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Purpose: Postural Orthostatic Tachycardia Syndrome (POTS) is a heterogenous disorder of the autonomic nervous system that is often disabling. There are no FDA-approved therapies for the treatment of this condition. While some patients recover with baseline non-pharmacological intervention, others require repeated trials of off-label pharmacological therapies. The reasoning for this variable treatment response is unknown. The purpose of this work is to identify potential factors that are associated with higher odds of starting pharmacotherapy and/or a higher rate of POTS treatment changes. Methods: Chart review of demographic, disease and treatment descriptions, medical history, and tilt table examinations of 322 POTS patients who were diagnosed between 2018 and 2020 at our tertiary care center was completed. We first identified the most significant factors associated with an increased odds of starting pharmacotherapy using variable selection techniques and logistic regression. We then identified the most significant factors associated with changes in POTS treatment strategies using variable selection techniques and negative binomial regression modeling. A significance level of 0.05 was utilized. Results: A total of 752 POTS-specific treatment courses were cataloged, and 429 treatment changes were observed. The most cited reason for a change in management was uncontrolled symptoms. History of migraine headaches, reported fatigue, reported palpitations and a previous POTS diagnosis at an outside institution were found to be associated with a higher odds of starting pharmacotherapy for POTS symptoms (Odds Ratio of 2.40, 1.94, 2.62, 2.08, respectively). History of migraine headaches, reported fatigue, and higher heart rate differences on tilt table examination were found to be associated with an increase in the rate of POTS treatment changes (44, 66, 13% increase in incidence rate, respectively), while reported neck pain was associated with a decrease (27% decrease in incidence rate). Conclusion: Our work identifies important areas of focus in the development of high-quality trials involving both the non-pharmacological and pharmacological treatment of POTS and highlights several characteristics of patients that may be more refractory to both baseline non-pharmacological treatments and current pharmacological treatment strategies. [ABSTRACT FROM AUTHOR]

Although weight gain is a serious but variable adverse effect of antipsychotics that has genetic underpinnings, a comprehensive meta-analysis of pharmacogenetics of antipsychotic-related weight gain is missing. In this review, random effects meta-analyses were conducted for dominant and recessive models on associations of specific single nucleotide polymorphisms (SNP) with prospectively assessed antipsychotic-related weight or body mass index (BMI) changes (primary outcome), or categorical increases in weight or BMI (≥7%; secondary outcome). Published studies, identified via systematic database search (last search: December 31, 2014), plus 3 additional cohorts, including 222 antipsychotic-naïve youth, and 81 and 141 first-episode schizophrenia adults, each with patient-level data at 3 or 4 months treatment, were meta-analyzed. Altogether, 72 articles reporting on 46 non-duplicated samples (n = 6700, mean follow-up = 25.1wk) with 38 SNPs from 20 genes/genomic regions were meta-analyzed (for each meta-analysis, studies = 2-20, n = 81-2082). Eleven SNPs from 8 genes were significantly associated with weight or BMI change, and 4 SNPs from 2 genes were significantly associated with categorical weight or BMI increase. Combined, 13 SNPs from 9 genes (Adrenoceptor Alpha-2A [ADRA2A], Adrenoceptor Beta 3 [ADRB3], Brain-Derived Neurotrophic Factor [BDNF], Dopamine Receptor D2 [DRD2], Guanine Nucleotide Binding Protein [GNB3], 5-Hydroxytryptamine (Serotonin) Receptor 2C [HTR2C], Insulin-induced gene 2 [INSIG2], Melanocortin-4 Receptor [MC4R], and Synaptosomal-associated protein, 25kDa [SNAP25]) were significantly associated with antipsychotic-related weight gain (P-values < .05-.001). SNPs in ADRA2A, DRD2, HTR2C, and MC4R had the largest effect sizes (Hedges' g's = 0.30-0.80, ORs = 1.47-1.96). Less prior antipsychotic exposure (pediatric or first episode patients) and short follow-up (1-2 mo) were associated with larger effect sizes. Individual antipsychotics did not significantly moderate effect sizes. In conclusion, antipsychotic-related weight gain is polygenic and associated with specific genetic variants, especially in genes coding for antipsychotic pharmacodynamic targets.

Purpose: Postural Orthostatic Tachycardia Syndrome (POTS) is a heterogenous disorder of the autonomic nervous system that is often disabling. There are no FDA-approved therapies for the treatment of this condition. While some patients recover with baseline non-pharmacological intervention, others require repeated trials of off-label pharmacological therapies. The reasoning for this variable treatment response is unknown. The purpose of this work is to identify potential factors that are associated with higher odds of starting pharmacotherapy and/or a higher rate of POTS treatment changes., Methods: Chart review of demographic, disease and treatment descriptions, medical history, and tilt table examinations of 322 POTS patients who were diagnosed between 2018 and 2020 at our tertiary care center was completed. We first identified the most significant factors associated with an increased odds of starting pharmacotherapy using variable selection techniques and logistic regression. We then identified the most significant factors associated with changes in POTS treatment strategies using variable selection techniques and negative binomial regression modeling. A significance level of 0.05 was utilized., Results: A total of 752 POTS-specific treatment courses were cataloged, and 429 treatment changes were observed. The most cited reason for a change in management was uncontrolled symptoms. History of migraine headaches, reported fatigue, reported palpitations and a previous POTS diagnosis at an outside institution were found to be associated with a higher odds of starting pharmacotherapy for POTS symptoms (Odds Ratio of 2.40, 1.94, 2.62, 2.08, respectively). History of migraine headaches, reported fatigue, and higher heart rate differences on tilt table examination were found to be associated with an increase in the rate of POTS treatment changes (44, 66, 13% increase in incidence rate, respectively), while reported neck pain was associated with a decrease (27% decrease in incidence rate)., Conclusion: Our work identifies important areas of focus in the development of high-quality trials involving both the non-pharmacological and pharmacological treatment of POTS and highlights several characteristics of patients that may be more refractory to both baseline non-pharmacological treatments and current pharmacological treatment strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tidd, Zhang, Cantrell, Nowacki, Singh and Wilson.)

Purpose/objective(s): To determine if patients with unfavorable intermediate-risk (UIR), high-risk (HR), or very high-risk (VHR) prostate cancer (PCa) treated with 125 I interstitial brachytherapy benefit from androgen deprivation therapy (ADT)., Materials/methods: We reviewed our institutional database of patients with UIR, HR, or VHR PCa, per 2018 NCCN risk classification, treated with definitive 125 I interstitial brachytherapy with or without ADT from 1998-2017. Outcomes including biochemical failure (bF), distant metastases (DM), and overall survival (OS) were analyzed with the Kaplan-Meier method and Cox proportional hazards regression. PCa-specific mortality (PCSM) was analyzed with Fine-Gray competing-risk regression., Results: Of 1033 patients, 262 (25%) received ADT and 771 (75%) did not. Median ADT duration was 6 months. By risk group, 764 (74%) patients were UIR, 219 (21%) HR, and 50 (5%) VHR. ADT was more frequently given to HR (50%) and VHR (56%) patients compared to UIR (16%; p<0.001), to older patients (p<0.001), corresponding with increasing PSA (p<0.001) and Grade Group (p<0.001). Median follow-up was 4.9 years (0.3-17.6 years). On multivariable analysis accounting for risk group, age, and year of treatment, ADT was not associated with bF, DM, PCSM, or OS (p≥0.05 each)., Conclusion: Among patients with UIR, HR, and VHR PCa, the addition of ADT to 125 I interstitial brachytherapy was not associated with improved outcomes, and no subgroup demonstrated benefit. Our findings do not support the use of ADT in combination with 125 I interstitial brachytherapy. Prospective studies are required to elucidate the role of ADT for patients with UIR, HR, and VHR PCa treated with prostate brachytherapy., (Copyright © 2021 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)