Screening Identifies Functional Differences in NK Cells After Early Life Psychosocial Stress.

Early Life Adversity (ELA) is closely associated with the risk for developing diseases later in life, such as autoimmune diseases, type-2 diabetes and cardiovascular diseases. In humans, early parental separation, physical and sexual abuse or low social-economic status during childhood are known to have great impact on brain development, in the hormonal system and immune responses. Maternal deprivation (MD) is the closest animal model available to the human situation.

Novel point-of-care biomarker combination tests to differentiate acute bacterial from viral respiratory tract infections to guide antibiotic prescribing: a systematic review.

Background: Acute respiratory tract infections (RTIs) are the most common reason to seek medical care, with many patients receiving inappropriate antibiotics. Novel testing approaches to identify aetiology at the point-of-care are required to accurately guide antibiotic treatment.

Objective: To assess the diagnostic accuracy of biomarker combinations to rapidly differentiate between acute bacterial or viral RTI aetiology.

Primary Care implementation of Germ Defence, a digital behaviour change intervention to improve household infection control during the COVID-19 pandemic: A structured summary of a study protocol for a randomised controlled trial.

Objectives: To examine the effectiveness of randomising dissemination of the Germ Defence behaviour change website via GP practices across England UK.

Trial Design: A two-arm (1:1 ratio) cluster randomised controlled trial implementing Germ Defence via GP practices compared with usual care.

Participants: Setting: All Primary care GP practices in England.

GP's perspectives on laboratory test use for monitoring long-term conditions: an audit of current testing practice.

Background: We have shown previously that current recommendations in UK guidelines for monitoring long-term conditions are largely based on expert opinion. Due to a lack of robust evidence on optimal monitoring strategies and testing intervals, the guidelines are unclear and incomplete. This uncertainty may underly variation in testing that has been observed across the UK between GP practices and regions.

Accuracy of potential diagnostic indicators for coeliac disease: a systematic review protocol.

Introduction: Coeliac disease (CD) is a systemic immune-mediated disorder triggered by gluten in genetically predisposed individuals. CD is diagnosed using a combination of serology tests and endoscopic biopsy of the small intestine. However, because of non-specific symptoms and heterogeneous clinical presentation, diagnosing CD is challenging.

What methods are being used to create an evidence base on the use of laboratory tests to monitor long-term conditions in primary care? A scoping review.

Background: Studies have shown unwarranted variation in test ordering among GP practices and regions, which may lead to patient harm and increased health care costs. There is currently no robust evidence base to inform guidelines on monitoring long-term conditions.

Objectives: To map the extent and nature of research that provides evidence on the use of laboratory tests to monitor long-term conditions in primary care, and to identify gaps in existing research.

Glucocorticoid receptor signaling in leukocytes after early life adversity.

Early life adversity (ELA) has been associated with inflammation and immunosenescence, as well as hyporeactivity of the HPA axis. Because the immune system and the HPA axis are tightly intertwined around the glucocorticoid receptor (GR), we examined peripheral GR functionality in the EpiPath cohort among participants who either had been exposed to ELA (separation from parents and/or institutionalization followed by adoption; n = 40) or had been reared by their biological parents (n = 72).Expression of the strict GR target genes FKBP5 and GILZ as well as total and 1F and 1H GR transcripts were similar between groups.

Comparison of Multiparametric Magnetic Resonance Imaging and Targeted Biopsy With Systematic Biopsy Alone for the Diagnosis of Prostate Cancer: A Systematic Review and Meta-analysis.

Importance: The current diagnostic pathway for patients with suspected prostate cancer (PCa) includes prostate biopsy. A large proportion of individuals who undergo biopsy have either no PCa or low-risk disease that does not require treatment. Unnecessary biopsies may potentially be avoided with prebiopsy imaging.

The utility of diagnostic selective nerve root blocks in the management of patients with lumbar radiculopathy: a systematic review.

Objective: Lumbar radiculopathy (LR) often manifests as pain in the lower back radiating into one leg (sciatica). Unsuccessful back surgery is associated with significant healthcare costs and risks to patients. This review aims to examine the diagnostic accuracy of selective nerve root blocks (SNRBs) to identify patients most likely to benefit from lumbar decompression surgery.

Blunted endocrine response to a combined physical-cognitive stressor in adults with early life adversity.

The negative health effects of early life adversity (ELA) continue long into adulthood. Changes in the physiological response to psychosocial stressors have been proposed to mediate this effect. However, many previous studies have come to contradicting conclusions as to whether ELA induces a long-term increase or decrease in stress reactivity.

Proinflammatory T Cell Status Associated with Early Life Adversity.

Early life adversity (ELA) has been associated with an increased risk for diseases in which the immune system plays a critical role. The ELA immune phenotype is characterized by inflammation, impaired cellular immunity, and immunosenescence. However, data on cell-specific immune effects are largely absent.

T Cell Immunosenescence after Early Life Adversity: Association with Cytomegalovirus Infection.

Early life adversity (ELA) increases the risk for multiple age-related diseases, such as diabetes type 2 and cardiovascular disease. As prevalence is high, ELA poses a major and global public health problem. Immunosenescence, or aging of the immune system, has been proposed to underlie the association between ELA and long-term health consequences.

The effects of early life adversity on the immune system.

Early life adversity (ELA) is associated with a higher risk for diseases in adulthood. Although the pathophysiological effects of ELA are varied, there may be a unifying role for the immune system in all of the long-term pathologies such as chronic inflammatory disorders (autoimmune diseases, allergy, and asthma). Recently, significant efforts have been made to elucidate the long-term effects ELA has on immune function, as well as the mechanisms underlying these immune changes.