Significant Cost Savings and Improved Early Clinical Outcomes in Medicare Patients Utilizing a Clinician-Controlled Telerehabilitation System Following Total Knee Arthroplasty.

BACKGROUND: The costs and benefits of different rehabilitation protocols following total knee arthroplasty are unclear. The emergence of telerehabilitation has introduced the potential for enhanced patient convenience and cost reduction. The purpose of this study was to assess the cost difference between standard physical therapy (SPT) and a telerehabilitation home-based clinician-controlled therapy system (HCTS). METHODS: A prospectively enrolled, consecutive series of 109 Medicare patients who received SPT were compared to 101 Medicare patients who were treated with a HCTS. The analysis focused on total rehabilitation costs and the assessment of outcome measures: knee range of motion, visual analog scale pain levels, and Knee Injury and Osteoarthritis Outcome Score for Joint Replacement. RESULTS: The HCTS group demonstrated not only statistically significantly lower average costs but also faster and sustained knee range of motion improvements. Furthermore, in comparison to SPT, the HCTS group exhibited superior visual analog scale pain scores and Knee Injury and Osteoarthritis Outcome Score for Joint Replacement functional scores at all assessment points postoperatively, which were statistically significant (all P < .001) and surpassed the minimal clinically important difference thresholds. CONCLUSIONS: The HCTS used in this study exhibited a remarkable cost-saving advantage of $2,460 per patient compared to standard therapy. As approximately 500,000 primary total knee arthroplasties in the United States are covered by Medicare annually, a switch to HCTS could yield total cost savings of more than $1.23 billion per year for our taxpayer-funded health care system. Furthermore, the HCTS cohort demonstrated superior functional outcomes and improved pain scores across all assessment time points, exceeding the minimal clinically important difference.

Alprazolam exposure during adolescence induces long-lasting dysregulation in reward sensitivity to morphine and second messenger signaling in the VTA-NAc pathway.

Increased use of benzodiazepines in adolescents have been reported, with alprazolam (ALP) being the most abused. Drug abuse during adolescence can induce changes with lasting consequences. This study investigated the neurobiological consequences of ALP exposure during adolescence in C57BL/6J male mice. Mice received ALP (0, 0.5, 1.0 mg/kg) once/daily (postnatal day 35-49). Changes in responsiveness to morphine (2.5, 5.0 mg/kg), using the conditioned place preference paradigm, were assessed 24-h and 1-month after ALP exposure. In a separate experiment, mice received ALP (0, 0.5 mg/kg) and then sacrificed 24-h or 1-month after treatment to assess levels of extracellular signal regulated kinase 1/2 (ERK1/2) gene expression, protein phosphorylation, and downstream targets (CREB, AKT) within the ventral tegmental area (VTA) and nucleus accumbens (NAc). ALP-pretreated mice developed a strong preference to the compartment(s) paired with a subthreshold dose (2.5 mg/kg) of MOR short-term, and this effect was also present in the 1-month group. Adolescent ALP exposure resulted in dysregulation of ERK-signaling within the VTA-NAc pathway 24-h and 1-month after ALP exposure. Results indicate ALP exposure during adolescence potentiates the rewarding properties of MOR and induces persistent changes in ERK-signaling within the VTA-NAc pathway, a brain circuit highly implicated in the regulation of both drug reward and mood- related behaviors.

Exposure to Vicarious Social Defeat Stress and Western-Style Diets During Adolescence Leads to Physiological Dysregulation, Decreases in Reward Sensitivity, and Reduced Antidepressant Efficacy in Adulthood.

A dramatic increase in the prevalence of major depression and diet-related disorders in adolescents has been observed over several decades, yet the mechanisms underlying this comorbidity have only recently begun to be elucidated. Exposure to western-style diet (WSD), high in both fats (45% kcal) and carbohydrates (35% kcal): e.g., high fat diet (HFD), has been linked to the development of metabolic syndrome-like symptoms and behavioral dysregulation in rodents, as similarly observed in the human condition. Because adolescence is a developmental period highlighted by vulnerability to both stress and poor diet, understanding the mechanism(s) underlying the combined negative effects of WSDs and stress on mood and reward regulation is critical. To this end, adolescent male C57 mice were exposed to vicarious social defeat stress (VSDS), a stress paradigm capable of separating physical (PS) versus psychological/emotional (ES) stress, followed by normal chow (NC), HFD, or a separate control diet high in carbohydrates (same sucrose content as HFD) and low in fat (LFD), while measuring body weight and food intake. Non-stressed control mice exposed to 5 weeks of NC or HFD showed no significant differences in body weight or social interaction. Mice exposed to VSDS (both ES and PS) gain weight rapidly 1 week after initiation of HFD, with the ES-exposed mice showing significantly higher weight gain as compared to the HFD-exposed control mice. These mice also exhibited a reduction in saccharin preference, indicative of anhedonic-like behavior. To further delineate whether high fat was the major contributing factor to these deficits, LFD was introduced. The mice in the VSDS + HFD gained weight more rapidly than the VSDS + LFD group, and though the LFD-exposed mice did not gain weight as rapidly as the HFD-exposed mice, both the VSDS + LFD- and VSDS + HFD-exposed mice exhibited attenuated response to the antidepressant fluoxetine. These data show that diets high in both fats and carbohydrates are responsible for rapid weight gain and reduced reward sensitivity; and that while consumption of diet high in carbohydrate and low in fat does not lead to rapid weight gain, both HFD and LFD exposure after stress leads to reduced responsiveness to antidepressant treatment.

Ketamine: The final frontier or another depressing end?

Two decades ago, the observation of a rapid and sustained antidepressant response after ketamine administration provided an exciting new avenue in the search for more effective therapeutics for the treatment of clinical depression. Research elucidating the mechanism(s) underlying ketamine's antidepressant properties has led to the development of several hypotheses, including that of disinhibition of excitatory glutamate neurons via blockade of N-methyl-d-aspartate (NMDA) receptors. Although the prominent understanding has been that ketamine's mode of action is mediated solely via the NMDA receptor, this view has been challenged by reports implicating other glutamate receptors such as AMPA, and other neurotransmitter systems such as serotonin and opioids in the antidepressant response. The recent approval of esketamine (Spravato™) for the treatment of depression has sparked a resurgence of interest for a deeper understanding of the mechanism(s) underlying ketamine's actions and safe therapeutic use. This review aims to present our current knowledge on both NMDA and non-NMDA mechanisms implicated in ketamine's response, and addresses the controversy surrounding the antidepressant role and potency of its stereoisomers and metabolites. There is much that remains to be known about our understanding of ketamine's antidepressant properties; and although the arrival of esketamine has been received with great enthusiasm, it is now more important than ever that its mechanisms of action be fully delineated, and both the short- and long-term neurobiological/functional consequences of its treatment be thoroughly characterized.