David J Hunter

Newcastle University | NCL · Institute of Population Health Sciences

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have...

Importance A combination of conservative treatments is commonly used in clinical practice for thumb base osteoarthritis despite limited evidence for this approach. Objective To determine the efficacy of a 6-week combination of conservative treatments compared with an education comparator. Design, Setting, and Participants Randomized, parallel tri...

A Correction to this paper has been published: https://doi.org/10.1038/s41588-021-00786-2.

Objective Towards developing an instrument to measure knee and hip osteoarthritis (KHOA) flare, the Outcome Measures in Rheumatology (OMERACT) Flares in OA Working Group first sought to identify and define relevant domains of flare in KHOA. Methods Guided by OMERACT Filter 2.1, candidate domains were identified from data generated in interviews, i...

Importance: Thigh muscle weakness is associated with knee discomfort and osteoarthritis disease progression. Little is known about the efficacy of high-intensity strength training in patients with knee osteoarthritis or whether it may worsen knee symptoms. Objective: To determine whether high-intensity strength training reduces knee pain and kne...

Objective: Aims were to assess 1.) whether odds for incident radiographic osteoarthritis (ROA) differ between men and women in regard to body mass index (BMI) and inflammatory magnetic resonance imaging (MRI) markers one and two years prior and 2.) whether presence of inflammation on MRI differs between normal-weight, and overweight/obese persons...

Objective The RADIANT study aimed to investigate the efficacy and safety of a complementary medicine supplement combination in people with hand osteoarthritis (HOA). Method This was an internet-based, double-blind, randomised, placebo-controlled trial. Participants aged over 40 years with symptomatic HOA with radiographic confirmation (Kellgren La...

Background: Symptomatic knee osteoarthritis (SKOA) is a chronic, disabling condition, requiring long-term pain management; over 800,000 SKOA patients in the USA use opioids chronically. We aim to characterize the societal economic burden of opioid use in this population. Methods: We used the Osteoarthritis Policy Model, a validated computer simu...

Objective To identify factors associated with hypertension control among treated middle-aged UK adults. Methods A cross-sectional population-based study including 99 468 previously diagnosed, treated hypertensives enrolled in the UK Biobank. Hypertension control was defined as systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm...

Background Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. Methods We carried out a genome-wide association study of urinary oestrone-3-glucur...

Background: It is not known if modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype. Methods: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer-specific) over 10 years. Cox regression was...

Background Population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and management in women with inherited pathogenic variants. Methods In a population-based case–control study, we performed sequencing using a custom multigene ampli...

Introduction Postsurgical rehabilitation is critical for optimal recovery in people undergoing orthopaedic surgery. Currently, knee and lumbar spine postsurgical care is not standardised, economically sustainable, nor based on quality evidence, contributing to substantial clinical variation, poor outcomes and increasing healthcare costs. This proto...

Objective To determine the optimal combination of imaging and biochemical biomarkers to predict knee osteoarthritis (OA) progression. Methods Nested case‐control study from the FNIH OA Biomarkers Consortium of participants with Kellgren‐Lawrence grade 1–3 and complete biomarker data (n=539 to 550). Cases were knees with radiographic and pain progr...

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringi...

Objective: To study the longitudinal performance of fully automated cartilage segmentation in knees with radiographic osteoarthritis (ROA). We evaluate the sensitivity to change in progressor knees from the Foundation National Institutes of Health OA Biomarkers Consortium between the automated and previously reported manual expert segmentation, and...

Objective Duloxetine is an FDA‐approved treatment for both osteoarthritis (OA) pain and depression, but uptake of duloxetine in knee OA management varies. We examined the cost‐effectiveness of adding duloxetine to knee OA care with or without depression screening. Methods We used the Osteoarthritis Policy Model, a validated computer microsimulatio...

Introduction The infrapatellar fat pad (IPFP) is commonly resected during total knee arthroplasty (TKA) for better exposure. However, our previous studies have suggested that IPFP size was protective against, while IPFP signal intensity alteration was detrimental on knee symptoms and structural abnormalities. We hypothesise that an IPFP with normal...

Objectives: To evaluate the association between psychological factors and pain exacerbations in people with hip OA. Methods: Eligible participants with symptomatic hip OA were instructed to complete online questionnaires every 10 days over a 90-day follow-up period. In addition, they were required to complete the questionnaire whenever they perc...

The association between proximal tibiofibular joint (PTFJ) and knee OA has been understudied. The objective of this study was to determine whether the morphology of PTFJ has predictive value for the risk of total knee replacement (TKR). Case knees from Osteoarthritis Initiative participants with TKR at 24-60 months follow up (cases) were 1:1 matche...

Background: Osteoarthritis (OA) is a common chronic disease in older adults. Currently, there are no effective therapies to reduce disease severity and progression of knee OA (KOA), particularly in mid- to late-stages. This study aims to examine the effect of methotrexate (MTX) on knee effusion-synovitis and pain in symptomatic patients with mid-...

Background: Osteoarthritis (OA) is one of the most common chronic joint diseases and a leading cause of pain and disability in Australia. A National Osteoarthritis Strategy (the Strategy) was developed to outline a national plan to achieve optimal health outcomes for people at risk of, or with, OA. Objective: This article focuses on the theme of...

Introduction Due to the complex shape of the carpometacarpal (CMC) joint, a fixed joint collapse deformity of the thumb CMC (CMC1) and metacarpophalangeal (MCP1) joint can present in the advanced stages of CMC1 osteoarthritis (OA), resulting in adduction of the first metacarpal (MC) and hyperextension of the MCP1. The aim of this study was to deter...

In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study...

The etiology of osteoarthritis (OA) pain exacerbations is not well understood. The purpose of this study is to evaluate the association of heel height and duration of wearing shoes with higher heels with pain exacerbations in people with hip OA. Eligible participants with symptomatic hip OA were instructed to complete online questionnaires every 10...

The COVID-19 epidemic can probably be ended and normal life restored, perhaps quite quickly, by weekly SARS-CoV-2 RNA testing together with household quarantine and systematic contact tracing. Isolated outbreaks could then be contained by contact tracing, supplemented if necessary by temporary local reintroduction of population testing or lockdown....

Introduction: Hypertension is a leading risk factor for cardiovascular mortality and an emerging public health concern in sub-Saharan Africa. Few studies have examined performance on the management of hypertension in this region, where the context may be distinct from other developing regions. Objectives: We aimed to determine the prevalence and...

We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72,284 cases and 80,354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression, and a newly developed case-only method, fo...

Osteoarthritis is the most prevalent joint condition that continues to increase with an ever-aging population and the rising tide of obesity. There are multiple recommendations/guidelines for the management of osteoarthritis. The basis of management should focus on self-management and education, lifestyle modifications, exercise and when appropriat...

Background: Folate deficiency decreases thymidylate synthesis from deoxyuridylate, which results in an imbalance of deoxyribo-nucleotide that may lead to excessive uracil misincorporation (UrMis) into DNA during replication and repair. Objective: We evaluated the relation between UrMis in different tissues and the effect of folate supplementation o...

Objective To assess whether quantitative changes in the meniscus predict progression from early knee osteoarthritis (KOA) to knee replacement (KR). Methods A nested case‐control study was conducted among Osteoarthritis Initiative participants: All 35 case knees with baseline Kellgren‐Lawrence‐Grade (KLG) ≤2 that had KR between 36‐60 months were ma...

Purpose: Following publication of a new vision for the English National Health Service (NHS) in 2014, known as the NHS Five-Year Forward View, a Vanguard programme was introduced by NHS England charged with the task of designing and delivering a range of new care models (NCMs) aimed at tackling deep-seated problems of a type facing all health syst...

Objective Physical activity (PA) in the US knee osteoarthritis (OA) population is low, despite well-established health benefits. PA program implementation is often stymied by sustainability concerns. We sought to establish parameters that would make a short-term (three-year efficacy) PA program a cost-effective component of long-term OA care. Meth...

Objective To investigate whether baseline cartilage thickness and its longitudinal change are associated with incident widespread full-thickness cartilage loss (wsFTCL) in knee osteoarthritis, and whether there are optimal cut-off values for predicting wsFTCL. Methods Central medial tibial (cMT) and femoral (cMF) cartilage were assessed using quan...

Introduction: Symptomatic osteoarthritis (OA) in the knee is defined as the presence of OA radiographic features in combination with knee symptoms. Pain has not been shown to correlate meaningfully to radiographic severity. We aimed to determine the relationship between a tear of the anterior cruciate ligament (ACL) with knee symptoms and radiogra...

Introduction: Osteoarthritis (OA) is the leading cause of pain, loss of function and disability in the elderly, with the knee being the most impactful joint affected. Currently, there is still no ‘cure’ in OA treatment. Areas covered: The authors review the current and emerging therapies for knee OA including traditional OA medications (oral and to...

Objective: To evaluate the effects of the updated version of an evidence-based osteoarthritis (OA) resource and consumer hub, 'My Joint Pain' website, on health education and quality of care over 12 months. Methods: Using a classic quasi-experimental design, participants with symptomatic hip or knee OA were recruited across Australia to evaluate...

Introduction This protocol outlines the rationale, design and methods for the process and feasibility evaluations of the primary care management on knee pain and function in patients with knee osteoarthritis (PARTNER) study. PARTNER is a randomised controlled trial to evaluate a new model of service delivery (the PARTNER model) against ‘usual care’...

Objective: To determine if qualitative and quantitative measures of prefemoral fat pad (PFP) and quadriceps fat pad (QFP) are associated with incident radiographic osteoarthritis (iROA) over 4 years in the Osteoarthritis Initiative (OAI) study. Design: Participants in this nested case-control study were selected from the OAI study with knees tha...

p>Genome-wide association studies (GWAS) for late stage age-related macular degeneration (AMD) have identified 52 independent genetic variants with genome-wide significance at 34 genomic loci. Typically, such an approach rarely results in the identification of functional variants implicating a defined gene in the disease process. We now performed a...

Objective: To test the effectiveness of a 32-week stepped-care intervention on disease remission rates in overweight and obese people with medial tibiofemoral osteoarthritis (OA) compared to control. Methods: In this randomised controlled trial, eligible participants were ≥50 years-old with a body mass index ≥28 kg/m2 and radiographic evidence o...

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457...

This chapter derives lessons about reform in the UK’s National Health Service through the development of the Vanguard new care models programme. These new models of care proposed changes that are not concerned solely with structures or top-down reform edicts but are seeking new ways of working and joining up care across a whole system driven by tho...

Background: Conventional epidemiologic studies have evaluated associations between circulating lipid levels and breast cancer risk, but results have been inconsistent. As Mendelian randomization analyses may provide evidence for causal inference, we sought to evaluate potentially unbiased associations between breast cancer risk and four geneticall...

Objective: Develop a generic trans-disciplinary, skills-based capability framework for health professionals providing care for people with OA. Design: e-Delphi survey. An international inter-professional Delphi Panel (researchers; clinicians; consumer representatives) considered a draft framework (adapted from elsewhere) of 131 specific capabili...

Osteoarthritis (OA) is a disease of an entire synovial joint characterized by clinical symptoms and distortion of joint tissues including cartilage, muscles, ligaments, and bone. Although OA is a disease of all joint tissues, it is a defined accessible compartment and is thus amenable to topical surgical and regenerative therapies, including stem c...

Background & aims: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk var...

Background: Alcohol intake may be associated with a lower risk of Parkinson's disease (PD), but findings from previous studies have been inconclusive. Objective: To determine the association between alcohol intake and PD risk in the Million Women Study, a large, prospective study of women in the UK. Methods: Between 1996 and 2001, approximatel...

Objective To examine the interaction between APOE genotypes and both treated and untreated hypertension on cognitive function in an updated analysis of Nurses’ Health Study (NHS) data. Design At baseline (1995–2001) and 3 biennial follow-up assessments over ~6 years, cognitive function was assessed. Setting and participants 8300 NHS participants...

Background: To evaluate the effectiveness and safety of technology-assisted rehabilitation following total hip/knee replacement (THR/TKR). Methods: Six electronic databases were searched without language or time restrictions for relevant studies: MEDLINE, EMBASE, Cochrane Library, CINAHL, SPORTDiscus, Physiotherapy Evidence Database (PEDro); fro...

Objective To examine lessons learnt from the implementation of five Vanguard initiatives in the North East of England. Design Data collection comprised semistructured interviews with key informants at each site. Setting The study took place across six local authority areas in the North East of England and within six clinical commissioning groups...

Objective: To determine whether the morphology of proximal tibiofibular joint (PTFJ) is associated with increased risk of incident radiographic osteoarthritis (iROA) over 4 years in the OA Initiative (OAI) study. Methods: A nested matched case-control study design was used to select participants from OAI study. Case knees were defined as those w...

Objective: To determine the feasibility of a clinical trial comparing a podiatry intervention to usual general practitioner (GP) care for people with first metatarsophalangeal (MTP) joint osteoarthritis (OA). Methods: A two-arm, participant- and assessor-blinded, randomised feasibility study was conducted over 12-weeks. Participants were aged ov...

Objective: Diet and exercise (D+E) for knee osteoarthritis (OA) is effective and cost-effective. However, cost-effectiveness does not imply affordability; the impact of knee OA-specific D+E programs on insurer budgets is unknown. Methods: We estimated changes in undiscounted medical expenditures (2016 US dollars) with and without a D+E program....

Objectives: Dietary supplements are increasingly used by people with osteoarthritis. Boswellia serrata extract, curcumin, pine bark extract and methylsulfonylmethane have been identified as having the largest effects for symptomatic relief in a systematic review. It is important to understand whether any pharmacokinetic interactions are among the...

The Intensive Diet and Exercise for Arthritis (IDEA) trial was an 18-month randomized controlled trial that enrolled 454 overweight and obese older adults with symptomatic and radiographic knee osteoarthritis (OA). Participants were randomized to either exercise (E), intensive diet-induced weight loss (D), or intensive diet-induced weight loss plus...

Purpose: Our aim was to introduce a simplified MRI instrument, Rapid OsteoArthritis MRI Eligibility Score (ROAMES), for defining structural eligibility of patients for inclusion in disease-modifying osteoarthritis drug trials using a tri-compartmental anatomic approach that enables stratification of knees into different structural phenotypes and i...

Objectives The paper reports on an empirical study of Health and Wellbeing Boards (HWBs) in England. Established by the Health and Social Care Act 2012, HWBs act as place-based hubs for leaders in health, social care, local government and other sectors to come together to address health improvement and the wider determinants of health. Methods We...

The Department of Health and Social Care (DHSC) wanted to know whether a support programme for local authorities to help implement the Care act 2014 had been helpful. We were also asked to provide general insights into how the Department could best support successful implementation of national policies. Our research examined the way central govern...

BACKGROUND Online support groups (OSGs) are one way for people with chronic diseases, their family or friends and health professionals to communicate, gain information and provide social support. As the number of OSGs grow, it is important to gain insight into the different designs of groups available, who is accessing them, if and how they may be...

Background Online support groups (OSGs) are one way for people with chronic diseases, their family or friends, and health professionals to communicate, gain information, and provide social support. As the number of peer-to-peer OSGs for chronic musculoskeletal conditions grows, it is important to gain insight into the different designs of groups av...

Objectives The recombinant zoster vaccine (RZV) containing a strong non-aluminium adjuvant is associated with increased risk of gout flares, presumably via NLRP3 inflammasome activation. We tested the possibility that other vaccines may also be associated with gout flares. Methods We conducted an online case-crossover study of patients with gout t...

Objective: Half of the 14 million persons in the US with knee osteoarthritis (OA) are not physically active, despite evidence that physical activity (PA) is associated with improved health. We estimated both the quality-adjusted life-year (QALY) losses in the US knee OA population due to physical inactivity and the health benefits associated with...

The classification and monitoring of individuals with early knee osteoarthritis (OA) are important considerations for the design and evaluation of therapeutic interventions and require the identification of appropriate outcome measures. Potential outcome domains to assess for early OA include patient-reported outcomes (such as pain, function and qu...