Healthy weight loss maintenance with exercise, GLP-1 receptor agonist, or both combined followed by one year without treatment: a post-treatment analysis of a randomised placebo-controlled trial.

Background: New obesity medications result in large weight losses. However, long-term adherence in a real-world setting is challenging, and termination of obesity medication results in weight regain towards pre-treatment body weight. Therefore, we investigated whether weight loss and improved body composition are sustained better at 1 year after termination of active treatment with glucagon-like peptide-1 (GLP-1) receptor agonist, supervised exercise program, or both combined for 1 year. Methods: We conducted a post-treatment study in extension of a randomised, controlled trial in Copenhagen. Adults with obesity (aged 18-65 years and initial body mass index 32-43 kg/m2) completed an eight-week low-calorie diet-induced weight loss of 13.1 kg (week -8 to 0) and were randomly allocated (1:1:1:1) to one-year weight loss maintenance (week 0-52) with either supervised exercise, the GLP-1 receptor agonist once-daily subcutaneous liraglutide 3.0 mg, the combination of exercise and liraglutide, or placebo. 166 Participants completed the weight loss maintenance phase. All randomised participants were invited to participate in the post-treatment study with outcome assessments one year after treatment termination, at week 104. The primary outcome of the post-treatment assessment was change in body weight from after the initial weight loss (at randomisation, week 0) to one year after treatment termination (week 104) in the intention-to-treat population. The secondary outcome was change in body-fat percentage (week 0-104). The study is registered with EudraCT, 2015-005585-32, and with ClinicalTrials.gov, NCT04122716. Findings: Between Dec 17, 2018, and Dec 17, 2020, 109 participants attended the post-treatment study. From randomisation to one year after termination of combined exercise and liraglutide treatment (week 0-104), participants had reduced body weight (-5.1 kg [95% CI -10.0; -0.2]; P = 0.040) and body-fat percentage (-2.3%-points [-4.3 to -0.3]; P = 0.026) compared with after termination of liraglutide alone. More participants who had previously received combination treatment maintained a weight loss of at least 10% of initial body weight one year after treatment termination (week -8 to 104) compared with participants who had previously received placebo (odds ratio [OR] 7.2 [2.4; 21.3]) and liraglutide (OR 4.2 [1.6; 10.8]). More participants who had previously received supervised exercise maintained a weight loss of at least 10% compared with placebo (OR 3.7 [1.2; 11.1]). During the year after termination of treatment (week 52-104), weight regain was 6.0 kg [2.1; 10.0] larger after termination of liraglutide compared with after termination of supervised exercise and 2.5 kg [-1.5 to 6.5] compared with after termination of combination treatment. Interpretation: The addition of supervised exercise to obesity pharmacotherapy seems to improve healthy weight maintenance after treatment termination compared with treatment termination of obesity pharmacotherapy alone. Body weight and body composition were maintained one year after termination of supervised exercise, in contrast to weight regain after termination of treatment with obesity pharmacotherapy alone. Funding: Helsefonden and the Novo Nordisk Foundation.

Caregiver openness in emotionally focused family therapy: A critical shift.

Through the application of a discovery-oriented task analysis, this research delineated specific therapist behaviors that resulted in a successful caregiver openness event in emotionally focused family therapy (EFFT). EFFT experts were recruited via email and asked to submit family therapy recordings where they believed a caregiver openness event occurred. Ten family therapy recordings were submitted by three experts. Within these recordings, 12 caregiver openness events were discovered and critically analyzed. Nine themes were identified and interventions therapists applied to accomplish these themes were delineated using the emotionally focused therapy-coding scheme (EFT-CS). These themes included: (1) validating and reframing the child's protected stance, (2) processing the impact of the child's unmet attachment longings, (3) validating the caregiver's blocked relational stance, (4) expanding caregiving intentions, (5) enacting the caregiver's intentions to meet the child's attachment longings, (6) processing the enactment, (7) processing and promoting caregiver accessibility to the child's response, (8) heightening the caregiver's accessible stance, and (9) enhancing shifting family dynamics. Additional findings, implications for clinical practice, training, and future research are discussed.

Exploratory analysis of eating- and physical activity-related outcomes from a randomized controlled trial for weight loss maintenance with exercise and liraglutide single or combination treatment.

Weight regain after weight loss remains a major challenge in obesity treatment and may involve alteration of eating and sedentary behavior after weight loss. In this randomized, controlled, double-blind trial, adults with obesity were randomized, in a 1:1:1:1 ratio stratified by sex and age group (<40 years and ≥40 years), to one-year weight loss maintenance with exercise, the GLP-1 receptor agonist liraglutide, or the combination, as compared with placebo, after low-calorie diet-induced weight loss. Primary outcome was change in body weight, which has been published. Here, we investigated the effects of weight loss maintenance with exercise, liraglutide, or the combination on weight loss-induced changes in the pre-specified explorative outcomes, eating and sedentary behavior in 130 participants who completed the trial according to the study protocol (exercise (n = 26), liraglutide (n = 36), combination (n = 29), and placebo (n = 39)). One year after weight loss, the placebo group had decreased postprandial appetite suppression score by 14%, and increased sedentary time by 31 min/day and regained weight. Liraglutide prevented the decrease in postprandial appetite suppression score compared with placebo (0% vs. -14%; P = 0.023) and maintained weight loss. Exercise after weight loss did not increase appetite or sedentary behavior compared with placebo, despite increased exercise energy expenditure and maintained weight loss. The combination of exercise and liraglutide increased cognitive restraint score (13% vs. -9%; P = 0.042), reflecting a conscious restriction of food intake, and decreased sedentary time by 41 min/day (-10 vs. 31 min/day; 95%CI, -82.3 to -0.2; P = 0.049) compared with placebo, which may have facilitated the additional weight loss. Targeting both eating and sedentary behavior could be the most effective for preventing weight regain.Trial registration: EudraCT number, 2015-005585-32; clinicaltrials.gov number, NCT04122716.

Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined.

BACKGROUND: Weight regain after weight loss is a major problem in the treatment of persons with obesity. METHODS: In a randomized, head-to-head, placebo-controlled trial, we enrolled adults with obesity (body-mass index [the weight in kilograms divided by the square of the height in meters], 32 to 43) who did not have diabetes. After an 8-week low-calorie diet, participants were randomly assigned for 1 year to one of four strategies: a moderate-to-vigorous-intensity exercise program plus placebo (exercise group); treatment with liraglutide (3.0 mg per day) plus usual activity (liraglutide group); exercise program plus liraglutide therapy (combination group); or placebo plus usual activity (placebo group). End points with prespecified hypotheses were the change in body weight (primary end point) and the change in body-fat percentage (secondary end point) from randomization to the end of the treatment period in the intention-to-treat population. Prespecified metabolic health-related end points and safety were also assessed. RESULTS: After the 8-week low-calorie diet, 195 participants had a mean decrease in body weight of 13.1 kg. At 1 year, all the active-treatment strategies led to greater weight loss than placebo: difference in the exercise group, -4.1 kg (95% confidence interval [CI], -7.8 to -0.4; P = 0.03); in the liraglutide group, -6.8 kg (95% CI, -10.4 to -3.1; P<0.001); and in the combination group, -9.5 kg (95% CI, -13.1 to -5.9; P<0.001). The combination strategy led to greater weight loss than exercise (difference, -5.4 kg; 95% CI, -9.0 to -1.7; P = 0.004) but not liraglutide (-2.7 kg; 95% CI, -6.3 to 0.8; P = 0.13). The combination strategy decreased body-fat percentage by 3.9 percentage points, which was approximately twice the decrease in the exercise group (-1.7 percentage points; 95% CI, -3.2 to -0.2; P = 0.02) and the liraglutide group (-1.9 percentage points; 95% CI, -3.3 to -0.5; P = 0.009). Only the combination strategy was associated with improvements in the glycated hemoglobin level, insulin sensitivity, and cardiorespiratory fitness. Increased heart rate and cholelithiasis were observed more often in the liraglutide group than in the combination group. CONCLUSIONS: A strategy combining exercise and liraglutide therapy improved healthy weight loss maintenance more than either treatment alone. (Funded by the Novo Nordisk Foundation and others; EudraCT number, 2015-005585-32; ClinicalTrials.gov number, NCT04122716.).

Protocol for a randomised controlled trial of the combined effects of the GLP-1 receptor agonist liraglutide and exercise on maintenance of weight loss and health after a very low-calorie diet.

INTRODUCTION: The success rate of weight loss maintenance is limited. Therefore, the purpose of this study is to investigate the maintenance of weight loss and immunometabolic health outcomes after diet-induced weight loss followed by 1-year treatment with a glucagon-like peptide-1 receptor agonist (liraglutide), physical exercise or the combination of both treatments as compared with placebo in individuals with obesity. METHODS AND ANALYSIS: This is an investigator-initiated, randomised, placebo-controlled, parallel group trial. We will enrol expectedly 200 women and men (age 18-65 years) with obesity (body mass index 32-43 kg/m2) to adhere to a very low-calorie diet (800 kcal/day) for 8 weeks in order to lose at least 5% of body weight. Subsequently, participants will be randomised in a 1:1:1:1 ratio to one of four study groups for 52 weeks: (1) placebo, (2) exercise 150 min/week+placebo, (3) liraglutide 3.0 mg/day and (4) exercise 150 min/week+liraglutide 3.0 mg/day. The primary endpoint is change in body weight from randomisation to end-of-treatment. ETHICS AND DISSEMINATION: The trial has been approved by the ethical committee of the Capital Region of Denmark and the Danish Medicines Agency. The trial will be conducted in agreement with the Declaration of Helsinki and monitored to follow the guidelines for good clinical practice. Results will be submitted for publication in international peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: 2015-005585-32.

Prevalence and Genetic Analysis of Salmonella enterica from a Cross-Sectional Survey of the New Zealand Egg Production Environment.

Epidemiological evidence suggests that Salmonella on New Zealand eggs is not an important pathway for human salmonellosis. However, robust nationally representative data for Salmonella contamination of eggs is not available to support this. To better understand the exposure of New Zealand commercial eggs to Salmonella, a cross-sectional survey collected data on prevalence and serotypes of Salmonella in the feed, laying sheds (feces, dust, and boot or manure belt swabs), and packhouses (egg contact surfaces) of New Zealand commercial egg layer farms. Salmonella was not detected on 16 of 28 surveyed farms, and 4 farms had only one positive sample. Of the 43 (13.3%) of 323 Salmonella-positive samples, dust samples had the highest prevalence (19 of 67, 28.4%), followed by boot or manure belt swabs (11 of 67, 16.4%), feces (7 of 67, 10.4%), packhouse egg contact surfaces (5 of 87, 5.7%), and feed (1 of 33, 3.0%). A significantly higher prevalence was from caged (33 of 75, 44.0%; P < 0.001) compared with cage-free (4 of 126, 3.2%) systems, yet multiple practices differ between laying systems, which could influence prevalence. Salmonella-positive packhouse samples were only identified on the three farms with the highest laying shed prevalence, and isolates were genetically related (as determined by single nucleotide polymorphism analyses) suggesting cross-contamination between the laying shed and packhouse surfaces. Serotypes isolated included Salmonella Infantis, Salmonella Thompson, Salmonella Typhimurium, Salmonella Anatum, and Salmonella Mbandaka. Importantly, Salmonella Enteritidis, which causes egg-associated outbreaks internationally, was not isolated. Genomic comparisons of isolates supported the presence of a common contamination source in the shed and farm environments rather than multiple sporadic contamination events. This survey establishes a benchmark of Salmonella prevalence and types in the New Zealand egg production environment and provides a reference point for assessing the impact of changes to practices on Salmonella prevalence.

Prognostic value of dyslipidemia for sick dogs hospitalized in the intensive care unit of a veterinary teaching hospital.

OBJECTIVE To evaluate the lipidemia status and serum concentrations of cholesterol and triglycerides of dogs when initially examined for hospitalization in the intensive care unit (ICU) of a veterinary teaching hospital and to determine whether these variables were predictive of survival to hospital discharge. DESIGN Retrospective cohort study. ANIMALS 549 client-owned sick (n = 398) and healthy (151) dogs. PROCEDURES Medical records of sick dogs hospitalized in the ICU at a veterinary teaching hospital between January 1, 2012, and September 30, 2015, and of healthy dogs evaluated at the teaching hospital during the same time frame were reviewed. Data collection included signalment, results of initial physical and clinicopathologic examinations, treatments, diagnosis, and survival to hospital discharge. Lipidemia status and serum concentrations of cholesterol and triglycerides were compared between healthy and sick dogs and between sick dogs that did and did not survive to hospital discharge. Regression analysis was performed to determine whether these variables were predictive of survival to hospital discharge in dogs. RESULTS Factors associated with increased odds of sick dogs not surviving to hospital discharge were hypocholesterolemia (OR, 1.87; 95% confidence interval [CI], 1.04 to 3.34), hypertriglyceridemia (OR, 3.20; 95% CI, 2.00 to 5.13), and concurrent hypocholesterolemia and hypertriglyceridemia (OR, 55.7; 95% CI, 3.2 to 959.6) at the time of initial evaluation. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that hypocholesterolemia and hypertriglyceridemia, alone or in combination, at initial examination were negative prognostic indicators for survival of dogs hospitalized in the ICU and that these conditions were easily identified with routine serum clinicopathologic analyses. (J Am Vet Med Assoc 2019;254:699-709).

Psychological factors can cause false pain classification on painDETECT.

Background and aims The painDETECT questionnaire (PD-Q) has been widely used as a screening tool for the identification of neuropathic pain (NeP) as well as a tool for the characterization of patients' pain profile. In contrast to other NeP screening tools, the PD-Q is the only screening tool with weighted sensory descriptors. It is possible that responses to the PD-Q sensory descriptors are influenced by psychological factors, such as catastrophizing or anxiety, which potentially might contribute to an overall higher score of PD-Q and a false positive identification of NeP. This study aimed to explore (i) the relationship between psychological factors (catastrophizing, anxiety, depression and stress) and the total PD-Q score and (ii) if psychological factors are associated with false positive identifications of NeP on the PD-Q compared to clinically diagnosed NeP. Methods The study was a retrospective review of 1,101 patients attending an outpatient pain centre. Patients were asked to complete the PD-Q, the Pain Catastrophizing Scale (PCS), the Depression, Anxiety and Stress Scale (DASS) and the Brief Pain Inventory (BPI). For patients who were identified by PD-Q as having NeP, their medical records were reviewed to establish if they had a clinical diagnosis of NeP. Results Accounting for missing data, complete datasets of 652 patients (mean age 51 (SD14) years, range 18-88; 57% females) were available for analysis. Based on PD-Q scoring, NeP was likely present in 285 (44%) patients. Depression, anxiety, stress, catastrophizing, BPI pain and BPI interference were all significantly related to each other (p < 0.0001) and patients displaying these traits were significantly more likely to have a positive PD-Q score (p < 0.0001). For patients classified by PD-Q as having NeP, only 50% of patients had a clinical diagnosis of NeP. Anxiety was significantly associated with a false positive classification of NeP on PD-Q (p = 0.0036). Conclusions Our retrospective study showed that psychological factors including catastrophizing, depression, anxiety, and stress were all influential in producing a higher score on the PD-Q. We observed a high rate of false positive NeP classification which was associated with the presence of anxiety. Implications Clinicians and researchers should be aware that a patient's psychological state may influence the responses to PD-Q and consequently the final PD-Q score and its NeP classification.

The Collaborative Payer Provider Model Enhances Primary Care, Producing Triple Aim Plus One Outcomes: A Cohort Study.

Rising health care costs are threatening the fiscal solvency of patients, employers, payers, and governments. The Collaborative Payer Provider Model (CPPM) addresses this challenge by reinventing the role of the payer into a full-service collaborative ally of the physician. From 2010 through 2014, a Medicare Advantage plan prospectively deployed the CPPM, averaging 30,561 members with costs that were 73.6% of fee-for-service (FFS) Medicare (p < 0.001). The health plan was not part of an integrated delivery system. After allocating $80 per member per month (PMPM) for primary care costs, the health plan had medical cost ratios averaging 75.1% before surplus distribution. Member benefits were the best in the market. The health plan was rated 4.5 Stars by the Centers for Medicare and Medicaid Services for years 1-4, and 5 Stars in study year 5 for quality, patient experience, access to care, and care process metrics. Primary care and specialist satisfaction were significantly better than national benchmarks. Savings resulted from shifts in spending from inpatient to outpatient settings, and from specialists to primary care physicians when appropriate. The CPPM is a scalable model that enables a win-win-win system for patients, providers, and payers.

Review of gunshot injuries in cats and dogs and utility of a triage scoring system to predict short-term outcome: 37 cases (2003-2008).

OBJECTIVE: To describe the signalment, wound characteristics, and treatment of gunshot injuries in cats and dogs in urban and rural environments, and to evaluate the utility of the animal trauma triage (ATT) score as an early predictor of survival to discharge from the hospital. DESIGN: Retrospective case series. ANIMALS: 29 dogs and 8 cats. PROCEDURES: Medical records of cats and dogs evaluated for gunshot wounds from 2003 and 2008 at a private urban referral practice in Cedar Rapids, Iowa, and an urban veterinary teaching hospital in Ames, Iowa, were reviewed. Information collected included signalment, chief reason for evaluation, circumstance of the injury, general physical examination findings, wound characteristics, treatments provided, cost of care, survival to discharge from the hospital (yes vs no), and duration of hospital stay. For each animal, ATT scores were calculated and evaluated as a prognostic tool. RESULTS: 37 animals met study inclusion criteria. Animals with higher ATT scores had a greater likelihood of poor outcome following gunshot injury. Animals with higher ATT scores, classified as low (< 4.5) or high (> 4.5), were found to have a longer duration of stay, classified as zero (0 days), short (1 to 3 days), or long (> 3 days). Young male dogs generally considered working breeds were overrepresented (29/37 [78.4%]). A preference for low-velocity, low-kinetic-energy firearms was identified (19/37 [52%]). The most numerous wounds were those inflicted to the limbs (12/37 [32.4%]), during low-visibility hours or hunting excursions. Calculated ATT scores on admission were higher in animals requiring blood products or surgical procedures and in nonsurvivors. CONCLUSIONS AND CLINICAL RELEVANCE: Results of the present study suggested that regional preferences in breed ownership and firearm choice are responsible for variation in gunshot injury characteristics and management in animals sustaining injuries in rural and urban settings in Iowa. In cats and dogs, calculation of an ATT score may provide a useful predictor of the need for surgery or blood products, duration of stay, and likelihood of survival to discharge from the hospital.

Supervising emotionally focused therapists: a systematic research-based model.

Emotionally Focused Therapy (EFT) is an empirically validated relational therapy that recognizes the complexity of couple's therapy and supports the need for specialized training of therapists. Until now, there has been little research on effective methods for EFT supervision and no systematic model for conducting EFT supervision. The findings of a qualitative study of certified EFT therapists' experiences with EFT supervision and training are presented in this study, along with a systematic model of EFT supervision. The model of EFT supervision is based on the findings of this study, relevant research regarding effective clinical supervision, and the authors' experiences with EFT supervision. This model of EFT supervision is isomorphic to the clinical practice of EFT, in that it is theoretically grounded in attachment theory and emphasizes experiential and emotionally based processes.

Characterization of two recessive genes controlling resistance to all races of bacterial spot in peppers.

Bacterial spot, one of the most damaging diseases of pepper, is caused by Xanthomonas euvesicatoria. This pathogen has worldwide distribution and it is particularly devastating in tropical and sub-tropical regions where high temperatures and frequent precipitation provide ideal conditions for disease development. Three dominant resistance genes have been deployed singly and in combination in commercial cultivars, but have been rendered ineffectual by the high mutation rate or deletion of the corresponding cognate effector genes. These genes are missing in race P6, and their absence makes this race virulent on all commercial pepper cultivars. The breeding line ECW12346 is the only source of resistance to race P6 in Capsicum annuum, and displays a non-hypersensitive type of resistance. Characterization of this resistance has identified two recessive genes: bs5 and bs6. Individual analysis of these genes revealed that bs5 confers a greater level of resistance than bs6 at 25 degrees C, but in combination they confer full resistance to P6 indicating at least additive gene action. Tests carried out at 30 degrees C showed that both resistances are compromised to a significant extent, but in combination they provide almost full resistance to race P6 indicating a positive epistatic interaction at high temperatures. A scan of the pepper genome with restriction fragment length polymorphism and AFLP markers led to the identification of a set of AFLP markers for bs5. Allele-specific primers for a PCR-based bs5-marker have been developed to facilitate the genetic manipulation of this gene.

Distribution and accumulation of a mixture of arsenic, cadmium, chromium, nickel, and vanadium in mouse small intestine, kidneys, pancreas, and femur following oral administration in water or feed.

Manufactured gas plant (MGP) sites are contaminated with coal tar and may contain metals such as arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), and vanadium (V). These metals are known to cause cancer or other adverse health conditions in humans, and the extent and cost of remediating MGP sites may be influenced by the presence of these metals. Studies assessed the distribution of these metals in female B6C3F1 mice ingesting (1) a metal mixture in water or (2) an MGP mixture in NIH-31 feed. The highest metal levels were measured in the small intestine and kidneys of mice receiving the metal mixture in water. For mice receiving the metal mixture in water, levels of As, Cd, and Cr, in the small intestine, levels of As, Cd, Cr, and V in the kidneys, levels of As and Cd in the pancreas, and levels of Cr and V in the femur were significantly greater than controls at 4, 8, 12, 16, and 24 wk. Except for Ni levels in the small intestine and femur and Cr levels in the kidneys, levels of metals were much lower in mice administered the MGP mixture in feed. The highest concentrations of metals in mice ingesting the MGP mixture in feed were found in the small intestine and kidneys, but few were significantly greater than controls. Levels of As in the small intestine at 6 and 18 wk and levels of Cr in the kidneys at 12, 18, and 24 wk were significantly greater than in controls. The data suggest that tissue burdens in small intestine, kidneys, pancreas, and femur of arsenic, cadmium, chromium, and vanadium are less when metals are present as an MGP mixture in feed than as a mixture in water. The reduced distribution and accumulation of metals in the organs of mice ingesting the MGP mixture in feed compared to the levels in organs of mice ingesting the metal mixture in water suggests that metals may be less likely to accumulate in humans ingesting MGP mixtures, thereby presenting a lower overall human health risk. The data presented indicate that the matrix in which metals are present will affect the uptake of individual metals and the organ specificity.

Heat curing Metaseiulus occidentalis (Nesbitt) (Acari, Phytoseiidae) of a fitness-reducing microsporidium.

Laboratory colonies of the predatory mite Metaseiulus occidentalis in Gainesville, FL were found to be infected with an undescribed microsporidium. Experiments were performed to quantify the effect of infection on the fitness of M. occidentalis and to determine if heat treatment can cure mites of the microsporidium. The colonies tested were derived from an isofemale line so that differences in performance could be attributed to the presence of microsporidia. A subcolony of an uninfected isofemale line was infected with the microsporidium by feeding females infected eggs from another colony of M. occidentalis. Infected mites had a shorter mean (+/-SD) female life span (7.4 +/- 2.9 vs. 10.0 +/- 2.8 days), lower mean oviposition (1.6 +/- 0.7 vs. 2.2 +/- 0.4 eggs/day), and a male-biased sex ratio (43 +/- 16% vs. 57 +/- 15% female progeny). The infection was reduced temporarily in colonies initiated from mites that were reared in a growth chamber at 33 degrees C from egg to adult, but healthy colonies only were established from the progeny of the heat-treated adults. These colonies remained free of infection for 10 weeks.