Effect of communicating DNA based risk assessments for Crohn's disease on smoking cessation: randomised controlled trial.

OBJECTIVE: To test the hypothesis that communicating risk of developing Crohn's disease based on genotype and that stopping smoking can reduce this risk, motivates behaviour change among smokers at familial risk. DESIGN: Parallel group, cluster randomised controlled trial. SETTING: Families with Crohn's disease in the United Kingdom. PARTICIPANTS: 497 smokers (mean age 42.6 (SD 14.4) years) who were first degree relatives of probands with Crohn's disease, with outcomes assessed on 209/251 (based on DNA analysis) and 217/246 (standard risk assessment). INTERVENTION: Communication of risk assessment for Crohn's disease by postal booklet based on family history of the disease and smoking status alone, or with additional DNA analysis for the NOD2 genotype. Participants were then telephoned by a National Health Service Stop Smoking counsellor to review the booklet and deliver brief standard smoking cessation intervention. Calls were tape recorded and a random subsample selected to assess fidelity to the clinical protocol. MAIN OUTCOME MEASURE: The primary outcome was smoking cessation for 24 hours or longer, assessed at six months. RESULTS: The proportion of participants stopping smoking for 24 hours or longer did not differ between arms: 35% (73/209) in the DNA arm versus 36% (78/217) in the non-DNA arm (difference -1%, 95% confidence interval -10% to 8%, P=0.83). The proportion making a quit attempt within the DNA arm did not differ between those who were told they had mutations putting them at increased risk (36%), those told they had none (35%), and those in the non-DNA arm (36%). CONCLUSION: Among relatives of patients with Crohn's disease, feedback of DNA based risk assessments does not motivate behaviour change to reduce risk any more or less than standard risk assessment. These findings accord with those across a range of populations and behaviours. They do not support the promulgation of commercial DNA based tests nor the search for gene variants that confer increased risk of common complex diseases on the basis that they effectively motivate health related behaviour change. TRIAL REGISTRATION: Current Controlled Trials ISRCTN21633644.

Trial Protocol: Communicating DNA-based risk assessments for Crohn's disease: a randomised controlled trial assessing impact upon stopping smoking.

BACKGROUND: Estimates of the risk of developing Crohn's disease (CD) can be made using DNA testing for mutations in the NOD2 (CARD15) gene, family history, and smoking status. Smoking doubles the risk of CD, a risk that is reduced by stopping. CD therefore serves as a timely and novel paradigm within which to assess the utility of predictive genetic testing to motivate behaviour change to reduce the risk of disease. The aim of the study is to describe the impact upon stopping smoking of communicating a risk of developing CD that incorporates DNA analysis. We will test the following main hypothesis:Smokers who are first degree relatives (FDRs) of CD probands are more likely to make smoking cessation attempts following communication of risk estimates of developing CD that incorporate DNA analysis, compared with an equivalent communication that does not incorporate DNA analysis. METHODS/DESIGN: A parallel groups randomised controlled trial in which smokers who are FDRs of probands with CD are randomly allocated in families to undergo one of two types of assessment of risk for developing CD based on either: i. DNA analysis, family history of CD and smoking status, or ii. Family history of CD and smoking status. The primary outcome is stopping smoking for 24 hours or longer in the six months following provision of risk information. The secondary outcomes are seven-day smoking abstinence at one week and six month follow-ups. Randomisation of 470 smoking FDRs of CD probands, with 400 followed up (85%), provides 80% power to detect a difference in the primary outcome of 14% between randomised arms, at the 5% significance level. DISCUSSION: This trial provides one of the strongest tests to date of the impact of communicating DNA-based risk assessment on risk-reducing behaviour change. Specific issues regarding the choice of trial design are discussed.

The role of Sr2+ on the structure and reactivity of SrO-CaO-ZnO-SiO2 ionomer glasses.

The suitability of Glass Polyalkenoate Cements (GPCs) for use in orthopaedics is retarded by the presence in the glass phase of aluminium, a neurotoxin. Unfortunately, the aluminium ion plays an integral role in the setting process of GPCs and its absence is likely to hinder cement formation. However, the authors have previously shown that aluminium free GPCs may be formulated based on calcium zinc silicate glasses and these novel materials exhibit significant potential as hard tissue biomaterials. To further improve their potential, and given that Strontium (Sr) based drugs have had success in the treatment of osteoporosis, the authors have substituted Calcium (Ca) with Sr in the glass phase of a series of aluminium free GPCs. However to date little data exists on the effect SrO has on the structure and reactivity of SrO-CaO-ZnO-SiO(2) glasses. The objective of this work was to characterise the effect of the Ca/Sr substitution on the structure of such glasses, and evaluate the subsequent reactivity of these glasses with an aqueous solution of Polyacrylic acid (PAA). To this end (29)Si MAS-NMR, differential scanning calorimetry (DSC), X-ray diffraction, and network connectivity calculations, were used to characterize the structure of four strontium calcium zinc silicate glasses. Following glass characterization, GPCs were produced from each glass using a 40 wt% solution of PAA (powder:liquid = 2:1.5). The working times and setting times of the GPCs were recorded as per International standard ISO9917. The results acquired as part of this research indicate that the substitution of Ca for Sr in the glasses examined did not appear to significantly affect the structure of the glasses investigated. However it was noted that increasing the amount of Ca substituted for Sr did result in a concomitant increase in setting times, a feature that may be attributable to the higher basicity of SrO over CaO.

Study comparing two types of screening provision for people with von Hippel-Lindau disease.

Patients diagnosed with von Hippel-Lindau disease (vHL) require life-long surveillance for this multi-system disease. It is therefore important to assess the comprehensiveness of screening provision, as well as identify what type of screening service is most likely to encourage regular patient attendance. This descriptive study reports on two types of screening service: single appointment One Stop (OS) clinics and multiple appointment Ad Hoc (AH) clinics. One hundred and seventeen vHL patients from eight regional genetics centres were approached to take part. Seventy-two (61.5%) returning a completed study questionnaire: fifty-four (75%) were screened at OS clinics and eighteen (25%) at AH clinics. Comprehensiveness of screening, attendance rates, patient ratings of quality of care and levels of psychological morbidity were compared between the two types of service. While levels of disease severity were similar in patients screened at OS and AH clinics, those seen at OS clinics were screened for twice as many site-specific vHL manifestations compared to those seen at AH clinics (P < 0.0001). More patients at OS clinics regularly attended their screening appointments compared to those at AH clinics (P = 0.0045). There was no difference in the quality of care reported by patients attending the two types of screening service and few problems were reported. Twenty-nine percent of respondents were categorised as clinically anxious and 13% as clinically depressed. These findings suggest that an optimum vHL screening service is one based on OS clinics offering regular comprehensive surveillance and psychological support.

Patients' and professionals' opinions of services for people at an increased risk of colorectal cancer: an exploratory qualitative study.

OBJECTIVES: To explore the views and opinions of patients with a family history of colorectal cancer, and of primary and secondary care health professionals, on how to improve current services for individuals with a family history of colorectal cancer. DESIGN: Focus group and interview study. SETTING: Primary and secondary care centres in south east London, UK. PARTICIPANTS: A total of 53 people participated in this qualitative study: 18 individuals with a family history of colorectal cancer were interviewed in three focus groups and 35 health professionals were interviewed either in focus groups or individually. Visual qualitative analysis of transcribed interviews was used to identify the key themes which emerged. MAIN OUTCOME MEASURES: Interviewees' needs, views and opinions of current services and ways to improve them. RESULTS: Several areas of concern were identified. The role of primary care needs to be clarified. Education and information about services should be provided for patients and caregivers and better support is required for those undergoing screening and surveillance. Methods to ensure effective and meaningful risk communication are inadequate and require further exploration. Standardisation of care is required to ensure consistency of advice and treatment. CONCLUSION: These interviews revealed substantial shortfalls in the provision of services for patients at increased genetic risk of colorectal cancer. Current systems for the assessment of risk, delivery of advice, and for surveillance are inconsistent and sometimes maybe inadequate. The role of primary care physicians in service delivery requires clarification. Significant opportunities exist for the development of new, more appropriate models of service to provide better standards of care.

The experience of lower limb lymphedema for women after treatment for gynecologic cancer.

PURPOSE/OBJECTIVES: To describe women's experiences with lower limb lymphedema to inform both preventive and management clinical practices. DESIGN: A retrospective survey. SETTING: The gynecology/oncology unit of a tertiary referral women's hospital in Australia. SAMPLE: 82 women who developed lower limb lymphedema after surgical and radiation treatment for gynecologic cancers. METHODS: Structured interviews. MAIN RESEARCH VARIABLES: Psychosocial and emotional impact, physical effects, knowledge, support, treatment modalities. FINDINGS: Women identified changes in appearance and sensation in the legs and the triggers that both preceded and exacerbated symptoms. Women described seeking help and receiving inappropriate advice with as many as three assessments prior to referral to lymphedema specialists. Many women implemented self-management strategies. Lower limb lymphedema had an impact on appearance, mobility, finances, and self-image. CONCLUSIONS: Increasing longevity after gynecologic oncology treatment requires all practitioners to be aware of known or potential triggers of lower limb lymphedema and the appropriate referral and management strategies available. Women at risk need to know early signs and symptoms and where to seek early care. IMPLICATIONS FOR NURSING: The role of nursing in acute and community care of women at risk for developing lower limb lymphedema includes (a) engaging women in protecting their legs from infection or trauma pre- and postoperatively, (b) providing nursing care and education during the pre- and postoperative phases, and (c) ensuring that women being discharged are aware of early signs and symptoms of lower limb lymphedema and how to access qualified, specialized therapists so that early and effective management can be initiated.

Aetiology and prevalence of lower limb lymphoedema following treatment for gynaecological cancer.

OBJECTIVE: To determine the prevalence and incidence of lower limb lymphoedema (LLL) in a cohort of women who had treatment for gynaecological cancer between May 1995 and April 2000. DESIGN: A retrospective survey. SETTING: The study took place at an urban referral centre in an Australian tertiary referral women's hospital. SAMPLE: The data collection was based on 66% of 743 women on the database of the Gynaecological Cancer Centre. METHODS: Interviews and assessments were conducted to determine the status of lower limbs; medical records were reviewed for age, weight, site and type of cancer and treatment. MAIN OUTCOME MEASURES: Leg swelling, diagnosed lower limb lymphoedema, no swelling of the legs and type of surgery were determined as the main outcome measures. RESULTS AND CONCLUSIONS: The diagnosis of lower limb lymphoedema was made in 18% of the total sample: 53% of these were diagnosed within 3 months of treatment, a further 18% within 6 months, 13% within 12 months and the remaining 16% up to 5 years following treatment. Women most at risk for developing LLL were those who had treatment for vulvar cancer with removal of lymph nodes and follow up radiotherapy. For this subsample, the prevalence was 47%. The finding that LLL occurs within the first year is earlier than hitherto generally believed. It is therefore imperative for all health professionals to include care and assessment of the legs particularly during the immediate pre- and postoperative period.