Real world study of sacituzumab govitecan in metastatic triple-negative breast cancer in the United Kingdom.

BACKGROUND: Treatment options for pre-treated patients with metastatic triple-negative breast cancer (mTNBC) remain limited. This is the first study to assess the real-world safety and efficacy of sacituzumab govitecan (SG) in the UK. METHODS: Data was retrospectively collected from 16 tertiary UK cancer centres. Pts had a diagnosis of mTNBC, received at least two prior lines of treatment (with at least one being in the metastatic setting) and received at least one dose of SG. RESULTS: 132 pts were included. Median age was 56 years (28-91). All patients were ECOG performance status (PS) 0-3 (PS0; 39, PS1; 76, PS2; 16, PS3;1). 75% (99/132) of pts had visceral metastases including 18% (24/132) of pts with CNS disease. Median PFS (mPFS) was 5.2 months (95% CI 4.5-6.6) with a median OS (mOS) of 8.7 months (95% CI 6.8-NA). The most common adverse events (AEs) were fatigue (all grade; 82%, G3/4; 14%), neutropenia (all grade; 55%, G3/4; 29%), diarrhoea (all grade; 58%, G3/4, 15%), and nausea (all grade; 38%, G3/4; 3%). SG dose reduction was required in 54% of pts. CONCLUSION: This study supports significant anti-tumour activity in heavily pre-treated pts with mTNBC. Toxicity data aligns with clinical trial experience.

Genomic testing in high-grade serous ovarian cancer: current options and future development.

Understanding the genomic complexity of high-grade serous ovarian cancer is now essential in guiding patient management, particularly in the first-line setting. Our knowledge in this area has expanded rapidly in recent years, with biomarkers developing in parallel to agents designed to exploit cancer-associated genetic aberrations. In this review we will take stock of the current landscape of genetic testing and look towards the future with developments that aim to refine personalized treatment paradigms and track treatment resistance in real time.

Health utility in community-dwelling adults with dysvascular lower limb loss.

PURPOSE: Adults with dysvascular lower extremity amputation (LEA) experience a large number of secondary health conditions yet there is a gap in the literature on health utility scores for this population. A health utility score relates to a person's state of well-being, and is a single metric anchored at 0 (death) and 1 (perfect health). This study aimed to provide a descriptive account of health utility scores in community-dwelling adults with dysvascular LEA. METHODS: Participants were adults with dysvascular LEA who were 3 months post-amputation. Data collected included socio-demographic characteristics, the Special Interest Group in Amputee Medicine (SIGAM) grades, the dysvascular conditions scale (DCS), which is a scale developed for this study, and the Short Form-36 (SF-36). SF-6D health utility scores were derived from the SF-36 using a software algorithm. Participants were grouped into low-impact and high-impact groups based on self-reported severity of symptoms using the DCS. Health utility scores were compared between the low-impact and high-impact groups using independent t-tests. RESULTS: A total of 231 participants were enrolled in the study. The mean SF-6D health utility score was 0.689 (0.127). A significant association was found between health utility score and SIGAM grade (p < 0.001, η2 = .09). Health utility was positively associated with age (r = 0.137, p = 0.037) and months post-amputation (r = 0.141, p = 0.032), and negatively associated with DCS severity (r = -0.526, p < 0.001). Health utility scores were lower for participants in the DCS high-impact groups for conditions such as diabetes mellitus, phantom limb pain, musculoskeletal pain, back pain, psychological distress, depression, vision problems, and other pain. CONCLUSION: Cost-utility analyses rely on health utility estimates and our findings provide data for future economic evaluations that may assist policy makers in evidence informed allocation of healthcare resources for this population.

A case of immune-mediated encephalitis related to daclizumab therapy.

This report will detail a case of immune-mediated encephalitis in the context of daclizumab therapy. Daclizumab is a humanised monoclonal antibody which, prior to its recent worldwide withdrawal due to safety concerns, was utilised as a disease-modifying therapy in relapsing-remitting multiple sclerosis. The withdrawal of this therapy was prompted by concerns over 12 cases of serious immune-mediated adverse reactions in the central nervous system. We report an additional case, including clinical data and results of neuroimaging, cerebrospinal fluid (CSF) examination and brain biopsy.

Eating pathology and associations with long-term changes in weight and quality of life in the longitudinal assessment of bariatric surgery study.

OBJECTIVE: This study examines the course of eating pathology and its associations with change in weight and health-related quality of life following bariatric surgery. METHOD: Participants (N = 184) completed the eating disorder examination-bariatric surgery version (EDE-BSV) and the medical outcomes study 36-Item short form health survey (SF-36) prior to and annually following Roux-en-Y gastric bypass (RYGB) or laparoscopic adjustable gastric banding (LAGB) for up to 7 years. RESULTS: The prevalence of ≥ weekly loss of control (LOC) eating, picking/nibbling, and cravings declined post-RYGB and remained lower through 7 years (LOC: 5.4% at Year-7 vs. 16.2% pre-RYGB, p = .03; picking/nibbling: 7.0% vs. 32.4%, p < .001; and cravings: 19.4% vs. 33.6%, p = .02). The prevalence of picking/nibbling was significantly lower 7 years following LAGB vs. pre-LAGB (29.4% vs 45.8%, p = .049), while cravings (p = .13) and LOC eating (p = .95) were not. EDE-BSV global score and ratings of hunger and enjoyment of eating were lower 7 years following both RYGB and LAGB versus pre-surgery (p's for all <.05). LOC eating following RYGB was associated with less long-term weight loss from surgery (p < .01) and greater weight regain from weight nadir (p < .001). Higher post-surgery EDE-BSV global score was associated with less weight loss/greater regain (both p < .001) and worsening/less improvement from surgery in the SF-36 mental component summary scores (p < .01). DISCUSSION: Initial improvements in eating pathology following RYGB and LAGB were sustained across 7 years of follow-up. Individuals with eating pathology post-RYGB, reflected by LOC eating and/or higher EDE-BSV global score, may be at risk for suboptimal long-term outcomes.

The effect of acute weight restoration on dietary fat preference in hospitalized patients with anorexia nervosa.

OBJECTIVE: Individuals with anorexia nervosa (AN) restrict fat intake. The Geiselman Food Preference Questionnaire-I© (FPQ) is a validated self-report instrument that yields a fat preference score (>100 = high fat preference, <100 = low fat preference). The goal of the study was to assess the utility of the FPQ in patients with AN. SPECIFIC AIMS: (1) to examine change in fat preference scores before and after weight restoration in hospitalized patients; and (2) to compare patients' scores before and after weight restoration to scores from healthy participants (HPs). METHOD: The FPQ was completed by 88 patients and 115 HPs. RESULTS: Compared with HPs, patients had significantly lower fat preference scores before (74.03 ± 32.03 vs. 102.93 ± 16.89, P < 0.001) and after (81.51 ± 26.89 vs. 102.92 ± 16.89, P < 0.001) weight restoration. Fat preference scores increased with weight gain (74.03 + 32.03 vs. 81.51 + 26.89, P < 0.01) but did not normalize in AN. DISCUSSION: Acutely weight restored patients continue to endorse decreased preference for high fat foods. The FPQ may be a useful metric by which to assess improvements in diet during treatment. Further study is warranted to validate the FPQ against observed food intake in AN. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:148-151).

Assessment of the motivation to use artificial sweetener among individuals with an eating disorder.

Eating disorders are associated with a range of abnormalities in eating behavior. Some individuals consume large amounts of non-caloric artificial sweeteners, suggesting abnormalities in appetitive responding. The current study aimed to quantify hedonic and motivating effects of artificial sweetener in individuals with and without an eating disorder. Two laboratory studies were conducted. Hedonic preference was estimated using the number of artificial sweetener packets (0-10) added to unsweetened cherry flavored Kool-Aid (study 1). Motivation to obtain sweetener was assessed by a progressive ratio (PR) work task (study 2). Ninety-three participants (25 anorexia nervosa restricting type (AN-R), 23 AN binge/purge type (AN-B/P), 20 bulimia nervosa (BN), and 25 normal controls (NC)) completed the study. No significant difference in hedonic preference was found among participant groups. Work completed at the PR task ranged from 0 to 9500 key-board presses. The AN-B/P group had a significantly higher breakpoint and performed significantly more work for sweetener compared to the BN and NC groups. Among AN-B/P and AN-R participants, the preferred number of Equal packets was significantly correlated with the breakpoint and total work. The increased amount of work for sweetener among individuals with AN-B/P supports an enhanced reward value of sweet taste in this population, and suggests that the characteristic food avoidance in AN cannot be accounted for by decreased reward value of all taste-related stimuli. This study also supports the novel application of a PR ratio task to quantify the motivating effect of sweet taste among individuals with an eating disorder.

Psychiatric Disorders and Weight Change in a Prospective Study of Bariatric Surgery Patients: A 3-Year Follow-Up.

OBJECTIVES: To document changes in Axis I psychiatric disorders after bariatric surgery and examine their relationship with postsurgery weight loss. METHODS: As part of a three-site substudy of the Longitudinal Assessment of Bariatric Surgery Research Consortium, 199 patients completed the Structured Clinical Interview for DSM-IV before Roux-en-Y gastric bypass or laparoscopic adjustable gastric band. At 2 or 3 years after surgery, 165 (83%) patients completed a follow-up assessment (presurgery median body mass index = 44.8 kg/m, median age = 46 years, 92.7% white, 81.1% female). Linear-mixed modeling was used to test change in prevalence of psychiatric disorders over time, report remission and incidence, and examine associations between psychiatric disorders and weight loss. RESULTS: Compared with status presurgery, the prevalence of any Axis I psychiatric disorder was significantly lower at 2 and 3 years after surgery (30.2% versus 16.8% [p = .003] and 18.4% [p = .012], respectively). Adjusting for site, age, sex, race, presurgery body mass index, and surgical procedure, presurgery mood, anxiety, eating or substance use disorders (lifetime or current) were not related to weight change, nor were postsurgery mood or anxiety disorders (p for all > .05). However, having a postsurgery eating disorder was independently associated with less weight loss at 2 or 3 years (ß = 6.7%, p = .035). CONCLUSIONS: Bariatric surgery was associated with decreases in psychiatric disorders through 3 years after surgery. Postsurgical eating disorders were associated with less weight loss after surgery, adding to the literature suggesting that disordered eating after surgery is related to suboptimal weight loss.

Eating pathology and experience and weight loss in a prospective study of bariatric surgery patients: 3-year follow-up.

OBJECTIVE: Bariatric surgery results in significant long-term weight loss, albeit with considerable variability. This study examines the prognostic significance of eating pathology as determined by a structured interview, the Eating Disorder Examination-Bariatric Surgery Version (EDE-BSV). METHOD: Participants (N = 183) in this substudy of the Longitudinal Assessment of Bariatric Surgery (LABS) Research Consortium were assessed using the EDE-BSV, independent of clinical care, presurgery and annually postsurgery. We examined eating pathology and experiences at several frequency thresholds (present, ≥ monthly, ≥ weekly) over 3 years, and utilized mixed models to test their associations with percentage weight loss from baseline at years 1, 2, and 3. RESULTS: The prevalence of several forms of eating pathology declined pre- to 1-year postsurgery, including ≥weekly objective bulimic episodes (11.6-1.3%), loss of control (LOC) eating (18.3-6.2%) and picking/nibbling (36.0-20.2%) (P for all <0.01), and regular evening hyperphagia (16.5-5.0%, P = 0.01), but not cravings (P = 0.93). Mean EDE global score, and hunger and enjoyment scores, also declined (P for all <0.01). These metrics remained lower than baseline through year-3 (P for all <0.01). Presurgery eating variables were not related to weight loss (P for all ≥0.05). However, postsurgery higher EDE global score and greater hunger were independently associated with less weight loss postsurgery (P for both ≤0.01), while cravings were associated with greater weight loss (P = 0.03). DISCUSSION: Pathological eating behaviors and experiences are common presurgery and improve markedly following surgery. Postsurgery pathological eating-related experiences and attitudes and hunger may contribute to suboptimal weight loss. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:1058-1067).

The preventative power of "pink": Delineating the effects of social identification and protection motivation theory in breast cancer-related advertisements.

An online experiment was conducted to assess the extent gender-salient breast cancer awareness advertisements had on influencing risk perception, encouraging preventative behaviors, and gathering health information. Social identification theory and protection motivation theory postulate gender-salient pink-branded advertisements trigger defense mechanisms, countering desired outcomes. This study concludes gender-salient ads focusing on women, and displaying the Susan G. Komen logo caused aversive behaviors, whereas gender-neutral ads, showing medical providers and logos such as American Medical Association, improve health-related reporting. Results also highlight a disconnect between women who socially identify as breast cancer survivors/supporters, and those with no prior experience with breast cancer.

The Association Between Reduced Inflammation and Cognitive Gains After Bariatric Surgery.

OBJECTIVE: Bariatric surgery is associated with improved cognitive function, although the mechanisms are unclear. Elevated inflammation is common in obesity and associated with impaired cognition. Inflammation decreases after bariatric surgery, implicating it as a possible mechanism for cognitive improvement. The objective of this study was to examine whether reduced inflammation is a possible mechanism for postoperative cognitive improvement in bariatric surgery patients. METHODS: Participants were 77 bariatric surgery patients who completed cognitive testing before surgery and 1 year postsurgery. Cognitive domains assessed were attention/executive function, language, and memory. High-sensitivity C-reactive protein (CRP) was assessed at both time points. RESULTS: Patients exhibited preoperative cognitive impairment, although improvements 1 year postsurgery were seen in both attention/executive function (mean [M; standard deviation {SD}]baseline = 53.57 [8.68] versus M (SD)follow-up= 60.32 [8.19]) and memory (M [SD]baseline= 44.96 [7.98] versus M [SD]follow-up= 51.55 [8.25]). CRP was elevated at baseline and fell into the normative range postsurgery (M [SD]baseline= 0.9 [0.7] versus M [SD]follow-up= 0.2 [0.3] mg/dl). Preoperative CRP was not associated with baseline cognitive function (ß values = -0.10 to 0.02) and changes in CRP also did not correspond to changes in cognition postsurgery (ß values = 0.02-0.11; p values > .05 for all domains). A trend was detected for smaller improvements in memory among participants with elevated baseline CRP (>0.30 mg/dl) versus those with normal levels (group × time: p = .083). CONCLUSIONS: Improvements in high-sensitivity CRP were not associated with postoperative cognitive benefits. Future studies are needed to explore other inflammatory markers and potential mechanisms of cognitive improvement after bariatric surgery, including improved glycemic control and neurohormone changes.

Binge eating disorder and medical comorbidities in bariatric surgery candidates.

OBJECTIVE: To determine whether binge eating disorder (BED) status is associated with medical comorbidities in obese adults scheduled for bariatric surgery. METHOD: The study utilized Longitudinal Assessment of Bariatric Surgery-2 data obtained from six clinical centers around the United States. This is a well-phenotyped cohort of individuals who were evaluated within 30 days before their scheduled surgery using standardized protocols. In the cohort, 350 participants were classified as having BED and 1,875 as not having BED (non-BED). Multivariable logistic regression was used to determine whether BED status was independently related to medical comorbidities. As an exploratory analysis, significance was based on nominal p-values (p < .05). Holm's-adjusted p-values were also reported. RESULTS: After adjusting for age, sex, education, and body mass index, BED status was found to be independently associated with four of the 15 comorbidities (i.e., impaired glucose levels (odds ratio [OR] = 1.45 (95% confidence interval [CI]: 1.12-1.87)), high triglycerides (OR = 1.28 (95% CI: 1.002-1.63)), and urinary incontinence (OR = 1.30 (95% CI: 1.02-1.66)), all being more common among the BED sample, and severe walking limitations being less common in the BED sample (OR = 0.53 (95% CI: 0.29-0.96)). With further adjustment for psychiatric/emotional health indicators, BED status was independently associated with three comorbidities (impaired glucose levels (OR = 1.36 (95% CI: 1.04-1.79)), cardiovascular disease (OR = 0.50 (95% CI: 0.30-0.86)), and severe walking limitations (OR = 0.38 (95% CI: 0.19-0.77)). However, Holm's-adjusted p-values for all variables were greater than .05. DISCUSSION: The results suggest the possibility of a contribution of BED to risk of specific medical comorbidities in severely obese adults.

The influence of a concurrent cognitive task on lower limb reaction time among stroke survivors with right- or left-hemiplegia.

OBJECTIVE: To determine the impact of cognitive interference on foot pedal reaction time among stroke survivors with right- (RH) or left-hemiplegia (LH). DESIGN: Cross-sectional comparison without randomization. SUBJECTS/PATIENTS: 10 patients post-stroke with RH, 10 with LH; 10 age-matched controls. METHODS: Foot pedal response times were measured using three different reaction time (RT) paradigms: simple RT, dual-task RT (counting backward by serial 3 seconds), and choice RT (correct response contingent on stimuli to eliminate pre-programing). RH and LH used the non-paretic leg for all trials. Three 3 (RT task) × 3 (group) mixed-model factorial ANOVAs were used to compare RT, movement time (MT), total response time (TRT). RESULTS: Overall controls demonstrated faster RT than RH (332 ± 73 versus 474 ± 144 ms, P < 0.001) or LH (402 ± 127 ms, P < 0.05); LH group demonstrated faster RT than those with RH (P < 0.05). Control subjects demonstrated significantly faster RT than RH for all RT conditions (P < 0.05 for all). In contrast, controls achieved significantly faster RT than LH for the choice RT condition only (P < 0.05), but not for the simple (P = 0.12) or dual-task RT conditions (P = 0.25). CONCLUSIONS: Compared to controls, response time was significantly impaired among LH and RH when the response could not be pre-programmed. While current simple RT testing commonly employed by driver rehab specialists may be sufficient for detecting RT deficits in patients with RH, simple or dual-task RT tests alone may fail to detect RT deficiencies among LH, even when testing the non-paretic limb. Choice RT should be added to post-stroke driver fitness assessment, particularly for patients with LH.

Pre-operative history of depression and cognitive changes in bariatric surgery patients.

Obesity-associated cognitive impairments may be partially reversible through bariatric surgery. Depression, a prevalent comorbidity in bariatric surgery candidates, is linked with cognitive impairment and poorer surgical outcomes in other populations. No study has examined the effects of pre-operative depression on cognitive changes in bariatric surgery patients. Sixty-seven bariatric surgery patients completed a computerized cognitive test battery prior to surgery and 12 months post-operatively. The structured clinical interview for the DSM-IV Axis I disorders assessed major depressive disorder (MDD). Pre-surgery history of MDD was found in 47.8% of patients, but was not associated with greater baseline cognitive impairments. Repeated measures revealed improved cognitive abilities 12 months after surgery. Pre-surgery history of MDD did not influence post-operative cognitive function. Pre-operative history of MDD did not limit post-operative cognitive improvements. Larger studies with extended follow-ups are needed to clarify our findings and identify factors (e.g. older age) that may modify cognitive changes following surgery.

Suicidal Ideation and Behaviours Among Adolescents Receiving Bariatric Surgery: A Case-Control Study.

OBJECTIVE: This study examined the prevalence and correlates of suicidal ideation and behaviour (SI/B) among adolescents receiving bariatric surgery. METHOD: Charts of 206 adolescents receiving bariatric surgery were reviewed. Cases with SI/B (current/lifetime reported at baseline or event occurring in the programme n = 31, 15%) were case matched on gender, age and surgery type to 31 adolescents reporting current or past psychiatric treatment and 31 adolescents denying lifetime SI/B or psychiatric treatment. RESULTS: Before surgery, adolescents with SI/B reported significantly lower total levels of health-related quality of life (p = 0.01) and greater depressive symptoms (p = 0.004) in comparison with candidates who never received psychiatric treatment. No significant differences were found between groups for the change in depressive symptoms or body mass index following surgery. CONCLUSIONS: As in studies of adults, a notable subset of adolescents receiving bariatric surgery indicated pre-operative or post-operative SI/B. It is critical that clinicians evaluate and monitor adolescent patients undergoing bariatric surgery for risk of SI/B.

"Where Does the Circle End?": Representation as a Critical Aspect of Reflection in Teaching Social and Behavioral Sciences in Medicine.

OBJECTIVE: This paper describes a reflective learning program within a larger curriculum on behavioral and social science that makes use of close reading, written representation of experience, discussion, and textual response. This response may in turn lead to further reflection, representation, and response in a circular pattern. A unique feature of this program is that it pays attention to the representation itself as the pivotal activity within reflective learning. Using the narrative methods that are the hallmark of this program, faculty writings were analyzed to characterize the essential benefits that derive from these practices. METHODS: In the context of a faculty development seminar on the teaching of behavioral and social sciences in medical curricula, a group of 15 faculty members wrote brief narratives of reflective learning experiences in which they had made use of the methods described above. Their responses were submitted to iterative close reading and discussion, and potential themes were identified. RESULTS: Four themes emerged: writing as attention to self, writing as attention to other, writing as reader/writer contract, and writing as discovery. In each instance, writing provides a new or deepened perspective, and in each case, the dividends for the writer are amplified by the narrative skills of those who read, listen, and respond. CONCLUSIONS: The narrative pedagogy described and modeled herein provides a potentially promising approach to teaching the social, cultural, behavioral, and interpersonal aspects of medical education and practice. Future research will deepen our understanding of the benefits and limitations of this pedagogy and expand our appreciation of its applications.

Assessment of fat taste in individuals with and without anorexia nervosa.

OBJECTIVE: Avoidance of dietary fat is a highly characteristic eating behavior of individuals with anorexia nervosa (AN). To date, no study has determined whether these individuals are better able to perceive the fat content of foods than individuals without AN. The goal of this study was to compare blinded taste ratings of fat-free, low fat, and regular cream cheese in patients with AN and in normal controls (NC). METHOD: AN (n = 25) and control (NC; n = 25) participants were presented with a series of nine cream cheese samples of three differing fat contents and asked to taste and rate each sample from very low to very high fat. RESULTS: Repeated measures ANOVA found no significant main effect of fat content and no interaction between fat content and diagnosis; however, a significant three-way interaction between fat content, diagnosis, and trial was observed. Post hoc analysis revealed a significant fat content by trial interaction within the AN group, suggesting a significant trial effect for the fat-free samples only with improving ability to detect fat-free samples over repeated trials. DISCUSSION: The current study suggests that individuals with AN do not have a markedly greater ability to taste fat than NC, and that; therefore, fat avoidance is likely primarily based on cognitive factors.

Physical activity and cognitive function in bariatric surgery candidates.

Cognitive impairment is common in severe obesity. Lack of physical activity is a likely contributor to impairment in this population, as many obese persons are inactive and physical activity has been positively and independently associated with cognitive function in healthy and medically-ill samples. This study investigated whether physical activity, measured by self-report of aerobic physical activity in 85 bariatric surgery candidates, was associated with cognitive function. A subset of 31 participants also completed objective activity monitoring. Steps/d and high-cadence min/week, representative of ambulatory moderate to vigorous physical activity (MVPA), were calculated. Approximately one quarter of participants self-reported at least 30 min/d of aerobic MVPA, at least 5 d/week. Median steps/d was 7949 (IQR = 4572) and median MVPA min/week was 105 (IQR = 123). Cognitive deficits were found in 32% of participants (29% memory, 10% executive function, 13% language, 10% attention). Controlling for demographic and medical factors, self-reported aerobic physical activity was weakly correlated with lower attention (r = -0.21, p = 0.04) and executive function (r = -0.27, p < 0.01) and both self-reported aerobic physical activity and objectively-determined MVPA min/week were negatively correlated with memory (r = -0.20, p = 0.04; r = -0.46; p = 0.02, respectively). No other correlations between physical activity measures and cognitive function were significant. Contrary to expectations, greater levels of physical activity were not associated with better cognitive functioning. Such findings encourage future studies to clarify the association among cognitive function and physical activity in obese persons.