scholarly journals Expirience of implementation of personalized clinical decision support system for dosing of bromdihydrochlorphenylbenzodiazepine in patients with alcohol withdraw syndrome based on the pharmacogenomic markers

Author(s):  
М.С. Застрожин ◽  
А.С. Сорокин ◽  
Т.В. Агибалова ◽  
И.А. Бедина ◽  
Е.А. Гришина ◽  
...  

Введение: Имплементация систем поддержки принятия решений, способных формировать рекомендации по выбору лекарствен- ного средства и его дозы в соответствии с результатами фармакогенетического тестирования, является актуальной задачей, так как решение ее позволит повысить эффективность терапии и снизить риск развития нежелательных лекарственных реакций.Материалы и методы: В исследовании принимал участие 51 пациент (21 - основная группа, получавшая назначения в соответ- ствии с рекомендациями, основанными на результатах фармакогенетического тестирования, а 30 - группа сравнения, получавшая назначения без них) мужского пола с синдромом отмены алкоголя. Для оценки эффективности и безопасности терапии синдрома отмены алкоголя, которую осуществляли с использованием бензодиазепинового транквилизатора феназепама (бромдигидрохлор- фенилбензодиазепина), а также стандартной дезинтоксикационной и витаминотерапии, применялись международные психоме- трические шкалы и шкалы оценки выраженности нежелательных реакций. Определение полиморфизмов генов CYP2D6*4 (1846G>A, rs3892097), CYP2C19*2 (681G>A, rs4244285), CYP2C19*3 (636G>A, rs4986893), CYP2C19*17 (-806C>T, rs12248560), CYP3A5*3 (6986A>G, rs776746) и ABCB1*6 (3435C>T, rs1045642) осуществлялось методом полимеразной цепной реакции в реальном времени с аллель-специфиче- ской гибридизацией. Интерпретацию результатов фармакогенетического тестирования осуществляли с использованием свободно распространяемого программного обеспечения PharmacoGenomeX2 (www.pgx2.com).Результаты: Получены статистически значимые различия в количестве баллов по всем психометрическим шкалам у пациентов основной группы и группы сравнения. Например, по шкале оценки тяжести синдрома отмены алкоголя к 3-му дню исследования количество баллов в основной группе составляло 13,5 [11,2; 16,0], а в группе контроля - 18,0 [17,0; 22,0] (p < 0,001); к 5-му в основ- ной группе - 6,5 [4,2; 8,0], в группе контроля - 15,0 [14,0; 16,0] (p < 0,001). По шкале безопасности UKU также была получена стати- стически значимая разница. К 3-му дню исследования количество баллов по шкале UKU в основной группе составило 6,0 [5,0; 7,0], а в группе контроля - 7,0 [6,0; 8,0] (p = 0,030); к 5-му дню разница возрастала. В основной группе - 5,5 [3,0; 9,0], в группе контроля - 14,0 [12,0; 19,0] (p < 0,001). Группы были репрезентативны (при включении в исследование разница в количестве баллов отсутствовала). Выводы: Персонализация дозы лекарств в соответствии с фармакогенетическими алгоритмами у пациентов с синдромом отмены алкоголя, способна снизить риск развития нежелательных реакций и фармакорезистентности, что позволяет рекомендовать исполь- зование фармакогенетических систем поддержки принятия решений для подбора дозы лекарств. Introduction: Implementation of the clinical decision support systems capable of forming the recommendations on drug and dose selec- tion according to the results of pharmacogenetic testing is an urgent task. Fulfillment of this task will allow increasing the efficacy of ther- apy and decreasing the risk of undesirable side effects.Materials and methods: The study involved 51 patients (21 - the main group receiving appointments in accordance with the recommenda- tions based on the results of pharamogenetic testing, and 30 - the comparison control group receiving appointments without them) male with alcohol withdrawal syndrome. In order to assess the effectiveness and safety of alcohol withdrawal syndrome, which was performed with the benzodiazepine tranquilizer of phenazepam (bromodihydrochlorophenylbenzodiazepine), as well as standard detoxification and vitamin therapy, international psychometric scales and scales of assessment in expressions of adverse reactions. Genotyping Determination of genetic polymorphisms CYP2D6*4 (1846G>A, rs3892097), CYP2C19*2 (681G>A, rs4244285), CYP2C19*3 (636G>A, rs4986893), CYP2C19*17 (-806C>T, rs12248560), CYP3A5*3 (6986A>G, rs776746) and ABCB1*6 (3435C>T, rs1045642) were realized using real-time polymerase chain reaction with allele specific hybridization. Interpretation of the results of pharmacogenetic testing was carried out with the help of free soft- ware PharmacoGenomeX2 (www.pgx2.com)Results: Statistically significant differences in the number of scores for all psychometric scales in the patients of the main group and the comparison group were obtained. For example, on the scale of assessing the severity of alcohol withdrawal syndrome by the 3rd day of the study, the score in the main group was 13.5 [11.2; 16,0], and in the control group - 18,0 [17,0; 22.0] (p <0.001); to the 5th in the main group - 6.5 [4.2; 8.0], in the control group - 15.0 [14.0; 16.0] (p <0.001). On the UKU security scale, a statistically significant difference was also obtained. By the 3rd day of the study, the UKU score in the main group was 6.0 [5.0; 7,0], and in the control group - 7,0 [6,0; 8.0] (p = 0.030); by the 5th day the difference increased. In the main group, 5.5 [3.0; 9.0], in the control group - 14.0 [12.0; 19.0] (p <0.001). The groups were representative (when included in the study, the difference in the number of points was absent).Conclusion: Personalization of the dose of drugs in accordance with pharmacogenetic algorithms in patients with alcohol withdrawal syn- drome, can reduce the risk of unwanted reactions and pharmacoresistance, which allows to recommend the use of pharmacogenetic deci- sion support systems for drug dosage selection.

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Michael Zastrozhin ◽  
Valentin Skryabin ◽  
Alexander Sorokin ◽  
Oleg Buzik ◽  
Inessa Bedina ◽  
...  

AbstractObjectivesAlthough pharmacogenetic tests provide the information on a genotype and the predicted phenotype, these tests do not themselves provide the interpretation of data for a physician. Currently, there are approximately two dozen pharmacogenomic clinical decision support systems (CDSSs) used in psychiatry. Implementation of the CDSSs forming the recommendations on drug and dose selection according to the results of pharmacogenetic testing is an urgent task. Fulfillment of this task will allow increasing the efficacy of therapy and decreasing the risk of undesirable side effects.MethodsThe study included 118 male patients (48 in the main group and 70 in the control group) with affective disorders and comorbid alcohol use disorder. To evaluate the efficacy and safety of therapy, several international psychometric scales and rating scales to measure side effects were used. Genotyping was performed using the real-time polymerase chain reaction with allele-specific hybridization. Pharmacogenetic testing results were interpreted using free software PGX2 (LLE Medicine, Russian Federation, Biomedical Cluster of Skolkovo, Moscow Innovative Cluster; www.pgx2.com).ResultsThe statistically significant differences across the scores on psychometric scales were revealed. For instance, the total score on the Hamilton Rating Scale for Depression by day 9 was 9.0 [8.0; 10.0] for the main group and 11.0 [10.0; 12.0] (p<0.001) for the control group and by day 16 it was 4.0 [2.0; 6.0] for the main group and 14.0 [13.0; 14.0] (p<0.001) for the control group. The UKU Side-Effect Rating Scale (UKU) also revealed a statistically significant difference. The total score on the UKU scale by day 9 was 4.0 [4.0; 5.0] for the main group and 5.0 [5.0; 6.0] (p<0.001) for the control group and by day 16 this difference grew significantly: 3.0 [0.0; 4.2] for the main group and 9.0 [7.0; 11.0] (p<0.001) for the control group.ConclusionsPharmacogenetic-guided personalization of the drug dose in patients with affective disorders and comorbid alcohol use disorder can reduce the risk of undesirable side effects and pharmacoresistance. It allows recommending the use of pharmacogenetic CDSSs for optimizing drug dosage.


Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 2115
Author(s):  
Panos Papandreou ◽  
Aristea Gioxari ◽  
Frantzeska Nimee ◽  
Maria Skouroliakou

Clinical decision support systems (CDSS) are data aggregation tools based on computer technology that assist clinicians to promote healthy weight management and prevention of cardiovascular diseases. We carried out a randomised controlled 3-month trial to implement lifestyle modifications in breast cancer (BC) patients by means of CDSS during the COVID-19 pandemic. In total, 55 BC women at stages I-IIIA were enrolled. They were randomly assigned either to Control group, receiving general lifestyle advice (n = 28) or the CDSS group (n = 27), to whom the CDSS provided personalised dietary plans based on the Mediterranean diet (MD) together with physical activity guidelines. Food data, anthropometry, blood markers and quality of life were evaluated. At 3 months, higher adherence to MD was recorded in the CDSS group, accompanied by lower body weight (kg) and body fat mass percentage compared to control (p < 0.001). In the CDSS arm, global health/quality of life was significantly improved at the trial endpoint (p < 0.05). Fasting blood glucose and lipid levels (i.e., cholesterol, LDL, triacylglycerols) of the CDSS arm remained unchanged (p > 0.05) but were elevated in the control arm at 3 months (p < 0.05). In conclusion, CDSS could be a promising tool to assist BC patients with lifestyle modifications during the COVID-19 pandemic.


2018 ◽  
Vol 56 (7) ◽  
pp. 1063-1070 ◽  
Author(s):  
Enrique Rodriguez-Borja ◽  
Africa Corchon-Peyrallo ◽  
Esther Barba-Serrano ◽  
Celia Villalba Martínez ◽  
Arturo Carratala Calvo

Abstract Background: We assessed the impact of several “send & hold” clinical decision support rules (CDSRs) within the electronical request system for vitamins A, E, K, B1, B2, B3, B6 and C for all outpatients at a large health department. Methods: When ordered through electronical request, providers (except for all our primary care physicians who worked as a non-intervention control group) were always asked to answer several compulsory questions regarding main indication, symptomatology, suspected diagnosis, vitamin active treatments, etc., for each vitamin test using a drop-down list format. After samples arrival, tests were later put on hold internally by our laboratory information system (LIS) until review for their appropriateness was made by two staff pathologists according to the provided answers and LIS records (i.e. “send & hold”). The number of tests for each analyte was compared between the 10-month period before and after CDSRs implementation in both groups. Results: After implementation, vitamins test volumes decreased by 40% for vitamin A, 29% for vitamin E, 42% for vitamin K, 37% for vitamin B1, 85% for vitamin B2, 68% for vitamin B3, 65% for vitamin B6 and 59% for vitamin C (all p values 0.03 or lower except for vitamin B3), whereas in control group, the majority increased or remained stable. In patients with rejected vitamins, no new requests and/or adverse clinical outcome comments due to this fact were identified. Conclusions: “Send & hold” CDSRs are a promising informatics tool that can support in utilization management and enhance the pathologist’s leadership role as tests specialist.


2013 ◽  
Vol 04 (04) ◽  
pp. 569-582 ◽  
Author(s):  
X. Li ◽  
J. Grein ◽  
D.S. Bell ◽  
P. Silka ◽  
J.M. Pevnick

SummaryBackground: In determining whether clinical decision support (CDS) should be interruptive or non-interruptive, CDS designers need more guidance to balance the potential for interruptive CDS to overburden clinicians and the potential for non-interruptive CDS to be overlooked by clinicians.Objectives: (1)To compare performance achieved by clinicians using interruptive CDS versus using similar, non-interruptive CDS. (2)To compare performance achieved using non-interruptive CDS among clinicians exposed to interruptive CDS versus clinicians not exposed to interruptive CDS.Methods: We studied 42 emergency medicine physicians working in a large hospital where an interruptive CDS to help identify patients requiring contact isolation was replaced by a similar, but non-interruptive CDS. The first primary outcome was the change in sensitivity in identifying these patients associated with the conversion from an interruptive to a non-interruptive CDS. The second primary outcome was the difference in sensitivities yielded by the non-interruptive CDS when used by providers who had and who had not been exposed to the interruptive CDS. The reference standard was an epidemiologist-designed, structured, objective assessment.Results: In identifying patients needing contact isolation, the interruptive CDS-physician dyad had sensitivity of 24% (95% CI: 17%-32%), versus sensitivity of 14% (95% CI: 9%-21%) for the non-interruptive CDS-physician dyad (p = 0.04). Users of the non-interruptive CDS with prior exposure to the interruptive CDS were more sensitive than those without exposure (14% [95% CI: 9%-21%] versus 7% [95% CI: 3%-13%], p = 0.05).Limitations: As with all observational studies, we cannot confirm that our analysis controlled for every important difference between time periods and physician groups.Conclusions: Interruptive CDS affected clinicians more than non-interruptive CDS. Designers of CDS might explicitly weigh the benefits of interruptive CDS versus its associated increased clinician burden. Further research should study longer term effects of clinician exposure to interruptive CDS, including whether it may improve clinician performance when using a similar, subsequent non-interruptive CDS.Citation: Pevnick JM, Li X, Grein J, Bell DS, Silka P. A retrospective analysis of interruptive versus non-interruptive clinical decision support for identification of patients needing contact isolation. Appl Clin Inf 2013; 4: 569–582http://dx.doi.org/10.4338/ACI-2013-04-RA-0021


2018 ◽  
pp. emermed-2017-206997 ◽  
Author(s):  
Muhammad Fahmi Ismail ◽  
Kieran Doherty ◽  
Paula Bradshaw ◽  
Iomhar O’Sullivan ◽  
Eugene M Cassidy

IntroductionWe previously reported that benzodiazepine detoxification for alcohol withdrawal using symptom-triggered therapy (STT) with oral diazepam reduced length of stay (LOS) and cumulative benzodiazepine dose by comparison with standard fixed-dose regimen. In this study, we aim to describe the feasibility of STT in an emergency department (ED) short-stay clinical decision unit (CDU) setting.MethodsIn this retrospective cohort study, we describe our experience with STT over a full calendar year (2014) in the CDU. A retrospective chart review was conducted and data collection included demographics, clinical details, total cumulative dose of diazepam, receipt of parenteral thiamine, LOS and disposition.Results5% (n=174) of 3222 admissions to CDU required STT. Collapse or seizure (41%, n=71) and alcohol withdrawal (21%, n=37) were the most common reasons recorded for admission to CDU in those who required STT. Median Alcohol Use Disorders Identification Test score was 25 and 112 patients (64%) had at least one Clinical Institute Withdrawal Assessment for Alcohol revised measurement ≥10, triggering a dose of diazepam (20 mg). The median cumulative oral diazepam dose was 20 mg while 24 (15%) patients received a cumulative dose of 100 mg or more. Median time for STT was 12 hours (IQR=12, R=1–48). 3% (n=5) of patients required further general hospital admission and median LOS in CDU, was 22 hours (IQR=20, R=1–168).ConclusionSTT is potentially feasible as a rapid and effective approach to managing alcohol withdrawal syndrome in the ED/CDU short-stay inpatient setting where patient LOS is generally less than 24 hours.


2020 ◽  
Vol 48 (4) ◽  
pp. 030006052091005
Author(s):  
Yun Song ◽  
Xiaobin Xue ◽  
Haibin Han ◽  
Cuiluan Li ◽  
Jia Jian ◽  
...  

Objective To compare the efficacy of transcutaneous electrical acupoint stimulation (TEAS) combined with diazepam against diazepam alone for treatment of acute alcohol withdrawal syndrome (AWS). Methods In this double-blind randomized sham-controlled trial, men with acute AWS were randomly allocated to either a group treated with TEAS combined with diazepam (n = 57) or a control group treated with sham TEAS combined with diazepam (n = 60). Treatment was performed at four acupoints twice a day for 14 days. The Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar), visual analogue scale (VAS), Pittsburgh Sleep Quality Index (PSQI) and modified Epworth Sleepiness Scale (mESS) were used to evaluate treatment efficacy. Results All scores improved significantly in both groups during the trial. CIWA-Ar scores were lower in the TEAS group than in the control group from day 3 until the end of observation. VAS and mESS scores were also lower in the TEAS group than in the control group on day 7. VAS and PSQI scores were lower in the TEAS group on day 14. Conclusion Combining diazepam with TEAS may result in milder AWS symptoms than diazepam alone, improve sleep quality and reduce sleepiness.


2021 ◽  
Vol 25 (4) ◽  
pp. 605-609
Author(s):  
Y. V. Volkova ◽  
S. S. Dubivska ◽  
A. V. Omelchenko-Seliukova ◽  
O. V. Biletskyi

Annotation. Polytrauma is considered the main cause of death among people younger 45 years. Among trauma patiens 15-20% regularly take alcohol, close to 32% of patients who needed intensive therapy to alcohol withdrawal syndrome (AWS), and 5-20% of the progressed to alcohol delirium. The aim of the study is to analyze the dynamics of autoimmune response to markers of neurodestruction in the blood of patients with moderate polytrauma and alcohol withdrawal, complicated by alcohol delirium and assessment of cognitive functions depending on the method of sedation. The study involved 80 patients with moderate polytrauma with alcohol withdrawal, complicated by alcohol delirium. The median age was 45 years (39-54). Patients in Group 1 (n=40) were given dexmedetomidine as a sedation method, and in Group 2 (n=40) diazepam sedation was used according to the symptom-trigger protocol. The content of antibodies to neuron-specific enolase (NSE), myelin basic protein (MBP), total human brain antigen (THBA), S-100 calcium were determined by enzyme-linked immunosorbent assay on days 1, 3, 7 and 14 after alcohol delirium. Assessment of cognitive function was performed (after withdrawal from sedation if present) on days 4 and 14 using the Montreal Cognitive Assessment Scale (MoCa). Mathematical processing of the obtained results was performed in accordance with the generally accepted methods of statistical analysis. The critical value of the significance level (p) was taken as ≤5%. Signs, the distribution of which differed from normal, are presented in the form of Me (median), the confidence interval within the first and third quarters [QI - QIII]. To assess the causal role of various factors in the development of lesions used χ-square with the inclusion of the Yates correction and the odds ratio. In the first 24 hours after the manifestation of AD, the levels of autoantibodies in the two groups of patients did not differ significantly from the level of healthy volunteers. Estimation of the level of antibodies to the S-100B protein showed that in group 1 this indicator increased by a maximum of 24.4% and amounted to 15.8 [14.7 - 17.6], while in the second group increased by 32.6% and became 17.5 [15.3 - 19.7]. From the 7th day, the number of antibodies began to decrease in both groups and was 15.6 [13.6 - 16.8] in group 1 and 16.3 [14.1-19.2] in group 2 on the 7th day, and 14.0 [11.6 - 15.3] and 15.2 [ 13.1 - 18.3], respectively, on the 14th day after hospitalization in ICU. The level of antibodies to NSE was maximum on the 3rd day of the study and was 29.8 [28.4 - 31.8] in patients of group 1, which is higher than the initial level by 26.8%, and in patients of group 2 was 31.6 [29.5 -33.2], which exceeds baseline by 33.9% (p=0.0114 between groups 1 and 2). Subsequently, there was a decrease in the level of antibodies to NSE on the 7th and 14th day after the onset of AD, while maintaining a significant difference between the comparison groups. Antibodies to MBP did not differ between groups up to and including day 3, but were significantly higher than in healthy volunteers. On the 7th day, the level of antibodies to MBP in group 1 was 26.8 [24.4 - 28.8], which corresponded to the values of the control group, and in group 2 was 29.3 [27.7 - 31.5], which is significantly more than the first group (p = 0.0017). In the study on day 14, this trend was maintained: the level of antibodies to OBM among patients in group 2 was 28.6 [27.0 - 30.8], while in group 1 it was 26.2 [23.7 - 28.2]. Antibody levels to THBA on day 3 were significantly higher than baseline and were 30.8 [28.4 - 34.5] in group 1 and 32.7 [30.6 - 36.1] in group 2 (p=0.0056). On day 7 and day 14, the number of antibodies THBA in patients of group 1 did not differ significantly from the control group, while in patients of group 2 they were significantly higher on day 7 - 31.5 [29.4 - 34.9] and normalized on day 14. When analyzing the results of the MoCa test after eliminating the main manifestations of alcohol withdrawal syndrome (4 days after admission to ICU), the number of points in the study groups was significantly lower than the control values: in group 1 1.3 times (p <0.0001), in group 2 – 1.6 times (p<0.0001). The differences between the studied groups of patients are significant (p = 0.000087). Thus, the use of dexmedetomidine for the sedation of patients with hypertension and polytrauma reduces autumnal neurodestruction, which improves the prognosis for the restoration of cognitive function.


2020 ◽  
Vol 75 (1) ◽  
pp. 69-76
Author(s):  
Anton A. Chernov ◽  
E. B. Kleymenova ◽  
Dmitry A. Sychev ◽  
Liubov P. Yashina ◽  
Maria D. Nigmatkulova ◽  
...  

Background: Physicians adherence to recommendations for appropriate antithrombotic therapy of venous thromboembolism (VTE) can reduce the risk of recurrent VTE, pulmonary hypertension, bleeding and other adverse events. Clinical decision support systems (CDSS) are shown to increase physicians adherence to clinical guidelines. Aims: To assess effectivenes and safety of CDSS for anticoagulant prescribing for inhospital patients with VTE. Methods: A prospective cohort study was conducted in a Moscow general hospital from 06.30.2017 to 06.23.2018 to compare physicians compliance with clinical guidelines for DVT anticoagulant therapy, the rate of drug errors and direct costs of anticoagulant therapy before and after CDSS implementation (55 patients in control group and 49 in experimental group). Results: The rate of anticoagulant prescribing for patients with DVT did not alter significantly after CDSS implementation (96% compared with 91% before CDSS), but physicians compliance with recommendations on anticoagulant dosage increased from 32.7% to 73.5% (p = 0.0003) with corresponding decrease in the rate of anticoagulant prescribing errors from 1.35 to 0.65 per 1 patient (p = 0.0005). The length of stay and hemorrhagic complication rate did not differ between control and experimental groups. LMWH replacement with new oral anticoagulants has reduced the cost of anticoagulant therapy for 1 patient from 11.800 rubles (IQR = 7000) to 5.430 rubles (IQR = 5700) (p 0.005). Conclusions: СDSS can increase physicians adherence to recommended anticoagulant therapy for patients with DVT: to prevent unreasonable under-/overdosing or prolongation of anticoagulant therapy. CDSS for DVT drug therapy can be economically feasible.


2020 ◽  
Vol 16 ◽  
Author(s):  
Rashmi Saxena Pal ◽  
Amrita Mishra

Background: Alcohol withdrawal syndrome leads to irritability, aggressiveness, body posture and motor abnormalities, sensory hyper reactivity and changes in various enzyme levels. Dhatryadi ghrita penetrates the blood- brain barrier to decrease the cravings for alcohol in this syndrome. Objective: To evaluate the effect of alcoholic extract of Dhatryadi ghrita on alcohol withdrawal syndrome in Wistar rats. Material & Methods: A liquid diet with 7.2%, v/v ethanol was administered to the Wistar rats for 21 days. Control group animals received saline and normal diet. After alcohol withdrawal, rats were examined at 6th and 24th hour for anxiety and hyper locomotor activity as major withdrawal signs. Anxiety due to ethanol withdrawal was tested with the help of elevated plus maze, light and dark models. The hyper locomotor activity was assessed using Actophotometer. The hepatic enzymes level was determined with the help of the Bio-chemical Analyzer. Ghrita extract (100, 200,300 mg/kg, oral) were administered to different groups and diazepam as standard (2 mg/kg, i.p) were administered to the treatment group animals 30 minutes before alcohol withdrawal estimation. Drug treatment was administered 30 minutes before the second observation at the 24th hour. Results: Findings from the present study revealed that Ghrita extract treatment at doses 100, 200 and 300 mg/kg, oral in ethanol-dependent rats had a significant protective effect on signs and symptoms of ethanol withdrawal in alcohol-dependent rats. Conclusion: Dhatryadi extract acts effectively for the treatment of alcohol abstinence syndrome. The extract treat¬ment has beneficial effects on ethanol withdrawal depressive-like behavior in rats.


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