scholarly journals Routine clozapine assay monitoring to improve the management of treatment-resistant schizophrenia

2021 ◽  
pp. 1-4
Author(s):  
David Kitchen ◽  
Alex Till ◽  
Panchu Xavier
Keyword(s):  
High Risk ◽  
Clinical Utility ◽  
Target Range ◽  
Therapeutic Drug ◽  
Treatment Resistant ◽  
Clozapine Therapy ◽  
Routine Monitoring ◽  
Number Of Patients ◽  
Routine Therapeutic Drug Monitoring ◽  
Health Trust

Aims and method Routine therapeutic drug monitoring in clozapine therapy has previously not been considered justifiable. Using observational data, the clinical utility of annual clozapine assay monitoring is explored within a large mental health trust. Results After the introduction of routine monitoring, the rate of clozapine assays rose to 2.3 per patient per year, with a consistent reduction in high-risk clozapine assays (<0.1 mg/L or >1.0 mg/L or any result more than 24 months old). High-risk assays are associated with a mortality rate of 31.6 deaths per 1000 patients, more than twice that of those within the target range (0.35–0.60 mg/L and conducted within the past 12 months) (P = 0.048). Clinical implications Routine clozapine assay monitoring has significant clinical utility. Our simple but targeted approach can be readily implemented to reduce the number of patients with high-risk clozapine assay levels, potentially reduce all-cause mortality and provide optimal treatment for those with treatment-resistant schizophrenia.

scholarly journals Validated Simple HPLC-UV Method for Mycophenolic Acid (MPA) Monitoring in Human Plasma. Internal Standardization: Is It Necessary?

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7252
Author(s):  
Paweł K. Kunicki ◽  
Aleksandra Wróbel
Keyword(s):  
Mycophenolic Acid ◽  
Internal Standard ◽  
Therapeutic Drug ◽  
Stability Parameters ◽  
High Agreement ◽  
Routine Monitoring ◽  
Accuracy Of Measurements ◽  
Internal Standardization ◽  
Routine Therapeutic Drug Monitoring ◽  
Trough Plasma

The aim of the work was to prepare a simple but reliable HPLC-UV method for the routine monitoring of mycophenolic acid (MPA). Sample preparation was based on plasma protein precipitation with acetonitrile. The isocratic separation of MPA and internal standard (IS) fenbufen was made on Supelcosil LC-CN column (150 × 4.6 mm, 5 µm) using a mobile phase: CH3CN:H2O:0.5M KH2PO4:H3PO4 (260:700:40:0.4, v/v). UV detection was set at 305 nm. The calibration covered the MPA concentration range: 0.1–40 µg/mL. The precision was satisfactory with RSD of 0.97–7.06% for intra-assay and of 1.92–5.15% for inter-assay. The inaccuracy was found between −5.72% and +2.96% (+15.40% at LLOQ) and between −8.82% and +5.31% (+19.00% at LLOQ) for intra- and inter-assay, respectively, fulfilling acceptance criteria. After a two-year period of successful application, the presented method has been retrospectively calibrated using the raw data disregarding the IS in the calculations. The validation and stability parameters were similar for both calculation methods. MPA concentrations were recalculated and compared in 1187 consecutive routine therapeutic drug monitoring (TDM) trough plasma samples from mycophenolate-treated patients. A high agreement (r2 = 0.9931, p < 0.0001) of the results was found. A Bland–Altman test revealed a mean bias of −0.011 μg/mL (95% CI: −0.017; −0.005) comprising −0.14% (95% Cl: −0.39; +0.11), whereas the Passing–Bablok regression was y = 0.986x + 0.014. The presented method can be recommended as an attractive analytical tool for medical (hospital) laboratories equipped with solely basic HPLC apparatus. The procedure can be further simplified by disapplying an internal standard while maintaining appropriate precision and accuracy of measurements.

scholarly journals Establishing the characteristics of an effective pharmacogenetic test for clozapine induced agranulocytosis

2014 ◽  
Author(s):  
Moira Verbelen ◽  
David A Collier ◽  
Dan Cohen ◽  
James H MacCabe ◽  
Cathryn M Lewis
Keyword(s):  
High Risk ◽  
Clinical Utility ◽  
Risk Group ◽  
High Sensitivity ◽  
High Risk Group ◽  
Low Risk ◽  
Treatment Resistant ◽  
Pharmacogenetic Test ◽  
Evidence Based Therapy ◽  
The Relationship

Clozapine is the only evidence-based therapy for treatment resistant schizophrenia, but it induces agranulocytosis, a rare but potentially fatal haematological adverse reaction, in less than 1% of users. To improve safety, the drug is subject to mandatory haematological monitoring throughout the course of treatment, which is burdensome for the patient and one of the main reasons clozapine is underused. Therefore, a pharmacogenetic test is clinically useful if it identifies a group of patients for whom the agranulocytosis risk is low enough to alleviate monitoring requirements. Assuming a genotypic marker stratifies patients into a high risk and a low risk group, we explore the relationship between test sensitivity, group size and agranulocytosis risk. High sensitivity minimizes the agranulocytosis risk in the low risk group and is essential for clinical utility, in particular in combination with a small high risk group.

A review of the clinical utility of serum clozapine and norclozapine levels

2015 ◽  
Vol 5 (2) ◽  
pp. 68-73 ◽  
Author(s):  
Justin C. Ellison ◽  
Robert L. Dufresne
Keyword(s):  
Therapeutic Efficacy ◽  
Clinical Utility ◽  
Smoking Status ◽  
Serum Levels ◽  
Current Evidence ◽  
Therapeutic Drug ◽  
Central Nervous System Toxicity ◽  
Clozapine Therapy ◽  
Efficacious Treatment ◽  
Utmost Care

Abstract Treatment refractory schizophrenia is a serious issue affecting at least 30% of all patients with schizophrenia despite the continued emergence of new agents aimed at treating this disease. Clozapine therapy remains the most efficacious treatment for patients with schizophrenia who have failed two prior antipsychotics or those deemed an imminent harm to themselves or others. Because data are lacking on how to proceed if a patient should prove nonresponsive to clozapine therapy, the utmost care should be taken to ensure the optimization of clozapine. Therapeutic drug monitoring (TDM) is used with many other psychoactive agents to ensure the optimal therapeutic efficacy while minimizing adverse effects. The unique pharmacology of clozapine and the inter- and intraindividual variations in its pharmacokinetics make it a difficult agent with which to use TDM. The consensus is that 350 ng/mL is the lower threshold of therapeutic efficacy to define an adequate trial of clozapine. As of this writing, no clearly defined threshold exists for the upper limit of therapeutic efficacy or toxicity. TDM of clozapine can be useful in the following circumstances: when a clozapine-induced central nervous system toxicity is suspected, a medication that can inhibit or induce the metabolism of clozapine is being added or withdrawn, a change in smoking status has occurred, concerns for medication nonadherence are present, or decompensation while on a previously effective clozapine dosage is observed. The psychiatric pharmacist may play a crucial role in the interpretation and effective utilization of serum clozapine and norclozapine levels. This review will examine the current evidence for the clinical utility of monitoring serum levels of clozapine and its metabolites.

scholarly journals Active surveillance with telemedicine in patients on anticoagulants during the national lockdown (COVID-19 phase) and comparison with pre-COVID-19 phase

2020 ◽  
Vol 72 (1) ◽  
Author(s):  
Gurbhej Singh ◽  
Samir Kapoor ◽  
Vasu Bansal ◽  
Mehtab Grewal ◽  
Bhupinder Singh ◽  
...  
Keyword(s):  
High Risk ◽  
Health Education ◽  
Oral Anticoagulation ◽  
Oral Anticoagulants ◽  
Likert Scale ◽  
Target Range ◽  
High Risk Patients ◽  
Number Of Patients ◽  
Significant Difference ◽  
Risk Patients

Abstract Background The COVID-19 pandemic brought restriction to the movement of people due to the implementation of lockdown across various regions around the world. In India, most of the patients belong to rural areas and hence were unable to come for a follow-up visit. Hence, we reached out to patients on oral anticoagulation using telemedicine with aim of communicating with the patient concerning drug compliance, titration of dose of anticoagulation, health education, and identification of high-risk patients needing referral to the nearest health facility/our institute. This study was conducted at the Hero DMC heart institute (a tertiary care center for cardiac diseases). The study design is cross-sectional and involves a comparison of the pre-COVID-19 phase with the COVID-19 phase. We asked a five-component (Likert scale) questionnaire from patients for satisfaction after the consult. All symptoms, need for hospitalization and clinical events were recorded. The events were compared in both groups. Results We contacted 628 patients through telemedicine and 600 patients gave consent for participation in the study. For comparison, we analyzed data of 614 patients in the pre-COVID-19 phase. The mean age during the pre-COVID-19 phase was 55.27 + 17.09 years and the COVID-19 phase was 56.97 + 15.09 years with males more than females in both groups. There was no significant difference in the number of patients on oral anticoagulants and novel oral anticoagulants (NOAC). However, there were higher number of  patients on antiplatelets in the pre-COVID phase (p value0.01). 37% in the pre-COVID-19 phase and 40.31 % in the COVID-19 phase were noted to have out of target range INR (International normalized ratio). There was no difference in the number of bleeding or thromboembolic events seen. Patient response as assessed by a questionnaire (Likert scale) showed that >75% of patients were satisfied. Conclusion Through telemedicine, we were able to approach our patients on oral anticoagulation and achieved titration of anti-coagulation, and health education similar to pre-COVID-19 times. During pandemics, telemedicine offers a promising option for patient management with chronic cardiac conditions. It also provides us an opportunity for the management of patients on oral anticoagulation involving titration of drug dosages (anti-coagulation), identification of high-risk patients, and health education.

Neuroblastoma: An Updated Review on Biology and Treatment

2020 ◽  
Vol 20 (13) ◽  
pp. 1014-1022 ◽  
Author(s):  
Suresh Mallepalli ◽  
Manoj Kumar Gupta ◽  
Ramakrishna Vadde
Keyword(s):  
Survival Rate ◽  
High Risk ◽  
Molecular Mechanisms ◽  
Definitive Treatment ◽  
Therapeutic Drug ◽  
Mycn Amplification ◽  
Dependent Manner ◽  
High Risk Patients ◽  
Treatment And Prevention ◽  
Risk Patients

Background: Neuroblastoma (NB) is the second leading extracranial solid tumors of early childhood and clinically characterized by the presence of round, small, monomorphic cells with excess nuclear pigmentation (hyperchromasia).Owing to a lack of definitive treatment against NB and less survival rate in high-risk patients, there is an urgent requirement to understand molecular mechanisms associated with NB in a better way, which in turn can be utilized for developing drugs towards the treatment of NB in human. Objectives: In this review, an approach was adopted to understand major risk factors, pathophysiology, the molecular mechanism associated with NB, and various therapeutic agents that can serve as drugs towards the treatment of NB in humans. Conclusions: Numerous genetic (e.g., MYCN amplification), perinatal, and gestational factors are responsible for developing NB. However, no definite environmental or parental exposures responsible for causing NB have been confirmed to date. Though intensive multimodal treatment approaches, namely, chemotherapy, surgery &radiation, may help in improving the survival rate in children, these approaches have several side effects and do not work efficiently in high-risk patients. However, recent studies suggested that numerous phytochemicals, namely, vincristine, and matrine have a minimal side effect in the human body and may serve as a therapeutic drug during the treatment of NB. Most of these phytochemicals work in a dose-dependent manner and hence must be prescribed very cautiously. The information discussed in the present review will be useful in the drug discovery process as well as treatment and prevention on NB in humans.

scholarly journals Assessing the clinical utility of genetic risk scores for targeted cancer screening

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Carly A. Conran ◽  
Zhuqing Shi ◽  
William Kyle Resurreccion ◽  
Rong Na ◽  
Brian T. Helfand ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Primary Care ◽  
High Risk ◽  
Risk Score ◽  
Genetic Risk ◽  
Clinical Utility ◽  
Low Risk ◽  
Risk Scores ◽  
Average Risk ◽  
Genetic Risk Scores

Abstract Background Genome-wide association studies have identified thousands of disease-associated single nucleotide polymorphisms (SNPs). A subset of these SNPs may be additively combined to generate genetic risk scores (GRSs) that confer risk for a specific disease. Although the clinical validity of GRSs to predict risk of specific diseases has been well established, there is still a great need to determine their clinical utility by applying GRSs in primary care for cancer risk assessment and targeted intervention. Methods This clinical study involved 281 primary care patients without a personal history of breast, prostate or colorectal cancer who were 40–70 years old. DNA was obtained from a pre-existing biobank at NorthShore University HealthSystem. GRSs for colorectal cancer and breast or prostate cancer were calculated and shared with participants through their primary care provider. Additional data was gathered using questionnaires as well as electronic medical record information. A t-test or Chi-square test was applied for comparison of demographic and key clinical variables among different groups. Results The median age of the 281 participants was 58 years and the majority were female (66.6%). One hundred one (36.9%) participants received 2 low risk scores, 99 (35.2%) received 1 low risk and 1 average risk score, 37 (13.2%) received 1 low risk and 1 high risk score, 23 (8.2%) received 2 average risk scores, 21 (7.5%) received 1 average risk and 1 high risk score, and no one received 2 high risk scores. Before receiving GRSs, younger patients and women reported significantly more worry about risk of developing cancer. After receiving GRSs, those who received at least one high GRS reported significantly more worry about developing cancer. There were no significant differences found between gender, age, or GRS with regards to participants’ reported optimism about their future health neither before nor after receiving GRS results. Conclusions Genetic risk scores that quantify an individual’s risk of developing breast, prostate and colorectal cancers as compared with a race-defined population average risk have potential clinical utility as a tool for risk stratification and to guide cancer screening in a primary care setting.

Personalized antibiotic therapy – a rapid high performance liquid chromatography–tandem mass spectrometry method for the quantitation of eight antibiotics and voriconazole for patients in the intensive care unit

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Tony Böhle ◽  
Ulrike Georgi ◽  
Dewi Fôn Hughes ◽  
Oliver Hauser ◽  
Gudrun Stamminger ◽  
...  
Keyword(s):  
Intensive Care ◽  
Antibiotic Therapy ◽  
High Performance ◽  
High Specificity ◽  
Serum Levels ◽  
Turnaround Time ◽  
Target Range ◽  
Therapeutic Drug ◽  
Monitoring Method ◽  
Adjustment Procedure

AbstractObjectivesFor a long time, the therapeutic drug monitoring of anti-infectives (ATDM) was recommended only to avoid the toxic side effects of overdosing. During the last decade, however, this attitude has undergone a significant change. Insufficient antibiotic therapy may promote the occurrence of drug resistance; therefore, the “one-dose-fits-all” principle can no longer be classified as up to date. Patients in intensive care units (ICU), in particular, can benefit from individualized antibiotic therapies.MethodsPresented here is a rapid and sufficient LC-MS/MS based assay for the analysis of eight antibiotics (ampicillin, cefepime, cefotaxime, ceftazidime, cefuroxime, linezolid, meropenem, and piperacillin) applicated by continuous infusion and voriconazole. In addition a dose adjustment procedure for individualized antibiotic therapy has been established.ResultsThe suggested dose adjustments following the initial dosing of 121 patient samples from ICUs, were evaluated over a period of three months. Only a minor percentage of the serum levels were found to be within the target range while overdosing was often observed for β-lactam antibiotics, and linezolid tended to be often underused. The results demonstrate an appreciable potential for β-lactam savings while enabling optimal therapy.ConclusionsThe presented monitoring method provides high specificity and is very robust against various interferences. A fast and straightforward method, the developed routine ensures rapid turnaround time. Its application has been well received by participating ICUs and has led to an expanding number of hospital wards participating in ATDM.

scholarly journals Self-Care IoT Platform for Diabetic Mellitus

2021 ◽  
Vol 11 (5) ◽  
pp. 2006
Author(s):  
Jai-Chang Park ◽  
Seongbeom Kim ◽  
Je-Hoon Lee
Keyword(s):  
Blood Glucose ◽  
Self Care ◽  
Target Range ◽  
Process Data ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Iot Platform ◽  
Number Of Patients ◽  
Glucose Management ◽  
The Relationship

Diabetes mellitus is a severe chronic disease, and the number of patients has increased. To manage blood glucose levels, patients should frequently measure their blood glucose and analyze which lifestyle habits affect blood glucose levels. However, it is hard to record and analyze the relationship between their blood glucose levels and lifestyle. The internet of things (IoT) is useful to interconnect, monitor, obtain, and process data between various devices used in everyday life to fulfill a common objective. This paper proposes an intelligent self-care platform using IoT technology that helps patients with chronic diabetes manage their blood glucose levels in their target range. In particular, we developed various devices called the self-care IoT pack. It consists of five different types of devices to obtain blood glucose levels, physical activities, food intake, medication, sleeping, and so on. They can collect blood glucose levels with lifestyles that automatically impact the patient’s blood glucose level. We also devised a self-care application to display and analyze the data obtained from the IoT pack. Consequently, the proposed self-care IoT platform collects the blood glucose levels and the lifestyles without any burden of record. By reviewing the accumulated information, the patients can find bad habits in blood glucose management and improve their lifestyle.

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