Long-Term Antitumor Activity and Safety of Enzalutamide Monotherapy in Hormone Naïve Prostate Cancer: 3-Year Open Label Followup Results.

PURPOSE: A phase 2 study of enzalutamide monotherapy in patients with hormone naïve prostate cancer demonstrated high prostate specific antigen response rates at 25 weeks, 1 year and 2 years with minimal effects on total body bone mineral density and favorable safety. In this followup analysis we evaluated enzalutamide antitumor activity and safety at 3 years. MATERIALS AND METHODS: In a single arm analysis 67 patients with hormone naïve prostate cancer and noncastrate testosterone (230 ng/dl or greater) received enzalutamide 160 mg per day orally until disease progression or unacceptable toxicity. The primary end point was the prostate specific antigen response (80% or greater decline from baseline). RESULTS: No patients discontinued treatment during year 3. Of 42 patients with prostate specific antigen assessments at 3 years 38 (90.5%, 95% CI 77.4-97.3) maintained a prostate specific antigen response. Of 26 patients with metastases at baseline 17 (65.4%) had a complete or partial response as the best overall response during 3 years. In patients who completed the 3-year visit minimal mean changes from baseline were observed in total body bone mineral density or bone mineral density of the femoral neck, trochanter, spine L1-L4 or forearm (range -2.7% to -0.1%). At 3 years total body fat had increased a mean of 16.5%, total lean body mass had decreased a mean of -6.5% and global health status had minimally decreased from baseline. Common adverse events were gynecomastia, fatigue, hot flush and nipple pain. CONCLUSIONS: Enzalutamide antitumor activity was maintained in patients with hormone naïve prostate cancer at 3 years. Overall bone mineral density, global health status and safety results were similar to those at 2 years.

Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study.

BACKGROUND: The androgen receptor inhibitor enzalutamide is approved for the treatment of metastatic castration-resistant prostate cancer that has progressed on docetaxel. Our aim was to assess the activity and safety of enzalutamide monotherapy in men with hormone-naive prostate cancer. METHODS: This trial is an ongoing open-label, single-arm, phase 2 study, done across 12 European sites. Men aged over 18 years, with hormone-naive prostate cancer for whom hormone therapy was indicated, and who had non-castration levels of testosterone and prostate-specific antigen (PSA) of 2 ng/mL or greater at screening, and an Eastern Cooperative Oncology Group score of 0, received oral enzalutamide 160 mg/day. The primary outcome was the proportion of patients with an 80% or greater decline in PSA at week 25. All analyses included all patients who had received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT01302041. FINDINGS: 67 men were enrolled into the study. 62 patients (92.5%, 95% CI 86.2-98.8) had a decline in PSA of 80% or greater at week 25. The most commonly reported treatment-emergent adverse events up to week 25 were gynaecomastia (n=24), fatigue (n=23), nipple pain (n=13), and hot flush (n=12), all of which were of mild to moderate severity. Nine patients had a treatment-emergent adverse event of grade 3 or higher, most of which were reported in one patient each, except for pneumonia (grade 3, two patients) and hypertension (grade 3, four patients). Five patients reported serious adverse events, none of which were deemed to be treatment related. INTERPRETATION: Our findings suggest that enzalutamide monotherapy in men with hormone-naive prostate cancer of varying severity provides a level of disease suppression, and was generally well tolerated. These findings provide a rationale for further investigation of clinical response and outcomes with enzalutamide in non-castrate men with prostate cancer.

Prostate HistoScanning: a screening tool for prostate cancer?

OBJECTIVE: To evaluate Prostate HistoScanning as a screening tool for prostate cancer in a pilot study. METHODS: During a 6-month period, 94 men with normal or suspicious digital rectal examination, normal or elevated prostate-specific antigen, or an increased prostate-specific antigen velocity were examined with Prostate HistoScanning. Based on these parameters and HistoScanning analysis, 41 men were referred for prostate biopsy under computer-aided ultrasonographic guidance. The number of random biopsy cores varied depending on the prostate volume. Targeted biopsies were taken in the case of computer-aided ultrasonographic area suspicious for malignancy. A logistic regression analysis was carried out to estimate the probability of resulting in a positive prostate biopsy based on the HistoScanning findings. RESULTS: Following a logistic regression analysis, after adjusting for age, digital rectal examination, serum prostate-specific antigen level, prostate volume and tumor lesion volume, every cancer volume increase of 1 mL estimated by HistoScanning was associated with a nearly threefold increase in the probability of resulting in a positive biopsy (odds ratio 2.9; 95% confidence interval 1.2-7.0; P-value 0.02). Prostate cancer was found in 17 of 41 men (41%). In patients with cancer, computer-aided ultrasonography-guided biopsy was 4.5-fold more likely to detect cancer than random biopsy. The prostate cancer detection rate for random biopsy and directed biopsy was 13% and 58%, respectively. HistoScanning-guided biopsy significantly decreased the number of biopsies necessary (P-value <0.0001). CONCLUSIONS: Our findings suggest that Prostate HistoScanning might be helpful for the selection of patients in whom prostate biopsies are necessary. This imaging technique can be used to direct biopsies in specific regions of the prostate with a higher cancer detection rate.

Livelihoods, power, and food insecurity: adaptation of social capital portfolios in protracted crises--case study Burundi.

The failure of food security and livelihood interventions to adapt to conflict settings remains a key challenge in humanitarian responses to protracted crises. This paper proposes a social capital analysis to address this policy gap, adding a political economy dimension on food security and conflict to the actor-based livelihood framework. A case study of three hillsides in north Burundi provides an ethnographic basis for this hypothesis. While relying on a theoretical framework in which different combinations of social capital (bonding, bridging, and linking) account for a diverse range of outcomes, the findings offer empirical insights into how social capital portfolios adapt to a protracted crisis. It is argued that these social capital adaptations have the effect of changing livelihood policies, institutions, and processes (PIPs), and clarify the impact of the distribution of power and powerlessness on food security issues. In addition, they represent a solid way of integrating political economy concerns into the livelihood framework.

Detection, localisation and characterisation of prostate cancer by prostate HistoScanning(™).

UNLABELLED: What's known on the subject? and What does the study add? Prostate cancer is one of the few solid-organ cancers in which imaging is not used in the diagnostic process. Novel functional magnetic resonance imaging techniques offer promise but may not be cost-effective. Prostate HistoScanning(™) (PHS) is an ultrasound-based tissue characterisation technique that has previously shown encouraging results in the detection of clinically significant prostate cancer. The present study reports on the open 'unblinded' phase of a European multicentre study. The prospective 'blind' phase is currently in progress and will determine the value of PHS in a robust fashion overcoming many of the biases inherent in evaluating prostate imaging. OBJECTIVE: To evaluate the ability of prostate HistoScanning(™) (PHS) an ultrasound (US)-based tissue characterization application, to detect cancer foci by correlating results with detailed radical prostatectomy (RP) histology. PATIENT AND METHODS: In all, 31 patients with organ-confined prostate cancer, diagnosed on transrectal biopsies taken using US guidance, and scheduled for RP were recruited from six European centres. Before RP three-dimensional (3D) US raw data for PHS analysis was obtained. Histology by Bostwick Laboratories (London) examined sections obtained from whole mounted glands cut every 3-4 mm. Location and volume estimation of cancer foci by PHS were undertaken using two methods; a manual method and an embedded software tool. In this report we evaluate data obtained from a planned open study phase. The second phase of the study is 'blinded', and currently in progress. RESULTS: 31 patients were eligible for this phase. Three patients were excluded from analysis due to inadequate scan acquisition and pathology violations of the standard operating procedure. One patient withdrew from the study after 3D TRUS examination. PHS detected cancer ≥ 0.20 mL in 25/27 prostates (sensitivity 93%). In all, 23 patients had an index focus ≥ 0.5 mL at pathology, of which 21 were identified as ≥ 0.5 mL by PHS using the manual method (sensitivity 91%) and 19 were correctly identified as ≥ 0.5 mL by the embedded tool (sensitivity 83%). In 27 patients, histological analysis found 32 cancerous foci ≥ 0.2 mL, located in 97 of 162 sextants. After sextant analysis, PHS showed a 90% sensitivity and 72% specificity for the localisation of lesions ≥ 0.2 mL within a sextant. CONCLUSIONS: PHS has the ability to identify and locate prostate cancer and consequently may aid in pre-treatment and pre-surgical planning. In men with a lesion identified, it has potential to enable improved targeting, allowing better risk stratification by obtaining more representative cores. However further verification from the results of the blinded phase of this study are awaited.

Designing the selenium and bladder cancer trial (SELEBLAT), a phase lll randomized chemoprevention study with selenium on recurrence of bladder cancer in Belgium.

BACKGROUND: In Belgium, bladder cancer is the fifth most common cancer in males (5.2%) and the sixth most frequent cause of death from cancer in males (3.8%). Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of bladder cancer. This suggests that selenium may also be suitable for chemoprevention of recurrence. METHOD: The SELEBLAT study opened in September 2009 and is still recruiting all patients with non-invasive transitional cell carcinoma of the bladder on TURB operation in 15 Belgian hospitals. Recruitment progress can be monitored live at http://www.seleblat.org. Patients are randomly assigned to selenium yeast (200 µg/day) supplementation for 3 years or matching placebo, in addition to standard care. The objective is to determine the effect of selenium on the recurrence of bladder cancer. Randomization is stratified by treatment centre. A computerized algorithm randomly assigns the patients to a treatment arm. All study personnel and participants are blinded to treatment assignment for the duration of the study. DESIGN: The SELEnium and BLAdder cancer Trial (SELEBLAT) is a phase III randomized, placebo-controlled, academic, double-blind superior trial. DISCUSSION: This is the first report on a selenium randomized trial in bladder cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00729287.

Normative ethics does not need a foundation: it needs more science.

The impact of science on ethics forms since long the subject of intense debate. Although there is a growing consensus that science can describe morality and explain its evolutionary origins, there is less consensus about the ability of science to provide input to the normative domain of ethics. Whereas defenders of a scientific normative ethics appeal to naturalism, its critics either see the naturalistic fallacy committed or argue that the relevance of science to normative ethics remains undemonstrated. In this paper, we argue that current scientific normative ethicists commit no fallacy, that criticisms of scientific ethics contradict each other, and that scientific insights are relevant to normative inquiries by informing ethics about the options open to the ethical debate. Moreover, when conceiving normative ethics as being a nonfoundational ethics, science can be used to evaluate every possible norm. This stands in contrast to foundational ethics in which some norms remain beyond scientific inquiry. Finally, we state that a difference in conception of normative ethics underlies the disagreement between proponents and opponents of a scientific ethics. Our argument is based on and preceded by a reconsideration of the notions naturalistic fallacy and foundational ethics. This argument differs from previous work in scientific ethics: whereas before the philosophical project of naturalizing the normative has been stressed, here we focus on concrete consequences of biological findings for normative decisions or on the day-to-day normative relevance of these scientific insights.

Bipolar transurethral resection in saline: the solution to avoid hyponatraemia and transurethral resection syndrome.

OBJECTIVE: To compare serum sodium changes and the incidence of transurethral resection (TUR) syndrome after monopolar transurethral resection of the prostate (TURP) and bipolar transurethral resection in saline (TURIS) for symptomatic benign prostatic hyperplasia. MATERIAL AND METHODS: Between January 2005 and August 2009, 550 consecutive patients with symptomatic benign prostate hyperplasia underwent TURP, by either a monopolar or bipolar technique. Preoperative and postoperative blood parameters were analysed to compare preoperative and postoperative electrolyte concentrations. RESULTS: Over 56 months, 265 patients underwent a conventional monopolar TURP and 285 patients had a bipolar TURIS (Olympus). Patient profiles regarding age, operation time, resection weight and resection speed were similar in both groups. A drop in sodium of 2.5 mmol/l was measured in the conventional monopolar resection group. The decline of 1.5 mmol/l in the bipolar group, although smaller, was still statistically significant (p = 0.001). With longer operation times (> 1 h) the difference between the groups became more important (p < 0.001). Two clinical TUR syndromes were observed in the monopolar group, while none occurred in the bipolar group. CONCLUSIONS: Bipolar TURP in saline is a safe technique and obviates the risk of TUR syndrome. Repeated serum analysis of electrolytes after TURIS can be omitted.

Conventional monopolar resection or bipolar resection in saline for the management of large (>60 g) benign prostatic hyperplasia: an evaluation of morbidity.

The objective of this study was to compare the efficacy and safety of bipolar transurethral resection in saline (TURIS) and conventional monopolar transurethral resection (TURP) in men with voiding difficulties due to high volume (>60g) benign prostatic hyperplasia. Between May 2005 and January 2009, 66 men with bladder outlet obstruction due to large benign hyperplasia (BPH) (>60 g) underwent transurethral resection, either by Olympus monopolar or Olympus bipolar TURIS technique. Perioperative and outcome data were recorded and compared. There was no significant difference in patient age, prostate size, PSA, uroflow rate, post voiding residual urine, operation time, catheterization time, and hospital stay. In the monopolar TURP group, an important drop in serum sodium was observed (3.12 mmol/L), statistically significantly different (p = 0.012) from the 1.30 mmol/L drop in the bipolar TURIS group. One case of clinical TUR syndrome was observed in the conventional monopolar TURP group. Early and late complications such as clot retention, urinary retention, bladder neck stenosis, and urethral stricture were identical in both groups. The bipolar TURIS device is a valid treatment option for patients with BPH-related voiding disorders due to high volume BPH. Obviating the risk of TUR syndrome, this minimally invasive procedure may be a good surgical option in the urologist's armamentarium.

Computer-aided ultrasonography (HistoScanning): a novel technology for locating and characterizing prostate cancer.

OBJECTIVE: To assess the extent to which prostate HistoScanning (PHS), a new ultrasound-based technology that uses computer-aided analysis to quantify tissue disorganization induced by malignant processes, can identify and characterize foci of prostate cancer compared with step-sectioned radical prostatectomy (RP) specimens. PATIENTS AND METHODS: Between September 2004 and February 2006, 29 men had PHS before their scheduled RP. A three-dimensional ultrasound raw-data file was acquired, and PHS analysed regions of interest (ROI) corresponding to tissue volumes of approximately 0.04 mL. In 13 men the histology was examined on sections of the whole-mount prostate onto which a grid of 5 x 5 mm squares was applied. On a test set of 14 of the 29 patients, PHS analysis was used before knowing the histology results (blinded data), to predict the maximum tumour diameter, focality, laterality and extraprostatic extension (EPE). RESULTS: Identification and characterization by PHS of the index tumour in the 14 patients in the test set correlated closely (r = 0.95, P < 0.001) with the reference test. The concordance in the attribution of multifocality (present/absent), unilateral/bilateral disease between PHS and histology was 100%. EPE as determined by PHS was attributed to all three pT3a pathological specimens in the blinded paired data. In the same set of data, EPE was attributed to one prostate cancer that on pathological inspection was deemed to be organ-confined (pT2b). CONCLUSIONS: PHS has the potential to identify and characterize prostate cancer foci noninvasively. The precision appears to be sufficient to suggest that PHS might be useful as a triage test for men deemed to be at risk of prostate cancer and who wish to avoid prostate biopsy.

The accuracy of transrectal ultrasonography supplemented with computer-aided ultrasonography for detecting small prostate cancers.

OBJECTIVE: To determine the extent to which computer-aided ultrasonography of the prostate (HistoScanning, Advanced Medical Diagnostics, Waterloo, Belgium) can identify tumour foci that correspond to a volume of >or=0.50 mL. PATIENTS AND METHODS: Between September 2004 and February 2006, 29 men were HistoScanned before scheduled radical prostatectomy. The three-dimensional raw (grey-scaled) data required for HistoScanning analysis were acquired by transrectal ultrasonography, and analysed using organ-specific tissue-characterization algorithms which form the core of the HistoScanning technology. The HistoScanning analysis results were compared with the histology of the whole-mounted prostate, step-sectioned sagittally at 5-mm intervals, and each slide analysed by 5 x 5 mm grid analysis. RESULTS: Of 29 patients, 13 had histology unknown to those evaluating the HistoScanning data. With 0.50 mL as the lower threshold for delineating and visualizing cancer volume, HistoScanning correctly predicted the presence of all 12 lesions that were subsequently confirmed to occupy >or=0.50 mL. In addition three lesions were predicted as being present and of >or=0.50 mL. These three lesions were subsequently confirmed to be present but were or=0.50 mL; these encouraging results will need to be verified in a larger group of patients.

Prognostic factors in prostate cancer.

In the nineteenth century the main goal of medicine was predictive: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted to cure the disease. Since the twentieth century, the word prognosis has also been used in nonmedical contexts, for example in corporate finance or elections. The most accurate form of prognosis is achieved statistically. Based on different prognostic factors it should be possible to tell patients how they are expected to do after prostate cancer has been diagnosed and how different treatments may change this outcome. A prognosis is a prediction. The word prognosis comes from the Greek word (see text) and means foreknowing. In the nineteenth century this was the main goal of medicine: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted towards seeking a cure. Prognostic factors in (prostate) cancer are defined as "variables that can account for some of the heterogeneity associated with the expected course and outcome of a disease". Bailey defined prognosis as "a reasoned forecast concerning the course, pattern, progression, duration, and end of the disease. Prognostic factors are not only essential to understand the natural history and the course of the disease, but also to predict possible different outcomes of different treatments or perhaps no treatment at all. This is extremely important in a disease like prostate cancer where there is clear evidence that a substantial number of cases discovered by prostate-specific antigen (PSA) testing are unlikely ever to become clinically significant, not to mention mortal. Furthermore, prognostic factors are of paramount importance for correct interpretation of clinical trials and for the construction of future trials. Finally, according to WHO national screening committee criteria for implementing a national screening programme, widely accepted prognostic factors must be defined before assessing screening.

Celebrities: From Teachers to Friends : A Test of Two Hypotheses on the Adaptiveness of Celebrity Gossip.

In this paper we present two compatible hypotheses to explain interest in celebrity gossip. The Learning Hypothesis explains interest in celebrity gossip as a by-product of an evolved mechanism useful for acquiring fitness-relevant survival information. The Parasocial Hypothesis sees celebrity gossip as a diversion of this mechanism, which leads individuals to misperceive celebrities as people who are part of their social network. Using two preliminary studies, we tested our predictions. In a survey with 838 respondents and in-depth interviews with 103 individuals, we investigated how interest in celebrity gossip was related to several dimensions of the participants' social lives. In support of the Learning Hypothesis, age proved to be a strong predictor of interest in celebrities. In partial support of the Parasocial Hypothesis, media exposure, but not social isolation, was a strong predictor of interest in celebrities. The preliminary results support both theories, indicate that across our life span celebrities move from being teachers to being friends, and open up a list of future research opportunities.

Management of BPH then 2000 and now 2016 - From BPH to BPO.

The diagnosis and treatment of benign prostatic obstruction (BPO) is based on a number of well-known lower urinary tract symptoms (LUTS) feared by all ageing males with functional testes. The ascent of modern urology turned this disease from lethal into an annoying but treatable health problem in the previous century. We are able to relieve the great majority of patients from their bothersome symptoms to a respectable quality of life by medication or removal of the obstructive part of the enlarged prostate. We can be proud of some progress made in the new millennium to reach a correct diagnosis and subsequent choice of treatment aiming for quality of life and cost-efficiency for public health. Still it remains symptomatic treatment and we expect the new generation of urologists to close some gaps in our knowledge on the regulation of prostatic growth to focus on prevention and elimination of the disease in the foreseeable future.

The sociobiology of genes: the gene's eye view as a unifying behavioural-ecological framework for biological evolution.

Although classical evolutionary theory, i.e., population genetics and the Modern Synthesis, was already implicitly 'gene-centred', the organism was, in practice, still generally regarded as the individual unit of which a population is composed. The gene-centred approach to evolution only reached a logical conclusion with the advent of the gene-selectionist or gene's eye view in the 1960s and 1970s. Whereas classical evolutionary theory can only work with (genotypically represented) fitness differences between individual organisms, gene-selectionism is capable of working with fitness differences among genes within the same organism and genome. Here, we explore the explanatory potential of 'intra-organismic' and 'intra-genomic' gene-selectionism, i.e., of a behavioural-ecological 'gene's eye view' on genetic, genomic and organismal evolution. First, we give a general outline of the framework and how it complements the-to some extent-still 'organism-centred' approach of classical evolutionary theory. Secondly, we give a more in-depth assessment of its explanatory potential for biological evolution, i.e., for Darwin's 'common descent with modification' or, more specifically, for 'historical continuity or homology with modular evolutionary change' as it has been studied by evolutionary developmental biology (evo-devo) during the last few decades. In contrast with classical evolutionary theory, evo-devo focuses on 'within-organism' developmental processes. Given the capacity of gene-selectionism to adopt an intra-organismal gene's eye view, we outline the relevance of the latter model for evo-devo. Overall, we aim for the conceptual integration between the gene's eye view on the one hand, and more organism-centred evolutionary models (both classical evolutionary theory and evo-devo) on the other.

Future of keeping pet reptiles and amphibians: towards integrating animal welfare, human health and environmental sustainability.

The keeping of exotic pets is currently under debate and governments of several countries are increasingly exploring the regulation, or even the banning, of exotic pet keeping. Major concerns are issues of public health and safety, animal welfare and biodiversity conservation. The keeping of reptiles and amphibians in captivity encompasses all the potential issues identified with keeping exotic pets, and many of those relating to traditional domestic pets. Within the context of risks posed by pets in general, the authors argue for the responsible and sustainable keeping of reptile and amphibian pets by private persons, based on scientific evidence and on the authors' own expertise (veterinary medicine, captive husbandry, conservation biology).

Urinary incontinence in patients with cystic fibrosis.

OBJECTIVE: Owing to evolution in treatment, the average life expectancy of patients with cystic fibrosis (CF) has increased. This has been followed by an increase in urological complications such as urinary incontinence. As stress incontinence occurs during exercise, it may have a negative effect on the implementation of respiratory physiotherapy. The purpose of this study is to determine the prevalence of urinary incontinence and its effect on the quality of life and physiotherapy in a population with CF. MATERIALS AND METHODS: Questionnaires were used to determine the prevalence of incontinence in patients of the Cystic Fibrosis Clinic of the University Hospital in Brussels. Two different surveys were used, depending on the age of the patients (< 12 or ≥ 12 years). The different characteristics of incontinence were emphasized. RESULTS: Questionnaires were completed by 122 participants aged 6-59 years, showing an overall prevalence of 27% for urinary incontinence. Mainly adults reported urinary incontinence, with a prevalence of 11% in men and 68% in women aged 12 and above. The amount of urinary leakage was usually only a few drops and it was mainly triggered by coughing. Many of the participants had never mentioned this symptom to anyone. CONCLUSIONS: Doctors' and physical therapists' attention should be drawn to the fact that urinary incontinence is part of the complication spectrum of CF. A quarter of the study population refrained from coughing up phlegm and from physiotherapy. It is important to actively question and inform about this problem, to enable its detection and treatment.

Changes in Body Image in Patients with Prostate Cancer over 2 Years of Treatment with a Gonadotropin-Releasing Hormone Analogue (Triptorelin): Results from a Belgian Non-Interventional Study.

BACKGROUND: Androgen deprivation therapy has been associated with worsened body image in prostate cancer patients. Body image and physical presentation changes were investigated in patients receiving a gonadotropin-releasing hormone analogue (triptorelin) as part of treatment for locally advanced or metastatic prostate cancer. OBJECTIVE: The aim was to evaluate the changes in self-perception of the body and to assess the relationship of these changes over a period of 2 years in men treated with triptorelin as primary therapy for advanced or locally advanced prostate cancer. METHODS: Data were collected for 2 years in accordance with routine clinical practice. Body image was assessed using the body image scale (BIS). Patient body mass index (BMI) and waist circumference were also measured. RESULTS: BIS and BMI data for both baseline and a least one post-baseline visit were available for 98 of the 145 patients enrolled. The median change in BIS score for patients assessed around 12 or 24 months after baseline and at the last observation was zero, indicating no body image deterioration in at least half of patients. Statistically significant BIS score increases were detected in assessments around 6, 12 and 18 months, but not after 2 years, indicating some patients experienced body image deterioration at some point during treatment. Changes in BMI from baseline were modest and generally not statistically significant. Waist circumference increased during the study (mean ± standard deviation increase of 1.00 ± 5.01 cm at the last observation). Positive correlations were determined between increases in BIS score and both BMI and waist circumference (r = 0.235 and 0.267, respectively; p = 0.020 and 0.008) at the last observation for all patients, as well as during the second year of the study. CONCLUSIONS: Most patients did not experience clinically meaningful worsening of body image perception during the study. BMI and waist circumference had a modest impact on body image during study year 2.