Cost-effectiveness of a novel urethral catheter safety device in preventing catheterization injuries in the UK.

AIMS: Intraurethral catheter balloon inflation is a substantial contributor to significant catheter-related urethral injury. A novel safety valve has been designed to prevent these balloon-inflation injuries. The purpose of this evaluation was to assess the cost-effectiveness of urethral catheterisation with the safety valve added to a Foley catheter versus the current standard of care (Foley catheter alone). MATERIALS AND METHODS: The analysis was conducted from the UK public payer perspective on a hypothetical cohort of adults requiring transurethral catheterization. A decision tree was used to capture outcomes in the first 30 days following transurethral catheterization, followed by a Markov model to estimate outcomes over a person's remaining lifetime. Clinical outcomes included catheter balloon injuries [CBIs], associated short-term complications, urethral stricture disease, life years and QALYs. Health-economic outcomes included total costs, incremental cost-effectiveness ratio, net monetary benefit (NMB) and net health benefit. RESULTS: Over a person's lifetime, the safety valve was predicted to reduce CBIs by 0.04 per person and CBI-related short-term complications by 0.03 per person, and nearly halve total costs. The safety valve was dominant, resulting in 0.02 QALYs gained and relative cost savings of £93.19 per person. Probabilistic sensitivity analysis indicated that the safety valve would be cost-saving in 97% of simulations run versus standard of care. CONCLUSIONS: The addition of a novel safety valve aiming to prevent CBIs during transurethral catheterization to current standard of care was estimated to bring both clinical benefits and cost savings.

An exploratory cost-effectiveness analysis of a novel tissue valve compared with mechanical valves for surgical aortic valve replacement in subgroups of people aged 55-64 and 65+ with aortic stenosis in the UK.

OBJECTIVE: Exploratory analysis to conceptualize and evaluate the potential cost-effectiveness and economic drivers of using a novel tissue valve compared with mechanical heart valves for surgical aortic valve replacement (SAVR) in people aged 55-64 and 65+ with aortic stenosis (AS) from a National Health Service (NHS) UK perspective. METHODS: A decision-analytic model was developed using a partitioned survival model. Parameter inputs were obtained from published literature. Deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted to explore the uncertainty around the parameters. RESULTS: The novel tissue valve was potentially associated with higher quality-adjusted life years (QALYs) of 0.01 per person. Potential cost savings were greatest for those aged 55-64 (£408) versus those aged 65+(£53). DSA indicated the results to be most dependent on relative differences in general mortality, procedure costs, and reoperation rates. PSA estimated around 75% of the iterations to be cost-effective at £20,000 per QALY for those aged 55-64, and 57% for those aged 65+. CONCLUSIONS: The exploratory analysis suggests that the novel tissue valve could be a cost-effective intervention for people over the age of 55 with AS who are suitable for SAVR in the UK.

A Double-Blind Randomized Controlled Trial of Doxazosin for Co-Occurring PTSD and Alcohol Use Disorder in Veterans.

Objective: The aim of this study was to determine the efficacy of doxazosin, an α1-adrenergic antagonist, for the treatment of co-occurring posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD).Methods: This 12-week, double-blind, randomized controlled trial of doxazosin (16 mg/d) was conducted between June 2016 and December 2019 at the Ralph H. Johnson VA Medical Center in Charleston, South Carolina. Participants were military veterans (N = 141) who met DSM-5 criteria for current PTSD and AUD and were randomly assigned to receive doxazosin (n = 70) or placebo (n = 71). Primary outcome measures were the Clinician Administered PTSD Scale (CAPS-5), the PTSD Checklist for DSM-5 (PCL-5), and the Timeline Follow-Back (TLFB).Results: Findings from the intent-to-treat analyses revealed that participants in both groups demonstrated statistically significant reductions in CAPS-5 and PCL-5 scores (P < .0001), but, contrary to hypotheses, no significant differences were observed between groups. Percent drinking days and percent heavy drinking days also decreased significantly during treatment, but there were no differences between groups (P < .0001). Abstinence during treatment was significantly higher in the doxazosin versus the placebo group (22% vs 7%, P = .017); however, participants in the doxazosin group consumed a greater number of drinks on drinking days (6.15 vs 4.56, P = .0096). A total of 74.5% of the sample completed the treatment phase, and there were no group differences in retention or adverse events.Conclusions: Doxazosin was safe and tolerable but was not more effective than placebo in reducing PTSD or AUD severity in this dually diagnosed sample. Clinical considerations such as heterogeneity of PTSD and AUD presentation and potential moderators are discussed in the context of future research directions.Trial Registration: ClinicalTrials.gov Identifier: NCT02500602.

Economic evaluation of a vision-based patient monitoring and management system in an acute adult and an older adult mental health hospital in England.

BACKGROUND AND AIMS: Patients on acute adult and older adult inpatient mental health wards are at an increased risk of accidental injuries and deliberate harm to self and others. A vision-based patient monitoring and management (VBPMM) system was designed by Oxehealth Limited to support ward staff to provide better and more efficient care and to reduce incidents. The VBPMM system uses an infrared-sensitive camera, installed in a patient's room, that works with cleared medical device software to deliver contact-free vital sign and activity insights to clinical teams. Data from two studies undertaken at an English National Health Service (NHS) mental health trust were used to inform an early economic assessment of VBPMM implementation into acute adult and older adult mental health wards. METHODS: A cost calculator was used to compare the introduction of the VBPMM system as an adjunct to standard care versus standard care alone. Observational data were collected at two English NHS mental health trusts. Both compared data pre- and post-VBPMM implementation using a 12-month baseline period. The model estimated cost per occupied bed day, cost per patient, annual cost per average-sized ward, and total cost to NHS mental health trusts across England. Costs were modeled from an NHS perspective over a 12-month time horizon. Scenario analysis was conducted to test the uncertainty of results using statistical significance of key inputs. RESULTS AND CONCLUSIONS: This early analysis indicated that the VBPMM system is likely to be cost saving within both settings examined, with an estimated cost saving of £272 per acute adult mental health patient and £4,591 per older adult mental health patient. This translates to £22.3 and £63.3 million, respectively, across NHS mental health trusts in England every year. VBPMM, therefore, has the potential to augment standard care, leading to positive clinical outcomes and monetary savings.

Economic evaluation of a vision-based patient monitoring and management system in addition to standard care for adults admitted to psychiatric intensive care units in England.

BACKGROUND AND AIMS: Treating patients in psychiatric intensive care units (PICUs) is costly for the English National Health Service (NHS), requiring significant staff time. Oxevision, a non-contact system, providing vision-based patient monitoring and management (VBPMM) has been introduced in some NHS mental health trusts which aims to help clinicians to deliver safer and more efficient care. The objective of this early economic evaluation was to explore the impact of introducing VBPMM with standard care, versus standard care alone on health and economic outcomes in PICUs across England. METHODS: The model uses a cost calculator approach to evaluate the potential benefits of introducing VBPMM, capturing differences in observation hours and critical events such as assaults. Effectiveness data were primarily based on a 24-month observational before and after study undertaken in an NHS mental health trust using VBPMM. Outcomes reported in this study are incremental costs and reduction in clinical events presented as per occupied bed days, per patient, per average ward, and for the English NHS overall. Scenario analysis was conducted to test the uncertainty of results using statistical significance of key inputs. RESULTS AND CONCLUSIONS: The analysis indicates that introducing VBPMM may be cost saving compared with standard care alone. The biggest driver of estimated cost savings was from the potential reduction in one to one observation hours, which may have significant impact in PICUs. Limitations of the analysis include the single center data underpinning the analysis and assumptions made about transferability of clinical data to different sized wards. Scenario analysis was conducted, and the results were robust to statistically significant changes in input parameters. This study suggests that introducing VBPMM on PICUs has the potential to reduce costs and improve efficiency of resource allocation, but results should be confirmed with additional clinical study evidence.

Pragmatic Weight Management Program for Patients With Obesity and Heart Failure With Preserved Ejection Fraction.

Background Obesity is associated with heart failure with preserved ejection fraction (HFpEF). Weight loss can improve exercise capacity in HFpEF. However, previously reported methods of weight loss are impractical for widespread clinical implementation. We tested the hypothesis that an intensive lifestyle modification program would lead to relevant weight loss and improvement in functional status in patients with HFpEF and obesity. Methods and Results Patients with ejection fraction >45%, at least 1 objective criteria for HFpEF, and body mass index ≥30 kg/m2 were offered enrollment in an established 15-week weight management program that included weekly visits for counseling, weight checks, and provision of meal replacements. At baseline, 15 weeks, and 26 weeks, Minnesota Living With Heart Failure score, 6-minute walk distance, echocardiography, and laboratory variables were assessed. A total of 41 patients completed the study (mean body mass index, 40.8 kg/m2), 74% of whom lost >5% of their baseline body weight following the 15-week program. At 15 weeks, mean 6-minute walk distance increased from 223 to 281 m (P=0.001) and then decreased to 267 m at 26 weeks. Minnesota Living With Heart Failure score improved from 59.9 to 37.3 at 15 weeks (P<0.001) and 37.06 at 26 weeks. Changes in weight correlated with change in Minnesota Living With Heart Failure score (r=0.452; P=0.000) and 6-minute walk distance (r=-0.388; P<0.001). Conclusions In a diverse population of patients with obesity and HFpEF, clinically relevant weight loss can be achieved with a pragmatic 15-week program. This is associated with significant improvements in quality of life and exercise capacity. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02911337.

Pilot evaluation of a personalized commercial program on weight loss, health outcomes, and quality of life.

WW is a validated behavioral weight management program that encourages healthy habits. WW developed a method of personalizing the SmartPoints® budget depending on dietary and lifestyle preferences, and participants were placed into one of three plans as a pilot evaluation of this new program. In this 6-month, single-arm pilot study, participants attended weekly workshops and used an app to monitor eating and physical activity. Baseline and 6-month assessments included weight, waist circumference, blood pressure, energy intake, cravings, happiness, health-related quality of life, hunger, and fullness. Of 145 adults assessed at baseline, 126 (87%) provided follow-up data. Pre-post changes showed significant reductions in body weight (7.39% ± 5.93%), calories consumed (24.79% ± 32.35%) and significant improvements in cravings, happiness, all SF-36 scales and hunger but not in fullness. Greater % weight loss was related to greater improvements in happiness (r = .38, p < .001), general health perceptions (r = .29, p = .001), and health change (r = .31, p = .001), and greater reduction in role limitations due to personal or emotional problems (r = .24, p = .01). Greater % reduction in caloric intake was associated with greater reductions in cravings (r = .23, p = .01), as well as with greater improvements in happiness (r = .23, p = .01), physical functioning (r = .23, p = .01), and general health perceptions (r = .23, p = .01). Participants in this modified program achieved significant weight loss, regardless of dietary plan, as well as improvements in a variety of other physical and psychological constructs. Those who achieved greater reductions in weight also reported greater improvements in cravings, happiness and some quality of life measures.

Impact of Fatty Acid Supplementation on Cognitive Performance among United States (US) Military Officers: The Ranger Resilience and Improved Performance on Phospholipid-Bound Omega-3's (RRIPP-3) Study.

Studies have assessed omega-3 fatty acids and cognitive decline among older adults and cognitive development among children, although less is known about cognitive or neurological effects among young adults. We examined whether omega-3 supplementation from krill oil could improve cognition and resilience among young military officers compared to a control. This double-blind, placebo-controlled trial enrolled 555 officers (mean age 23.4 ± 2.8, 98.6% male) entering the United States (US) Army Infantry Basic Officer Leaders Course (IBOLC) with the intention to complete the US Ranger Course. Volunteer participants consumed eight dietary supplements daily of krill oil containing 2.3 g omega-3 or control (macadamia nut oil) over an approximate 20-week period. Cognitive functioning, resilience, and mood were assessed during a well-rested period at approximately 14 weeks and after a battlefield simulation at 16 weeks. Blood spot samples were collected to monitor compliance and dietary intake was assessed. All hypotheses were tested using both 'Intention to Treat' (ITT) and 'As Per Protocol' (APP) approaches. Of the 555 randomized individuals, 245 (44.1%) completed the study. No statistically significant group-by-time interactions indicating treatment effect were found on any outcomes. Poor compliance was indicated by lower than expected omega-3 elevations in the treatment group, and may have contributed to a failure to detect a response.

The Vaginal Microbiota, Bacterial Biofilms and Polymeric Drug-Releasing Vaginal Rings.

The diversity and dynamics of the microbial species populating the human vagina are increasingly understood to play a pivotal role in vaginal health. However, our knowledge about the potential interactions between the vaginal microbiota and vaginally administered drug delivery systems is still rather limited. Several drug-releasing vaginal ring products are currently marketed for hormonal contraception and estrogen replacement therapy, and many others are in preclinical and clinical development for these and other clinical indications. As with all implantable polymeric devices, drug-releasing vaginal rings are subject to surface bacterial adherence and biofilm formation, mostly associated with endogenous microorganisms present in the vagina. Despite more than 50 years since the vaginal ring concept was first described, there has been only limited study and reporting around bacterial adherence and biofilm formation on rings. With increasing interest in the vaginal microbiome and vaginal ring technology, this timely review article provides an overview of: (i) the vaginal microbiota, (ii) biofilm formation in the human vagina and its potential role in vaginal dysbiosis, (iii) mechanistic aspects of biofilm formation on polymeric surfaces, (iv) polymeric materials used in the manufacture of vaginal rings, (v) surface morphology characteristics of rings, (vi) biomass accumulation and biofilm formation on vaginal rings, and (vii) regulatory considerations.

N-acetylcysteine for the treatment of comorbid alcohol use disorder and posttraumatic stress disorder: Design and methodology of a randomized clinical trial.

Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) are two prevalent psychiatric conditions in the U.S. The co-occurrence of AUD and PTSD is also common, and associated with a more severe clinical presentation and worse treatment outcomes across the biopsychosocial spectrum (e.g., social and vocational functioning, physical health) as compared to either disorder alone. Despite the high co-occurrence and negative outcomes, research on effective medications for AUD/PTSD is sparse and there is little empirical evidence to guide treatment decisions. The study described in this paper addresses this knowledge gap by testing the efficacy of N-acetylcysteine (NAC) in reducing alcohol use and PTSD symptoms. Animal studies and prior clinical research suggest a role for NAC in the treatment of substance use disorders and PTSD via glutamate modulation. NAC is a cysteine pro-drug that stimulates the cystine-glutamate exchanger, normalizes glial glutamate transporters, and restores glutamatergic tone on presynaptic receptors in reward regions of the brain. Moreover, NAC is available over-the-counter, has a long-established safety record, and does not require titration to achieve the target dose. This paper describes the rationale, study design, and methodology of a 12-week, randomized, double-blind, placebo-controlled trial of NAC (2400 mg/day) among adults with co-occurring AUD and PTSD. Functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (1H-MRS) are utilized to investigate the neural circuitry and neurochemistry underlying comorbid AUD/PTSD and identify predictors of treatment outcome. This study is designed to determine the efficacy of NAC in the treatment of co-occurring AUD/PTSD and provide new information regarding mechanisms of action implicated in co-occurring AUD/PTSD.

Changes in weight control behaviors and hedonic hunger in a commercial weight management program adapted for individuals with type 2 diabetes.

BACKGROUND: A WW (formerly Weight Watchers) program adapted for persons with type 2 diabetes mellitus (T2DM) previously was found to be more effective than standard care (SC) intervention for weight loss, improved glycemic control, and weight- and diabetes-related quality of life measures. With data from the same national trial, this study examined whether WW adapted for persons with T2DM also increased engagement in weight control behaviors and decreased hedonic hunger, each of which could contribute to improved diabetes management. INTERVENTION AND METHODS: Individuals with T2DM (n = 563) and overweight or obesity participated in a 12-month, 16-site, randomized trial of WW with diabetes counseling or SC. Hierarchical linear modeling (HLM) evaluated whether 12-month changes in weight control behaviors (Eating Behavior Inventory; EBI) and hedonic hunger (Power of Food Scale; PFS) differed by treatment condition. If a significant treatment effect was found, 12-month changes in EBI/PFS were regressed on 12-month changes in HbA1c and percent weight loss to explore potential treatment differences in these associations. RESULTS: EBI scores increased significantly over the 12-months (p < 0.001), with greater improvements in WW than SC (p < 0.001). PFS decreased significantly in the 12-months (p < 0.001), with no differences between treatment groups (p = 0.15). HLM analyses that followed up on the significant treatment effect for 12-month change in EBI revealed no significant differences by treatment condition for the relationship between change in EBI scores and change in HbA1c (p = 0.14) or percent weight loss (p = 0.32). Across all participants, 12-month improvements in EBI and PFS were related to improved HbA1c (r = 0.22; -0.13, respectively) and greater percent weight loss (r = 0.41; -0.18, respectively) (ps < 0.01). CONCLUSIONS: WW with diabetes counseling produced greater engagement in weight control behaviors in those with T2DM than did SC. Across both groups, improved weight control behaviors and hedonic hunger were related to improved glycemic control and weight loss.

Design and methods for the Ranger Resilience and Improved Performance on Phospholipid bound Omega-3's (RRIPP-3 study).

Intake of nutrients fundamental for optimal neuronal function is of increasing interest. The potential importance of omega-3 highly unsaturated fatty acids (HUFAs) for optimizing emotional states, cognitive function, and mental health has been demonstrated in observational studies and randomized controlled trials. Omega-3 (HUFAs), specifically EPA (eicosapentaenoic acid) and docosahexaenoic acid (DHA), are concentrated in neural tissues and are essential for neural function, normative neurodevelopment, neurotransmitter, and neural immune functions. Omega-3 HUFAs must be obtained from the diet, predominantly from marine sources such as fish and other seafood. HUFAs also can be found in a variety of dietary supplements (omega-3 fatty acid esters, fish oil and krill oil). As dietary supplements, omega-3 HUFAs (fatty acid esters, fish and krill oils) differ substantially in their physicochemical properties and nutrient content. Here we present the design and methods for the Ranger Resilience and Improved Performance on Phospholipid bound Omega-3's (RRIPP-3) study. RRIPP-3 was a double blind, randomized, controlled trial among individuals in the United States (US) Army Infantry Basic Officer Leaders Course (IBOLC) and following US Ranger School training (RC) at Fort Benning, GA of omega-3 HUFA on krill oil versus placebo supplementation. The RRIPP-3 study sought to determine if krill oil supplementation with omega-3 HUFAs supports aspects of cognitive functioning critical to battlefield success when measured immediately after an intense combat simulation. Sub-analyses addressed basic improvements in IBOLC performance. We also describe additional outcome measures critical for interpretation of the study results, such as diet and other dietary supplement use.

Machine learning algorithms for systematic review: reducing workload in a preclinical review of animal studies and reducing human screening error.

BACKGROUND: Here, we outline a method of applying existing machine learning (ML) approaches to aid citation screening in an on-going broad and shallow systematic review of preclinical animal studies. The aim is to achieve a high-performing algorithm comparable to human screening that can reduce human resources required for carrying out this step of a systematic review. METHODS: We applied ML approaches to a broad systematic review of animal models of depression at the citation screening stage. We tested two independently developed ML approaches which used different classification models and feature sets. We recorded the performance of the ML approaches on an unseen validation set of papers using sensitivity, specificity and accuracy. We aimed to achieve 95% sensitivity and to maximise specificity. The classification model providing the most accurate predictions was applied to the remaining unseen records in the dataset and will be used in the next stage of the preclinical biomedical sciences systematic review. We used a cross-validation technique to assign ML inclusion likelihood scores to the human screened records, to identify potential errors made during the human screening process (error analysis). RESULTS: ML approaches reached 98.7% sensitivity based on learning from a training set of 5749 records, with an inclusion prevalence of 13.2%. The highest level of specificity reached was 86%. Performance was assessed on an independent validation dataset. Human errors in the training and validation sets were successfully identified using the assigned inclusion likelihood from the ML model to highlight discrepancies. Training the ML algorithm on the corrected dataset improved the specificity of the algorithm without compromising sensitivity. Error analysis correction leads to a 3% improvement in sensitivity and specificity, which increases precision and accuracy of the ML algorithm. CONCLUSIONS: This work has confirmed the performance and application of ML algorithms for screening in systematic reviews of preclinical animal studies. It has highlighted the novel use of ML algorithms to identify human error. This needs to be confirmed in other reviews with different inclusion prevalence levels, but represents a promising approach to integrating human decisions and automation in systematic review methodology.

Patients' reasons for weight loss and their relations to clinical weight loss outcomes in a comprehensive lifestyle intervention.

OBJECTIVE: Research suggests that individuals seeking weight loss treatment do so for a variety of reasons. Limited work has explored relations of reasons for weight loss to patient characteristics or to weight loss outcomes. The current study examined these relations. METHODS: The sample consisted of 588 patients in a 15-week fee-for-service weight loss programme. Prior to the intervention, patients completed questionnaires including items on reasons for weight loss, demographic characteristics, and a variety of weight-based characteristics. Patients' weight change outcomes were expressed as percent weight loss and also categorized into one of three previously described weight loss trajectories. RESULTS: The results of chi-squared and t-test analyses suggested that endorsement of health concerns, mobility concerns, or another person's recommendation was associated with higher body mass index (BMI) and older age. These reasons were more likely to be endorsed by White patients than Black patients and by male patients than female patients. Endorsement of doctor recommendation was more likely to be seen among Black patients than White patients. There was no significant relation of any weight loss reason with weight loss outcome. CONCLUSIONS: While certain reasons for weight loss were more often cited by certain patient groups, no specific reason predicted a better or worse outcome.

Administration of galacto-oligosaccharide prebiotics in the Flinders Sensitive Line animal model of depression.

INTRODUCTION: Major depressive disorder is the leading source of disability globally and current pharmacological treatments are less than adequate. Animal models such as the Flinders Sensitive Line (FSL) rats are used to mimic aspects of the phenotype in the human disorder and to characterise candidate antidepressant agents. Communication between the gut microbiome and the brain may play an important role in psychiatric disorders such as depression. Interventions targeting the gut microbiota may serve as potential treatments for depression, and this drives increasing research into the effect of probiotics and prebiotics in neuropsychiatric disorders. Prebiotics, galacto-oligosaccharides and fructooligosaccharides that stimulate the activity of gut bacteria have been reported to have a positive impact, reducing anxiety and depressive-like phenotypes and stress-related physiology in mice and rats, as well as in humans. Bimuno, the commercially available beta-galacto-oligosaccharide, has been shown to increase gut microbiota diversity. AIM: Here, we aim to investigate the effect of Bimuno on rat anxiety-like and depressive-like behaviour and gut microbiota composition in the FSL model, a genetic model of depression, in comparison to their control, the Flinders Resistant Line (FRL) rats. METHODS: Sixty-four male rats aged 5-7 weeks, 32 FSL and 32 FRL rats, will be randomised to receive Bimuno or control (4 g/kg) daily for 4 weeks. Animals will be tested by an experimenter unaware of group allocation on the forced swim test to assessed depressive-like behaviour, the elevated plus maze to assess anxiety-like behaviour and the open field test to assess locomotion. Animals will be weighed and food and water intake, per kilogram of bodyweight, will be recorded. Faeces will be collected from each animal prior to the start of the experiment and on the final day to assess the bacterial diversity and relative abundance of bacterial genera in the gut. All outcomes and statistical analysis will be carried out blinded to group allocation, group assignments will be revealed after raw data have been uploaded to Open Science Framework. Two-way analysis of variance will be carried out to investigate the effect of treatment (control or prebiotic) and strain (FSL or FRL) on depressive-like and anxiety-like behaviours.

Efficacy of Ketamine in the Treatment of Substance Use Disorders: A Systematic Review.

Background: Despite advances in behavioral and pharmacotherapy interventions, substance use disorders (SUDs) are frequently refractory to treatment. Glutamatergic dysregulation has received increasing attention as one common neuropathology across multiple substances of abuse. Ketamine is a potent N-methyl-D-aspartate (NMDA) glutamatergic receptor antagonist which has been found to be effective in the treatment of severe depression. Here we review the literature on the efficacy of ketamine in the treatment of SUDs. Methods: A systematic review of the PubMed, Scopus, and ClinicalTrials.gov databases was undertaken to identify completed and ongoing human studies of the effectiveness of ketamine in the treatment of SUDs between January 1997 and January 2018. Results and conclusion: Seven completed studies were identified. Two studies focused on alcohol use disorder, two focused on cocaine use disorder, and three focused on opioid use disorder. Both cocaine studies found improvements in craving, motivation, and decreased cocaine use rates, although studies were limited by small sample sizes, a homogeneous population and short follow-up. Studies of alcohol and opioid use disorders found improvement in abstinence rates in the ketamine group, with significant between-group effects noted for up to two years following a single infusion, although these were not placebo-controlled trials. These results suggest that ketamine may facilitate abstinence across multiple substances of abuse and warrants broader investigation in addiction treatment. We conclude with an overview of the six ongoing studies of ketamine in the treatment of alcohol, cocaine, cannabis, and opioid use disorders and discuss future directions in this emerging area of research.

Repetitive transcranial magnetic stimulation (rTMS) administration to heavy cannabis users.

BACKGROUND: Cannabis use disorder (CUD) is a common condition with few treatments. Several studies in other substance use disorders have found that applying repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC) decreases cue-elicited craving and possibly decreases use. To date, there have been no studies attempting to use rTMS in CUD. OBJECTIVES: This study was conducted to determine if rTMS could be feasibly delivered to a group of non-treatment seeking CUD participants. Secondarily, the study aimed to estimate the effect of rTMS on craving. METHODS: In a double-blind, sham-controlled, crossover design, a single session of active or sham rTMS (Left DLPFC, 10 Hz, 110% rMT, 4000 pulses) was delivered during a validated cannabis cue paradigm. Participants crossed over to complete the other condition one week later. The feasibility and tolerability were measured by the rate of retention, and the percentage of participants able to tolerate full dose rTMS, respectively. Craving was measured using the Marijuana Craving Questionnaire (MCQ). RESULTS: Eighteen non-treatment seeking CUD participants were recruited from the community; 16 (three women) completed the trial (89% retained for the three study visits). All of the treatment completers tolerated rTMS at full dose without adverse effects. There was not a significant reduction in the total MCQ when participants received active rTMS as compared to sham rTMS. CONCLUSION: rTMS can be safely and feasibly delivered to CUD participants, and treatment is well tolerated. A single session of rTMS applied to the DLPFC may not reduce cue-elicited craving in heavy cannabis users.

Characteristics of Weight Loss Trajectories in a Comprehensive Lifestyle Intervention.

OBJECTIVE: Focusing on average weight loss (WL) from interventions provides useful efficacy data but masks large variability across patients. In this study, parameters of weight loss trajectories were determined that differentiated individuals during a 15-week clinical lifestyle intervention. METHODS: Patients (n = 595) were in a fee-for-service WL lifestyle program with a partial meal replacement diet and lifestyle change counseling. Parameters used in latent class analyses were percent WL (%WL), weight nadir, number of weekly weight gains, maximum weekly percent weight gain, standard deviation of weekly weight changes, linear slope values, and change in slope. RESULTS: Average %WL was 9.73%. Latent class analyses revealed three groups with considerable overlap in %WL ranges but differing significantly on all trajectory parameters (Ps < 0.001). Group 1 had the most variable and least successful pattern of weight changes. Group 3 had the least variable and most successful pattern of weight changes. Group 2 fell between the others on all parameters. CONCLUSIONS: Emphasis on average WL likely obscures considerable variability in individual courses of weight change. Moreover, patients with similar %WL can have different WL trajectories. Identification of behavioral/physiological characteristics associated with different weight loss trajectories may facilitate the development of more tailored interventions, particularly for trajectories associated with less optimal outcomes.

Ethanol Interactions With Dexmethylphenidate and dl-Methylphenidate Spheroidal Oral Drug Absorption Systems in Healthy Volunteers.

BACKGROUND/PURPOSE: Ethanol coadministered with immediate-release dl-methylphenidate (dl-MPH) or dexmethylphenidate (d-MPH) significantly increases the geomean maximum plasma concentration (Cmax) of d-MPH 22% and 15%, respectively, and elevates overall drug exposure and psychostimulant effects. We asked the question: Are these ethanol-MPH interactions based more fundamentally on (1) inhibition of postabsorption d-MPH metabolism or (2) acceleration of MPH formulation gastric dissolution by ethanol in the stomach? This was investigated using the pulsatile, distinctly biphasic, spheroidal oral drug absorption systems of dl-MPH and d-MPH. METHODS: In a randomized, 4-way crossover study, 14 healthy subjects received pulsatile dl-MPH (40 mg) or d-MPH (20 mg), with or without ethanol (0.6 g/kg), dosed 4 hours later. These 4 hours allowed the delayed-release second MPH pulse to reach a more distal region of the gut to preclude gastric biopharmaceutical influences. Plasma was analyzed using a highly sensitive chiral method. Subjective/physiological effects were recorded. FINDINGS/RESULTS: Ethanol increased the second pulse of d-MPH Cmax for dl-MPH by 35% (P < 0.01) and the partial area under the plasma concentration curve from 4 to 8 hours by 25% (P < 0.05). The respective values for enantiopure d-MPH were 27% (P = 0.001) and 20% (P < 0.01). The carboxylesterase 1-mediated transesterification metabolite ethylphenidate served as a biomarker for coexposure. Ethanol significantly potentiated stimulant responses to either formulation. IMPLICATIONS/CONCLUSIONS: These findings support drug dispositional interactions between ethanol and MPH as dominant over potential biopharmaceutical considerations. Understanding the pharmacology underlying the frequent coabuse of MPH-ethanol provides rational guidance in the selection of first-line pharmacotherapy for comorbid attention-deficit/hyperactivity disorder-alcohol use disorder.