Psychological interventions for women with non-metastatic breast cancer.

BACKGROUND: Breast cancer is the most common cancer affecting women worldwide. It is a distressing diagnosis and, as a result, considerable research has examined the psychological sequelae of being diagnosed and treated for breast cancer. Breast cancer is associated with increased rates of depression and anxiety and reduced quality of life. As a consequence, multiple studies have explored the impact of psychological interventions on the psychological distress experienced after a diagnosis of breast cancer. This review is an update of a Cochrane Review first published in 2015. OBJECTIVES: To assess the effect of psychological interventions on psychological morbidities and quality of life among women with non-metastatic breast cancer.  SEARCH METHODS: We searched the Cochrane Breast Cancer Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov up to 16 March 2021. We also scanned the reference lists of relevant articles. SELECTION CRITERIA: Randomised controlled trials that assessed the effectiveness of psychological interventions for women with non-metastatic breast cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently appraised, extracted data from eligible trials, and assessed risk of bias and certainty of the evidence using the GRADE approach. Any disagreement was resolved by discussion. Extracted data included information about participants, methods, the intervention and outcomes. MAIN RESULTS: We included 60 randomised controlled trials comprising 7998 participants. The most frequent reasons for exclusion were non-randomised trials and the inclusion of women with metastatic disease. The updated review included 7998 randomised women; the original review included 3940 women. A wide range of interventions was evaluated. Most interventions were cognitive- or mindfulness-based, supportive-expressive, and educational. The interventions were mainly delivered face-to-face (56 studies) and in groups (50 studies) rather than individually (10 studies). Most intervention sessions were delivered on a weekly basis with an average duration of 14 hours. Follow-up time ranged from two weeks to 24 months.  Pooled standardised mean differences (SMD) from baseline indicated that the intervention may reduce depression (SMD -0.27, 95% confidence interval (CI) -0.52 to -0.02; P = 0.04; 27 studies, 3321 participants, I2 = 91%, low-certainty evidence); anxiety (SMD -0.43, 95% CI -0.68 to -0.17; P = 0.0009; 22 studies, 2702 participants, I2 = 89%, low-certainty evidence); mood disturbance in the intervention group (SMD -0.18, 95% CI -0.31 to -0.04; P = 0.009; 13 studies, 2276 participants, I2 = 56%, low-certainty evidence); and stress (SMD -0.34, 95% (CI) -0.55 to -0.12; P = 0.002; 8 studies, 564 participants, I2 = 31%, low-certainty evidence). The intervention is likely to improve quality of life in the intervention group (SMD 0.78, 95% (CI) 0.32 to 1.24; P = 0.0008; 20 studies, 1747 participants, I2 = 95%, low-certainty evidence). Adverse events were not reported in any of the included studies. AUTHORS' CONCLUSIONS: Based on the available evidence, psychological intervention may have produced favourable effects on psychological outcomes, in particular depression, anxiety, mood disturbance and stress. There was also an improvement in quality of life in the psychological intervention group compared to control group. Overall, there was substantial variation across the studies in the range of psychological interventions used, control conditions, measures of the same outcome and timing of follow-up.

Efficacy and cost-effectiveness of nurse-led care involving education and engagement of patients and a treat-to-target urate-lowering strategy versus usual care for gout: a randomised controlled trial.

BACKGROUND: In the UK, gout management is suboptimum, with only 40% of patients receiving urate-lowering therapy, usually without titration to achieve a target serum urate concentration. Nurses successfully manage many diseases in primary care. We compared nurse-led gout care to usual care led by general practitioners (GPs) for people in the community. METHODS: Research nurses were trained in best practice management of gout, including providing individualised information and engaging patients in shared decision making. Adults who had experienced a gout flare in the previous 12 months were randomly assigned 1:1 to receive nurse-led care or continue with GP-led usual care. We assessed patients at baseline and after 1 and 2 years. The primary outcome was the percentage of participants who achieved serum urate concentrations less than 360 µmol/L (6 mg/dL) at 2 years. Secondary outcomes were flare frequency in year 2, presence of tophi, quality of life, and cost per quality-adjusted life-year (QALY) gained. Risk ratios (RRs) and 95% CIs were calculated based on intention to treat with multiple imputation. This study is registered with www.ClinicalTrials.gov, number NCT01477346. FINDINGS: 517 patients were enrolled, of whom 255 were assigned nurse-led care and 262 usual care. Nurse-led care was associated with high uptake of and adherence to urate-lowering therapy. More patients receiving nurse-led care had serum urate concentrations less than 360 µmol/L at 2 years than those receiving usual care (95% vs 30%, RR 3·18, 95% CI 2·42-4·18, p<0·0001). At 2 years all secondary outcomes favoured the nurse-led group. The cost per QALY gained for the nurse-led intervention was £5066 at 2 years. INTERPRETATION: Nurse-led gout care is efficacious and cost-effective compared with usual care. Our findings illustrate the benefits of educating and engaging patients in gout management and reaffirm the importance of a treat-to-target urate-lowering treatment strategy to improve patient-centred outcomes. FUNDING: Arthritis Research UK.

Novel Genetic Variants for Cartilage Thickness and Hip Osteoarthritis.

Osteoarthritis is one of the most frequent and disabling diseases of the elderly. Only few genetic variants have been identified for osteoarthritis, which is partly due to large phenotype heterogeneity. To reduce heterogeneity, we here examined cartilage thickness, one of the structural components of joint health. We conducted a genome-wide association study of minimal joint space width (mJSW), a proxy for cartilage thickness, in a discovery set of 13,013 participants from five different cohorts and replication in 8,227 individuals from seven independent cohorts. We identified five genome-wide significant (GWS, P≤5·0×10-8) SNPs annotated to four distinct loci. In addition, we found two additional loci that were significantly replicated, but results of combined meta-analysis fell just below the genome wide significance threshold. The four novel associated genetic loci were located in/near TGFA (rs2862851), PIK3R1 (rs10471753), SLBP/FGFR3 (rs2236995), and TREH/DDX6 (rs496547), while the other two (DOT1L and SUPT3H/RUNX2) were previously identified. A systematic prioritization for underlying causal genes was performed using diverse lines of evidence. Exome sequencing data (n = 2,050 individuals) indicated that there were no rare exonic variants that could explain the identified associations. In addition, TGFA, FGFR3 and PIK3R1 were differentially expressed in OA cartilage lesions versus non-lesioned cartilage in the same individuals. In conclusion, we identified four novel loci (TGFA, PIK3R1, FGFR3 and TREH) and confirmed two loci known to be associated with cartilage thickness.The identified associations were not caused by rare exonic variants. This is the first report linking TGFA to human OA, which may serve as a new target for future therapies.

Participants' Experiences of a Sexual Counseling Intervention During Cardiac Rehabilitation: A Nested Qualitative Study Within the CHARMS Pilot Randomized Controlled Trial.

BACKGROUND: International guidelines recommend sexual assessment and counseling be offered to all patients with cardiovascular disease during cardiac rehabilitation. However, sexual problems are infrequently addressed. The Cardiac Health and Relationship Management and Sexuality (CHARMS) intervention is a complex, multilevel intervention designed to increase the provision of sexual counseling in cardiac rehabilitation. It was piloted in 2 cardiac rehabilitation centers to assess the acceptability and feasibility of the intervention and to inform and refine a definitive cluster randomized controlled trial protocol. OBJECTIVES: The aim of this study was to explore the experiences, perceptions, and opinions of patients, partners, and cardiac rehabilitation staff who participated in the CHARMS staff-led patient education class. METHODS: A qualitative, descriptive study using semistructured interviews to collect the data. Cardiac rehabilitation staff (n = 8) were interviewed when the intervention commenced in their center and 3 months later (n = 6). Patients (n = 19) and partners (n = 2) were interviewed after delivery of the class; 7 were interviewed again 3 months postintervention to explore temporal changes in opinions. RESULTS: Most cardiac rehabilitation staff were comfortable delivering the CHARMS intervention but would prefer a less structured format. Some staff perceived discomfort among patients. Few patients reported discomfort. Most patients and partners considered that the intervention was a welcome and acceptable part of a cardiac rehabilitation program. CONCLUSION: Incorporating sexual counseling into cardiac rehabilitation programs is feasible. Although the views of the patients and staff diverged on a number of issues including the perceived comfort of patients, its inclusion was welcomed by patients and was acceptable overall to both staff and patients.

Synergistic effects of brain-derived neurotrophic factor (BDNF) and exercise intensity on memory in the adolescent brain: a commentary.

This commentary highlights the recently published study by Jeon and Ha (Environ Health Prev Med 22:27, 2017) examining the effects of exercise intensity and brain-derived neurotrophic factor (BDNF) on memory in adolescents. This 12-week training study elicited increases in BDNF and improvements in working memory during moderate- and high-intensity exercise, which may have been achieved through improved brain tissue oxygenation, nutrient delivery, and BDNF mRNA expression. These improvements highlight the positive neuroendocrinological effects of BDNF and its role as a potential candidate molecule, as a mediator of synaptic plasticity. In this commentary, we aim to highlight the strengths and potential areas of consideration of Jeon and Ha (Environ Health Prev Med 22:27, 2017). We also offer insight into the clinical implications of this study, such as advocating for exercise in healthy children and as adjunctive therapy in pathological states. This study is promising and further highlights the importance of cardiorespiratory exercise in improving physiological health and cognitive functioning in youth through the phenomenon of neuroplasticity.

Association Between Sexual Problems and Relationship Satisfaction Among People With Cardiovascular Disease.

BACKGROUND: Relationship satisfaction is generally positively correlated with sexual satisfaction, but this relation has been poorly examined in people with cardiovascular disease who are at increased risk of sexual problems compared with the general population. AIM: To document reported changes to sex after a diagnosis of cardiac disease and determine whether there is an association between sexual function and relationship satisfaction. METHODS: Semistructured telephone interviews focused on relationship satisfaction and sexual problems were conducted with 201 people with cardiovascular disease who were currently in a sexual relationship with one main partner and were recruited from six hospital cardiac rehabilitation centers in Ireland. Comparisons between groups were conducted using t-tests and multivariate analysis of variance for continuous variables and χ2 tests for categorical variables. Predictors of relationship satisfaction were assessed using multiple linear regression analysis. OUTCOMES: Data were gathered on demographic and clinical variables, sexual problems, and relationship satisfaction, including satisfaction with the physical, emotional, affection, and communication aspects of relationships. RESULTS: Just less than one third of participants (n = 61, 30.3%) reported that sex had changed for the worse since their cardiac event or diagnosis, with approximately half of these stating that this was a serious problem for them. Satisfaction with relationships was high among patients surveyed; more than 70% of the sample reported being very or extremely satisfied with the physical and emotional aspects and showing affection during sex. Satisfaction with communication about sex was lower, with only 58% reporting being very or extremely satisfied. We did not find significant associations between reporting of sexual problems or deterioration of sex as a result of disease and relationship satisfaction. CLINICAL IMPLICATIONS: Cardiac rehabilitation programs should address these sexual problems, potentially by enhancing communication within couples about sex. STRENGTHS AND LIMITATIONS: The strength is that data are presented on the sexual experiences and relationship satisfaction of a relatively large sample of people diagnosed with cardiac disease, a relatively underexplored research area. Limitations include the possibility of selection bias of study participants and bias associated with self-report measurement. CONCLUSIONS: Sexual problems were significant in this population but were not related to relationship satisfaction in this cross-sectional survey. Byrne M, Murphy P, D'Eath M, et al. Association Between Sexual Problems and Relationship Satisfaction Among People With Cardiovascular Disease. J Sex Med 2017;14:666-674.

Local anaesthesia versus spinal anaesthesia in inguinal hernia repair: A systematic review and meta-analysis.

BACKGROUND: Inguinal hernias are a significant cause of morbidity. The purpose of this systematic review and meta-analysis is to determine the totality of evidence regarding the effectiveness of local anaesthesia when compared to spinal anaesthesia in individuals undergoing open inguinal hernia repair. METHODS: A systematic literature search was conducted. Inclusion criteria were randomised controlled trials (RCTs) comparing spinal and local anaesthesia on clinical and self-reported outcomes, in patients undergoing open inguinal hernia repairs. The methodological quality was assessed using the Cochrane risk of bias tool. The mode of analysis used was the difference in outcomes between the groups post-surgery and at follow-up time points. Statistical heterogeneity was assessed using the I2 statistic. RESULTS: Ten original RCTs were included, with a total of 1379 patients. There was no significant difference in operative time between the groups [Random Effects Model, MD -0.70 min (95% CI, -5.80 to 4.40 min), p = 0.79, I2 = 84%]. Patients in the local anaesthetic group experienced significantly less pain than those in the spinal group [Fixed Effects Model, SMD -0.63 (95% CI, -0.81 to -0.46), p < 0.01, I2 = 49%], lower rates of urinary retention [FEM, RR 0.03 (95% CI 0.01-0.08), p < 0.01, I2 = 0%], decreased rates of anaesthetic failure [FEM, OR 0.17 (95% CI 0.06-0.45), p < 0.01, I2 = 0%], and increased satisfaction with the anaesthetic [FEM, OR 3.40 (95% CI 2.09-5.52), p < 0.01, I2 = 0%]. The methodological quality of studies was variable. CONCLUSION: Our findings support the use of local anaesthetic in adult patients undergoing open repair for a primary inguinal hernia.

Erosive and osteoarthritic structural progression in early rheumatoid arthritis.

OBJECTIVES: To investigate factors associated with joint damage in early RA, and how comorbid OA might influence patient assessment and outcomes. METHODS: Baseline radiographs of hands and feet from 512 participants in the Early RA Network cohort, and after 3 (±1) years, 166 of those participants yielded complete scores for RA [erosions, joint space narrowing (JSN)] and OA [JSN, osteophytes (OST)] using validated atlases. DAS28-P is the proportion of DAS28 attributed to patient-reported factors. Adjusted odds ratios were calculated using logistic regression. RESULTS: OA was common at baseline in early RA (40% hand and 48% foot) and associated with RA radiographic score. Higher baseline RA scores were associated with increasing age and ESR, and lower DAS28-P. OST scores were associated with higher age. DAS28 and patient-reported outcomes improved, whereas RA and OA radiographic scores deteriorated by follow-up. Erosive progression was predicted by higher baseline erosions, female gender, better mental health and lower DAS28-P. Hand OST progression was predicted by baseline OST scores. Inflammatory disease activity was associated with erosive, but not with OA progression. Baseline hand OA predicted worse physical function at follow-up, but radiographic progression did not explain changes in patient-reported outcomes. CONCLUSION: OA is a common comorbidity that might confound radiographic and clinical assessment, but does not fully explain erosive progression or patient-reported outcomes in early RA. Early RA management should address psychosocial factors and comorbidities, as well as joint inflammation.

Intercritical circulating levels of neo-epitopes reflecting matrixmetalloprotease-driven degradation as markers of gout and frequent gout attacks.

OBJECTIVE: Recurrent flares constitute the main clinical burden of gout. Our aim was to assess whether biomarkers measuring MMP tissue degradation could be used as markers of frequent gout flares. METHODS: Fasting plasma samples from 112 men with gout and 170 controls, along with serum samples from 447 men with gout collected at baseline from an ongoing clinical trial, were analysed by ELISA for neo-epitopes from MMP degradation of collagens type I (C1M) and type III (C3M). The log10 levels of both markers were compared between cases and controls and between gout patients with three or more gout attacks in the past year and those with two or less attacks. RESULTS: The circulating levels of C1M and C3M correlated with gout status in the case-control study. Levels of both markers were associated with frequent gout flares (⩾3 attacks in the past year) in both cohorts (odds ratio, OR = 3.1; 95% CI: 1.4, 6.8; P = 0.0056 for log10C1M, and OR = 6.7; 95% CI: 2.3, 19.3; P = 0.0005 for log10C3M). The area under the curve in a receiver operating characteristic analysis of frequent flares increased from 0.68 to 0.74 in one cohort and from 0.60 to 0.66 in the other when log10C1M and log10C3M were added to clinical variables of the model. CONCLUSION: C1M and C3M, reflective of interstitial matrix destruction, are associated with gout status and with frequent gout flares in men, suggesting that increased MMP activity may contribute to gout flares. Further research is needed to find out whether this is independent of dietary and lifestyle risk factors for acute gout.

Sexual counselling for sexual problems in patients with cardiovascular disease.

BACKGROUND: Sexual problems are common among people with cardiovascular disease. Although clinical guidelines recommend sexual counselling for patients and their partners, there is little evidence on its effectiveness. OBJECTIVES: To evaluate the effectiveness of sexual counselling interventions (in comparison to usual care) on sexuality-related outcomes in patients with cardiovascular disease and their partners. SEARCH METHODS: We searched CENTRAL, MEDLINE, EMBASE, and three other databases up to 2 March 2015 and two trials registers up to 3 February 2016. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs, including individual and cluster RCTs. We included studies that compared any intervention to counsel adult cardiac patients about sexual problems with usual care. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included three trials with 381 participants. We were unable to pool the data from the included studies due to the differences in interventions used; therefore we synthesised the trial findings narratively.Two trials were conducted in the USA and one was undertaken in Israel. All trials included participants who were admitted to hospital with myocardial infarction (MI), and one trial also included participants who had undergone coronary artery bypass grafting. All trials followed up participants for a minimum of three months post-intervention; the longest follow-up timepoint was five months.One trial (N = 92) tested an intensive (total five hours) psychotherapeutic sexual counselling intervention delivered by a sexual therapist. One trial (N = 115) used a 15-minute educational video plus written material on resuming sexual activity following a MI. One trial (N = 174) tested the addition of a component that focused on resumption of sexual activity following a MI within a hospital cardiac rehabilitation programme.The quality of the evidence for all outcomes was very low.None of the included studies reported any outcomes from partners.Two trials reported sexual function. One trial compared intervention and control groups on 12 separate sexual function subscales and used a repeated measures analysis of variance (ANOVA) test. They reported statistically significant differences in favour of the intervention. One trial compared intervention and control groups using a repeated measures analysis of covariance (ANCOVA), and concluded: "There were no significant differences between the two groups [for sexual function] at any of the time points".Two trials reported sexual satisfaction. In one trial, the authors compared sexual satisfaction between intervention and control and used a repeated measured ANOVA; they reported "differences were reported in favour of the intervention". One trial compared intervention and control with a repeated measures ANCOVA and reported: "There were no significant differences between the two groups [for sexual satisfaction] at any of the timepoints".All three included trials reported the number of patients returning to sexual activity following MI. One trial found some evidence of an effect of sexual counselling on reported rate of return to sexual activity (yes/no) at four months after completion of the intervention (relative risk (RR) 1.71, 95% confidence interval (CI) 1.26 to 2.32; one trial, 92 participants, very low quality of evidence). Two trials found no evidence of an effect of sexual counselling on rate of return to sexual activity at 12 week (RR 1.01, 95% CI 0.94 to 1.09; one trial, 127 participants, very low quality of evidence) and three month follow-up (RR 0.98, 95% CI 0.88 to 1.10; one trial, 115 participants, very low quality of evidence).Two trials reported psychological well-being. In one trial, no scores were reported, but the trial authors stated: "No treatment effects were observed on state anxiety as measured in three points in time". In the other trial no scores were reported but, based on results of a repeated measures ANCOVA to compare intervention and control groups, the trial authors stated: "The experimental group had significantly greater anxiety at one month post MI". They also reported: "There were no significant differences between the two groups [for anxiety] at any other time points".One trial reporting relationship satisfaction and one trial reporting quality of life found no differences between intervention and control.No trial reported on satisfaction in how sexual issues were addressed in cardiac rehabilitation services. AUTHORS' CONCLUSIONS: We found no high quality evidence to support the effectiveness of sexual counselling for sexual problems in patients with cardiovascular disease. There is a clear need for robust, methodologically rigorous, adequately powered RCTs to test the effectiveness of sexual counselling interventions for people with cardiovascular disease and their partners.

Genome-wide association and functional studies identify a role for IGFBP3 in hip osteoarthritis.

OBJECTIVES: To identify genetic associations with hip osteoarthritis (HOA), we performed a meta-analysis of genome-wide association studies (GWAS) of HOA. METHODS: The GWAS meta-analysis included approximately 2.5 million imputed HapMap single nucleotide polymorphisms (SNPs). HOA cases and controls defined radiographically and by total hip replacement were selected from the Osteoporotic Fractures in Men (MrOS) Study and the Study of Osteoporotic Fractures (SOF) (654 cases and 4697 controls, combined). Replication of genome-wide significant SNP associations (p ≤5×10(-8)) was examined in five studies (3243 cases and 6891 controls, combined). Functional studies were performed using in vitro models of chondrogenesis and osteogenesis. RESULTS: The A allele of rs788748, located 65 kb upstream of the IGFBP3 gene, was associated with lower HOA odds at the genome-wide significance level in the discovery stage (OR 0.71, p=2×10(-8)). The association replicated in five studies (OR 0.92, p=0.020), but the joint analysis of discovery and replication results was not genome-wide significant (p=1×10(-6)). In separate study populations, the rs788748 A allele was also associated with lower circulating IGFBP3 protein levels (p=4×10(-13)), suggesting that this SNP or a variant in linkage disequilibrium could be an IGFBP3 regulatory variant. Results from functional studies were consistent with association results. Chondrocyte hypertrophy, a deleterious event in OA pathogenesis, was largely prevented upon IGFBP3 knockdown in chondrocytes. Furthermore, IGFBP3 overexpression induced cartilage catabolism and osteogenic differentiation. CONCLUSIONS: Results from GWAS and functional studies provided suggestive links between IGFBP3 and HOA.

Genome-wide association and functional studies identify the DOT1L gene to be involved in cartilage thickness and hip osteoarthritis.

Hip osteoarthritis (HOA) is one of the most disabling and common joint disorders with a large genetic component that is, however, still ill-defined. To date, genome-wide association studies (GWAS) in osteoarthritis (OA) and specifically in HOA have yielded only few loci, which is partly explained by heterogeneity in the OA definition. Therefore, we here focused on radiographically measured joint-space width (JSW), a proxy for cartilage thickness and an important underlying intermediate trait for HOA. In a GWAS of 6,523 individuals on hip-JSW, we identified the G allele of rs12982744 on chromosome 19p13.3 to be associated with a 5% larger JSW (P = 4.8 × 10(-10)). The association was replicated in 4,442 individuals from three United Kingdom cohorts with an overall meta-analysis P value of 1.1 × 10(-11). The SNP was also strongly associated with a 12% reduced risk for HOA (P = 1 × 10(-4)). The SNP is located in the DOT1L gene, which is an evolutionarily conserved histone methyltransferase, recently identified as a potentially dedicated enzyme for Wnt target-gene activation in leukemia. Immunohistochemical staining of the DOT1L protein in mouse limbs supports a role for DOT1L in chondrogenic differentiation and adult articular cartilage. DOT1L is also expressed in OA articular chondrocytes. Silencing of Dot1l inhibited chondrogenesis in vitro. Dot1l knockdown reduces proteoglycan and collagen content, and mineralization during chondrogenesis. In the ATDC5 chondrogenesis model system, DOT1L interacts with TCF and Wnt signaling. These data are a further step to better understand the role of Wnt-signaling during chondrogenesis and cartilage homeostasis. DOT1L may represent a therapeutic target for OA.

A variant in MCF2L is associated with osteoarthritis.

Osteoarthritis (OA) is a prevalent, heritable degenerative joint disease with a substantial public health impact. We used a 1000-Genomes-Project-based imputation in a genome-wide association scan for osteoarthritis (3177 OA cases and 4894 controls) to detect a previously unidentified risk locus. We discovered a small disease-associated set of variants on chromosome 13. Through large-scale replication, we establish a robust association with SNPs in MCF2L (rs11842874, combined odds ratio [95% confidence interval] 1.17 [1.11-1.23], p = 2.1 × 10(-8)) across a total of 19,041 OA cases and 24,504 controls of European descent. This risk locus represents the third established signal for OA overall. MCF2L regulates a nerve growth factor (NGF), and treatment with a humanized monoclonal antibody against NGF is associated with reduction in pain and improvement in function for knee OA patients.

The effect of FTO variation on increased osteoarthritis risk is mediated through body mass index: a Mendelian randomisation study.

OBJECTIVE: Variation in the fat mass and obesity-associated (FTO) gene influences susceptibility to obesity. A variant in the FTO gene has been implicated in genetic risk to osteoarthritis (OA). We examined the role of the FTO polymorphism rs8044769 in risk of knee and hip OA in cases and controls incorporating body mass index (BMI) information. METHODS: 5409 knee OA patients, 4355 hip OA patients and up to 5362 healthy controls from 7 independent cohorts from the UK and Australia were genotyped for rs8044769. The association of the FTO variant with OA was investigated in case/control analyses with and without BMI adjustment and in analyses matched for BMI category. A mendelian randomisation approach was employed using the FTO variant as the instrumental variable to evaluate the role of overweight on OA. RESULTS: In the meta-analysis of all overweight (BMI≥25) samples versus normal-weight controls irrespective of OA status the association of rs8044769 with overweight is highly significant (OR[CIs] for allele G=1.14 [01.08 to 1.19], p=7.5×10(-7)). A significant association with knee OA is present in the analysis without BMI adjustment (OR[CIs]=1.08[1.02 to 1.14], p=0.009) but the signal fully attenuates after BMI adjustment (OR[CIs]=0.99[0.93 to 1.05], p=0.666). We observe no evidence for association in the BMI-matched meta-analyses. Using mendelian randomisation approaches we confirm the causal role of overweight on OA. CONCLUSIONS: Our data highlight the contribution of genetic risk to overweight in defining risk to OA but the association is exclusively mediated by the effect on BMI. This is consistent with what is known of the biology of the FTO gene and supports the causative role of high BMI in OA.

Sexual counselling for individuals with cardiovascular disease and their partners: a consensus document from the American Heart Association and the ESC Council on Cardiovascular Nursing and Allied Professions (CCNAP).

After a cardiovascular event, patients and their families often cope with numerous changes in their lives, including dealing with consequences of the disease or its treatment on their daily lives and functioning. Coping poorly with both physical and psychological challenges may lead to impaired quality of life. Sexuality is one aspect of quality of life that is important for many patients and partners that may be adversely affected by a cardiac event. The World Health Organization defines sexual health as '… a state of physical, emotional, mental and social well-being in relation to sexuality; it is not merely the absence of disease, dysfunction or infirmity. Sexual health requires a positive and respectful approach to sexuality and sexual relationships, as well as the possibility of having pleasurable and safe sexual experiences ….'(1(p4)) The safety and timing of return to sexual activity after a cardiac event have been well addressed in an American Heart Association scientific statement, and decreased sexual activity among cardiac patients is frequently reported.(2) Rates of erectile dysfunction (ED) among men with cardiovascular disease (CVD) are twice as high as those in the general population, with similar rates of sexual dysfunction in females with CVD.(3) ED and vaginal dryness may also be presenting signs of heart disease and may appear 1-3 years before the onset of angina pectoris. Estimates reflect that only a small percentage of those with sexual dysfunction seek medical care;(4) therefore, routine assessment of sexual problems and sexual counselling may be of benefit as part of effective management by physicians, nurses, and other healthcare providers.

Physical activity and sedentary behaviour of Bahraini people with type 2 diabetes: A cross-sectional study.

Objective: Study patterns of physical activity and sedentary behaviour and the influence of demographics and body mass index (BMI) on these behaviours amongst Bahraini adults with type 2 diabetes over 10 weeks using an activity tracker. Method: This cross-sectional observational study was conducted at a Bahrain government health centre. Thirty-three Bahraini Arab adults, 30-60 years old, with controlled type 2 diabetes, wore a Fitbit Flex 2TM activity tracker for 10 weeks. Data on age, sex, marital and employment status, education and BMI were collected at the start of the study. Results: A total of N = 32 participants completed the study. The average steps per day were 7859 ± 4131, and there were no differences between baseline, week 5 and 10. A third of participants were sedentary, based on a threshold of 5000 steps/day. Females accumulated fewer average daily steps than males (6728 ± 2936 vs. 10,281 ± 4623, p = 0.018). Daily averages for physical activity intensity were as follows: sedentary (786 ± 109 min), light (250 ± 76 min), moderate (9 ± 10 min) and vigorous (12 ± 18 min). Males had higher daily averages versus females for moderate (13 ± 9 vs. 5 ± 9 min, p = 0.018) and vigorous physical activity (21 ± 23 vs. 5 ± 7 min, p = 0.034). 91% of participants wore the device ≥10 h/day. The adherence rate was 79% based on percentage of days the device was worn continuously over 10 weeks. Conclusion: Future physical activity interventions should target sedentary and female participants with type 2 diabetes. In addition, we need to understand the facilitators and barriers to physical activity and the physical activity preferences of these two subgroups.

Identification of new susceptibility loci for osteoarthritis (arcOGEN): a genome-wide association study.

BACKGROUND: Osteoarthritis is the most common form of arthritis worldwide and is a major cause of pain and disability in elderly people. The health economic burden of osteoarthritis is increasing commensurate with obesity prevalence and longevity. Osteoarthritis has a strong genetic component but the success of previous genetic studies has been restricted due to insufficient sample sizes and phenotype heterogeneity. METHODS: We undertook a large genome-wide association study (GWAS) in 7410 unrelated and retrospectively and prospectively selected patients with severe osteoarthritis in the arcOGEN study, 80% of whom had undergone total joint replacement, and 11,009 unrelated controls from the UK. We replicated the most promising signals in an independent set of up to 7473 cases and 42,938 controls, from studies in Iceland, Estonia, the Netherlands, and the UK. All patients and controls were of European descent. FINDINGS: We identified five genome-wide significant loci (binomial test p≤5·0×10(-8)) for association with osteoarthritis and three loci just below this threshold. The strongest association was on chromosome 3 with rs6976 (odds ratio 1·12 [95% CI 1·08-1·16]; p=7·24×10(-11)), which is in perfect linkage disequilibrium with rs11177. This SNP encodes a missense polymorphism within the nucleostemin-encoding gene GNL3. Levels of nucleostemin were raised in chondrocytes from patients with osteoarthritis in functional studies. Other significant loci were on chromosome 9 close to ASTN2, chromosome 6 between FILIP1 and SENP6, chromosome 12 close to KLHDC5 and PTHLH, and in another region of chromosome 12 close to CHST11. One of the signals close to genome-wide significance was within the FTO gene, which is involved in regulation of bodyweight-a strong risk factor for osteoarthritis. All risk variants were common in frequency and exerted small effects. INTERPRETATION: Our findings provide insight into the genetics of arthritis and identify new pathways that might be amenable to future therapeutic intervention. FUNDING: arcOGEN was funded by a special purpose grant from Arthritis Research UK.

The genetic contribution to severe post-traumatic osteoarthritis.

OBJECTIVE: to compare the combined role of genetic variants loci associated with risk of knee or hip osteoarthritis (OA) in post-traumatic (PT) and non-traumatic (NT) cases of clinically severe OA leading to total joint replacement. METHODS: A total of 1590 controls, 2168 total knee replacement (TKR) cases (33.2% PT) and 1567 total hip replacement (THR) cases (8.7% PT) from 2 UK cohorts were genotyped for 12 variants previously reported to be reproducibly associated with risk of knee or hip OA. A genetic risk score was generated and the association with PT and NT TKR and THR was assessed adjusting for covariates. RESULTS: For THR, each additional genetic risk variant conferred lower risk among PT cases (OR=1.07, 95% CI 0.96 to 1.19; p=0.24) than NT cases (OR 1.11, 95% CI 1.06 to 1.17; p=1.55×10⁻5). In contrast, for TKR, each risk variant conferred slightly higher risk among PT cases (OR 1.12, 95% CI 1.07 to 1.19; p=1.82×10⁻5) than among NT cases (OR 1.08, 95% CI 1.03 to 1.1; p=0.00063). CONCLUSIONS: Based on the variants reported to date PT TKR cases have at least as high a genetic contribution as NT cases.

The Cardiac Health and Assessment of Relationship Management and Sexuality study: a qualitative inquiry of patient, general practitioner, and cardiac rehabilitation staff views on sexual assessment and counseling for cardiac patients.

BACKGROUND: Sexual dysfunction is a problem for some patients with cardiovascular disease. This study was the final phase of the Cardiac Health and Assessment of Relationship Management and Sexuality (CHARMS) study of sexual function, assessment, and counseling for people with coronary heart disease in Ireland. OBJECTIVES: The aim of this study was to explore the perspectives of patients, cardiac rehabilitation staff, and general practitioners on the provision of sexual assessment and counseling within Irish health services and how it can be optimized. METHODS: Group interviews with cardiac rehabilitation staff (n = 14) and patients (n = 13) and telephone interviews with general practitioners (n = 9) were conducted. The interviews were semistructured, digitally recorded, transcribed verbatim, and analyzed using qualitative, descriptive analysis. RESULTS: All 3 stakeholder groups reported that the problem of sexual dysfunction among cardiac patients was an important issue that was underaddressed in practice. Patients want the issue to be addressed in an explicit way throughout and after the rehabilitation process by confident and knowledgeable professionals. Cardiac rehabilitators widely acknowledged the role that they could play in the provision of sexual assessment and counseling, but many were constrained by a perceived lack of knowledge and confidence. Most cardiac rehabilitation staff would welcome relevant guidelines and training. General practitioners were unlikely to initiate a discussion about sexual dysfunction; however, most were confident that patients would be comfortable in raising it. General practitioners would welcome more awareness raising but did not identify a need for specific training or resources. CONCLUSIONS: Perspectives differed both across and within stakeholder groups about current services and the development of future services. A disconnect exists between the service that the professionals perceive they give and that experienced by patients. Sexual assessment and counseling should be addressed more explicitly, and patients should be empowered to seek individual assessment and counseling at a time that is appropriate for them.

Genetic contribution to radiographic severity in osteoarthritis of the knee.

OBJECTIVE: Knee osteoarthritis (OA) has a significant genetic component. The authors have assessed the role of three variants reported to influence risk of knee OA with p<5×10-8 in determining patellofemoral and tibiofemoral Kellgren Lawrence (K/L) grade in knee OA cases. METHODS: 3474 knee OA cases with sky-line and weight-bearing antero-posterior x-rays of the knee were selected based on the presentation of K/L grade ≥2 at either the tibiofemoral or patellofemoral compartments for one or both knees. Patients belonging to three UK cohorts, were genotyped for rs143383, rs4730250 and rs11842874 mapping to the GDF5, COG5 and MCF2L genes, respectively. The association between tibiofemoral K/L grade and patellofemoral K/L grade was assessed after adjusting for age, gender and body mass index. RESULTS: No significant association was found between the rs4730250 and radiographic severity. The rs11842874 mapping to MCF2L was found to be nominally significantly associated with patellofemoral K/L grade as a quantitative trait (p=0.027) but not as a binary trait. The GDF5 single nucleotide polymorphism rs143383 was associated with tibiofemoral K/L grade (ß=0.05 (95% CI 0.02 to 0.08) p=0.0011). CONCLUSIONS: Our data indicate that within individuals affected by radiographic knee OA, OAGDF5 has a modest but significant effect on radiographic severity after adjustment for the major risk factors.