OBJECTIVE: Major depressive disorder (MDD) is projected to be a leading cause of disability globally by 2030. Only a minority of patients remit with antidepressants. If assay of polymorphisms influencing central nervous system (CNS) bioavailability could guide prescribers to more effectively dose patients, remission rates may improve and the burden of disease from MDD reduce. Hepatic and blood brain barrier (BBB) polymorphisms appear to influence antidepressant CNS bioavailability. METHODS: A 12-week prospective double blind randomized genetically guided versus unguided trial of antidepressant dosing in Caucasian adults with MDD (n=148) was conducted. RESULTS: Subjects receiving genetically guided prescribing had a 2.52-fold greater chance of remission (95% confidence interval [CI]=1.71-3.73, z=4.66, p<0.0001). The number needed to genotype (NNG)=3 (95% CI=1.7-3.5) to produce an additional remission. CONCLUSION: These data suggest that a pharmacogenetic dosing report (CNSDose(R)) improves antidepressant efficacy. The effect size was sufficient that translation to clinical care may arise if results are independently replicated.
Adult ; Antidepressive Agents ; Biological Availability ; Blood-Brain Barrier ; Central Nervous System ; Depression* ; Depressive Disorder, Major ; Genotype ; Humans ; Precision Medicine ; Pharmacogenetics ; Prospective Studies

Purpose: Adjuvant radiotherapy (RT) in buccal mucosa cancers is guided by histopathological factors. The decision to treat ipsilateral or bilateral draining lymph node is on physician discretion and guidelines do not have a defined indication regarding this. We aimed to analyze the failure patterns and survival in buccal mucosa cancers treated with adjuvant ipsilateral RT. Materials and Methods: One hundred sixteen cases of post-operative buccal mucosa cancers—pT3 or more, node positive, close margins (1–5 mm), lymphovascular invasion positive, perineural invasion positive, depth of invasion >4 mm—treated with RT to primary and ipsilateral nodes from May 2013 to May 2019 were retrospectively analyzed. Patients were treated to a dose of 60–66 Gy (44 Gy in the first phase and a coned down boost of 16–22 Gy in the second phase) with three-dimensional conformal radiotherapy on a linear accelerator. Primary end point was to assess control rates and secondary end point was to evaluate the overall survival (OS) and disease-free survival (DFS) outcomes. Results: Median age was 46 years with male; female ratio of 110:6. The edition of the American Joint Committee on Cancer stage distributions were I (3.4%), II (34.4%), III (24.1%), and IV (37.9%). At a median follow-up of 22 months, crude rates of local failure, regional failure, and contralateral neck failure were 9.4%, 10.3%, and 3.4%, respectively. The 2-year contralateral neck control rate was 94.9%. Pathological positive node portended poorer OS (86.6% vs. 68.6%; p = 0.015) and DFS (86.5% vs. 74.9%; p = 0.01). Conclusion Incidence of contralateral recurrence with ipsilateral irradiation in buccal mucosa cancers is low with descent survival outcomes, particularly in node negative cases.

Objective: To explore illness-related factors in patients with major depressive disorder (MDD) recipients of adjunctive minocycline (200 mg/day) treatment. The analysis included participants experiencing MDD from a 12-week, double blind, placebo-controlled, randomized clinical trial (RCT). Methods: This is a sub-analysis of a RCT of all 71 participants who took part in the trial. The impact of illness chronicity (illness duration and number of depressive episodes), systemic illness (endocrine, cardiovascular and obesity), adverse effects and minocycline were evaluated as change from baseline to endpoint (12-week) using ANCOVA. Results: There was a consistent but statistically non-significant trend on all outcomes in favour of the use of adjunctive minocycline for participants without systemic illness, less illness chronicity, and fewer adverse effects. Conclusion Understanding the relationship between MDD and illness chronicity, comorbid systemic illness, and adverse effects, can potentially better characterise those individuals who are more likely to respond to adjunctive anti-inflammatory medications.