James Mackay

The psychological consequences of offering mutation searching in the family for those at risk of hereditary breast and ovarian cancer--a pilot study.

Aim: To describe the short and longer‐term psychological consequences of waiting for the results of mutation searching (MS) amongst those at risk of hereditary breast and ovarian cancer (HBOC).

The psychological impact of a cancer family history questionnaire completed in general practice

Editor—On the basis of family history, it is possible to identify subjects at significantly increased genetic risk of breast or colorectal cancer.1 2 Evaluation of the benefits of screening these patients to facilitate early diagnosis and treatment forms the subject of continuing studies. For colorectal cancer, the benefits of colonoscopic surveillance have been reported,3 but for breast cancer more data are needed to confirm the value of mammographic screening.4 At present, patients with a significant family history who seek advice from their general practitioner are likely to be referred to a cancer genetics clinic and offered screening. If further research confirms the benefits of screening for patients at increased genetic risk, effective strategies for their ascertainment in primary care will be needed. One possible method is a postal family history questionnaire sent to the patient by their general practitioner. We report elsewhere on the effectiveness of this approach.5 An important issue is whether this method of ascertainment raises anxieties, particularly among the majority of patients who do not have a significant family history. The collection of cancer family history information constitutes a form of screening. There is a large body of evidence that health related screening can have unintended adverse effects, the most studied of which is raised anxiety, particularly among those found to be at an increased risk.6 As knowledge of the genetic component of common diseases increases,7 more patients may be asked to provide information about their family history. It is therefore timely to consider whether such a task may inadvertently raise general levels of anxiety or worries about the disease in question. To our knowledge, there have been no previous studies of the psychological consequences of screening using a postal questionnaire to obtain information about relatives affected by cancer. …

Subchondral bone in osteoarthritis: Association between MRI texture analysis and histomorphometry

OBJECTIVEnMagnetic resonance imaging (MRI) texture analysis is a method of analyzing subchondral bone alterations in osteoarthritis (OA). The objective of this study was to evaluate the association between MR texture analysis and ground-truth subchondral bone histomorphometry at the tibial plateau.nnnDESIGNnThe local research ethics committee approved the study. All subjects provided written, informed consent. This was a cross-sectional study carried out at our institution between February and August 2014. Ten participants aged 57-84 with knee OA scheduled for total knee arthroplasty (TKA) underwent pre-operative MRI of the symptomatic knee at 3T using a high spatial-resolution coronal T1 weighted sequence. Tibial plateau explants obtained at the time of TKA underwent histological preparation to allow calculation of bone volume fraction (BV.TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp) and trabecular number (Tb.N). Texture analysis was performed on the tibial subchondral bone of MRI images matched to the histological sections. Regression models were created to assess the association of texture analysis features with BV.TV, Tb.Th, Tb.Sp and Tb.N.nnnRESULTSnMRI texture features were significantly associated with BV.TV (R2xa0=xa00.76), Tb.Th (R2xa0=xa00.47), Tb.Sp (R2xa0=xa00.75) and Tb.N (R2xa0=xa00.60, all Pxa0<xa00.001). Simple gray-value histogram based texture features demonstrated the highest standardized regression coefficients for each model.nnnCONCLUSIONnMRI texture analysis features were significantly associated with ground-truth subchondral bone histomorphometry at the tibial plateau.

Systematic review and meta-analysis of the reliability and discriminative validity of cartilage compositional MRI in knee osteoarthritis

OBJECTIVEnTo assess reliability and discriminative validity of cartilage compositional magnetic resonance imaging (MRI) in knee osteoarthritis (OA).nnnDESIGNnThe study was carried out per PRISMA recommendations. We searched MEDLINE and EMBASE (1974 - present) for eligible studies. We performed qualitative synthesis of reliability data. Where data from at least two discrimination studies were available, we estimated pooled standardized mean difference (SMD) between subjects with and without OA. Discrimination analyses compared controls and subjects with mild OA (Kellgren-Lawrence (KL) grade 1-2), severe OA (KL grade 3-4) and OA not otherwise specified (NOS) where not possible to stratify. We assessed quality of the evidence using Quality Appraisal of Diagnostic Reliability (QAREL) and Quality Assessment of Diagnostic Accuracy (QUADAS-2) tools.nnnRESULTSnFifty-eight studies were included in the reliability analysis and 26 studies were included inxa0thexa0discrimination analysis, with data from a total of 2,007 knees. Intra-observer, inter-observer and test-retestxa0reliability of compositional techniques were excellent with most intraclass correlation coefficients >0.8 and coefficients of variation <10%. T1rho and T2 relaxometry were significant discriminators between subjects with mild OA and controls, and between subjects with OA (NOS) and controls (Pxa0<xa00.001). T1rho showed best discrimination for mild OA (SMD [95% CI]xa0=xa00.73 [0.40 to 1.06], Pxa0<xa00.001) and OA (NOS) (0.60 [0.41 to 0.80], Pxa0<xa00.001). Quality of evidence was moderate for both parts of the review.nnnCONCLUSIONSnCartilage compositional MRI techniques are reliable and, in the case of T1rho and T2 relaxometry, can discriminate between subjects with OA and controls.

A critical evaluation of the process of cancer genetic counselling: From research-based investigation to clinical diagnosis

The discovery of two genes that predispose individuals to breast cancer has led to great excitement in the scientific world, with enormous interest shown by the media and public. This has often led to misunderstandings about the benefits of these discoveries to individuals with a family history of breast cancer. The pathway to the clinic is often difficult and full of inconsistent explanations. This increases the anxiety experienced by patients and may raise their expectations. It is necessary to be cautious when explaining the application of these discoveries to patients in the clinical setting so that they are offered a balanced view of the realities of detecting faulty genes and of the preventative measures available. Ongoing support and access to health professionals are suggested as vital components of a clinical service, and ongoing evaluation of the advantages and disadvantages of cancer genetic counselling is warrented.

Effusion-synovitis and infrapatellar fat pad signal intensity alteration differentiate accelerated knee osteoarthritis

OBJECTIVESnTo determine whether greater effusion-synovitis volume and infrapatellar fat pad (IFP) signal intensity alteration differentiate incident accelerated knee OA (KOA) from a gradual onset of KOA or no KOA.nnnMETHODSnWe classified three sex-matched groups of participants in the Osteoarthritis Initiative who had a knee with no radiographic KOA at baseline (recruited 2004-06; Kellgren-Lawrence <2; n = 125/group): accelerated KOA: ⩾1 knee progressed to Kellgren-Lawrence grade ⩾3 within 48 months; common KOA: ⩾1 knee increased in radiographic scoring within 48 months; and no KOA: both knees had the same Kellgren-Lawrence grade at baseline and 48 months. The observation period included up to 2 years before and after when the group criteria were met. Two musculoskeletal radiologists reported presence of IFP signal intensity alteration and independent readers used a semi-automated method to segment effusion-synovitis volume. We used generalized linear mixed models with group and time as independent variables, as well as testing a group-by-time interaction.nnnRESULTSnStarting at 2 years before disease onset, adults who developed accelerated KOA had greater effusion-synovitis volume than their peers (accelerated KOA: 11.94 ± 0.90 cm3, KOA: 8.29 ± 1.19 cm3, no KOA: 8.14 ± 0.90 cm3) and have greater odds of having IFP signal intensity alteration than those with no KOA (odds ratio = 2.07, 95% CI = 1.14-3.78). Starting at 1 year prior to disease onset, those with accelerated KOA have greater than twice the odds of having IFP signal intensity alteration than those with common KOA.nnnCONCLUSIONnPeople with IFP signal intensity alteration and/or greater effusion-synovitis volume in the absence of radiographic KOA may be at high risk for accelerated KOA, which may be characterized by local inflammation.

Association of subchondral bone texture on magnetic resonance imaging with radiographic knee osteoarthritis progression: data from the Osteoarthritis Initiative Bone Ancillary Study.

ObjectivesTo assess whether initial or 12–18-month change in magnetic resonance imaging (MRI) subchondral bone texture is predictive of radiographic knee osteoarthritis (OA) progression over 36 months.MethodsThis was a nested case-control study including 122 knees/122 participants in the Osteoarthritis Initiative (OAI) Bone Ancillary Study, who underwent MRI optimised for subchondral bone assessment at either the 30- or 36-month and 48-month OAI visits. Case knees (n = 61) had radiographic OA progression between the 36- and 72-month OAI visits, defined as ≥ 0.7 mm minimum medial tibiofemoral radiographic joint space (minJSW) loss. Control knees (n = 61) without radiographic OA progression were matched (1:1) to cases for age, sex, body mass index and initial medial minJSW. Texture analysis was performed on the medial femoral and tibial subchondral bone. We assessed the association of texture features with radiographic progression by creating a composite texture score using penalised logistic regression and calculating odds ratios. We evaluated the predictive performance of texture features for predicting radiographic progression using c-statistics.ResultsInitial (odds ratio [95% confidence interval] = 2.13 [1.41–3.40]) and 12– 18-month change (3.76 [2.04–7.82]) texture scores were significantly associated with radiographic OA progression. Combinations of texture features were significant predictors of radiographic progression using initial (c-statistic [95% confidence interval] = 0.65 [0.64–0.65], p = 0.003) and 12–18-month change (0.68 [0.68-0.68], p < 0.001) data.ConclusionsInitial and 12–18-month changes in MRI subchondral bone texture score were significantly associated with radiographic progression at 36 months, with better predictive performance for 12–18-month change in texture. These results suggest that texture analysis may be a useful biomarker of subchondral bone in OA.Key Points• Subchondral bone MRI texture analysis is a promising knee osteoarthritis imaging biomarker.• In this study, subchondral bone texture was associated with knee osteoarthritis progression.• This demonstrates predictive and concurrent validity of MRI subchondral bone texture analysis.• This method may be useful in clinical trials with interventions targeting bone.

Characterizing the distinct structural changes associated with self-reported knee injury among individuals with incident knee osteoarthritis: Data from the osteoarthritis initiative: Structural Changes in Self-Reported Knee Injury

We aimed to characterize the agreement between distinct structural changes on magnetic resonance (MR) imaging and self‐reported injury in the 12 months leading to incident common or accelerated knee osteoarthritis (KOA). We conducted a descriptive study using data from baseline and the first 4 annual visits of the Osteoarthritis Initiative. Knees had no radiographic KOA at baseline (Kellgren‐Lawrence [KL]<2). We classified two groups: (1) accelerated KOA: a knee developed advanced‐stage KOA (KLu2009=u20093 or 4) within 48 months and (2) common KOA: a knee increased in radiographic severity (excluding those with accelerated KOA). Adults were 1:1 matched based on sex. The index visit was when a person met the accelerated or common KOA criteria. We limited our sample to people with MR images and self‐reported injury data at index visit and year prior. Among 226 people, we found fair agreement between self‐reported injuries and distinct structural changes (kappau2009=u20090.24 to 0.31). Most distinct structural changes were medial meniscal pathology. No distinct structural changes (e.g., root or radial tears) appeared to differ between adults who reported or did not report an injury; except, all subchondral fractures occurred in adults who developed accelerated KOA and reported an injury. While there is fair agreement between self‐reported knee injuries and distinct structural changes, there is some discordance. Self‐reported injury may represent a different construct from distinct structural changes that occur after joint trauma. Clin. Anat. 31:330–334, 2018.

Genetic tests debate

Lack of accurate information on genetic testing may lead to unrealistic patient expectations.