The ALERT-B questionnaire: A screening tool for the detection of gastroenterological late effects after radiotherapy for prostate cancer.

There is an increasing need to measure treatment-related side effects in normal tissues following cancer therapy. The ALERT-B (Assessment of Late Effects of RadioTherapy - Bowel) questionnaire is a screening tool that is composed of four items related specifically to bowel symptoms. Those patients that respond with a "yes" to any of these items are referred on to gastroenterologist in order to improve the long-term consequences of these side effects of radiological treatment. Here we wish to test the ability of this questionnaire to identify these subsequent gastroenterological complications by tracking prostate cancer patients that were positive with respect to ALERT-B. We also carry out receiver-operator curve (ROC) analysis for baseline data for an overall ALERT-B questionnaire score with respect to subscale data for the Gastrointestinal Symptom Rating Scale (GSRS) and the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire. 84.4% and 95.7% of patients identified by the ALERT-B questionnaire demonstrated complications diagnosed at 6 and 12 months post-treatment, respectively. ROC curve analysis of baseline data showed that ALERT-B detected clinically relevant levels of side effects established at baseline by the GSRS diarrhoea subscale (AUC = 0.867, 95% CI = 0.795 to 0.926) and at the minimally important level of side effects for the EPIC bowel subscale (AUC = 0.765, 95% CI = 0.617 to 0.913). These results show that ALERT-B provides a simple and effective screening tool for identifying gastroenterological complications after treatment for prostate cancer.

Safety, tolerability and efficacy of intra-articular Progenza in knee osteoarthritis: a randomized double-blind placebo-controlled single ascending dose study.

BACKGROUND: Cell therapies are being investigated as potential disease modifying treatment options for osteoarthritis (OA). Progenza (PRG) comprises in vitro expanded mesenchymal stem cells derived from human donor adipose tissue combined with cell culture supernatant. The primary objective of this first-in-human study was to evaluate the safety and tolerability of PRG. METHODS: We conducted a single centre, randomized, double-blind, placebo-controlled, single ascending dose study. Twenty patients aged 40-65 years with symptomatic Kellgren-Lawrence grade 1-3 knee OA were treated in two cohorts and randomized 4:1 to PRG or placebo. Cohort 1: 3.9 million cells (PRG 3.9M, n = 8) or placebo (n = 2) and cohort 2: 6.7 million cells (PRG 6.7M, n = 8) or placebo (n = 2). Each patient received a single intra-articular injection and was followed-up for 12 months. RESULTS: The study population comprised 20 patients (placebo, n = 4; PRG 3.9M, n = 8; PRG 6.7M, n = 8). All patients reported at least one treatment-emergent adverse event (TEAE). The majority of events [143/169 (84.6%)] were mild with 34 (20.1%) being considered by the investigator to be treatment related. There were no serious AEs or withdrawals due to AEs during the study. There was a statistically significant within group improvement in VAS pain scores from baseline at all timepoints for the PRG combined group, with highly significant improvements seen at months 3, 6, 9 and 12 (p ≤ 0.005) while VAS pain scores in the placebo group showed marginal improvement. A statistically significant improvement was also seen in WOMAC pain subscale scores from baseline at all timepoints for the PRG combined group while a marginal improvement in the placebo group was not statistically significant. Between screening and month 12, there was no decrease in average lateral tibial cartilage volume in the PRG 3.9M group while the placebo group showed a statistically significant cartilage loss. This difference between the placebo and PRG 3.9M group was statistically significant (LSM difference 106.47 mm3, 95% CI 13.56 mm3, 199.37 mm3, p = 0.028). CONCLUSION: When administered as a single intra-articular injection to patients with symptomatic knee OA, PRG was safe and well tolerated. Furthermore, measurable improvements in symptoms and knee structure outcomes warrant further studies on PRG's potential for disease modification in OA. Trial registration ANZCTR, ACTRN12615000439549. Date registered: 7th May 2015, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368355.

The Three-item ALERT-B Questionnaire Provides a Validated Screening Tool to Detect Chronic Gastrointestinal Symptoms after Pelvic Radiotherapy in Cancer Survivors.

AIMS: Although pelvic radiotherapy is an effective treatment for various malignancies, around half of patients develop significant gastrointestinal problems. These symptoms often remain undetected, despite the existence of effective treatments. This study developed and refined a simple screening tool to detect common gastrointestinal symptoms in outpatient clinics. These symptoms have a significant effect on quality of life. This tool will increase detection rates and so enable access to specialist gastroenterologists, which will in turn lead to improved symptom control and quality of life after treatment. MATERIALS AND METHODS: A literature review and expert consensus meeting identified four items for the ALERT-B (Assessment of Late Effects of RadioTherapy - Bowel) screening tool. ALERT-B was face tested for its usability and acceptability using cognitive interviews with 12 patients experiencing late gastrointestinal symptoms after pelvic radiotherapy. Thematic analysis and probe category were used to analyse interview transcripts. Interview data were presented to a group of experts to agree on the final content and format of the tool. ALERT-B was assessed for reliability and tested for validity against the Gastrointestinal Symptom Rating Scale in a clinical study (EAGLE). RESULTS: Overall, the tool was found to be acceptable in terms of wording, response format and completion time. Participant-reported experiences, including lifestyle modifications and the psychological effect of the symptoms, led to further modifications of the tool. The refined tool includes three questions covering rectal bleeding, incontinence, nocturnal bowel movements and impact on quality of life, including mood, relationships and socialising. ALERT-B was successfully validated against the Gastrointestinal Symptom Rating Scale in the EAGLE study with the tool shown broadly to be internally consistent (Cronbach's α = 0.61 and all item-subscale correlation [Spearman] coefficients are > 0.6). CONCLUSION: The ALERT-B screening tool can be used in clinical practice to improve post-treatment supportive care by triggering the clinical assessment of patients suitable for referral to a gastroenterologist.

Interventions to improve risk communication in clinical genetics: systematic review.

OBJECTIVE: Effective risk communication may enable clients to participate effectively in decision-making about their health and health care. A systematic review of existing literature on risk communication in genetics, and its effects on key outcomes for clients, was undertaken. METHOD: Systematic searching of six electronic databases and data extraction from included studies; narrative synthesis of results. RESULTS: Twenty-eight studies were included, principally from cancer genetics. Sixteen communication interventions have been evaluated, generally showing improvements in cognitive outcomes for users, such as knowledge, understanding and risk perception, and without adverse effects on anxiety, cancer-related worry and depression. However, often it was the supportive or emotional elements of counselling that provided benefits to users, rather than the informational or educational elements. Similar results were found in 12 further studies of decision aids which also appear to achieve shorter consultations that can focus more on the supportive elements of counselling. CONCLUSION: For both communication models and decision aids, the supportive or emotional elements of counselling provided more benefits to users than the informational or educational elements. PRACTICE IMPLICATIONS: Debate is required on how to strike a balance between the medical model, its agenda and perceived requirements to disclose or discuss a range of issues and the sometimes competing goals of addressing users' concerns, needs for support, issues of loss and relationship problems.

Cancer genetic risk assessment for individuals at risk of familial breast cancer.

BACKGROUND: The recognition of an inherited component to breast cancer has led to an increase in demand for information, reassurance, and genetic testing, resulting in the creation of genetics clinics for familial cancer. The first step for patients referred to a cancer genetic clinic is a risk assessment. OBJECTIVES: To evaluate the impact of cancer genetic risk assessment services on patients at risk of familial breast cancer. SEARCH STRATEGY: The specialised register maintained by the Cochrane Breast Cancer Group was searched. We also searched MEDLINE, EMBASE, CINAHL, PsycLIT, CENTRAL, DARE, ASSIA, Web of Science, SIGLE and LILACS. The searches covered the period 1985 to February 2005. We also hand-searched relevant journals. SELECTION CRITERIA: Trials looking at interventions for cancer genetic risk assessment delivery for familial breast cancer were considered for inclusion. Trials assessed outcomes such as understanding of risk, satisfaction and psychological well-being. Studies were excluded if they concerned cancers other than breast cancer or if participants were not at risk of breast cancer. Trials concerning the provision of information or education were also excluded as it was intended to review these separately. Participants could be individuals of any age or gender, with or without a known BRCA mutation, but without a previous history of breast cancer or any other serious illness. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. Additional information was sought from investigators as necessary. Due to the heterogeneity of both the interventions and outcomes, data were analysed descriptively. MAIN RESULTS: Fifty-eight papers were identified as relevant to the review, 54 of these were subsequently excluded. The three included trials (pertaining to five papers), provide data on 1251 participants and assessed the impact of cancer genetic risk assessment on outcomes including perceived risk, and psychological distress. This review suggests that cancer genetic risk assessment services help to reduce distress, improve the accuracy of the perceived risk of, and increase knowledge about, breast cancer and genetics. The health professional delivering the risk assessment does not appear to have a significant impact on these outcomes. AUTHORS' CONCLUSIONS: This review found favourable outcomes for patients' risk assessment for familial breast cancer. However, there were too few papers to make any significant conclusions about how best to deliver cancer genetic risk assessment services. Further research is needed assessing the best means of delivering cancer risk assessment, by different health professionals, in different ways and in alternative locations.

An exploratory comparison of genetic counselling protocols for HNPCC predictive testing.

Most UK genetics centres offering predictive testing for hereditary non-polyposis colorectal cancer (HNPCC) use an extended counselling protocol originally developed for Huntington's disease. Shortened counselling may be more appropriate in the context of treatable genetic conditions such as HNPCC. Twenty-six high-risk individuals were randomized to extended genetic counselling (two sessions of education and reflection held 1 month apart) or shortened genetic counselling (a single educational session) prior to HNPCC testing. Prospective questionnaires, interviews and transcripts of counselling sessions were analysed. Participants were unsure what to expect prior to genetic counselling and had already decided to undergo genetic testing. There was no evidence of psychological harm caused by shortened genetic counselling, with a high level of satisfaction with the counselling received in both groups. Reflective counselling occurred in both groups but was framed in terms of practical action and information. Participants expressed differing preferences for the level of information received. This exploratory study indicates that shortened genetic counselling may be an appropriate means of supporting decisions already made by individuals about HNPCC testing. However, participants would benefit from preparatory information to help them reflect on issues not previously considered, which can then be explored more fully as part of a tailored counselling approach.