Integrative Pharmacology in the Treatment of Substance Use Disorders.

The detrimental physical, mental, and socioeconomic effects of substance use disorders (SUDs) have been apparent to the medical community for decades. However, it has become increasingly urgent in recent years to develop novel pharmacotherapies to treat SUDs. Currently, practitioners typically rely on monotherapy. Monotherapy has been shown to be superior to no treatment at all for most substance classes. However, many randomized controlled trials (RCTs) have revealed that monotherapy leads to poorer outcomes when compared with combination treatment in all specialties of medicine. The results of RCTs suggest that monotherapy frequently fails since multiple dysregulated pathways, enzymes, neurotransmitters, and receptors are involved in the pathophysiology of SUDs. As such, research is urgently needed to determine how various neurobiological mechanisms can be targeted by novel combination treatments to create increasingly specific yet exceedingly comprehensive approaches to SUD treatment. This article aims to review the neurobiology that integrates many pathophysiologic mechanisms and discuss integrative pharmacology developments that may ultimately improve clinical outcomes for patients with SUDs. Many neurobiological mechanisms are known to be involved in SUDs including dopaminergic, nicotinic, N-methyl-D-aspartate (NMDA), and kynurenic acid (KYNA) mechanisms. Emerging evidence indicates that KYNA, a tryptophan metabolite, modulates all these major pathophysiologic mechanisms. Therefore, achieving KYNA homeostasis by harmonizing integrative pathophysiology and pharmacology could prove to be a better therapeutic approach for SUDs. We propose KYNA-NMDA-α7nAChRcentric pathophysiology, the "conductor of the orchestra," as a novel approach to treat many SUDs concurrently. KYNA-NMDA-α7nAChR pathophysiology may be the "command center" of neuropsychiatry. To date, extant RCTs have shown equivocal findings across comparison conditions, possibly because investigators targeted single pathophysiologic mechanisms, hit wrong targets in underlying pathophysiologic mechanisms, and tested inadequate monotherapy treatment. We provide examples of potential combination treatments that simultaneously target multiple pathophysiologic mechanisms in addition to KYNA. Kynurenine pathway metabolism demonstrates the greatest potential as a target for neuropsychiatric diseases. The investigational medications with the most evidence include memantine, galantamine, and N-acetylcysteine. Future RCTs are warranted with novel combination treatments for SUDs. Multicenter RCTs with integrative pharmacology offer a promising, potentially fruitful avenue to develop novel therapeutics for the treatment of SUDs.

Association of Cellulitis With Obesity: Systematic Review and Meta-Analysis.

BACKGROUND: Cellulitis is a bacterial skin infection that tends to recur. Previous studies have identified several risk factors that may contribute to its pathogenesis. Obesity is an increasingly prevalent worldwide disease that has been associated with skin and soft tissue infections. OBJECTIVE: The aim of our systematic review and meta-analysis was to investigate the association of cellulitis with obesity. METHODS: The Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science databases were searched for the relevant studies from the inception of each respective database to March 13, 2021. Case-control, cross-sectional, or cohort studies that examined the odds or risk of increased BMI in patients with cellulitis were included. This study was carried out in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The Newcastle-Ottawa scale (NOS) was used to evaluate the risk of bias in included studies. RESULTS: In total, 9 case-control studies were included in our quantitative meta-analysis with a total of 68,148 study participants. A significant association was found between cellulitis and obesity (pooled odds ratio [OR] 2.67, 95% CI 1.91-3.71). No significant association was observed between cellulitis and being overweight (pooled OR 1.69, 95% CI 0.99-2.88). Patients with cellulitis were also found to have 1.63-fold increased odds of being male (pooled OR 1.63, 95% CI 1.12-2.38). CONCLUSIONS: Our findings suggest that cellulitis is significantly associated with obesity. Maintaining a healthy BMI may be indicated for patients presenting with cellulitis.

Association Between Atopic Dermatitis and Impaired Mobility among Adults in the United States: Findings from the 2001-2006 National Health and Nutrition Examination Survey.

Objective: Atopic dermatitis (AD) is an inflammatory skin condition affecting both mental and physical health. Although research has shown reduced physical activity levels among patients with AD, there is a scarcity of studies examining baseline mobility, which refers to the standard level of functional ambulation or movement capability. We analyzed the relationship between AD and baseline mobility among U.S. adults ages 20 to 59, utilizing the National Health and Nutrition Examination Survey (NHANES). Methods: We merged three, 2-year cycles of NHANEs data (2001-2006). Patients were categorized as having "impaired mobility" by the following question: "Because of a health problem, do you have difficulty walking without using any special equipment?" Multivariable logistic regression analyses were performed using STATA/SE 18.0. Results: Our analysis included 6,540 participants. The prevalence of impaired mobility was 7.1 percent among patients with AD and 3.9 percent among those without AD. This difference was statistically significant among patients aged 20 to 59 after adjusting for potential confounding variables (adjusted odds ratio [AOR], 1.65; 95% CI, 1.19-3.25; P=0.010). Subgroup analysis showed increased rates of impaired mobility among males with AD (AOR, 2.55; 95% CI, 1.21-5.40; P=0.016), and among adults aged 40 to 59 (AOR, 1.94; 95% CI, 1.03-3.68; P=0.042). Limitations: Limitations to our study include lack of specificity in the survey questionnaire, self-reporting bias, and an age limit of 59 years old. Conclusion: Our study demonstrated a statistically significant elevation in impaired mobility among individuals with AD compared to those without AD. This underscores the importance of comprehensive care for AD patients.

Support Group Participation Among Patients With Alopecia Areata.

This cross-sectional study describes support group use and experience among patients with alopecia areata.