HIV-1 infection kinetics, drug resistance, and long-term safety of pre-exposure prophylaxis with emtricitabine plus tenofovir alafenamide (DISCOVER): week 144 open-label extension of a randomised, controlled, phase 3 trial.

BACKGROUND: Data characterising the long-term use and safety of emtricitabine plus tenofovir disoproxil fumarate as daily oral pre-exposure prophylaxis (PrEP) are scarce and there are uncertainties regarding the value of routine HIV-1 RNA testing during oral PrEP follow-up. METHODS: The DISCOVER trial was a randomised, controlled, phase 3 trial in which cisgender men and transgender women aged 18 years and older with a high likelihood of acquiring HIV were recruited from 94 clinics in Europe and North America and randomly assigned to receive either emtricitabine plus tenofovir disoproxil fumarate (200/25 mg) tablets daily, with matched placebo tablets, or emtricitabine plus tenofovir alafenamide (200/300 mg) tablets daily, with matched placebo tablets, for at least 96 weeks. After completion of the trial, participants were offered enrolment in this 48-week open-label extension study of emtricitabine plus tenofovir alafenamide. In participants diagnosed with HIV during the randomised and open-label phases of the study, we characterised HIV-1 test results and measured HIV-1 RNA viral load retrospectively when available. Adherence based on tenofovir diphosphate concentrations in dried blood spots and genotypic resistance were assessed in participants diagnosed with HIV. Safety assessments included adverse events, laboratory parameters, and, in a subset of participants, bone mineral density. HIV-1 incidence in participants initially randomly assigned to receive emtricitabine plus tenofovir alafenamide was estimated using a Poisson distribution. Changes from baseline in safety endpoints were described in participants assigned to received emtricitabine plus tenofovir alafenamide and in those who switched from emtricitabine plus tenofovir disoproxil fumarate during the open-label phase. This trial is registered with ClinicalTrials.gov, NCT02842086, and is ongoing. FINDINGS: Between Sept 13, 2016, and June 30, 2017, 5399 participants were enrolled and randomly assigned in DISCOVER. 2699 were assigned to receive emtricitabine plus tenofovir disoproxil fumarate and 2700 were assigned to receive emtricitabine plus tenofovir alafenamide, of whom 2693 and 2694, respectively, received at least one dose of study drug. 2115 (79%) assigned to emtricitabine plus tenofovir disoproxil fumarate switched to emtricitabine plus tenofovir alafenamide in the open-label phase, and 2070 (77%) continued with emtricitabine plus tenofovir alafenamide in the open-label phase. As of data cutoff (Dec 10, 2020), after 15 817 person-years of follow-up, 27 new HIV-1 diagnoses were observed across the total study period, with three occurring during the open-label phase. In participants who were initially assigned to emtricitabine plus tenofovir alafenamide, the incidence was 0·13 per 100 person-years (95% CI 0·061-0·23; ten of 2670). Stored plasma samples were available for 23 of 27 participants, including 22 with incident infection. In four (17%) of 23 participants, retrospective testing detected HIV-1 RNA before serological HIV-1 test positivity; one was a suspected baseline infection. Of the three incident cases, all three were non-adherent to PrEP and none developed drug resistance. Among participants taking emtricitabine plus tenofovir alafenamide for up to 144 weeks, markers of glomerular filtration and proximal renal tubule dysfunction (ß2-microglobulin to creatinine ratio and retinol-binding protein to creatinine ratio) improved or remained stable at 144 weeks compared with baseline, bone mineral density in hip and lumbar spine increased or remained stable from baseline to week 144 (n=191), cholesterol and glucose concentrations remained stable, and median bodyweight increased by less than 1 kg per year. In participants who switched from emtricitabine plus tenofovir disoproxil fumarate during the open-label phase (2115 [79%] of 2693), markers of glomerular filtration and proximal renal tubule dysfunction improved or remained stable, bone mineral density increased, cholesterol concentrations increased, glucose concentrations were similar, and median bodyweight increased more compared with those who remained on emtricitabine and tenofovir alafenamide. INTERPRETATION: Routine HIV-1 RNA testing for follow-up of individuals on daily oral PrEP provides modest additional clinical benefit. Long-term use of emtricitabine and tenofovir alafenamide as daily oral PrEP is safe and well tolerated and can be an especially appropriate choice for people with bone or renal morbidities. FUNDING: Gilead Sciences.

Healthcare professional perspectives following implementation of an infection management care pathway for pediatric patients with cancer: a qualitative study.

PURPOSE: The Pediatric Oncology Group of Ontario (POGO) supported an effort to implement infection management care pathways based on clinical practice guidelines, to improve the consistency of infection management in pediatric cancer patients. The objective of this qualitative study was to describe the perspective of healthcare professionals (HCPs) following implementation. METHODS: Four tertiary pediatric oncology centers in Ontario, Canada, implemented the pathways. We randomly identified three HCPs per group (clinical pharmacists; nurse case managers, educators or practitioners and physician assistants; pediatric oncology fellows; or pediatric oncology staff physicians) per site and invited them to participate in a qualitative interview. One-on-one interviews were conducted remotely, followed by thematic analysis of interview transcripts. RESULTS: A total of 66 invitations were extended and 42 HCPs participated. Identified themes were: (1) implementation approach, (2) access and navigation, (3) engagement, (4) concerns, (5) workplace benefits, (6) reception, and (7) provincial harmonization. HCPs preferred in-person implementation strategies over e-mail communication. They identified teaching/educational utility and benefits to non-oncology departments and non-tertiary centers participating in shared care of patients. Other positive aspects related to evidence-based practice, safety, supporting oncology HCPs, and benefits to patients and families. Concerns included need to ensure users applied clinical judgement and loss of autonomy. Provincial harmonization of practice was viewed positively, although potential logistical and institutional cultural barriers were raised. CONCLUSIONS: Following infection management care pathway implementation, HCPs described educational utility and benefits to non-oncology departments, oncology HCPs, patients, and families. Our findings may facilitate future infection management care pathway provincial harmonization.

Sexual orientation moderates the relationship between internalized weight bias and binge eating symptoms among adults pursuing bariatric surgery.

BACKGROUND: Sexual minorities have higher rates of anxiety, depression, and binge eating compared to heterosexual peers. Internalized weight bias (IWB) is also higher for sexual minorities when compared to heterosexual peers. However, research has not examined whether the relationships between IWB and anxiety, depression, and binge eating differ among heterosexual and sexual minority adults pursuing bariatric surgery. OBJECTIVES: To examine whether sexual orientation (heterosexual or sexual minority) moderated the relationships between IWB and anxiety, depression, and binge eating among adults pursuing bariatric surgery. SETTING: University hospital, United States METHODS: Participants included 811 adults who presented for bariatric surgery, 45 (5.5%) of which identified as a sexual minority. Self-reported data were collected as part of a standard preoperative psychological evaluation for surgical clearance. Three separate moderation models were run to test hypotheses. RESULTS: Sexual orientation did not moderate the association of IWB with anxiety or depression. The IWB by sexual orientation interaction was significant for binge eating (F 1856) = 4.84, P = .03, R2 = .27 such that the association between IWB and binge eating was significantly stronger for sexual minority patients (b = .54, 95% confidence interval {CI} [.36, .70]), compared to heterosexual patients (b = .33, 95% CI [.30, .38]). CONCLUSIONS: Minority stress from identifying as a sexual minority may increase vulnerability to binge eating from IWB among bariatric candidates. Future research examining the directionality of the relationship between IWB and binge eating among sexual minorities is warranted.

A Multimodal Intervention to Reduce C. difficile Infections and Stool Testing.

BACKGROUND AND OBJECTIVES: The introduction of multiplex gastrointestinal panels at our institution resulted in increased Clostridioides difficile (C. difficile) detection and stool test utilization. We aimed to reduce hospital-onset C. difficile infections (HO-CDIs), C. difficile detection, and overall stool testing by 20% within 1 year. METHODS: We conducted a quality improvement project from 2018 to 2020 at a large children's hospital. Interventions included development of a C. difficile testing and treatment clinical care pathway, new options for gastrointestinal panel testing with or without C. difficile (results were suppressed if not ordered), clinical decision support tool to restrict testing, and targeted prevention efforts. Outcomes included the rate of HO-CDI (primary), C. difficile detection, and overall stool testing. All measures were evaluated monthly among hospitalized children per 10 000 patient-days (PDs) using statistical process-control charts. For balancing measures, we tracked suppressed C. difficile results that were released during real-time monitoring because of concern for true infection and C. difficile-related adverse events. RESULTS: HO-CDI decreased by 55%, from 11 to 5 per 10 000 PDs. C. difficile detection decreased by 44%, from 18 to 10 per 10 000 PDs, and overall test utilization decreased by 29%, from 99 to 70 per 10 000 PDs. The decrease in stool tests resulted in annual savings of $55 649. Only 2.3% of initially suppressed positive C. difficile results were released, and no patients had adverse events. CONCLUSIONS: Diagnostic stewardship strategies, coupled with an evidence-based clinical care pathway, can be used to decrease C. difficile and improve overall test utilization.

Psychometric Properties of the Brief Coping Orientation to Problems Experienced Inventory Among Patients Pursuing Bariatric Surgery.

The Brief COPE Inventory is a widely used scale that measures how a person copes with a specific situation. Despite its widespread use, the factor structure of this scale is somewhat unclear and has not been tested among patients pursuing bariatric surgery. We tested competing factor analytic models of the Brief COPE Inventory among patients pursuing bariatric surgery to identify the best fitting factor model for use in pre-surgical psychological evaluations. We also examined reliability and validity of the subscales from the best fitting model of coping. Participants included 1984 patients pursuing bariatric surgery (Mage = 42.58 years, SD = 10.89, 81.39% female). The best fitting model of the Brief COPE Inventory among patients pursuing bariatric surgery was a three-factor model including interpersonal, intrapersonal, and maladaptive coping strategies. These results were replicated in a subset of the original sample and demonstrated appropriate convergent and discriminant validity with several key outcomes. The Brief COPE Inventory can be conceptualized as a multidimensional scale assessing interpersonal coping, intrapersonal coping, and maladaptive coping among patients pursuing bariatric surgery. Future work should examine how these subscales are related to surgical outcomes among people receiving treatment for excess weight.

The role of anxiety and depression in understanding the relationship between coping and weight loss 24 months after bariatric surgery.

BACKGROUND: The relationship between coping (i.e., how a person deals with stress) and weight loss after bariatric surgery is relatively inconsistent. Anxiety and depression may contribute to the lack of consistent findings in this area. It is possible that coping, including interpersonal, intrapersonal, and maladaptive coping, predicts weight loss among individuals with higher levels of anxiety or depression but not among those with lower levels of anxiety and depression. OBJECTIVE: The aim of this study was to examine the moderating role of anxiety and depression on the association between coping and weight loss in patients 24 months after bariatric surgery. SETTING: University Hospital, West Virginia, U.S.A. METHODS: Participants included 841 patients who underwent bariatric surgery, 396 of whom had 24-month weight loss data (mean age, 43.21 yr [SD, ±11.40 yr]). We ran 3 moderation models to test whether the relationship between various coping styles and postoperative weight loss was moderated by anxiety and depression symptoms. RESULTS: There was a statistically significant interaction between anxiety and depression on the association between interpersonal coping and percent excess weight loss (%EWL). Anxiety and depression also moderated the relationship between maladaptive coping and %EWL. Anxiety and depression did not moderate the association between intrapersonal coping and %EWL, but intrapersonal coping positively predicted %EWL at 24 months after bariatric surgery. CONCLUSIONS: Maladaptive coping predicted less weight loss for patients with high levels of anxiety and/or depression. Interpersonal coping predicted more weight loss for patients with low levels of anxiety and/or depression. Clinicians should take patient levels of anxiety and depression into account when making recommendations to promote weight loss among patients pursuing bariatric surgery.

Rural health care worker wellness during COVID-19: Compassion fatigue, compassion satisfaction & utilization of wellness resources.

OBJECTIVE: The goal of this study was to identify factors associated with compassion fatigue (CF) and compassion satisfaction (CS) among rural health care workers (HCWs) during the COVID-19 pandemic. The secondary purpose was to assess utilization of wellness resources and preferences for new resources. METHODS: A survey was distributed (October-December 2020) and completed by faculty, clinicians and staff (n = 406) at a rural university. Measures included a modified version of the Professional Quality of Life Scale (PROQOL-21), the Patient Health Questionnaire-4 and the Brief Resilience Coping Scale. Respondents reported their use of wellness resources and their preferences for new resources. RESULTS: The mean CF score was 21.1, the mean CS score was 26.8 and 42.0% screened positive for depression or anxiety. Few of the existing wellness resources were utilized and respondents' preferences for new wellness resources included time off (70.7%), onsite food trucks (43.0%) and support animals (36.5%). Younger age, depression and anxiety were associated with higher CF. Older age, better mental health and resilience were associated with higher CS. CONCLUSIONS: Rural HCWs have high CF, yet few utilize wellness resources. Rural health care organizations may foster wellness by providing time off for self-care, expanding mental health services and building resilience.

Effect of recombinant human nerve growth factor treatment on corneal nerve regeneration in patients with neurotrophic keratopathy.

Introduction: Neurotrophic Keratopathy (NK) is a neurodegenerative corneal disease that results in diminished corneal sensation. Previous studies have found that Cenegermin 0.002%, a recombinant human nerve growth factor (rhNGF), improves corneal epithelial healing in stage 2 and 3 NK patients. However, rhNGF effect on corneal sensation and nerve regeneration has not been well established. Thus, this study aims to analyze the effect of rhNGF on corneal nerve regeneration using in vivo confocal microscopy (IVCM) and on corneal sensitivity in NK patients. Methods: This is a retrospective, longitudinal, case-control study that included patients with NK, treated with rhNGF for at least 4 weeks, with pre- and post-treatment IVCM images available for analysis. Chart reviews were conducted documenting prior medical and surgical history, clinical signs and symptoms, and corneal sensation using Cochet-Bonnet esthesiometry. Corneal nerve parameters were assessed by IVCM. Sex- and age-matched reference controls were selected from a database of healthy subjects for comparison. Results: The study included 25 patients, with 22 (88%) stage 1, two (8%) stage 2, and 1 (4%) stage 3 NK patients, with a median age of 64 years (range: 30-93 years). Total, main, and branch nerve densities [median (range) in mm/mm2] were lower in the NK group pre-treatment [2.3 (0.0-21.1); 1.7 (0.0-13.0); 0.5 (0.0-10.2); respectively] vs. controls [22.3 (14.9-29.0); 10.1 (3.2-15.4); and 12.1 (6.2-18.4), (p < 0.0001 for all), respectively]. Post-treatment nerve densities increased compared to pre-treatment to 5.3 (0.0-19.4, p = 0.0083) for total, 3.5 (0.0-13.2, p = 0.0059) for main, and 2.0 (0.0-10.4, p = 0.0251) for branch nerves, but remained lower than controls (p < 0.0001 for all). Corneal sensation increased from 2.3 ± 1.1 cm pre-treatment to 4.1 ± 1.4 cm post-treatment (p = 0.001). Median best corrected visual acuity significantly increased following rhNGF treatment from 0.4 (0.0-1.6) to 0.12 (-0.1 to 1.6) (p = 0.007). Conclusion: Patients with NK treated with at least 4 weeks of rhNGF, showed a significant increase in corneal nerve densities after treatment. A significant increase in corneal sensation, as well as best corrected visual acuity, was observed following treatment.

Intrapersonal coping predicts greater weight loss 24 months after bariatric surgery.

PURPOSE: Coping is related to numerous health outcomes, including weight loss. However, the relationship between coping and weight loss after bariatric surgery remains unclear. OBJECTIVES: The first objective of this study was to examine cross-sectional relationships between coping, anxiety, and depression. The second objective was to determine whether baseline anxiety and depression predicted weight loss 24 months after bariatric surgery. The final objective was to identify which aspects of coping are related to weight loss 24 months after bariatric surgery. MATERIALS AND METHODS: Participants included 1203 adults who completed a pre-surgical bariatric evaluation, including 841 patients who underwent bariatric surgery, 396 of whom had 24-month weight data. Psychological variables were collected during a pre-surgical psychological evaluation. Weight-related variables were obtained through patients' electronic medical records 24 months after surgery. RESULTS: Baseline intrapersonal coping (e.g., problem-solving, acceptance) predicted both weight loss variables at 24 months after surgery. However, baseline interpersonal and maladaptive coping were not related to weight loss. Baseline anxiety and depression similarly did not predict weight loss after surgery. CONCLUSION: Use of intrapersonal coping strategies at baseline predicted weight loss 24 months after bariatric surgery. Clinicians should assess and bolster these self-reliant coping strategies prior to surgery to improve patient outcomes.

Addressing Adverse Childhood Experiences and Psychological Symptoms Among Bariatric Patients.

Adverse Childhood Experiences (ACEs) have been shown to be prevalent in bariatric surgery candidates with comorbid psychological symptoms. While bariatric patients who have mental illness or a history of ACEs are less likely to lose weight, presence of a support system has been reported to mitigate ACEs' effects and to maintain long-term weight loss. The current study aims to examine the association between ACEs and psychological symptoms and the effect of potential protective factors on the association among bariatric patients. The study included a total of 199 subjects seeking bariatric surgery who completed a psychological evaluation including ACEs, psychological symptoms, and presence of support system as part of the presurgical multidisciplinary weight management consultations at a large university hospital. Multivariate regression models were used to examine the association between ACEs and psychological symptoms and potential effect of support system on the association. The study found that there is a significant association between ACEs and psychological symptoms. The study also revealed that patients who reported having a childhood supportive person were significantly associated with a lower BMI, while those who reported having adulthood supportive person showed significantly less symptoms of depression, anxiety, and binge eating. The findings have significant implications that addressing ACEs in preoperative surgical process in relation to psychological conditions and therapeutic interventions within their close environmental system will be beneficial for patients to achieve optimal surgical outcomes.

Antiviral activity of tenofovir alafenamide (TAF) against HIV-1 clinical isolates harboring K65R.

Tenofovir alafenamide (TAF) is a prodrug of the nucleoside reverse transcriptase (RT) inhibitor tenofovir (TFV). Compared to the earlier TFV prodrug, TFV disoproxil fumarate (TDF), TAF achieves more than fourfold-higher intracellular levels of its active metabolite TFV diphosphate (TFV-DP) in clinical studies, while achieving a significant reduction of TFV systemic exposure. Resistance to TFV has been well established, with the K65R mutation in RT as the signature mutation. Here we evaluated the in vitro activity of TAF and TDF in patient-derived HIV-1 isolates harboring the K65R mutation. Clinical isolates containing K65R were cloned into the pXXLAI construct (n = 42). In vitro phenotypic susceptibility of the constructs to TAF and TDF was evaluated in an MT-2 cell HIV assay and in viral breakthrough assays modeling physiological concentrations of TAF and TDF. TAF and TDF susceptibility were highly correlated in K65R-containing mutants, ranging from 2.7- to 3.0-fold (K65R alone) and 1.2- to 27.6-fold (K65R+ other RT mutations) relative to wild-type. In viral breakthrough assays mimicking differences in physiological concentrations, TAF inhibited breakthrough of 40 of 42 clinical isolates, while the TDF equivalent only inhibited 32 of 42 isolates tested. TAF displayed a higher barrier to resistance than TDF in this panel of K65R-containing clinical isolates.

Preoperative and early adjuvant weight loss medications in bariatric surgery patients with body mass index over 60 or suboptimal initial response to surgery.

BACKGROUND: Few studies have examined the adjuvant use of antiobesity medications with surgery, especially in the pre- and early postoperative periods. OBJECTIVE: Evaluate the impact of adjuvant pharmacotherapy on bariatric surgery outcomes. SETTING: University hospital, United States. METHODS: A retrospective chart review of patients receiving adjuvant pharmacotherapy for obesity treatment and bariatric surgery. Patients received pharmacotherapy either preoperatively if their body mass index was >60, or in the first or second postoperative years for suboptimal weight loss. Outcome measures included percentage of total body weight loss as well as comparison with the expected weight loss curve as determined by the Metabolic and Bariatric Surgery Risk/Benefit Calculator. RESULTS: A total of 98 patients were included in the study, with 93 (94.9%) undergoing sleeve gastrectomy and 5 (5.1%) undergoing Roux-en-Y gastric bypass surgery. During the study period, patients were prescribed phentermine and/or topiramate. At postoperative year 1, patients who received pharmacotherapy preoperatively lost 31.3% of their total body weight (TBW) compared with 25.3% TBW for patients with suboptimal weight loss who received medication in the first postoperative year, and 20.8% TBW for patients who did not receive any antiobesity medication in the first postoperative year. Using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) curve for comparison, patients receiving medication preoperatively weighed 2.4% less than expected, whereas patients receiving medication during the first postoperative year weighed 4.8% higher than expected. CONCLUSION: For patients having bariatric surgery who fall below the expected MBSAQIP weight loss curve, early initiation of antiobesity medications can improve the weight loss, with preoperative pharmacotherapy having the greatest effect.

How Soon Do Depression and Anxiety Symptoms Improve after Bariatric Surgery?

Depression and anxiety are prevalent among bariatric surgery candidates, yet little is known about the course of symptoms after surgery. This study aimed to identify how soon changes in depression and anxiety occur after surgery. A retrospective review of patients treated at a university hospital was conducted. Participants attended a presurgical psychological evaluation, completed surgery, and attended follow-up visits with bariatric medical providers (2 weeks, 6 weeks, 3 months, and 6 months postoperatively). Depression and anxiety symptoms were assessed at all time points by the Patient-Reported Outcomes Measurement Information System (PROMIS) Depression and Anxiety. Generalized estimating equations models with repeated measures by person over time were used to examine change in depression and anxiety symptoms across time. Among 27 patients, anxiety (incident rate ratio (IRR) = 0.81, p = 0.04) and depression (IRR = 0.78, p = 0.05) significantly improved both 6 weeks and 3-6 months after bariatric surgery, after controlling for education, marital status, surgery type, age, and baseline body mass index. This is the first known study to show faster improvement in anxiety compared to depression after bariatric surgery. Understanding reductions in anxiety and depression symptoms may be important for postoperative care and timing of weight maintenance interventions.

Corneal nerve regeneration is affected by scar location in herpes simplex keratitis: A longitudinal in vivo confocal microscopy study.

PURPOSE: To assess the effect of corneal scar location on corneal nerve regeneration in patients with herpes simplex virus (HSV) keratitis in their affected and contralateral eyes over a 1-year period by in vivo confocal microscopy (IVCM), and to correlate these findings to corneal sensation measured by Cochet-Bonnet Esthesiometer. METHODS: Prospective, longitudinal, case-control study. Bilateral corneal nerve density and corneal sensation were analyzed centrally and peripherally in 24 healthy controls and 23 patients with unilateral HSV-related corneal scars using IVCM. RESULTS: In the central scar (CS) group, total nerve density in the central cornea remained significantly lower compared to controls at follow-up (11.05 ± 1.97mm/mm2, p < 0.001), and no significant nerve regeneration was observed (p = 0.090). At follow-up, total nerve density was not significantly different from controls in the central and peripheral cornea of the peripheral scar (PS) group (all p > 0.05), but significant nerve regeneration was observed in central corneas (16.39 ± 2.39mm/mm2, p = 0.007) compared to baseline. In contralateral eyes, no significant corneal nerve regeneration was observed in central or peripheral corneas of patients with central scars or peripheral scars at 1-year follow-up, compared to baseline (p > 0.05). There was a positive correlation between corneal nerve density and sensation in both central (R = 0.53, p < 0.0001) and peripheral corneas (R = 0.27, p = 0.0004). In the CS group, the corneal sensitivity was <4 cm in 4 (30.8%) and 7 (53.8%) patients in the central and peripheral corneas at baseline, and in 5 (38.5%) and 2 subjects (15.4%) at follow-up, whereas in the PS group only 1 patient (10%) showed a corneal sensation < 4 cm in the central cornea at baseline, and only 1 (10.0%), 3 (30.0%) and 1 (10.0%) patients at follow-up in the central, affected and opposite area of the cornea, respectively. CONCLUSION: The location of HSV scarring in the cornea affects the level of corneal nerve regeneration. Eyes with central corneal scar have a diminished capacity to regenerate nerves in central cornea, show a more severe reduction in corneal sensation in the central and peripheral corneas that persist at follow-up, and have a reduced capability to restore the corneal sensitivity above the cut-off of 4 cm. Thus, clinicians should be aware that CS patients would benefit from closer monitoring for potential complications associated with neurotrophic keratopathy, as they have a lower likelihood for nerve regeneration.

Understanding the Intersectional Relationship of Pain Stigma, Weight Bias Internalization, and Clinical Indicators in a Rural Population with Back Pain: A Survey-Based Study.

BACKGROUND: Stigma is understood to be intersectional, meaning multiple characteristics can be stigmatizing, and they may be both overlapping and coconstitutive. Chronic pain and overweight are common complaints in the spinal surgery clinic. Since being overweight may relate to back pain in a complex fashion, we sought to understand if there is a moderating effect between weight bias and pain stigma. METHODS: This study involves a survey-based, quantitative, cross-sectional, observational design using previously validated measures and demographic and clinical information. There were 192 participants. Statistical calculations were done with statistical package for the social sciences. RESULTS: Pain stigma was not significantly correlated with BMI (body mass index), and weight bias was not significantly correlated with back pain. There was a strong positive correlation between weight bias and pain stigma. There was a strong positive correlation between weight bias and BMI when pain stigma was also high. CONCLUSIONS: Given the relationship between weight stigma and pain, the intersection of weight and pain stigma is important because it indicates the vulnerability of patients with higher BMI to other forms of stigma, such as stigma for their pain complaints. Clinicians should be mindful of expressing pain stigma more significantly amongst patients with higher BMI.

Binge eating in patients pursuing bariatric surgery: understanding relationships with food insecurity and adverse childhood experiences.

BACKGROUND: Positive relationships exist between adult food insecurity and binge eating, and between adverse childhood experiences and binge eating. However, the nature of these relationships remains to be determined. OBJECTIVES: The current study sought to examine the association between binge eating and childhood abuse and/or neglect and household dysfunction and to explore whether the strength of the relationship between adverse childhood experiences and binge eating differs across levels of food insecurity in patients seeking bariatric surgery. SETTING: University Hospital in the Appalachian region of United States. METHODS: A total of 366 adults seeking bariatric surgery completed validated questionnaires as a component of a routine psychological evaluation prior to surgery. RESULTS: Only childhood experiences of abuse and/or neglect were positively related to adult binge eating, r(363) = .13, P = .011. Food insecurity moderated the relationship between adverse childhood experiences and binge eating, F(4, 358) = 242.98, P < .001, such that the relationship was stronger for individuals who endorsed the presence of both food insecurity and adverse childhood experiences (M = 15.90; standard deviation [SD] = 8.38), relative to individuals who endorsed the absence of both food insecurity and adverse childhood experiences (M = 11.19; SD = 7.91; Tukey P = .005; d = .58). CONCLUSIONS: Food insecurity strengthens the relationship between adverse childhood experiences and adult binge eating. Results suggest that healthcare providers should include assessments of both adverse childhood experiences and food insecurity to identify patients who may be at risk for disordered eating prior to surgery, as these individuals may require additional interventions to address binge eating and related factors.

Binge Eating Before and After Bariatric Surgery.

PURPOSE OF REVIEW: The purpose is to review the state of the literature of binge eating in the context of bariatric surgery including prevalence, conceptualization, assessment, course, and related sequela throughout the perioperative continuum, particularly highlighting new advancements and future directions. RECENT FINDINGS: Accurate assessment of binge eating in bariatric samples is essential for optimization of patient outcomes. Binge eating is less prevalent after bariatric surgery; however, prevalence rates increase over time. Most studies do not find a relationship between pre-operative binge eating and suboptimal weight outcomes after surgery. Refinement in understanding and conceptualization of post-operative binge eating is needed; new conceptualizations have proposed such a definition. Emerging constructs relevant to binge eating for bariatric patients include food addiction and food insecurity. Despite the introduction of formal diagnostic criteria for binge eating disorder, many uncertainties regarding the prevalence, course, and effects of binge eating currently exist; varied assessment methods continue to be a barrier to research on binge eating in bariatric surgery samples. Consensus on operational definitions for post-operative binge eating and best practices for assessment are areas for future consideration.

The Roles of Depression and Binge Eating in the Relationship Between Adverse Childhood Experiences (ACEs) and Obesity.

OBJECTIVE: Research has demonstrated that adverse childhood experiences (ACEs) were related to elevated lifetime risk of developing obesity, but the underlying mechanisms between ACEs and development of obesity are yet to be fully elucidated. The current study aims to extend exiting evidence on underlying mechanisms between ACEs and development of obesity by examining whether depressive symptom and binge eating symptom have independently significant mediating effects on the association. METHODS: The study used data from a total of 473 patients seeking bariatric surgery who completed psychological evaluation including ACEs, depressive symptom, and binge eating scale as a part of presurgical multidisciplinary weight management consultations. Mediation analyses were conducted using the PROCESS macro for SPSS to examine the research objective. RESULTS: The study found that depressive symptom uniquely mediated the relationship between ACEs and obesity, but binge eating symptom did not significantly mediate the relationship independently of depression. CONCLUSIONS: The unique role of depression in relation to childhood trauma in this study argues for more focus on a mental health intervention with bariatric patients during the preoperative period. Addressing ACEs for bariatric patients who present psychiatric symptoms during preoperative process could have potential benefits to patient care.

A Single Administration of OC-01 (Varenicline Solution) Nasal Spray Induces Short-Term Alterations in Conjunctival Goblet Cells in Patients with Dry Eye Disease.

INTRODUCTION: Dry eye disease is characterized by a persistently unstable or deficient tear film causing discomfort or visual impairment. Varenicline is a small-molecule nicotinic acetylcholine receptor agonist recently approved for use as a preservative-free nasal spray (OC-01 [varenicline solution] nasal spray [OC-01 VNS]) to treat signs and symptoms of dry eye disease, but its effect on conjunctival goblet cells has not been studied. METHODS: In this phase 2, single-center, vehicle-controlled study, patients aged 18 years or more with a diagnosis of dry eye disease and Ocular Surface Disease Index© score of at least 23 were randomized 2:1 to receive a 50-µL single dose of OC-01 0.06 mg VNS or vehicle nasal spray in each nostril. Image assessments for area and perimeter were performed pre and 10 min post treatment for goblet cells by in vivo confocal microscopy and for meibomian glands by infrared meibography. Non-parametric Wilcoxon signed-rank test compared pre- and post-treatment measurements for each treatment group. Treatment-emergent adverse events (TEAEs) were assessed. RESULTS: The study randomized 18 patients (mean age 61 years); 6 received vehicle (3/6 [50%] female) and 12 patients received OC-01 VNS (11/12 [92%] female). OC-01 VNS treatment decreased mean goblet cell area (pre-treatment, 106.4 µm2; post-treatment, 67.6 µm2; p = 0.02) and perimeter (pre-treatment, 38.9 µm; post-treatment, 31.2 µm; p = 0.03) but not vehicle did not (p = 0.25). There were no significant changes in mean meibomian gland area with either treatment (p ≥ 0.05). All TEAEs were non-ocular, non-serious, and mild. CONCLUSIONS: This study demonstrated that a single administration of OC-01 0.06 mg VNS in patients with dry eye disease reduced conjunctival goblet cell area and perimeter, suggesting goblet cell degranulation and associated release of lubricating mucin. By activating the natural tear film, OC-01 VNS may provide benefits over topical medications. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03688802.

Anxiety predicts reduced weight loss 30 months after bariatric surgery.

BACKGROUND: Though psychosocial factors are routinely examined in presurgical psychological evaluations, the predictive value of some psychosocial factors on postsurgical weight loss is still relatively unknown. Additional research examining the predictive value of psychological constructs preoperatively and long-term weight outcomes is needed to enhance the clinical utility of the presurgical psychological evaluations. OBJECTIVE: This study aimed to examine psychosocial factors as predictors of weight outcomes 30 months after bariatric surgery. SETTING: University hospital in the Appalachian region of United States. METHODS: Participants included 196 adults who underwent bariatric surgery. Psychosocial data were collected as part of a routine psychological evaluation prior to bariatric surgery. Objective weight was obtained through patients' medical records at 12, 24, and 30 months after surgery. RESULTS: Linear mixed models was used to examine presurgical psychosocial factors predicting postsurgical weight loss (n at 12 months = 153, n at 24 months = 130, n at 30 months = 92). Anxiety had a significant interaction effect with time (estimate = -.01, P = .013), indicating that higher anxiety was associated with less weight loss over time. Those with severe anxiety before surgery lost the most weight 12 months after surgery but also regained the most weight 30 months after surgery. Other predictors were not statistically significant. CONCLUSION: Anxiety assessed prior to surgery predicted reduced weight loss 30 months after bariatric surgery, after controlling for surgery type, baseline weight, sex, and age. Results highlight the importance of evaluation and treatment of anxiety in presurgical bariatric candidates.