Evidence-based decision-making in a climate of political expediency: insights from local government.

AIMS: Local authorities in England are responsible for public health and health promotion. This article sought to explore how research and decision-making co-exist in a local authority in England. METHODS: An Embedded Researcher was based within the local authority and used qualitative methodology to address the research aim. Interviews and focus groups were employed to ascertain a range of stakeholder views in the local authority. All transcripts were coded on NVivo 12 by the Embedded Researcher and two members of the research team cross-checked a sample for coding accuracy. Data were analysed using framework analysis. RESULTS: The data suggest several barriers to using research to inform decision-making in health promotion and public health. The study shows that research is valued in local authorities, but not always privileged - this is due to cultural factors and practical political reasons which often means that decisions need to be made expediently. Participants outlined a juxtaposition between academic credibility; timeliness to complete the research and the financial cost associated with it; against the independence and credibility that independent academics could bring. CONCLUSION: Policy formulation and delivery is an integral aspect of health promotion and critical to achieving improved population health and reductions in health inequalities. However, there exists tensions between gathering research evidence and making research-informed decisions. The article concludes by advocating the use of Embedded Researchers to fully understand how research is gathered and used to support public health and health promotion policymaking.

The epidemiology of tick infestation in dog breeds in the UK.

OBJECTIVES: The purpose of this study is to report the prevalence and risk factors for tick infestation in dogs in the UK based on anonymised electronic patient records. MATERIALS AND METHODS: Clinical records of dogs under veterinary care in 2016 at clinics participating in the VetCompass Programme were followed over a 5-year period to identify cases of tick infestation. Risk factor analysis used multivariable logistic regression modelling. RESULTS: The study included 905,553 dogs. From a random sample, 1903 tick infestation cases were identified. The estimated 5-year (2014 to 2018) period prevalence was 2.03% (95% confidence interval: 2.00 to 2.06). Sixteen breeds showed increased odds compared with non-designer-crossbreed dogs. Breeds with the highest odds included Cairn terrier (odds ratio 2.86, 95% confidence interval 1.64 to 4.98), standard poodle (odds ratio 2.80, 95% confidence interval 1.25 to 6.29) and Goldendoodle (odds ratio 2.63, 95% confidence interval 1.17 to 5.91). Six breeds showed reduced odds, with lowest odds shown by Staffordshire bull terrier (odds ratio 0.35, 95% confidence interval 0.25 to 0.50), Rottweiler (odds ratio 0.35, 95% confidence interval 0.15 to 0.85) and Chihuahua (odds ratio 0.38, 95% confidence interval 0.26 to 0.55). Males had 1.24 (95% confidence interval 1.13 to 1.36) times the odds of females. Compared with non-designer-crossbred dogs, designer-crossbreed dogs had increased odds (odds ratio 1.81, 95% confidence interval 1.52 to 2.15). Compared with breeds with short coats, breeds with medium length coats (odds ratio 2.20, 95% confidence interval 1.96 to 2.48) showed increased odds. Breeds with V-shaped drop and pendulous ear carriage had higher odds compared with breeds with erect ear carriage. CLINICAL SIGNIFICANCE: These findings provide an evidence base for veterinary professionals to raise awareness of tick infestation as a preventable disorder in dogs in the UK and to support more effective prevention and therapeutic protocols based on targeted approaches.

High bone mass and cam morphology are independently related to hip osteoarthritis: findings from the High Bone Mass cohort.

BACKGROUND: High bone mass (HBM, BMD Z-score ≥ + 3.2) and cam morphology (bulging of lateral femoral head) are associated with greater odds of prevalent radiographic hip osteoarthritis (rHOA). As cam morphology is itself a manifestation of increased bone deposition around the femoral head, it is conceivable that cam morphology may mediate the relationship between HBM and rHOA. We therefore aimed to determine if individuals with HBM have increased odds of prevalent cam morphology. In addition, we investigated whether the relationship between cam and prevalent and incident osteoarthritis was preserved in a HBM population. METHODS: In the HBM study, a UK based cohort of adults with unexplained HBM and their relatives and spouses (controls), we determined the presence of cam morphology using semi-automatic methods of alpha angle derivation from pelvic radiographs. Associations between HBM status and presence of cam morphology, and between cam morphology and presence of rHOA (or its subphenotypes: osteophytes, joint space narrowing, cysts, and subchondral sclerosis) were determined using multivariable logistic regression, adjusting for age, sex, height, weight, and adolescent physical activity levels. The association between cam at baseline and incidence of rHOA after an average of 8 years was determined. Generalised estimating equations accounted for individual-level clustering. RESULTS: The study included 352 individuals, of whom 235 (66.7%) were female and 234 (66.5%) had HBM. Included individuals contributed 694 hips, of which 143 had a cam deformity (20.6%). There was no evidence of an association between HBM and cam morphology (OR = 0.97 [95% CI: 0.63-1.51], p = 0.90) but a strong relationship was observed between cam morphology and rHOA (OR = 3.96 [2.63-5.98], p = 5.46 × 10-11) and rHOA subphenotypes joint space narrowing (OR = 3.70 [2.48-5.54], p = 1.76 × 10-10), subchondral sclerosis (OR = 3.28 [1.60-6.60], p = 9.57 × 10-4) and osteophytes (OR = 3.01 [1.87-4.87], p = 6.37 × 10-6). Cam morphology was not associated with incident osteoarthritis (OR = 0.76 [0.16-3.49], p = 0.72). CONCLUSIONS: The relationship between cam morphology and rHOA seen in other studies is preserved in a HBM population. This study suggests that the risk of OA conferred by high BMD and by cam morphology are mediated via distinct pathways.

Machine learning outperforms clinical experts in classification of hip fractures.

Hip fractures are a major cause of morbidity and mortality in the elderly, and incur high health and social care costs. Given projected population ageing, the number of incident hip fractures is predicted to increase globally. As fracture classification strongly determines the chosen surgical treatment, differences in fracture classification influence patient outcomes and treatment costs. We aimed to create a machine learning method for identifying and classifying hip fractures, and to compare its performance to experienced human observers. We used 3659 hip radiographs, classified by at least two expert clinicians. The machine learning method was able to classify hip fractures with 19% greater accuracy than humans, achieving overall accuracy of 92%.

Improvement in Dysphagia Outcomes Following Clinical Target Volume Reduction in the De-ESCALaTE Study.

AIMS: The De-ESCALaTE study showed an overall survival advantage for the administration of synchronous cisplatin chemotherapy with radiotherapy in low-risk oropharyngeal cancer when compared with synchronous cetuximab. During the trial, a radiotherapy quality assurance protocol amendment permitted centres to swap from the original radiotherapy contouring protocol (incorporating the whole oropharynx into the high-dose clinical target volume (CTV); anatomical protocol) to a protocol that incorporated the gross tumour volume with a 10 mm margin into the CTV (volumetric protocol). The purpose of this study was to examine both toxicity and tumour control related to this protocol amendment. MATERIALS AND METHODS: Overall survival and recurrence at 2 years were used to compare tumour control in the two contouring cohorts. For toxicity, the cohorts were compared by both the number of severe (grades 3-5) and all grades acute and late toxicities. In addition, quality of life and swallowing were compared using EORTC-C30 and MD Anderson Dysphagia Inventory, respectively. RESULTS: Of 327 patients included in this study, 185 were contoured according to the anatomical protocol and 142 by the volumetric protocol. The two cohorts were well balanced, with the exception of significantly more patients in the anatomical cohort undergoing prophylactic feeding tube insertion (P < 0.001). With a minimum of 2 years of follow-up there was no significant difference in overall survival or recurrence between the two contouring protocols. Similarly, there was no significant difference in the rate of reported severe or all grades acute or late toxicity and no sustained significant difference in quality of life. However, there was a significant difference in favour of volumetric contouring in several domains of the MD Anderson Dysphagia Inventory questionnaire at 1 year, which persisted to 2 years in the dysphagia functional (P = 0.002), dysphagia physical (P = 0.009) and dysphagia overall function (P = 0.008) domains. CONCLUSION: In the context of the unplanned post-hoc analysis of a randomised trial, measurable improvement in long-term dysphagia has been shown following a reduction in the CTV. Further reductions in the CTV should be subject to similar scrutiny within the confines of a prospective study.

Socio-economic inequalities in fragility fracture incidence: a systematic review and meta-analysis of 61 observational studies.

Individuals with low socio-economic status (SES) have a more than 25% higher risk of fragility fractures than individuals with high SES. Body mass index and lifestyle appear to mediate the effect of SES on fracture risk. Strategies to prevent fractures should aim to reduce unhealthy behaviours through tackling structural inequalities. INTRODUCTION: This systematic review and meta-analysis aimed to evaluate the impact of socio-economic status (SES) on fragility fracture risk. METHODS: Medline, Embase, and CINAHL databases were searched from inception to 28 April 2021 for studies reporting an association between SES and fragility fracture risk among individuals aged ≥50 years. Risk ratios (RR) were combined in meta-analyses using random restricted maximum likelihood models, for individual-based (education, income, occupation, cohabitation) and area-based (Index of Multiple Deprivation, area income) SES measures. RESULTS: A total of 61 studies from 26 different countries including more than 19 million individuals were included. Individual-based low SES was associated with an increased risk of fragility fracture (RR 1.27 [95% CI 1.12, 1.44]), whilst no clear association was seen when area-based measures were used (RR 1.08 [0.91, 1.30]). The strength of associations was influenced by the type and number of covariates included in statistical models: RR 2.69 [1.60, 4.53] for individual-based studies adjusting for age, sex and BMI, compared with RR 1.06 [0.92, 1.22] when also adjusted for health behaviours (smoking, alcohol, and physical activity). Overall, the quality of the evidence was moderate. CONCLUSION: Our results show that low SES, measured at the individual level, is a risk factor for fragility fracture. Low BMI and unhealthy behaviours are important mediators of the effect of SES on fracture risk. Strategies to prevent fractures and reduce unhealthy behaviours should aim to tackle structural inequalities in society thereby reducing health inequalities in fragility fracture incidence.

Osteoarthritis: Insights Offered by the Study of Bone Mass Genetics.

PURPOSE OF REVIEW: This paper reviews how bone genetics has contributed to our understanding of the pathogenesis of osteoarthritis. As well as identifying specific genetic mechanisms involved in osteoporosis which also contribute to osteoarthritis, we review whether bone mineral density (BMD) plays a causal role in OA development. RECENT FINDINGS: We examined whether those genetically predisposed to elevated BMD are at increased risk of developing OA, using our high bone mass (HBM) cohort. HBM individuals were found to have a greater prevalence of OA compared with family controls and greater development of radiographic features of OA over 8 years, with predominantly osteophytic OA. Initial Mendelian randomisation analysis provided additional support for a causal effect of increased BMD on increased OA risk. In contrast, more recent investigation estimates this relationship to be bi-directional. However, both these findings could be explained instead by shared biological pathways. Pathways which contribute to BMD appear to play an important role in OA development, likely reflecting shared common mechanisms as opposed to a causal effect of raised BMD on OA. Studies in HBM individuals suggest this reflects an important role of mechanisms involved in bone formation in OA development; however further work is required to establish whether the same applies to more common forms of OA within the general population.

Correction to: Lean mass and lower limb muscle function in relation to hip strength, geometry and fracture risk indices in community-dwelling older women.

The original version of this article, published on 14 December 2018, unfortunately contained a mistake.

Individuals with high bone mass have increased progression of radiographic and clinical features of knee osteoarthritis.

OBJECTIVE: High bone mass (HBM) is associated with an increased prevalence of radiographic knee OA (kOA), characterized by osteophytosis. We aimed to determine if progression of radiographic kOA, and its sub-phenotypes, is increased in HBM and whether observed changes are clinically relevant. DESIGN: A cohort with and without HBM (L1 and/or total hip bone mineral density Z-score≥+3.2) had knee radiographs collected at baseline and 8-year follow-up. Sub-phenotypes were graded using the OARSI atlas. Medial/lateral tibial/femoral osteophyte and medial/lateral joint space narrowing (JSN) grades were summed and Δosteophytes, ΔJSN derived. Pain, function and stiffness were quantified using the WOMAC questionnaire. Associations between HBM status and sub-phenotype progression were determined using multivariable linear/poisson regression, adjusting for age, sex, height, baseline sub-phenotype grade, menopause, education and total body fat mass (TBFM). Generalized estimating equations accounted for individual-level clustering. RESULTS: 169 individuals had repeated radiographs, providing 330 knee images; 63% had HBM, 73% were female, mean (SD) age was 58 (12) years. Whilst HBM was not clearly associated with overall Kellgren-Lawrence measured progression (RR = 1.55 [0.56.4.32]), HBM was positively associated with both Δosteophytes and ΔJSN individually (adjusted mean differences between individuals with and without HBM 0.45 [0.01.0.89] and 0.15 [0.01.0.29], respectively). HBM individuals had higher WOMAC knee pain scores (ß = 7.42 [1.17.13.66]), largely explained by adjustment for osteophyte score (58% attenuated) rather than JSN (30% attenuated) or TBFM (16% attenuated). The same pattern was observed for symptomatic stiffness and functional limitation. CONCLUSIONS: HBM is associated with osteophyte progression, which appears to contribute to increased reported pain, stiffness and functional loss.

Evaluation of Response to Stereotactic Radiosurgery in Brain Metastases Using Multiparametric Magnetic Resonance Imaging and a Review of the Literature.

AIMS: Following stereotactic radiosurgery (SRS), brain metastases initially increase in size in up to a third of cases, suggesting treatment failure. Current imaging using structural magnetic resonance imaging (MRI) cannot differentiate between tumour recurrence and SRS-induced changes, creating difficulties with patient management. Combining multiparametric MRI techniques, which assess tissue physiological and metabolic information, has shown promise in answering this clinical question. MATERIALS AND METHODS: Multiparametric MRI techniques, including spectroscopy, diffusion and perfusion imaging, were used for the differentiation of radiation-related changes and tumour recurrence after SRS for intracranial metastases in six cases. All patients presented with enlargement of the treated lesion, an increase in perilesional brain oedema and aggravation or appearance of neurological signs and symptoms from 7 to 29 weeks after primary treatment. RESULTS: Multiparametric imaging helped to differentiate features of tumour progression (n = 4) from radiation-related changes (n = 2). A low apparent diffusion coefficient (ADC) <1000 × 10-6 mm2/s, high relative cerebral blood volume (rCBV) ratio > 2.1, high choline:creatine (Cho:Cr) ratio > 1.8 suggested tumour recurrence. A high ADC > 1000 × 10-6 mm2/s, low rCBV ratio < 2.1, Cho:Cr ratio < 1.8 suggested SRS-induced radiation changes. Multiparametric MRI diagnosis was confirmed by histology or radiological and clinical follow-up. CONCLUSION: Multiparametric MRI was helpful in the early identification of radiation-related changes and tumour recurrence and may be useful for monitoring treatment changes in intracranial neoplasms after SRS treatment.

Lean mass and lower limb muscle function in relation to hip strength, geometry and fracture risk indices in community-dwelling older women.

In a population-based sample of British women aged over 70 years old, lean mass and peak lower limb muscle force were both independently associated with hip strength and fracture risk indices, thereby suggesting a potential benefit of promoting leg muscle strengthening exercise for the prevention of hip fractures in postmenopausal women. INTRODUCTION: To investigate cross-sectional associations of lean mass and physical performance, including lower limb muscle function, with hip strength, geometry and fracture risk indices (FRIs) in postmenopausal women. METHODS: Data were from the Cohort of Skeletal Health in Bristol and Avon. Total hip (TH) and femoral neck (FN) bone mineral density (BMD), hip geometry and total body lean mass (TBLM) were assessed by dual x-ray absorptiometry (DXA). Finite element analysis of hip DXA was used to derive FN, intertrochanteric and subtrochanteric FRIs. Grip strength, gait speed and chair rise time were measured objectively. Lower limb peak muscle force and muscle power were assessed by jumping mechanography. RESULTS: In total, 241 women were included (age = 76.4; SD = 2.6 years). After adjustment for age, height, weight/fat mass and comorbidities, TBLM was positively associated with hip BMD (ßTH BMD = 0.36, P ≤ 0.001; ßFN BMD = 0.26, P = 0.01) and cross-section moment of inertia (0.24, P ≤ 0.001) and inversely associated with FN FRI (- 0.21, P = 0.03) and intertrochanteric FRI (- 0.11, P = 0.05) (estimates represent SD difference in bone measures per SD difference in TBLM). Lower limb peak muscle force was positively associated with hip BMD (ßTH BMD = 0.28, P ≤ 0.001; ßFN BMD = 0.23, P = 0.008) and inversely associated with FN FRI (- 0.17, P = 0.04) and subtrochanteric FRI (- 0.18, P = 0.04). Associations of grip strength, gait speed, chair rise time and peak muscle power with hip parameters were close to the null. CONCLUSIONS: Lean mass and lower limb peak muscle force were associated with hip BMD and geometrical FRIs in postmenopausal women. Leg muscle strengthening exercises may therefore help prevent hip fractures in older women.

Dexamethasone-related adrenal insufficiency in patients with brain and skull base tumours.

PURPOSE: This study aimed to evaluate the prevalence of glucocorticoid-induced adrenal insufficiency in a cohort of patients with brain and skull base tumours and to identify factors which may predict its occurrence. METHODS: Patients with brain or skull base tumours attending for a short synacthen test (SST) (adrenocorticotropin hormone (ACTH) stimulation test) at a single institution over a 3-year period were retrospectively identified. Baseline demographics and dexamethasone exposure were examined. Only patients with dexamethasone exposure were included in the final analysis looking at the primary end point of SST failure. Fisher's exact test, Student's t test, Mann-Whitney test and the Kendall's tau-b test were used to evaluate the influence of age, gender, diagnosis and mean pituitary radiation dose on the primary endpoint. Receiver operating characteristic (ROC) curves were generated to explore the impact of duration and total exposure to dexamethasone on likelihood of SST failure. RESULTS: Thirty-one of 51 patients with previous dexamethasone exposure failed their first SST (61%). No significant relationship was demonstrated between age, gender, diagnosis or mean pituitary radiation dose and SST failure. Duration of and total exposure to dexamethasone were significantly associated with SST failure (p = 0.001 and p = 0.007, respectively). ROC curves generated values of 78 days and 171 mg days to give a sensitivity of 94 and 97%, respectively, to detect SST failure. CONCLUSIONS: Duration of dexamethasone use and total exposure predict for adrenal insufficiency in patients with brain and skull base tumours. Values derived from this study may be useful to identify patients at higher risk of adrenal suppression who require empirical hydrocortisone pending formal testing of the hypothalamic-pituitary-adrenal axis.

Feasibility of Dose-escalated Hypofractionated Chemoradiation in Human Papilloma Virus-negative or Smoking-associated Oropharyngeal Cancer.

AIMS: Oropharyngeal squamous cell carcinoma (OPSCC) can be divided into favourable and poor prognostic groups by association with human papilloma virus (HPV) and smoking. This study prospectively investigated a dose-intensified schedule in poor/intermediate prognosis OPSCC. MATERIALS AND METHODS: Patients with p16/HPV-negative or p16-positive N2b OPSCC with a greater than 10 pack-year smoking history were eligible. Patients were planned to receive 64 Gy in 25 fractions with cisplatin. The primary end point was absence of grade 3 mucositis at 3 months. RESULTS: Fifteen patients were recruited over 14 months. All patients completed a minimum of 2 years of follow-up. All patients completed full-dose radiotherapy within a median treatment time of 32 days (31-35). Grade 3 mucositis was absent in all patients at 3 months. There was one grade 4 toxicity event due to cisplatin (hypokalaemia). Complete response rates at 3 months were 100% and 93% for local disease and lymph nodes, respectively. One patient developed metastatic disease and subsequently died. Overall survival at 2 years was 93% (95% confidence interval 61-99%). CONCLUSIONS: The schedule of 64 Gy in 25 fractions with concomitant chemotherapy is tolerable in patients with poor and intermediate prognosis OPSCC.

Implementing Head and Neck Contouring Peer Review without Pathway Delay: The On-demand Approach.

AIMS: Peer review of contour volume is a priority in the radiotherapy treatment quality assurance process for head and neck cancer. It is essential that incorporation of peer review activity does not introduce additional delays. An on-demand peer review process was piloted to assess the feasibility and efficiency of this approach, as compared with a historic scheduled weekly approach. MATERIALS AND METHODS: Between November 2016 and April 2017 four head and neck clinicians in one centre took part in an on-demand peer review process. Cases were of radical or adjuvant intent of any histology and submitted on a voluntary basis. The outcome of contour peer review would be one of unchanged (UC), unchanged with variation or discretion noted (UV), minor change (M) or significant change (S). The time difference between the completion of the on-demand peer review was compared with the time difference to a hypothetical next Monday or Tuesday weekly peer review meeting. The time taken to review each case was also documented in the latter period of the pilot project. RESULTS: In total, 62 cases underwent peer review. Peer review on-demand provided dosimetrists with an average of an extra two working days available per case to meet treatment start dates. The proportion of cases with outcomes UC, UV, M and S were 45%, 16%, 26% and 13%, respectively. The mean peer review time spent per case was 17 min (12 cases). The main reason for S was discrepancy in imaging interpretation (4/8 cases). A lower proportion of oropharyngeal cases were submitted and had S outcomes. A higher proportion of complex cases, e.g. sinonasal/nasopharynx location or previous downstaging chemotherapy had S outcomes. The distribution of S outcomes appears to be similar regardless of clinician experience. The level of peer review activity among individuals differed by workload and job timetable. CONCLUSION: On-demand peer review of the head and neck contour volume is feasible, reduces delay to the start of dosimetry planning and bypasses the logistical barriers of weekly meetings. An audit of participation will be required to ensure successful implementation.

Feasibility and acceptability of using jumping mechanography to detect early components of sarcopenia in community-dwelling older women.

OBJECTIVE: To determine the feasibility and acceptability of using peak power and force, measured by jumping mechanography (JM), to detect early age-related features of sarcopenia in older women. METHODS: Community-dwelling women aged 71-87 years were recruited into this cross-sectional study. Physical function tests comprised the short physical performance battery (SPPB), grip strength and, if SPPB score≥6, JM. JM measured peak weight-adjusted power and force from two-footed jumps and one-legged hops respectively. Questionnaires assessed acceptability. RESULTS: 463 women were recruited; 37(8%) with SPPB⟨6 were ineligible for JM. Of 426 remaining, 359(84%) were able to perform ≥1 valid two-footed jump, 300(70%) completed ≥1 valid one-legged hop. No adverse events occurred. Only 14% reported discomfort. Discomfort related to JM performance, with inverse associations with both power and force (p⟨0.01). Peak power and force respectively explained 8% and 10% of variance in SPPB score (13% combined); only peak power explained additional variance in grip strength (17%). CONCLUSIONS: Peak power and force explained a significant, but limited, proportion of variance in SPPB and grip strength. JM represents a safe and acceptable clinical tool for evaluating lower-limb muscle power and force in older women, detecting distinct components of muscle function, and possibly sarcopenia, compared to those evaluated by more established measures.

The Role of Positron Emission Tomography/Computed Tomography Imaging in Head and Neck Cancer after Radical Chemoradiotherapy: a Single Institution Experience.

AIMS: Positron emission tomography/computed tomography (PET/CT) is used to restage head and neck cancer 3 months after chemoradiotherapy. The purpose of this study was to determine the negative predictive value (NPV) of a scan reported as having no abnormal uptake and the positive predictive values (PPV) for different maximum standardised uptake value (SUVmax) thresholds. MATERIALS AND METHODS: Patients with squamous cell carcinoma of the oro-/hypopharynx/larynx (n = 206) were included. SUVmax and subsequent locoregional recurrence were documented. RESULTS: The median SUVmax was 11.2 (range 4-33)/4.6 (range 2-30), respectively, in patients with/without definite primary site recurrence (P = 0.004). The median SUVmax was 4.4 (range 2.6-15.6)/3.1 (range 2.1-4.6), respectively, in patients with/without definite nodal recurrence (P = 0.003). The NPV for a scan reported as having no abnormal uptake was 92%. The PPV for the SUVmax thresholds 4, 6 and 8, respectively, were 53, 65 and 92% (primary site) and 93, 100 and 100% (nodes). CONCLUSIONS: The NPV of PET/CT after chemoradiation is consistent with the literature and underlines the importance of PET/CT in restaging the primary site if salvage neck dissection is considered. The overall PPV of PET/CT remains low but is high for nodal SUVmax > 4. These data could be used to design risk-stratified follow-up schedules.