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.

The Psychological Benefits of Cosmetic Surgery.

ABSTRACT: The objective of this review is to shed light on the literature regarding the psychological impact of invasive cosmetic surgery and to discuss future implications for research and clinical practice. Articles published through October 2021 were reviewed to answer the question, "Does cosmetic surgery improve a patient's overall psychological health?" Psychological well-being was examined through the lens of body image, self-esteem, anxiety, and depression scores. The studies revealed that although cosmetic surgery seems to boost patients' body image, other crucial aspects of psychological well-being may or may not similarly benefit. Notably, factors such as a patient's preoperative mental status, level of education, type of cosmetic procedure, postoperative healing time, sex, and age play a role in determining the direction and magnitude of psychological change after surgery. Limitations include the lack of diversity in study populations and the potential role of body dysmorphic disorder. Overall, researchers have concluded that cosmetic surgery improves body image but remain in disagreement on its effects on self-esteem, anxiety, and depression.

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.

Frontal fibrosing alopecia and personal care product use: a systematic review and meta-analysis.

BACKGROUND: Frontal fibrosing alopecia (FFA) is a cicatricial alopecia affecting the frontotemporal hairline. Given that this scarring, immune-mediated follicular destruction most commonly affects postmenopausal Caucasian women, researchers have postulated that there are hormonal and genetic components; however, the etiology of FFA is still unknown. Recently, dermatologists have reported cases of FFA as being potentially caused by cosmetic products, such as sunscreen and shampoo. Therefore, this systematic review and meta-analysis intend to be the first to analyze the relationship between FFA and cosmetic/personal care products and treatments, including sunscreen, moisturizer, foundation, shampoo, conditioner, hair mousse, hair gel, hair dye, hair straightening/rebonding, chemical/laser facial resurfacing, aftershave, and facial cleanser. METHODS: The Cochrane, PubMed, EMBASE, and Medline (Ovid) databases were searched for the relevant studies from the date of inception to August 2022. Case-control, cross-sectional, and cohort studies examining the effects of cosmetic/personal care product use on FFA, available in English full-text, were included. Analyses were performed using Review Manager, version 5.4. Results were reported as an odds ratio (OR) with a 95% confidence interval (CI); p values < 0.05 were considered significant. RESULTS: Nine studies were included in our quantitative analyses, totaling 1,248 FFA patients and 1,459 controls. There were significant positive associations found for FFA and sunscreen (OR 3.02, 95% CI 1.67-5.47; p = 0.0003) and facial moisturizer (OR 2.20, 95% CI 1.51-3.20; p < 0.0001) use. Gender sub-analyses demonstrated a positive association for FFA and facial moisturizer in men (OR 5.07, 95% CI 1.40-18.32; p = 0.01), but not in women (OR 1.58, 95% CI 0.83-2.98; p = 0.16). Both gender sub-analyses were significantly positive for the association with facial sunscreen (Male OR 4.61, 95% CI 1.54-13.78, p = 0.006; Female OR 2.74, 95% CI 1.32-5.70, p = 0.007). There was no association found for a facial cleanser (OR 1.14, 95% CI 0.33-1.52; p = 0.51), foundation (OR 1.13, 95% CI 0.83-1.55; p = 0.21), shampoo (OR 0.49, 95% CI 0.22-1.10; p = 0.08), hair conditioner (OR 0.81, 95% CI 0.52-1.26; p = 0.35), hair mousse (OR 1.37, 95% CI 0.75-2.51; p = 0.31), and hair gel (OR 0.90, 95% CI 0.48-1.69; p = 0.74), hair dye (OR 1.07, 95% CI 0.69-1.64; p = 0.77), hair straightening/rebonding (OR 0.88, 95% CI 0.08-9.32; p = 0.92), hair perming (OR 1.41, 95% CI 0.89-2.23; p = 0.14), facial toner (OR 0.51, 95% CI 0.12-2.21; p = 0.37), or aftershave (OR 1.64, 95% CI 0.28-9.49; p = 0.58). CONCLUSIONS: This meta-analysis strongly suggests that leave-on facial products, facial sunscreen and moisturizer, are associated with FFA. While the association with facial moisturizer did not persist when stratifying for female populations, gender sub-analyses remained significant for a facial sunscreen. There was no significant relationship found with hair products or treatments. These findings suggest a potential environmental etiology in the development of FFA, particularly UV-protecting chemicals.

Case series on aripiprazole and dopamine supersensitivity psychosis.

A potential link between switching to aripiprazole and worsening of psychosis was first reported in the early 2000s. There have since been numerous published case reports describing this phenomenon, but only recently has the concept of a theoretical aripiprazole-induced dopamine supersensitivity psychosis (DSP) caused by D2 receptor activation in patients undergoing a switch to aripiprazole appeared in the literature. There is less awareness in clinical practice of the possibility of inducing DSP with aripiprazole, which may be particularly severe in some patients. The objective of this article is to present four cases demonstrating rapid and dramatic onset of DSP during switching to aripiprazole. In each case, a patient with a Diagnostic and statistical manual of mental disorders (5th ed.) diagnosis of schizophrenia experienced severe worsening of psychosis within 4-5 days of abrupt switching to aripiprazole from a full D2 antagonist. To our knowledge, this is the first case series characterizing the previously well-documented worsening of psychosis during switching to aripiprazole specifically as aripiprazole-induced DSP. We discuss clinical relevance, prevention and future directions. Careful cross-titration per clinical practice guidelines may reduce occurrence of DSP during aripiprazole switching or augmentation treatment.

Support Group Participation Among Patients With Alopecia Areata.

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