Improving implementation of best practices in obesity management: Physician experiences in obesity care.

In this study, we sought to analyse experiences in weight management among physicians working in the area of obesity and contrast these experiences with best practices. By understanding experiences of physicians working in obesity management, we can better support implementation of best practices in their day-to-day practice. An online survey of Canadian primary care physicians, internists and endocrinologists recruited from a nationwide market research database was conducted. The survey captured demographic characteristics and perceptions about weight loss and its management. One hundred and ninety-two physicians (140 primary care, 22 internists and 30 endocrinologists) were recruited and completed the survey. Challenges identified by the physicians in helping patients lose weight included patients' poor compliance and lack of time and resources to address the issue. Most physicians reported considering obesity to be a chronic disease, but most did not incorporate a multi-dimensional, chronic disease model of obesity treatment (i.e., combination of lifestyle interventions with psychological, medical and/or surgical interventions). Endocrinologists reported management practices consistent with a chronic disease model more frequently than primary care physicians. These data highlight the need for improvement in obesity management, particularly in primary care. Despite proliferation of guidelines on best practices, implementation of these practices into daily practice remains low.

Ribavirin aerosol in hospitalized adults with respiratory distress and COVID-19: An open-label trial.

There is an unmet medical need for effective treatments for hospitalized patients with coronavirus disease 2019 (COVID-19). Ribavirin is a broad-spectrum antiviral with demonstrated in vitro activity against multiple viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This trial evaluated the potential of ribavirin inhalation solution (ribavirin aerosol) to reduce COVID-19 disease severity in adults with confirmed SARS-CoV-2 infection and a diagnosis of respiratory distress. This phase I, multicenter, open-label, nonrandomized trial was conducted from February 2021 through August 2021. Patients received ribavirin aerosol (100 mg/ml for 30 min or 50 mg/ml for 60 min) twice daily for up to 6 days. The primary end point was change from baseline in clinical status severity, rated on a 7-point scale (1 [death]; 7 [not hospitalized; no limitations on activities]), at day 7 (or end-of-treatment/early termination) and day 30 (follow-up). Fifty-one patients were treated with ribavirin aerosol (mean age, 51.5 years; 78.4% men); mean number of doses was 9.7 (range, 1-12). Improvement of ≥1 level in clinical status severity was observed in 31.4% (16/51) and 78.4% (40/51) of patients at end-of-treatment and day 30, respectively. Of 21 patients who required a ventilator, 16 (76.2%) were able to discontinue ventilator use. Five patients (9.8%) died between end-of-treatment and day 30. Three patients (5.9%) discontinued study treatment due to adverse events. No deaths were considered related to study treatment. These data provide preliminary evidence that ribavirin aerosol may be an efficacious treatment for respiratory distress in adults with COVID-19.

A randomized, placebo-controlled study to evaluate safety and pharmacokinetics of inhaled ribavirin.

Ribavirin is an inosine monophosphate dehydrogenase inhibitor. Studies suggest ribavirin aerosol could be a safe and efficacious treatment option in the fight against coronaviruses. However, current treatment is long (12-18 h per day, 3-7 days), limiting clinical utility. A reduction in treatment time would reduce treatment burden. We aimed to evaluate safety and pharmacokinetics (PK) of four, single-dose regimens of ribavirin aerosol in healthy volunteers. Thirty-two subjects were randomized, to four cohorts of aerosolized ribavirin (active) or placebo. Cohort 1 received 50 mg/ml ribavirin/placebo (10 ml total volume); cohort 2, 50 mg/ml ribavirin/placebo (20 ml total volume); cohort 3, 100 mg/ml ribavirin/placebo (10 ml total volume); and cohort 4, 100 mg/ml ribavirin/placebo (20 ml total volume). Intense safety monitoring and PK sampling took place on days 1, 2, 3, and 40. Subjects were (mean ± SD, active vs. placebo) aged 57 ± 4.5 vs. 60 ± 2.5 years; 83% vs. 88% were female; and 75% vs. 50% were Caucasian. Some 12.5% (3/24) and 25% (2/8) experienced at least one treatment-emergent adverse event (TEAE) (two moderate; five mild) in the active and placebo groups, respectively. No clinically significant safety concerns were reported. Mean maximum observed concentration (Cmax ) and area under the curve (AUC) values were higher in cohort 4, whereas cohorts 2 and 3 showed similar PK values. Ribavirin absorption reached Cmax within 2 h across cohorts. Four single-dose regimens of ribavirin aerosol demonstrated systemic exposure with minimal systemic effects. Results support continued clinical development of ribavirin aerosol as a treatment option in patients with coronaviruses.

The relationship between early weight loss and weight loss maintenance with naltrexone-bupropion therapy.

Background: Extended-release (ER) naltrexone/bupropion (NB) was associated with greater weight loss than placebo in four randomized, 56-week trials. The association of NB with longer-term maintenance of weight loss remains unknown. Methods: We conducted a post-hoc analysis of four phase III, randomized, double-blind, placebo-controlled, 56-week studies (COR-I, COR-II, COR-BMOD, and COR-DM), the placebo-controlled cardiovascular outcomes trial LIGHT (208 weeks), and the randomized, open-label trial IGNITE (78 weeks). Included subjects were treated with NB 32 mg/360 mg or placebo, with baseline, week 16, and final time point data. The primary outcome was Kaplan-Meier-estimated weight loss maintenance in each study for up to 204 weeks. Findings: Our analysis included data from 10,198 particpants (NB=5412; placebo=4786). Proportions of patients with ≥5% or ≥10% weight loss maintenance were numerically higher for NB vs. placebo in all studies and time points. Differences were statistically significant for ≥5% weight loss maintenance in COR-BMOD and COR-I/-II at weeks 52 and 56 and the LIGHT study at weeks 52, 104, and 208. For ≥10% weight loss maintenance, differences were statistically significant in COR-I/COR-II at weeks 52 and 56. Interpretation: These data suggest that NB could be used as part of long-term, comprehensive weight loss and weight loss maintenance strategies. Funding: Orexigen Therapeutics, Inc. and Bausch Health Canada.

The i-ACT™ in Obesity educational intervention: a pilot study on improving Canadian family physician care in obesity medicine.

BACKGROUND: Obesity is a chronic problem in Canada and although the Canadian Medical Association recognizes obesity as a disease, health care professionals (HCPs) are not necessarily proactively managing it as one. This study aimed to assess current obesity management knowledge and practices of Canadian family physicians (FPs) and evaluate the feasibility of an online self-directed learning platform, i-ACT™ in Obesity, in delivering learning and changing practice intentions to advance obesity management. METHODS: i-ACT™ in Obesity is an online self-directed learning program designed by Canadian obesity medicine experts to provide individualized learning curricula to participants. One hundred FPs, with an interest in weight management and managing patients with obesity, were recruited across Canada to participate in a pilot study. FP education was delivered in a stepwise manner. Each participant completed a practice profile assessment to determine knowledge gaps and educational needs. Learners then watched didactic videos across disciplines on topics assigned to their curriculum by the program algorithm based on the relative difference between indicated and desired current knowledge. FPs also completed 10 retrospective patient assessments to assess clinical management practices and planned behaviour change. Feasibility, acceptability, and satisfaction of the learning program were assessed to formulate the rationale for a more widespread deployment in the future. Survey responses and related data were analyzed using comparative measures and descriptive statistics. RESULTS: The program was piloted by ninety-one Canadian FPs, where 900 patients were assessed. FPs showed distinct differences between their current and desired levels of comfort in a variety of obesity-related topics. Participation was associated with an intention to use more obesity treatment interventions moving forward. The program received an overall satisfaction rating of 8.6 out of 10 and 100% of the evaluators indicated that they would recommend it to their colleagues. CONCLUSION: The program was overall well received and successfully changed obesity management intentions among participating FPs, thus setting the stage for a larger more comprehensive study to examine the efficacy of i-ACT™ in Obesity in addressing knowledge gaps and advancing evidence-based, guidelines-aligned approach to obesity treatment.

Clinical Performance of Samfilcon A Contact Lenses in Intensive Digital Device Users: A Multicenter, Prospective Clinical Study.

INTRODUCTION: To evaluate patient satisfaction with samfilcon A contact lenses (CLs) in intensive digital device users with myopia and to compare patient satisfaction with samfilcon A lenses to prior experience with senofilcon A or lotrafilcon B CLs. METHODS: This was a comparative, prospective, national study conducted at 14 centers in Turkey. Subjects were adults aged 18 and 45 years with myopia (range -0.25 D to -6.00 D) who spend a minimum of 3 hours viewing digital devices (e.g., computer, smartphone). A subgroup of patients were habitual lens wearers (senofilcon A or lotrafilcon B lens wear for at least 6 months prior to enrollment). The primary assessment was patient satisfaction with samfilcon A lenses (0-100 Likert scale). Secondary assessments included patient satisfaction with samfilcon A lenses compared to patients' habitual lenses, investigator satisfaction with samfilcon A lenses and investigator-evaluated slit lamp examination findings. RESULTS: Samfilcon A lenses were given high overall ratings from both patients and investigators, with a low incidence of ocular symptoms. Overall, patients were highly satisfied with samfilcon A lenses for comfort, vision and overall performance, and stated that they would consider wearing these lenses in the future. Among habitual senofilcon A or lotrafilcon B lens wearers, samfilcon A lenses were rated significantly better than the habitual lenses in regard to comfort, vision and overall performance. Investigator assessments were also highly favorable, both at initial fit and after 4 weeks of follow-up, with no significant findings noted on slit lamp examination. CONCLUSION: Samfilcon A lenses were rated highly by investigators in regard to fit, handling and slit lamp findings, and by novice and habitual lens wearers in regard to comfort, vision and overall performance. These results support the use of samfilcon A lenses among digital device users who seek day-long comfort and good visual acuity.

Ribavirin Aerosol in the Treatment of SARS-CoV-2: A Case Series.

Ribavirin is an inosine monophosphate dehydrogenase inhibitor with demonstrated activity against coronaviruses, including SARS-CoV-2. Five hospitalized patients with COVID-19 (confirmed by positive tests for SARS-CoV-2) received treatment with ribavirin for inhalation solution (ribavirin aerosol) as part of a compassionate use program. Patients included four men and one woman, with an age range of 29-72 years. Patients were managed according to international and Italian treatment guidelines for COVID-19. In addition, therapy with ribavirin aerosol 100 mg/mL was administered for 30 min twice daily for 6 days (i.e., 12 doses) in all patients. In order to address concerns about a possible increase in viral dispersal with the use of a nebulizer, healthcare providers remained outside the patient room during ribavirin aerosol administration. Pretreatment chest computed tomography (CT) scans showed pseudonodular areas of parenchymal thickening in the upper right lobe with associated ground glass opacities, multiple areas of parenchymal consolidation in both lower lobes with associated ground glass opacities, bilateral parenchymal thickening and multiple associated ground glass areas, or focal ground glass areas in the upper lobes bilaterally, which were almost completely resolved (three patients) or moderately cleared (one patient) on imaging at the end of ribavirin treatment. For a fifth patient, CT scans showed a stable pulmonary picture at the end of ribavirin treatment. No adverse reactions to ribavirin treatment were observed in any of the five patients. All patients recovered fully, and nasopharyngeal swabs obtained after hospital discharge tested negative for SARS-CoV-2. Ribavirin aerosol appears to be efficacious in the treatment of patients with COVID-19. A controlled trial of ribavirin aerosol is ongoing and will provide additional data across a broader patient population.

Extended-release naltrexone/bupropion is safe and effective among subjects with type 2 diabetes already taking incretin agents: a post-hoc analysis of the LIGHT trial.

BACKGROUND: Extended-release naltrexone/bupropion (NB) is indicated for chronic weight management. Incretin agents are recommended for patients with type 2 diabetes. This analysis looked at the add-on of NB to incretins to see if weight loss could occur in patients already stabilized on incretin agents. METHODS: This was a post-hoc analysis of NB vs. placebo (PL) among subjects with type 2 diabetes stable on an incretin agent prior to randomization in a double-blind, PL-controlled cardiovascular outcome trial (N = 1317). RESULTS: Over 1 year, mean weight loss was significantly greater among NB patients vs. PL among those taking DPP-4i (mean absolute difference 4.6% [p < 0.0001]) and those taking GLP-1RAs (mean absolute difference 5.2%, p < 0.0001). Proportions of subjects achieving 5% weight loss were significantly greater for NB vs. PL at weeks 26 and 52 among those taking DPP-4is or GLP-1RAs. There were no significant differences in effectiveness observed between NB + DPP-4i and NB + GLP-1RA or between PL + DPP-4i and PL + GLP-1RA in any of the analyses. Serious adverse events were reported by 9.1% and 11.1% for PL + DPP-4i and PL + GLP-1RA, respectively, and 13.3% and 12.4% of NB + DPP-4i and NB + GLP-1RA, respectively. CONCLUSION: NB appears to be effective in reducing weight in patients with T2DM and obesity/overweight who are taking DPP-4ihibitors or GLP-1RA. The SAE rates in all arms of this analysis were lower than have been reported in other cardiovascular outcome trials in type 2 diabetes.

Psychiatric Safety and Weight Loss Efficacy of Naltrexone/bupropion as Add-on to Antidepressant Therapy in Patients with Obesity or Overweight.

There is significant association between obesity and depression. Naltrexone/Bupropion (NB) is indicated for treatment of overweight and obesity (BMI ≥27 kg/m2 with a comorbidity or ≥30 kg/m2). This post-hoc analysis examines safety and efficacy of NB and placebo among individuals with overweight or obesity who were also taking antidepressant therapy during the LIGHT trial (N=8910). Subjects were divided into four subgroups: NB + antidepressants (n=1150), NB without antidepressants (n=3300), placebo + antidepressants (n=1127) and placebo without antidepressants (n=3317). Among subjects taking NB, the combined incidence of serious adverse events (AEs) and AEs leading to treatment discontinuation was not significantly different between those on antidepressants and those who were not. The key weight-loss efficacy analyses were performed on NB or placebo-treated subjects who remained on study therapy through 104 weeks and who did or did not have documented antidepressant use at each of the baseline, week 52 and week 104 visits (Completers: N=1811; 47.0% female, 86.9% white, mean age of 61 years, mean baseline BMI 37.4 kg/m2). The mean adjusted weight change in subjects taking antidepressants was numerically, but not significantly greater for NB vs. placebo (-6.3% vs. -4.3%). For those subjects not on antidepressants, weight loss was significantly greater for NB vs. PL (-6.8% vs. -3.6%). NB is generally well tolerated in patients with overweight or obesity who are on antidepressants and is effective in promoting weight loss regardless of antidepressant use. These results show that for patients on antidepressant therapy, NB may be an effective option for obesity management.

Extended-release naltrexone/bupropion and liver health: Pooled, post hoc analysis from four randomized controlled trials.

Sustained weight loss improves liver histology in non-alcoholic fatty liver disease. This post hoc analysis of four phase III, 56-week, randomized controlled trials investigated if extended-release naltrexone and bupropion (NB) affects alanine aminotransferase (ALT) and Fibrosis-4 (FIB-4) index in adults with overweight or obesity. Two thousand and seventy-three subjects (NB = 1310; placebo = 763; 79.0% female; 81.6% Caucasian) had baseline mean weight 101 kg, body mass index 36.2 kg/m2 , ALT 26.9 IU/L and FIB-4 0.79. At 56 weeks, NB-treated subjects experienced more weight loss than placebo (8.7 vs. 3.2 kg, respectively, P < .0001). Weight loss, independent of treatment, was associated with improved ALT and FIB-4 (P < .0001). There was a significant independent effect of NB on change from baseline for FIB-4 (P < .0001), but not for ALT (P = .54). Categorical ALT response (from above to within normal ranges: 10-40 IU/L for men; 7-35 IU/L for women) and achievement of 25% and 50% reduction in ALT were greater for NB versus placebo, and independently affected by weight loss (P < .0001), but not treatment. NB-associated weight loss may improve liver health by normalizing ALT values for those with high baseline levels.

Real-world effectiveness of treatments for type 2 diabetes, hypercholesterolemia, and hypertension in Canadian routine care - Results from the CardioVascular and metabolic treatment in Canada: Assessment of REal-life therapeutic value (CV-CARE) registry, 12-months results.

AIMS: The CV-CARE registry provides RWE in Canadian routine clinical practice. METHODS: CV-CARE is a multi-site, observational, prospective Canadian registry enrolling patients initiating treatment with metformin hydrochloride extended-release (MetER) for T2D; colesevelam (C) for HCh; and azilsartan (AZI), azilsartan/chlorthalidone (AZI/CHL) or diltiazem extended-release (TXC) for HTN. Patient characteristics/assessment were performed at baseline and 12 ± 6 months. Primary outcome was absolute change in HbA1c and FPG (MetER); % change in LDL-C (C); and absolute change in BP (AZI-AZI/CHL-TXC). RESULTS: Of the 4194 patients in the primary analysis population, 24% were taking MetER, 39% were taking C, 33% were taking AZI, 12% were taking AZI/CHL, and 3% were taking TXC. At 12 months, MetER-treated patients had an absolute mean (95% CI) change in HbA1c of -0.3% [-0.4; -0.2] and in FPG of 0.7 mmol/L [-1.0; -0.4]. C-treated patients had a mean (95% CI) % change in LDL-C of -13.0% [-14.6; -11.4]. Absolute mean (95% CI) changes in SBP were -18.7 mmHg [-19.7; -17.7](AZI), -21.3 mmHg [-23.1; -19.5](AZI/CHL), and -12.3 mmHg [-15.1; -9.6](TXC). CONCLUSION: In a real-world Canadian setting, MetER, C, AZI, AZI/CHL, and TXC show improvement of the cardiometabolic profile of T2D, HCh, and HTN patients.

Regional variability in Canadian routine care of type 2 diabetes, hypercholesterolemia, and hypertension: Results from the The Cardio-Vascular and metabolic treatments in Canada: Assessment of REal-life therapeutic value (CV-CARE) registry.

BACKGROUND: Regional differences in the profile and treatment strategies of patients with cardiometabolic diseases have been studied in several different countries. The Cardio-Vascular and metabolic treatments in Canada: Assessment of REal-life therapeutic value (CV-CARE) registry was designed to evaluate patient profiles and medical management of cardiometabolic diseases in routine clinical care settings across Canada. Primary objectives were to (1) evaluate regional variability of patient profiles with cardiometabolic disease(s) and (2) assess treatment differences of patients treated for type 2 diabetes (T2D), hypercholesterolemia (HCh), and hypertension (HTN) across Canada. METHODS: CV-CARE is a multi-center, observational, prospective registry that enrolled Canadian patients treated with metformin-extended release (MetER) for T2D, colesevelam (C) for HCh, azilsartan (AZI) for mild-to-moderate essential HTN and azilsartan/chlorthalidone (AZI/CHL) for severe, essential HTN. Patient characteristics and treatments were assessed at baseline. RESULTS: The registry enrolled 6960 patients, with a total of 4194 patients making up the primary analysis population [MetER (n=995); C (n=1639); AZI (n=1364); AZI/CHL (n=498)]. First-line use of MetER was more common in British Columbia (BC; 45.5%) compared to Ontario (ON; 29.8%), and Quebec (QC; 12.9%). C treatment for HCh was used as monotherapy most readily in BC (68.7%) compared with QC (59.7%) and ON (35.8%). Dual action of low-density lipoprotein cholesterol and hemoglobin A1c reduction was the predominant reason for C add-on therapy (46.8%), with highest usage seen in ON (62.9%). AZI treatment for HTN was most frequently used in BC (43.8%), and AZI/CHL was most commonly used in ON (12.0%). First-line use of AZI was more common in QC (50%) vs. ON (34.9%) and BC (24.1%). The primary reason for switching to AZI and AZI/CHL from prior treatment was lack of efficacy across provinces. CONCLUSION: This is the first regional description of the CV-CARE cohort. Significant variations in both baseline profile and treatments were observed which could have an impact on long-term outcomes.

Treatment-resistant depression: definitions, review of the evidence, and algorithmic approach.

BACKGROUND: Most adults with major depressive disorder (MDD) fail to achieve remission with index pharmacological treatment. Moreover, at least half will not achieve and sustain remission following multiple pharmacological approaches. Herein, we succinctly review treatment modalities proven effective in treatment-resistant depression (TRD). METHODS: We conducted a review of computerized databases (PubMed, Google Scholar) from 1980 to April 2013. Articles selected for review were based on author consensus, adequacy of sample size, the use of a standardized experimental procedure, validated assessment measures and overall manuscript quality. RESULTS: The evidence base supporting augmentation of conventional antidepressants with atypical antipsychotics (i.e., aripiprazole, quetiapine, and olanzapine) is the most extensive and rigorous of all pharmacological approaches in TRD. Emerging evidence supports the use of some psychostimulants (i.e., lisdexamfetamine) as well as aerobic exercise. In addition, treatments informed by pathogenetic disease models provide preliminary evidence for the efficacy of immune-inflammatory based therapies and metabolic interventions. Manual based psychotherapies remain a treatment option, with the most compelling evidence for cognitive behavioral therapy. Disparate neurostimulation strategies are also available for individuals insufficiently responsive to pharmacotherapy and/or psychosocial interventions. LIMITATIONS: Compared to non-treatment-resistant depression, TRD has been less studied. Most clinical studies on TRD have focused on pharmacotherapy-resistant depression, with relatively fewer studies evaluating "next choice" treatments in individuals who do not initially respond to psychosocial and/or neurostimulatory treatments. CONCLUSION: The pathoetiological heterogeneity of MDD/TRD invites the need for mechanistically dissimilar, and empirically validated, treatment approaches for TRD.