Pharmacogenomics guided versus standard antidepressant treatment in a community pharmacy setting: A randomized controlled trial

The literature on pharmacogenomics as a tool to support antidepressant precision is burgeoning. Recently, a more active role has been argued for pharmacists in pharmacogenomic testing, with both pharmacists and family physicians perceiving pharmacist‐led testing as a valuable method by which to scale this innovation for depression treatment. In this prospective, single‐blind randomized controlled design, we evaluated the impact of pharmacogenomics guided versus standard antidepressant treatment of depression and anxiety, implemented in three large community pharmacies. Participants were 213 outpatients diagnosed with major depressive disorder and/or generalized anxiety disorder, randomized to receive pharmacogenomics guided (n = 105) or standard antidepressant treatment (n = 108); participants were blinded to the study. Patient reported outcomes of depression, anxiety, disability, and treatment satisfaction were assessed at months 0, 1, 3, and 6. Hypotheses were investigated using mixed effect models on the full data. All clinical outcomes improved significantly. The primary outcome (depression) and two secondary outcomes (generalized anxiety and disability) exhibited significant time by group interactions indicating that they improved for participants who received pharmacogenomics guided treatment more so than they did for participants who received standard treatment. Treatment satisfaction improved similarly for both groups. Results contribute to a growing body of work evaluating the impact of pharmacogenomics testing to inform antidepressant medication treatment for depression and anxiety, and provides important initial evidence for the role of pharmacists in care delivery. Pharmacogenomic testing may be a valuable tool to allow pharmacists to more effectively collaborate in facilitating clinical treatment decisions. ClinicalTrials.gov registration: ({"type":"clinical-trial","attrs":{"text":"NCT03591224","term_id":"NCT03591224"}}NCT03591224).

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Findings are mixed on whether pharmacogenomic testing as a tool to guide antidepressant treatment improves depression response, remission, and symptom severity.

• WHAT QUESTION DID THIS STUDY ADDRESS?

We evaluated the impact of pharmacogenomics guided versus standard antidepressant treatment of depression and anxiety as they occur in the real‐world, implemented by pharmacists in three large community pharmacies.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Results from this study provide initial evidence in support of a pharmacist‐led pharmacogenomic testing program in the treatment of mental health difficulties, as well as evidence for the role of pharmacists in care delivery.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

In supporting the external validity of pharmacogenomic testing, this study has implications for how primary care clinicians may manage antidepressant medication use in their patients. In conjunction with measurement‐based care, pharmacogenomic testing may help pharmacists more confidently and effectively manage patients in a protocolized and evidence‐based manner.     

Prevalence of Traumatic Findings on Routine MRI in a Large Cohort of Professional Fighters

BACKGROUND AND PURPOSE:Previous studies investigating MR imaging abnormalities among fighters have had small sample sizes. This investigation assessed a large number of fighters using the same conventional sequences on the same scanner.MATERIALS AND METHODS:Conventional 3T MR imaging was used to assess 499 fighters (boxers, mixed martial artists, and martial artists) and 62 controls for nonspecific WM changes, cerebral microhemorrhage, cavum septum pellucidum, and cavum vergae. The lengths of the cavum septum pellucidum and cavum vergae and the ratio of cavum septum pellucidum to the septum pellucidum lengths were assessed.RESULTS:The prevalence of nonspecific WM changes was similar between groups. Fighters had a prevalence of cerebral microhemorrhage (4.2% versus 0% for controls, P = .152). Fighters had a higher prevalence of cavum septum pellucidum versus controls (53.1% versus 17.7%, P < .001) and cavum vergae versus controls (14.4% versus 0%, P < .001). The lengths of the cavum septum pellucidum plus the cavum vergae (P < .001), cavum septum pellucidum (P = .025), and cavum septum pellucidum to the septum pellucidum length ratio (P = .009) were higher in fighters than in controls. The number of fights slightly correlated with cavum septum pellucidum plus cavum vergae length (R = 0.306, P < .001) and cavum septum pellucidum length (R = 0.278, P < .001). When fighters were subdivided into boxers, mixed martial artists, and martial artists, results were similar to those in the whole-group analysis.CONCLUSIONS:This study assessed MR imaging findings in a large cohort demonstrating a significantly increased prevalence of cavum septum pellucidum among fighters. Although cerebral microhemorrhages were higher in fighters than in controls, this finding was not statistically significant, possibly partially due to underpowering of the study.

Multiple sports such as boxing, mixed martial arts, football, and soccer involve repetitive head trauma in young people, and this trauma is accumulated over many years. Many studies have attempted to describe conventional MR imaging findings associated with repetitive head trauma in the hope that an early in vivo diagnosis may preclude further trauma and help guide possible treatment.^1–9 However, these studies have often involved a small number of athletes, leading to variable findings and a low significance of results.^10,11 In some studies, MR imaging results were normal for athletes with head trauma,^7,9 whereas other studies demonstrated a variably increased prevalence of cerebral microhemorrhage (CMH),^4,5 nonspecific WM changes (NSWMCs),¹¹ or cavum septum pellucidum (CSP)/cavum septum pellucidum and vergae (CSPV).^1,2,10Regarding professional fighting, previous studies have similarly demonstrated the occurrence of imaging abnormalities, with imaging findings ranging from smaller volumes in structures such as the thalamus, vermis, and hippocampus and microhemorrhages in the parenchyma to macrohemorrhages such as subdural hematomas and parenchymal contusions.^{4–6,8,12,13} However, these studies were also limited by small sample sizes and a relatively low prevalence of microhemorrhages, so the calculated increased prevalence was not found to be statistically significant.^4,5Other studies have demonstrated a higher incidence of CSP among fighters, with some research finding a trend toward significance in fighters versus controls.¹⁰ However, an early large study of fighters demonstrated increased CSP prevalence in controls rather than in fighters.³ More recent studies in retired professional American football players found that the prevalence and size of the CSP were increased in the athletes versus controls.^2,14 Comparing these studies is complicated by differences in patient populations (eg, different sports, various age groups, current athletes versus retired athletes).^2,4,5,14 Additionally, even though an increased prevalence of CSP has been demonstrated among fighters in previous research, neuroradiologists disagree over whether this is a manifestation of trauma or simply a normal variant.Other conventional MR imaging findings in patients with repetitive head trauma include the presence of NSWMCs.⁷ However, some research into repetitive head trauma has demonstrated normal imaging findings in these patients.¹¹ This finding is consistent with our anecdotal experience.In this study, we chose to focus on a sport with a known high incidence of repetitive head trauma (professional fighters), using a large sample size and ensuring that all fighters were scanned with the same protocol on the same 3T MR imaging scanner. We sought to assess the prevalence of NSWMCs, CMH, and CSP/CSPV among these fighters versus the prevalence of these imaging abnormalities among healthy controls.     

Quantitative analysis of the effects of physiologic brain motion on point-resolved spectroscopy

BACKGROUND AND PURPOSE: Although single-voxel proton MR spectroscopy is a noninvasive method that enables measurement of brain metabolite concentrations, it has been shown that physiologic brain motion causes inaccuracies in measurement of metabolite concentrations and increases the overall SD of the measurements when the stimulated echo acquisition mode (STEAM) is used. We tested the hypothesis that the point-resolved spectroscopy (PRESS) technique is less sensitive to physiologic brain motion than the STEAM technique. METHODS: In 10 healthy subjects, spectra were obtained from a voxel located in the left basal ganglia by using the PRESS sequence with cardiac gating and without water suppression to assess global phase change as a function of physiologic brain motion. This was accomplished by acquiring data at various time delays from the R wave throughout the cardiac cycle. Subsequently, spectra were obtained in 10 healthy subjects by using PRESS both without and with cardiac gating, and with water suppression, to determine whether brain motion resulted in a statistically significant difference in mean and SD of measured metabolite concentration. RESULTS: At various time delays from the R wave throughout the cardiac cycle, no significant global phase difference was noted in water signal intensity. In addition, when PRESS data were obtained both without and with cardiac gating (by using an optimal delay obtained from previously published data by using STEAM), no significant difference was seen in measured metabolite concentrations and SDs. CONCLUSION: The PRESS technique is relatively insensitive to physiologic brain motion.     

Clinical and microbiologic effects of commercially available dentifrice containing aloe vera: a randomized controlled clinical trial

Background: Certain plants used in folk medicine serve as a source of therapeutic agents that have antimicrobial and other multipotential effects. This prospective, randomized, placebo, and positively controlled clinical trial was designed to evaluate the clinical and microbiologic effects of a commercially available dentifrice containing aloe vera on the reduction of plaque and gingival inflammation in patients with gingivitis. Methods: Ninety patients diagnosed with chronic generalized gingivitis were selected and randomly divided into three groups: group 1, placebo toothpaste; group 2, toothpaste containing aloe vera; and group 3, toothpaste with polymer and fluoride containing triclosan. Clinical evaluation was undertaken using a gingival index, plaque was assessed using a modification of the Quigley‐Hein index, and microbiologic counts were assessed at baseline, 6 weeks, 12 weeks, and 24 weeks. A subjective evaluation was also undertaken by questionnaire. Results: Toothpaste containing aloe vera showed significant improvement in gingival and plaque index scores as well as microbiologic counts compared with placebo dentifrice. These improvements were comparable to those achieved with toothpaste containing triclosan. Conclusion: Toothpaste containing aloe vera may be a useful herbal formulation for chemical plaque control agents and improvement in plaque and gingival status.     

Low Compliance in a Health‐Conscience Spending Era Likely Helps Obviates the Need for 6 month BI‐RADS 3 Breast MRI Follow‐up After 1 year

The goal of our IRB‐approved study was to assess if a follow‐up MRI every 6 months for 2 years is the most appropriate short‐interval follow‐up schedule. 203 breast MRI exams were performed from October 2009 to January 2014 as part of a BI‐RADS 3 follow‐up representing 2.6% of all breast MRIs (7,822) performed. We performed a retrospective longitudinal medical records review of compliance; malignancy rate of BI‐RADS 3 exams; and average time and number of breast MRIs necessary prior to definitive disposition. While 77.8% eventually returned, only 45.5% of patients were compliant with follow‐up at or near 6 months (4.5–7.5 months). Of those who eventually returned, it took an average of 1.31 follow‐up MRIs (95% CI: 1.20–1.43 exams) and 10.3 months (95% CI: 9.0–11.7 months) before definitive disposition. 93.5% of initial findings were dispositioned as benign after two follow‐up MRI exams (malignancy rate: 0.98%). Our results lend support to the possibility that the follow‐up interval for BI‐RADS 3 breast MRIs could be lengthened to 12 months if additional follow‐up MRIs are necessary after the first year of 6‐month follow‐up breast MRIs. Foremost, this appears to be a safe follow‐up alternative since benign definitive disposition can usually be made in less than 1 year. Supplemental reasons include persistent low‐patient compliance (as redemonstrated in our study) and the higher cost of breast MRI compared to mammogram/ultrasound follow‐up. Finally, this paper's findings further support the suggested MRI follow‐up interval in the newest BI‐RADS atlas.     

Aldoxorubicin for the treatment of soft tissue sarcoma

Intoduction: Soft tissue sarcomas (STS) encompass a group of rare tumors arising from mesenchymal tissue. Traditionally, anthracycline-based chemotherapy, with doxorubicin, is the main treatment for advanced STS.

Areas covered: Aldoxorubicin is a doxorubicin derivative containing a carboxylic hydrazone and serves as a prodrug of doxorubicin. It covalently binds to albumin in the blood until reaching the acidic tumor environment, which dissolves the hydrazone linker, thus releasing doxorubicin into the tissue. In this review paper, we analyze the pharmacokinetics, current phase I, phase II, and phase III trials, as well as adverse effect profile of aldoxorubicin in patients with advanced STS.

Expert opinion: Aldoxorubicin represents a promising drug for treatment of sarcomas. The drug has minimal cardiac toxicity, which represents a significant advantage to doxorubicin. Preliminary phase 3 study results demonstrate PFS advantage in patients with leiomyosarcoma and liposarcoma. However, more studies are needed to establish the role of aldoxorubicin in sarcoma treatment.     

Ureteroscopy under conscious sedation: A proof-of-concept study

IntroductionUreteroscopy (URS) is commonly performed under general anesthesia (GA) to maximize patient tolerability and minimize surgical complications; however, given the improvements in endoscopic technology and risks associated with GA, alternate forms of anesthesia have been postulated. We aimed to evaluate the outcomes of URS under conscious sedation.MethodsWe completed a retrospective cohort study from November 2019 to June 2020 at a tertiary-level hospital. All URSs that were performed under urologist-directed conscious sedation were included. Our primary outcome was the ability to complete URS, defined as success rate. Secondary outcomes included: stone-free rate, intraoperative complication rate, hospital admission rate, and sedation requirement. Univariate- and multivariate-adjusted logistic regression analyses were employed.ResultsNinety-nine URSs were included. Most (73/99, 73.7%) were performed for urolithiasis. The overall success rate was 83.8% (83/99), with 81.0% (34/42) intra-renal and 70.0% (16/23) proximal ureter success rates. The stone-free rate was 80.8% (59/73). No intraoperative complications nor hospital admissions were reported. The mean amount of sedation required was 3 mg (interquartile range [IQR] 2–4] of midazolam and 100 μg (100–150) of fentanyl. On multivariate analysis, midazolam was significantly associated with increased success (odds ratio 2.496, 95% confidence interval 1.057–5.892, p=0.037).ConclusionsWe have shown that proximal and intrarenal URS under conscious sedation is safe and effective. We were limited by our lack of followup, small sample size, selection bias to chose healthy patients, and lack of patient tolerability data. Patients and healthcare systems may benefit from implementing this innovation more broadly.

KEY MESSAGES

• We demonstrated the ability to effectively perform diagnostic and therapeutic ureteroscopy under urologist- directed conscious sedation, especially in the proximal ureter and renal pelvis. This approach may expedite patient care without compromising safety.
• This study is of extra importance during the restraints on our healthcare system during the COVID-19 pandemic.

     

Comparison of 3D plate and locking plate in treatment of mandibular fracture—a clinical study

Introduction

This study was performed to evaluate the efficacy and post-operative complication of 3-dimensional (3D) titanium miniplate and locking plate in mandibular fractures (parasymphysis, symphysis, body, and angle).

Materials and methods

Forty patients, with non-comminuted mandibular fractures treated with open reduction and internal fixation using 3D titanium miniplate system or locking plate system through an intra-oral approach, were included in this study. All patients were systematically monitored up to 2 months post-operatively. Parameters recorded were infection, occlusal discrepancies, hardware failure, wound dehiscence, sensory disturbance of the inferior alveolar nerve, and stability of fractured segments.

Results

Forty patients with mandibular fracture were divided into two groups randomly without any bias. The fractures of all 40 patients were found to be adequately fixed when checked intra-operatively after fixation. One patient (2.5%) of the 3D plate group developed an infection on the first and second post-operative visit and was treated by antibiotic coverage. One patient in the locking plate group (2.5%) reported wound dehiscence after the first week follow-up.

Conclusion

Both 3D titanium miniplates and locking plate are effective in the treatment of mandibular fractures, and overall complication rates are lesser. However, the 3D plating system uses less hardware in cases of parasymphysis and symphysis fractures and more hardware in cases of body and angle fractures.