Pharmacogenomics Testing Confirmation of Carbamazepine Induced DRESS Reaction of an HLA-A*31:01 Positive, Polypharmacy Patient

Pharmacogenomics (PGx) melds well with polypharmacy as another tool to identify medication related problems (MRPs) more specifically so they may be solved most effectively. PGx can pre-emptively assist in medication selection, medication dosing or identify better medications for patients already taking a medication. PGx can also confirm suspect medications of causing MRPs such as adverse drug reactions (ADRs) or drug interactions. In this case, PGx testing confirmed presence of a serious human leukocyte antigen (HLA) drug reaction with eosinophilia and systemic symptoms (DRESS) after a suspect medication had been stopped.

Results of combined treatment of uterine leiomyoma in women of reproductive age

The purpose of the work. To study the effectiveness of the combined treatment of uterine leiomyoma (UL), taking into account the possibility of realizing reproductive function.Material and methods. The total number of women of reproductive age examined with a large UL (a dominant node more than 50 mm in diameter) was 94. At the first stage, all patients received preoperative preparation. At the first stage all patients received preoperative preparation. 35 patients with concomitant endometrial hyperplasia and/or with the presence of the progesterone receptor gene polymorphism PGR progins received aGn-RH in an average therapeutic dose once in 28 days, 3 injections. 59 patients with the reference genotype without endometrial pathology received mifepristone 50 mg daily for 3 months. After preoperative preparation, the patients underwent conservative myomectomy by laparotomy. Menstrual function, pelvic pain syndrome, size of leiomatous nodules, drug tolerance, frequency of pregnancy and recurrence were assessed. Statistical data processing was performed using Microsoft Excel software. The main statistical indicators such as frequency, mean and standard deviation were taken into account. The results were considered significant at p < 0.05.Results. Excessive menstruation and AUB occurred in 81.9% of patients. Amenorrhea occurred in 79.8% of patients after 1 month of therapy and in all patients after 3 months. Recovery of menstruation was noted in 10.6% of patients a month after the operation, in 59.6% of patients after two months and on the third cycle menstruation resumed in all patients. The frequency of pain syndrome unrelated to the menstrual cycle decreased from 52.1% to 9.6%, dyspareunia from 12.8% to 4.3%, dysmenorrhea from 47.9% to 8.5%. According to ultrasound data, after 1 month in the group of women receiving aGn-RH the size of the nodules decreased by an average of 22.9%, and after mifepristone by 16.9%, and after 3 months by 51.4% and 45.8%. The uterine volume decreased by 28.6% and 30.5%. Starting from the second month of treatment, symptoms caused by estrogen deficiency were noted in 39.4% of patients treated with aGn-RH and 20.3% in the mifepristone group. Overall, the treatment was defined as effective in 88.6% of the women treated with aGn RH and 93.2% of those treated with mifepristone. Relapse occurred in 11.4% of women after aGn-RH and in 5.1% of those in the mifepristone group. Pregnancy occurred in 69.2% of patients and resulted in delivery in 90.8% of cases.Conclusions. The use of preoperative hormonal preparation and a differentiated approach to medication selection leads to normalization of the patient's condition and a reduction in the size of the nodules, which allows organ-preserving surgical treatment with minimal uterine trauma. Preference should be given to anti-gestagens because, with equal efficiency compared to aGn-RH, they are better tolerated by patients and have a more pronounced positive effect on process stabilization and disease recurrence. This combined approach improves treatment efficiency to 91.5%, preserves the uterus in reproductive-age women and promotes pregnancy in 69.2% of cases.

Attitudes and Willingness to Accept Long-Acting Injections for Patients With Schizophrenia in Beijing: A Cross-Sectional Investigation Based on Samples From the Communities

Background: Schizophrenia has brought a serious disease burden to China. Under the background that community rehabilitation has become the mainstream treatment model, the long-acting injection (LAI) can better prevent recurrence. Some districts in Beijing have also issued policies. This article aims to find out patient's current attitudes toward LAI and provide policy suggestions.Methods: Some patients with schizophrenia in the communities are selected, while the survey format is face-to-face conversation. The content of the self-made questionnaire includes patients' willingness and reasons for accepting LAI treatment. Descriptive statistics, t-test and F-test are used to process the data from questionnaire surveys.Results: About 10% of respondents have had experience using LAI and the current utilization rate is 2.4%. Respondents' willingness to accept LAI is generally low (only 18.1% are willing). The main reason for willingness is no need to take medication every day, while the main reasons for unwillingness are high cost, fear of injection and lack of understanding.Conclusion: Beijing community patients are not very optimistic about LAI's cognition and willingness. Medication habits play an important role in their medication selection decisions. Intervention such as educate clinicians and patients about LAI and provide free injections to patients can be imposed. The promotion of LAI still has a long way to go.

Pharmacoeconomics in Africa: needs, prospect and challenges

Africa as a continent has experienced a continuous increase in the cost of healthcare as its demands increase. With many of these African countries living below the poverty threshold, Africans continue to die from preventable and curable diseases. Population increases have led to an increase in demands for healthcare, which unfortunately have been met with inequitable distribution of drugs. Hence, the outcomes from healthcare interventions are frequently not maximized. These problems notably call for some economic principles and policies to guide medication selection, procurement, or donation for population prioritization or health insurance. Pharmacoeconomics drives efficient use of scarce or limited resources to maximize healthcare benefits and reduce costs. It also brings to play tools that rate therapy choice based on the quality of life added to the patient after a choice of intervention was made over an alternative. In this paper, we commented on the needs, prospect, and challenges of pharmacoeconomics in Africa.

Safety of Using a Combinatorial Pharmacogenomic Test for Patients with Major Depressive Disorder in the GUIDED trial

BackgroundPharmacogenomic testing has emerged to aid medication selection for patients with major depressive disorder (MDD) by identifying potential gene-drug interactions (GDI). Many pharmacogenomic tests are available with varying levels of supporting evidence, including direct-to-consumer and physician-ordered tests. We retrospectively evaluated the safety of using a physician-ordered combinatorial pharmacogenomic test (GeneSight) to guide medication selection for patients with MDD in a large, randomized, controlled trial (GUIDED).Materials and MethodsPatients diagnosed with MDD who had an inadequate response to ≥1 psychotropic medication were randomized to treatment as usual (TAU) or combinatorial pharmacogenomic test-guided care (guided-care). All received combinatorial pharmacogenomic testing and medications were categorized by predicted GDI (no, moderate, or significant GDI). Patients and raters were blinded to study arm, and physicians were blinded to test results for patients in TAU, through week 8. Measures included adverse events (AEs, present/absent), worsening suicidal ideation (increase of ≥1 on the corresponding HAM-D17 question), or symptom worsening (HAM-D17 increase of ≥1). These measures were evaluated based on medication changes [add only, drop only, switch (add and drop), any, and none] and study arm, as well as baseline medication GDI.ResultsMost patients had a medication change between baseline and week 8 (938/1,166; 80.5%), including 269 (23.1%) who added only, 80 (6.9%) who dropped only, and 589 (50.5%) who switched medications. In the full cohort, changing medications resulted in an increased relative risk (RR) of experiencing AEs at both week 4 and 8 [RR 2.00 (95% CI 1.41–2.83) and RR 2.25 (95% CI 1.39–3.65), respectively]. This was true regardless of arm, with no significant difference observed between guided-care and TAU, though the RRs for guided-care were lower than for TAU. Medication change was not associated with increased suicidal ideation or symptom worsening, regardless of study arm or type of medication change. Special attention was focused on patients who entered the study taking medications identified by pharmacogenomic testing as likely having significant GDI; those who were only taking medications subject to no or moderate GDI at week 8 were significantly less likely to experience AEs than those who were still taking at least one medication subject to significant GDI (RR 0.39, 95% CI 0.15–0.99, p=0.048). No other significant differences in risk were observed at week 8.ConclusionThese data indicate that patient safety in the combinatorial pharmacogenomic test-guided care arm was no worse than TAU in the GUIDED trial. Moreover, combinatorial pharmacogenomic-guided medication selection may reduce some safety concerns. Collectively, these data demonstrate that combinatorial pharmacogenomic testing can be adopted safely into clinical practice without risking symptom degradation among patients.FundingMyriad Neuroscience/Assurex Health

An individualized treatment rule to optimize probability of remission by continuation, switching, or combining antidepressant medications after failing a first-line antidepressant in a two-stage randomized trial

Background There is growing interest in using composite individualized treatment rules (ITRs) to guide depression treatment selection, but best approaches for doing this are not widely known. We develop an ITR for depression remission based on secondary analysis of a recently published trial for second-line antidepression medication selection using a cutting-edge ensemble machine learning method. Methods Data come from the SUN(^_^)D trial, an open-label, assessor blinded pragmatic trial of previously-untreated patients with major depressive disorder from 48 clinics in Japan. Initial clinic-level randomization assigned patients to 50 or 100 mg/day sertraline. We focus on the 1549 patients who failed to remit within 3 weeks and were then rerandomized at the individual-level to continuation with sertraline, switching to mirtazapine, or combining mirtazapine with sertraline. The outcome was remission 9 weeks post-baseline. Predictors included socio-demographics, clinical characteristics, baseline symptoms, changes in symptoms between baseline and week 3, and week 3 side effects. Results Optimized treatment was associated with significantly increased cross-validated week 9 remission rates in both samples [5.3% (2.4%), p = 0.016 50 mg/day sample; 5.1% (2.7%), p = 0.031 100 mg/day sample] compared to randomization (30.1–30.8%). Optimization was also associated with significantly increased remission in both samples compared to continuation [24.7% in both: 11.2% (3.8%), p = 0.002 50 mg/day sample; 11.7% (3.9%), p = 0.001 100 mg/day sample]. Non-significant gains were found for optimization compared to switching or combining. Conclusions An ITR can be developed to improve second-line antidepressant selection, but replication in a larger study with more comprehensive baseline predictors might produce stronger and more stable results.