Long-Term Impact of COVID-19 Related Disruption of National Health Service Elective Services on Emergency Major Lower Limb Amputations.

BACKGROUND: The COVID-19 pandemic has affected the healthcare systems worldwide since the dawn of 2020. In March 2020, the United Kingdom government announced the first national lockdown which severely disturbed all National Health Service (NHS) healthcare elective services. Our aim is to assess the long-term impact of COVID-19 related disruption of NHS elective services on emergency major lower limb amputations (MLLAs). METHODS: Patients' data for emergency MLLA for critical limb-threatening ischemia and diabetic foot infections performed at Aberdeen Royal Infirmary was collected through Trakcare and divided into the control prepandemic group (April 2018-March 2020) and the pandemic group (April 2020-March 2022). The statistical analysis was conducted using the IBM SPSS software (v28.0.1.1 [14]). RESULTS: A total of 358 patients underwent MLLA and 206 (57.5%) of these had diabetes mellitus. There was a 17% increase in the number of urgent referrals and every 1 in 5 of these finally underwent an amputation. There was an increase in the absolute number of Above- and Below-Knee amputations. There was a statistically significant increase by 33% in emergency MLLAs during the pandemic period (P < 0.05). A total of 165 postoperative deaths up to December 2022 were recorded with 30-day mortality rate of 7.26% (n = 26). CONCLUSIONS: NHS vascular management groups should update themselves with evolving technologies to optimize the care provided during future unprecedented times. Furthermore, more effective measures should also be implemented to avoid delayed presentations, which can potentially lead to higher rates of major limb amputations.

Neighborhood Cohesion Across the Life Course and Effects on Cognitive Aging.

OBJECTIVES: Greater neighborhood cohesion is associated with better cognitive function in adulthood and may serve as a protective factor against cognitive impairment and decline. We build on prior work by examining the effects of perceived neighborhood cohesion across the life course on level and change in cognitive function in adulthood. METHODS: Utilizing longitudinal data from the Health and Retirement Study (1998-2016) and its Life History Mail Survey, we leveraged data from 3,599 study participants (baseline age: 51-89) who participated in up to 10 waves. Respondents provided retrospective ratings of neighborhood cohesion at childhood (age 10), young adulthood (age at the first full-time job), early midlife (age 40), and concurrently at baseline (i.e., late midlife/adulthood); they completed the modified version of the Telephone Interview for Cognitive Status. We fit a univariate latent growth curve model of change in cognitive function across waves and tested whether neighborhood cohesion during each recollected life stage predicted level and change in cognitive function. RESULTS: Greater neighborhood cohesion during childhood and late midlife/adulthood each predicted higher cognitive function at baseline but not the rate of cognitive decline. The final model showed that greater neighborhood cohesion in childhood and in late midlife/adulthood remained significantly associated with higher baseline cognitive function, even after accounting for one another. DISCUSSION: Findings provide insight into life-course neighborhood contextual influences on cognitive aging. Our results emphasize the need for more research to understand the life-course dynamics between neighborhood environments and cognitive aging.

The Effects of Body Composition, Physical Fitness on Time of Useful Consciousness in Hypobaric Hypoxia.

INTRODUCTION: Several previous studies have reported that hypoxia accidents of fighter pilots are rarer than gravity-induced loss of consciousness and spatial disorientation; however, the risk is greater. Therefore, this study aimed to investigate the relationship between physical fitness and body composition on time of useful consciousness (TUC) in hypobaric hypoxia. MATERIALS AND METHODS: Body composition and physical fitness testing on human participants were performed; subsequently, they were exposed to hypobaric hypoxia at a simulated altitude of 25,000 ft. Cognitive testing of the participants was accomplished by having them perform arithmetic task tables until they stopped writing for a period exceeding 5 seconds, at which point, they were placed on 100% oxygen. TUC was measured from the time the participants removed their oxygen masks to the time when the oxygen masks were placed back on them. Pearson's correlation was used to determine the relationship between TUC and other variables, and multiple regression was performed to determine the independent variables that best explain the TUC. RESULTS: TUC was positively correlated with the maximum oxygen uptake, stroke volume, arteriovenous oxygen difference, and endurance (sit-up and push-up). The maximum heart rate on the ground, high altitude, body fat mass, and percent body fat were negatively correlated with TUC. A regression analysis showed that 84.5% of the TUC can be explained by body composition and physical fitness. CONCLUSIONS: Our results revealed that increased cardiorespiratory fitness and decreased body fat mass could significantly impact the TUC. Therefore, for Air Force pilots who are frequently at high altitudes and at risk for exposure to hypoxia, aerobic exercise is significant to hypoxia tolerance.

Functional Limitations, Volunteering, and Diurnal Cortisol Patterns in Older Adults.

OBJECTIVES: Older adults often experience functional limitations that affect their everyday lives, but many of them continue to make positive contributions to society and benefit from these contributions themselves. We examine (a) whether older adults' functional limitations are associated with diurnal cortisol patterns and (b) whether these associations vary on volunteering days versus nonvolunteering days. METHODS: Participants were adults aged older than 60 years (N = 435) from the National Study of Daily Experiences, part of the Midlife in the United States Study. They completed an initial interview on functional limitations and background characteristics, indicated volunteering activities in daily interviews, and also provided salivary samples across 4 days. RESULTS: Multilevel models showed that older adults with greater functional limitations exhibited dysregulated cortisol awakening responses and diurnal cortisol slopes throughout the rest of the day, compared to older adults with lower limitations. Yet, we also observed a significant moderating effect of volunteering on these associations. DISCUSSION: This study advances our understanding of functional limitations and cortisol stress responses, revealing the benefits of volunteering to older adults who experience these limitations. Rather than treating these older adults solely as care recipients, interventions should offer them opportunities to help others.

Using a Daily Diary Approach to Examine Substance Use and Negative Sexual Experiences Among College Students.

This article examined substance use and sexual behavior by conducting an analysis of college students' reported behaviors using a daily diary approach. By isolating particular sexual events across a 2-month period, we examined situational predictors of engagement in sex and of negative sexual experiences (coerced sex and/or sex that lacks perceived control) for college men and women. Data come from the daily diary sub-study of the Sexual Health Initiative to Foster Transformation. These data include 60 days of daily responses from 420 undergraduates at one New York City institution. This was a relatively diverse sample comprised of 49% women, 28% identifying as non-heterosexual, 60% non-white, and a roughly equal number of college freshman, sophomores, juniors, and seniors. Analyses examined the effects of alcohol use, binge drinking, marijuana use, and other drug use on sexual experiences. Between-person and within-person substance uses were related to an increased likelihood of having at least one sexual encounter during the study period. After adjusting for each participants' average substance use, both the number of alcoholic drinks consumed (AOR 1.13 (1.05-1.21)) and binge drinking scores (AOR 2.04 (1.10-3.79)) increased the likelihood of negative sex. Interaction analyses showed that compared to men, women were more likely to use alcohol and marijuana prior to sexual encounters. Given that sex and substance use are co-occurring, current prevention approaches should be paired with strategies that attempt to prevent negative sexual experiences, including sexual assault, more directly. These include consent education, bystander training, augmentation of sexual refusal skills, and structural change. Efforts promoting increased sex positivity might also help make all students, and women in particular, less likely to use substances in order to facilitate sex.

Efficacy and safety of subcutaneous infliximab versus adalimumab, etanercept and intravenous infliximab in patients with rheumatoid arthritis: a systematic literature review and meta-analysis.

OBJECTIVES: There are few comparative data for tumor necrosis factor inhibitors in patients with rheumatoid arthritis (RA). METHODS: Historical data for reference product/biosimilar intravenous infliximab, or adalimumab and etanercept, were pooled and compared with phase 3 study results for a subcutaneous (SC) formulation of the infliximab biosimilar CT-P13, in a systematic review and meta-analysis (PROSPERO: CRD42019149621). RESULTS: The authors identified 13 eligible controlled trials that randomized over 5400 participants to prespecified treatments of interest. Comparison with pooled historical data suggested a numerical advantage for CT-P13 SC over intravenous infliximab for almost every prespecified efficacy outcome evaluated, including Disease Activity Score in 28 joints (C-reactive protein/erythrocyte sedimentation rate), Clinical/Simplified Disease Activity Index scores, American College of Rheumatology responses, and multiple measures of disease remission and low disease activity; for the majority of outcomes, there was no overlap in 95% confidence intervals between groups. A numerical advantage for CT-P13 SC was also observed for safety outcomes (adverse events, infections, and discontinuations). Similar, but less marked, trends were observed for comparison with historical efficacy and safety data for adalimumab/etanercept. CONCLUSION: CT-P13 SC offers an improved or similar benefit-to-harm ratio compared with infliximab (intravenous) and adalimumab/etanercept, for the treatment of moderate-to-severe RA.

Recent Advances in Mechanically Loaded Human Mesenchymal Stem Cells for Bone Tissue Engineering.

Large bone defects are a major health concern worldwide. The conventional bone repair techniques (e.g., bone-grafting and Masquelet techniques) have numerous drawbacks, which negatively impact their therapeutic outcomes. Therefore, there is a demand to develop an alternative bone repair approach that can address the existing drawbacks. Bone tissue engineering involving the utilization of human mesenchymal stem cells (hMSCs) has recently emerged as a key strategy for the regeneration of damaged bone tissues. However, the use of tissue-engineered bone graft for the clinical treatment of bone defects remains challenging. While the role of mechanical loading in creating a bone graft has been well explored, the effects of mechanical loading factors (e.g., loading types and regime) on clinical outcomes are poorly understood. This review summarizes the effects of mechanical loading on hMSCs for bone tissue engineering applications. First, we discuss the key assays for assessing the quality of tissue-engineered bone grafts, including specific staining, as well as gene and protein expression of osteogenic markers. Recent studies of the impact of mechanical loading on hMSCs, including compression, perfusion, vibration and stretching, along with the potential mechanotransduction signalling pathways, are subsequently reviewed. Lastly, we discuss the challenges and prospects of bone tissue engineering applications.

Single-Cell RNA Sequencing and Its Combination with Protein and DNA Analyses.

Heterogeneity in cell populations poses a significant challenge for understanding complex cell biological processes. The analysis of cells at the single-cell level, especially single-cell RNA sequencing (scRNA-seq), has made it possible to comprehensively dissect cellular heterogeneity and access unobtainable biological information from bulk analysis. Recent efforts have combined scRNA-seq profiles with genomic or proteomic data, and show added value in describing complex cellular heterogeneity than transcriptome measurements alone. With the rising demand for scRNA-seq for biomedical and clinical applications, there is a strong need for a timely and comprehensive review on the scRNA-seq technologies and their potential biomedical applications. In this review, we first discuss the latest state of development by detailing each scRNA-seq technology, including both conventional and microfluidic technologies. We then summarize their advantages and limitations along with their biomedical applications. The efforts of integrating the transcriptome profile with highly multiplexed proteomic and genomic data are thoroughly reviewed with results showing the integrated data being more informative than transcriptome data alone. Lastly, the latest progress toward commercialization, the remaining challenges, and future perspectives on the development of scRNA-seq technologies are briefly discussed.

A Single Ketamine Infusion Combined With Motivational Enhancement Therapy for Alcohol Use Disorder: A Randomized Midazolam-Controlled Pilot Trial.

OBJECTIVE: Pharmacotherapy and behavioral treatments for alcohol use disorder are limited in their effectiveness, and new treatments with innovative mechanisms would be valuable. In this pilot study, the authors tested whether a single subanesthetic infusion of ketamine administered to adults with alcohol dependence and engaged in motivational enhancement therapy affects drinking outcomes. METHODS: Participants were randomly assigned to a 52-minute intravenous administration of ketamine (0.71 mg/kg, N=17) or the active control midazolam (0.025 mg/kg, N=23), provided during the second week of a 5-week outpatient regimen of motivational enhancement therapy. Alcohol use following the infusion was assessed with timeline followback method, with abstinence confirmed by urine ethyl glucuronide testing. A longitudinal logistic mixed-effects model was used to model daily abstinence from alcohol over the 21 days after ketamine infusion. RESULTS: Participants (N=40) were mostly middle-aged (mean age=53 years [SD=9.8]), predominantly white (70.3%), and largely employed (71.8%) and consumed an average of five drinks per day prior to entering the study. Ketamine significantly increased the likelihood of abstinence, delayed the time to relapse, and reduced the likelihood of heavy drinking days compared with midazolam. Infusions were well tolerated, with no participants removed from the study as a result of adverse events. CONCLUSIONS: A single ketamine infusion was found to improve measures of drinking in persons with alcohol dependence engaged in motivational enhancement therapy. These preliminary data suggest new directions in integrated pharmacotherapy-behavioral treatments for alcohol use disorder. Further research is needed to replicate these promising results in a larger sample.

Pregnancy Zone Protein Is Associated with Airway Infection, Neutrophil Extracellular Trap Formation, and Disease Severity in Bronchiectasis.

Rationale: PZP (pregnancy zone protein) is a broad-spectrum immunosuppressive protein believed to suppress T-cell function during pregnancy to prevent fetal rejection. It has not previously been reported in the airway.Objectives: To characterize PZP in the bronchiectasis airway, including its relationship with disease severity.Methods: Label-free liquid chromatography/mass spectrometry was performed for sputum protein profiling of patients with bronchiectasis confirmed by high-resolution computed tomography. Results for patients with and without Pseudomonas aeruginosa infection were compared. Sputum and serum PZP was measured by validated ELISA. Airway infection status was established by culture and 16S ribosomal RNA sequencing. Immunofluorescence, ELISA, and electron microscopy were used to identify the cellular source of PZP in neutrophils treated with multiple stimuli.Measurements and Main Results: Elevated PZP was identified by label-free liquid chromatography/mass spectrometry as being associated with P. aeruginosa infection. In a validation study of 124 patients, sputum but not serum concentrations of PZP were significantly associated with the Bronchiectasis Severity Index, the frequency of exacerbations, and symptoms. Airway infection with Proteobacteria such as P. aeruginosa was associated with higher concentrations of PZP. PZP in sputum was directly related to airway bacterial load. Neutrophils induced to form neutrophil extracellular traps (NETs) with phorbol myristate acetate released high concentrations of PZP in vitro, and fluorescence microscopy confirmed the presence of PZP in NETs, whereas fluorescence and electron microscopy localized PZP to the cytoplasm and nuclei of neutrophils. Effective antibiotic therapy reduced sputum PZP.Conclusions: PZP is released into NETs. We report a novel link between airway infection, NET formation, and disease severity in bronchiectasis during chronic airway inflammation.

Progress in Molecularly Imprinted Polymers for Biomedical Applications.

BACKGROUND: Molecularly Imprinted Polymers (MIPs), a type of biomimetic materials have attracted considerable interest owing to their cost-effectiveness, good physiochemical stability, favorable specificity and selectivity for target analytes, and long shelf life. These materials are able to mimic natural recognition entities, including biological receptors and antibodies, providing a versatile platform to achieve the desirable functionality for various biomedical applications. OBJECTIVE: In this review article, we introduce the most recent development of MIPs to date. We first highlight the advantages of using MIPs for a broad range of biomedical applications. We then review their various methods of synthesis along with their latest progress in biomedical applications, including biosensing, drug delivery, cell imaging and drug discovery. Lastly, the existing challenges and future perspectives of MIPs for biomedical applications are briefly discussed. CONCLUSION: We envision that MIPs may be used as potential materials for diverse biomedical applications in the near future.

Emerging Point-of-care Technologies for Food Safety Analysis.

Food safety issues have recently attracted public concern. The deleterious effects of compromised food safety on health have rendered food safety analysis an approach of paramount importance. While conventional techniques such as high-performance liquid chromatography and mass spectrometry have traditionally been utilized for the detection of food contaminants, they are relatively expensive, time-consuming and labor intensive, impeding their use for point-of-care (POC) applications. In addition, accessibility of these tests is limited in developing countries where food-related illnesses are prevalent. There is, therefore, an urgent need to develop simple and robust diagnostic POC devices. POC devices, including paper- and chip-based devices, are typically rapid, cost-effective and user-friendly, offering a tremendous potential for rapid food safety analysis at POC settings. Herein, we discuss the most recent advances in the development of emerging POC devices for food safety analysis. We first provide an overview of common food safety issues and the existing techniques for detecting food contaminants such as foodborne pathogens, chemicals, allergens, and toxins. The importance of rapid food safety analysis along with the beneficial use of miniaturized POC devices are subsequently reviewed. Finally, the existing challenges and future perspectives of developing the miniaturized POC devices for food safety monitoring are briefly discussed.

Recent advances in photo-crosslinkable hydrogels for biomedical applications.

Photo-crosslinkable hydrogels have recently attracted significant scientific interest. Their properties can be manipulated in a spatiotemporal manner through exposure to light to achieve the desirable functionality for various biomedical applications. This review article discusses the recent advances of the most common photo-crosslinkable hydrogels, including poly(ethylene glycol) diacrylate, gelatin methacryloyl and methacrylated hyaluronic acid, for various biomedical applications. We first highlight the advantages of photopolymerization and discuss diverse photosensitive systems used for the synthesis of photo-crosslinkable hydrogels. We then introduce their synthesis methods and review their latest state of development in biomedical applications, including tissue engineering and regenerative medicine, drug delivery, cancer therapies and biosensing. Lastly, the existing challenges and future perspectives of engineering photo-crosslinkable hydrogels for biomedical applications are briefly discussed.

Major depressive disorder during pregnancy: Psychiatric medications have minimal effects on the fetus and infant yet development is compromised.

Psychotropic medication use and psychiatric symptoms during pregnancy each are associated with adverse neurodevelopmental outcomes in offspring. Commonly, studies considering medication effects do not adequately assess symptoms, nor evaluate children when the effects are believed to occur, the fetal period. This study examined maternal serotonin reuptake inhibitor and polypharmacy use in relation to serial assessments of five indices of fetal neurobehavior and Bayley Scales of Infant Development at 12 months in N = 161 socioeconomically advantaged, non-Hispanic White women with a shared risk phenotype, diagnosed major depressive disorder. On average fetuses showed the expected development over gestation. In contrast, infant average Bayley psychomotor and mental development scores were low (M = 84.10 and M = 89.92, range of normal limits 85-114) with rates of delay more than 2-3 times what would be expected based on this measure's normative data. Controlling for prenatal and postnatal depressive symptoms, prenatal medication effects on neurobehavioral development were largely undetected in the fetus and infant. Mental health care directed primarily at symptoms may not address the additional psychosocial needs of women parenting infants. Speculatively, prenatal serotonin reuptake inhibitor exposure may act as a plasticity rather than risk factor, potentially enhancing receptivity to a nonoptimal postnatal environment in some mother-infant dyads.

Black Phosphorus and its Biomedical Applications.

Black phosphorus (BP), also known as phosphorene, has attracted recent scientific attention since its first successful exfoliation in 2014 owing to its unique structure and properties. In particular, its exceptional attributes, such as the excellent optical and mechanical properties, electrical conductivity and electron-transfer capacity, contribute to its increasing demand as an alternative to graphene-based materials in biomedical applications. Although the outlook of this material seems promising, its practical applications are still highly challenging. In this review article, we discuss the unique properties of BP, which make it a potential platform for biomedical applications compared to other 2D materials, including graphene, molybdenum disulphide (MoS2), tungsten diselenide (WSe2) and hexagonal boron nitride (h-BN). We then introduce various synthesis methods of BP and review its latest progress in biomedical applications, such as biosensing, drug delivery, photoacoustic imaging and cancer therapies (i.e., photothermal and photodynamic therapies). Lastly, the existing challenges and future perspective of BP in biomedical applications are briefly discussed.

Effects of mechanical loading on human mesenchymal stem cells for cartilage tissue engineering.

Today, articular cartilage damage is a major health problem, affecting people of all ages. The existing conventional articular cartilage repair techniques, such as autologous chondrocyte implantation (ACI), microfracture, and mosaicplasty, have many shortcomings which negatively affect their clinical outcomes. Therefore, it is essential to develop an alternative and efficient articular repair technique that can address those shortcomings. Cartilage tissue engineering, which aims to create a tissue-engineered cartilage derived from human mesenchymal stem cells (MSCs), shows great promise for improving articular cartilage defect therapy. However, the use of tissue-engineered cartilage for the clinical therapy of articular cartilage defect still remains challenging. Despite the importance of mechanical loading to create a functional cartilage has been well demonstrated, the specific type of mechanical loading and its optimal loading regime is still under investigation. This review summarizes the most recent advances in the effects of mechanical loading on human MSCs. First, the existing conventional articular repair techniques and their shortcomings are highlighted. The important parameters for the evaluation of the tissue-engineered cartilage, including chondrogenic and hypertrophic differentiation of human MSCs are briefly discussed. The influence of mechanical loading on human MSCs is subsequently reviewed and the possible mechanotransduction signaling is highlighted. The development of non-hypertrophic chondrogenesis in response to the changing mechanical microenvironment will aid in the establishment of a tissue-engineered cartilage for efficient articular cartilage repair.

Effects of the optimal flexor/extensor ratio on G-tolerance.

[Purpose] The aim of this study was to examine the flexor/extensor ratio of the knee joints and compare it with the results of Korean Air Force students in G-tolerance test. [Subjects and Methods] The body composition of Korea Air Force students (n=77) was measured by an impedance method. A muscular function test was performed using a Humac Norm (USA) at angular speeds of 60°/sec and 240°/sec and an isokinetic muscular function test was also conducted. [Results] In the failed C and passing groups, muscle mass and fat percentages were significantly higher than those of students in the failed A group. The BMI of the failed C and passing groups were significantly higher than that of the failed A group. The group that passed had a significantly higher value of left knee 60°/sec flexion peak torque than the failed B group. Moreover, the total work of left knee extension of the failed C group and the passing group was significantly higher than that of the failed A group. The C group and the passing group had significantly higher values of the trunk 60°/sec flexor/extensor ratio than the failed A group, and the total work flexor/extensor ratio of the passing group was significantly higher than that of the failed A group. [Conclusions] Based on these results, balance the right and left knee flexor/extensor ratio, and a high flexor/extensor ratio of the trunk are required to endure a high G-tolerance test (+6G/30 sec). Moreover, an improvement in the maximum muscular strength is necessary to endure a situation of rapidly increasing acceleration in the early stage.

Pilot trial of gabapentin for the treatment of benzodiazepine abuse or dependence in methadone maintenance patients.

BACKGROUND: Benzodiazepine use disorders are a common clinical problem among methadone maintenance treatment patients and have adverse effects on clinical outcomes. OBJECTIVES: To evaluate gabapentin for the outpatient treatment of benzodiazepine abuse or dependence in methadone maintenance patients. METHODS: Participants (n = 19) using benzodiazepines at least 4 days per week were enrolled into an 8-week randomized double-blind placebo-controlled outpatient pilot trial. All participants received a manual-guided supportive psychotherapy aimed to promote abstinence. Study medication was titrated over a 2-week period to a maximum dose of gabapentin 1200 mg or placebo three times a day. Benzodiazepine use was assessed using urine toxicology confirmed self-report. Benzodiazepines were not provided as part of study participation; participants were provided guidance to gradually reduce benzodiazepine intake. RESULTS: Sixteen participants had post-randomization data for analysis. Retention at week eight was 50%. The mean dose of gabapentin achieved by titration was 2666 mg/day (SD = ± 1446). There were no significant between group differences on benzodiazepine use outcomes (amount benzodiazepine per day [Mann-Whitney U = 27, p = 0.745], abstinent days per week [U = 28, p = 0.811]) and Clinical Instrument Withdrawal Assessment (CIWA)-benzodiazepines scale (U = 29.0, p = 0.913). One participant in the gabapentin group discontinued study medication because of peripheral edema. Two participants in the placebo group requested admission for inpatient detoxification treatment. CONCLUSION: In outpatient methadone-maintained patients with benzodiazepine use disorder, gabapentin did significantly decrease benzodiazepine use relative to placebo. The small sample recruited for this trial may have limited the ability to detect a group difference.

Dronabinol and lofexidine for cannabis use disorder: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Cannabis use disorder is associated with substantial morbidity and, after alcohol, is the most common drug bringing adolescents and adults into treatment. At present, there are no FDA-approved medications for cannabis use disorder. Combined pharmacologic interventions might be particularly useful in mitigating withdrawal symptoms and promoting abstinence. OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, and lofexidine, an alpha-2 agonist, in treating cannabis dependence. METHODS: One hundred fifty six cannabis-dependent adults were enrolled and following a 1-week placebo lead-in phase 122 were randomized in a double-blind, placebo-controlled, 11-week trial. Participants were randomized to receive dronabinol 20mg three times a day and lofexidine 0.6 mg three times a day or placebo. Medications were maintained until the end of week eight, were then tapered over two weeks and patients were monitored off medications during the last study week. All participants received weekly motivational enhancement and relapse prevention therapy. Marijuana use was assessed using the timeline follow-back method. RESULTS: There was no significant difference between treatment groups in the proportion of participants who achieved 3 weeks of abstinence during the maintenance phase of the trial (27.9% for the medication group and 29.5% for the placebo group), although both groups showed a reduction over time. CONCLUSIONS: Based on this treatment study, the combined intervention did not show promise as a treatment for cannabis use disorder.

The RAISE Connection Program for Early Psychosis: Secondary Outcomes and Mediators and Moderators of Improvement.

The aims of this study were to explore secondary outcomes of a coordinated specialty care program for persons with early psychosis, including quality of life and recovery, as well as to explore mediators and moderators of improvement in occupational and social functioning and symptoms. Sixty-five individuals across two sites were enrolled and received services for up to 2 years. Trajectories for individuals' outcomes over time were examined using linear and quadratic mixed-effects models with repeated measures. In addition, baseline prognostic factors of participant improvement in social and occupational functioning were explored based on previous literature and expert opinion of the analytic team. Results demonstrate that the program was effective in improving quality of life and recovery over time. Furthermore, processing speed was identified as a significant moderator of improvement in occupational Global Assessment of Function, and treatment fidelity, engagement, and family involvement were identified as mediators of improvement in social and occupational functioning.