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Objectives: In developing nations such as India, a disparity exists between the available resources for stroke rehabilitation and the substantial burden of stroke cases. Consequently, the provision of cost-effective and multidisciplinary post-stroke rehabilitation care to stroke survivors becomes of paramount importance. The utilization of mobile applications (apps) for stroke care has been on the rise, offering a personalized and pragmatic solution with the potential for wider reach in settings constrained by limited resources. To address the unmet needs in the prevention and management of post-stroke complications, we conceptualized a strategy known as a mobile application-based post-stroke care strategy for both survivors and their caregivers. Materials and Methods: The scope of the app's focus was determined based on the incidence of post-stroke complications within a prospective cohort of stroke patients, in conjunction with existing literature. An initial "web-based mobile app" prototype was crafted to align with the identified focus area. Before the development of the final app version, a feasibility study was conducted involving 30 participant dyads (comprising a patient and a caregiver). Content validity was evaluated by a panel of 20 stroke experts encompassing neurologists, nurses, physiotherapists, and psychologists. Results: The "Stroke Home Care" (SHC) mobile app was conceived as a web-based educational tool aimed at preventing and managing post-stroke complications. It seeks to train caregivers of immobile stroke patients in the administration of preventive and therapeutic care procedures, thereby potentially enhancing survivors' quality of life and alleviating caregivers' burden. The feasibility and validity studies indicated "high satisfaction" levels among most caregivers and experts (>75%), with the remainder expressing "satisfaction" and no "dissatisfaction" regarding app utilities. Stroke experts unanimously deemed the app "appropriate", with consensus on contents, video quality, video length, and voice clarity. Caregivers reported "satisfactory" user experiences, encountering no issues during app installation or operation. Suggestions from both caregivers and experts were integrated into the final app version. Conclusion: The "SHC" app represents a feasible and well-received innovation tailored for the use by caregivers of stroke survivors. Consequently, the initial feasibility of the developed app serves as a precursor to a randomized controlled clinical trial aimed at substantiating its effectiveness within the post-stroke survivor and caregiver population. Notably, within resource-constrained contexts, this app has the potential to be a pivotal tool for post-stroke care.
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BACKGROUND: Mycophenolic acid is widely used to treat lupus nephritis (LN). However, it exhibits complex pharmacokinetics with large interindividual variability. This study aimed to develop a population pharmacokinetic (popPK) model and a 3-sample limited sampling strategy (LSS) to optimize therapeutic drug monitoring in Indian patients with LN. METHODS: Five blood samples from each LN patient treated with mycophenolic acid were collected at steady-state predose and 1, 2, 4, and 6 hours postdose. Demographic parameters were tested as covariates to explain interindividual variability. PopPK analysis was performed using Monolix and the stochastic approximation expectation-maximization algorithm. An LSS was derived from 500 simulated pharmacokinetic (PK) profiles using maximum a posteriori Bayesian estimation to estimate individual PK parameters and area under the curve (AUC). The LSS-calculated AUC was compared with the AUC calculated using the trapezoidal rule and all the simulated samples. RESULTS: A total of 51 patients were included in this study. Based on the 245 mycophenolic acid concentrations, a 1-compartmental model with double absorption using gamma distributions best fitted the data. None of the covariates improved the model significantly. The model was internally validated using diagnostic plots, prediction-corrected visual predictive checks, and bootstrapping. The best LSS included samples at 1, 2, and 4 hours postdose and exhibited good performances in an external dataset (root mean squared error, 21.9%; mean bias, -4.20%). CONCLUSIONS: The popPK model developed in this study adequately estimated the PK of mycophenolic acid in adult Indian patients with LN. This simple LSS can optimize TDM based on the AUC in routine practice.
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OBJECTIVES: To study the effect of postmeal Fast-acting insulin Aspart (Fiasp®) on the frequency of hypoglycemia compared to premeal injection among preschool children with type 1 diabetes. METHODS: A single-center trial was conducted among 65 pre-school children (6 mo to 6 y) with Type 1 diabetes for at least 6 mo, on multiple daily insulin injections. Children were randomized to receive their meal bolus postmeal or premeal for the first 3 mo, followed by cross-over at 3 mo. The two groups were compared at the end of 6 mo for the change in frequency of hypoglycemia and hyperglycemia, HbA1c, glycemic variability, and parental satisfaction. Ten children (5 in each group) underwent pharmacokinetic studies. The trial was approved by Institutional Ethics Committee and registered with the Controlled Trial Registry of India vide no CTRI/2020/10/028750. RESULTS: Fifty-four children completed the study, with 27 children in each group. There were no significant differences in the frequency of clinical (p = 0.921), severe (p = 0.167) or serious (p = 0.753) hypoglycemia in the two groups. There were no differences in secondary outcome parameters and pharmacokinetics. CONCLUSIONS: The premeal or postmeal injection of Fiasp® does not affect the frequency of hypoglycemia or other glycemic control parameters among pre-school children with Type 1 diabetes. TRIAL REGISTRATION: The trial is registered with the Controlled Trial Registry of India vide no CTRI/2020/10/028750.
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Scedosporium aurianticum infection developed in 2 recipients of kidney transplants in India, acquired from the same deceased near-drowning donor. Given the substantial risk for death associated with Scedosporium infection among solid-organ transplant recipients, safety protocols for organ transplantation from nearly drowned donors should be thoroughly revaluated and refined.
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Transplante de Rim , Afogamento Iminente , Transplante de Órgãos , Humanos , Transplante de Rim/efeitos adversos , Doadores de TecidosRESUMO
Over the last three to four decades, Therapeutic Drug Monitoring (TDM) has shaped itself as therapeutic drug management, an integral component of precision medicine. The practice of TDM is not extensive in India, despite being one of the fastest-growing economies in the world. It is currently limited to a few academic medical centres and teaching hospitals. Apart from the immunosuppressive drugs, several other therapeutic areas, such as anticancer, antifungal, antibiotic and antitubercular, have demonstrated great potential to improve patient outcomes in Indian settings. Factors such as the higher prevalence of nutritional deficiencies, tropical diseases, widespread use of alternative medicines, unalike pharmacogenomics and sparse population-specific data available on therapeutic ranges of several drugs make the population of this subcontinent unique regarding the relevance of TDM. Despite the impact of TDM in clinical science and its widespread application, TDM has failed to receive the attention it deserves in India. This review intends to bring out a strength, weakness, opportunity and threats (SWOT) analysis for TDM in India so that appropriate steps for fostering the growth of TDM could be envisioned. The need of the hour is the creation of a cooperative group including all the stakeholders, such as TDM professionals, clinicians and the government and devising a National Action Plan to strengthen TDM. Nodal TDM centres should be established, and pilot programmes should be rolled out to identify the thrust areas for TDM in the country, capacity building and creating awareness to integrate TDM into mainstream clinical medicine.
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Monitoramento de Medicamentos , Imunossupressores , Humanos , Antituberculosos/uso terapêutico , ÍndiaRESUMO
ABSTRACT: Nirmatrelvir/ritonavir (Paxlovid) consists of a peptidomimetic inhibitor (nirmatrelvir) of the SARS-CoV-2 main protease and a pharmacokinetic enhancer (ritonavir). It is approved for the treatment of mild-to-moderate COVID-19. This combination of nirmatrelvir and ritonavir can mediate significant and complex drug-drug interactions (DDIs), primarily due to the ritonavir component. Indeed, ritonavir inhibits the metabolism of nirmatrelvir through cytochrome P450 3A (CYP3A) leading to higher plasma concentrations and a longer half-life of nirmatrelvir. Coadministration of nirmatrelvir/ritonavir with immunosuppressive drugs (ISDs) is particularly challenging given the major involvement of CYP3A in the metabolism of most of these drugs and their narrow therapeutic ranges. Exposure of ISDs will be drastically increased through the potent ritonavir-mediated inhibition of CYP3A, resulting in an increased risk of adverse drug reactions. Although a decrease in the dosage of ISDs can prevent toxicity, an inappropriate dosage regimen may also result in insufficient exposure and a risk of rejection. Here, we provide some general recommendations for therapeutic drug monitoring of ISDs and dosing recommendations when coadministered with nirmatrelvir/ritonavir. Particularly, tacrolimus should be discontinued, or patients should be given a microdose on day 1, whereas cyclosporine dosage should be reduced to 20% of the initial dosage during the antiviral treatment. Dosages of mammalian target of rapamycin inhibitors (m-TORis) should also be adjusted while dosages of mycophenolic acid and corticosteroids are expected to be less impacted.
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COVID-19 , Ritonavir , Humanos , Ritonavir/uso terapêutico , Monitoramento de Medicamentos , Citocromo P-450 CYP3A , Tratamento Farmacológico da COVID-19 , SARS-CoV-2 , Imunossupressores/efeitos adversosRESUMO
Arm Venous Segmentation plays a crucial role in smart venipuncture. The difficulties faced in locating veins for intravenous procedures can be diminished using computer vision for vein imaging. To facilitate this, a high-resolution dataset consisting of arm images was curated and has been presented in this study. Leveraging the ability of Near Infrared Imaging to easily detect veins, ambient lighting conditions were created inside a small enclosure to capture the images. The acquired images were annotated to create the corresponding masks for the dataset. To extend the scope and assert the usability of the dataset, the images, and corresponding masks were used to train an image segmentation model. In addition to using basic preprocessing and image augmentation based techniques, a U-Net based algorithmic architecture has been used to facilitate the task of segmentation. Subsequently, the results of performing image segmentation after applying the preprocessing methods have been compared using various evaluation metrics and have been visualised in the study. Furthermore, the possible applications of the presented dataset have been investigated in the study.
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Aprendizado Profundo , Braço , Processamento de Imagem Assistida por Computador/métodos , FlebotomiaRESUMO
A novel method for simultaneous quantification of cyclophosphamide along with its two major metabolites namely 4-hydroxycyclophosphamide (HCy) and carboxyethyl phosphoramide mustard (CEPM) in a single sample run was demonstrated in the present study. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) instrument was used for analysis. Semicarbazide was used as a stabilizing agent for HCy whereas ifosfamide, hexamethyl phosphoramide mustard and deuterated CEPM were the internal standards for quantification of Cy, HCy and CEPM respectively. Chromatographic separation was achieved by Chromsystems C18 reverse-phase column (50 mm × 4.6 mm, particle size 3.2 µm). The mobile phase was composed of eluent A (2 mM ammonium acetate in water with 2% formic acid) and eluent B (100 % acetonitrile). The flow rate was 1 ml/min. Linearity of the assay was assured in the range of 19.53 ng/ml to 10,000 ng/ml concentration in human plasma, which is adequate for pharmacokinetic studies of any dose Cy used clinically. The quality control(QC) accuracy was between 99.58% and 101.62%, 97.85% to 103.53% and 99.64% to 100.10% for Cy, HCy and CEPM respectively. Precision limits for QC samples were between 3.9% and 9.4%, 5.2% to 8.9% and 1.8% to 9.2% respectively. The analytical method was validated in ten leukaemia patients undergoing haploidentical hematopoietic cell transplantation.
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Transplante de Células-Tronco Hematopoéticas , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida , Ciclofosfamida , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Mostardas de Fosforamida/farmacocinética , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodosRESUMO
The COVID-19 pandemic has affected all the countries in the world with its droplet spread mode. The colossal amount of cases has strained all the healthcare systems due to the serious nature of infections especially for people with comorbidities. A very high specificity Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) test is the principal technique in use for diagnosing the COVID-19 patients. Also, CT scans have helped medical professionals in patient severity estimation & progression tracking of COVID-19 virus. In study we present our own extensible COVID-19 viral infection tracking prognosis technique. It uses annotated dataset of CT chest scan slice images created with the help of medical professionals. The annotated dataset contains bounding box coordinates of different features for COVID-19 detection like ground glass opacities, crazy paving pattern, consolidations, lesions etc. We qualitatively identify the severity of the patient for later prognosis stages in our study to assist medical staff for patient prioritization. First we detected COVID-19 positive patients with pre-trained Siamese Neural Network (SNN) which obtained 87.6% accuracy, 87.1% F1-Score & 95.1% AUC scores. These metrics were achieved after removal of 40% quantitatively highly similar images from the COVID-CT dataset. This reduced dataset was further medically annotated with COVID-19 features for bounding box detection. After this we assigned severity scores to detected COVID-19 features and calculated the cumulative severity score for COVID-19 patients. For qualitative patient prioritization with prognosis clinical assistance information, we finally converted this score into a multi-classification problem which obtained 47% weighted-average F1-score.
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AIM: To study the association of clozapine pharmacometabolomics and clozapine response in Asian patients with treatment-resistant schizophrenia (TRS). METHOD: A cross-sectional study was performed on 50 consecutive TRS patients following up in psychiatry department of the tertiary care hospital. Demographic details, response assessment, were collected on the case record form. A blood sample was also collected for trough concentration assessment of drug and its metabolites. Clozapine (CLZ) the parent drug and its two major metabolites - Clozapine N oxide (CNO) and N-Desmethyl clozapine (N-DSMC) levels were assessed using a high-performance liquid chromatography method. Clozapine responders and nonresponders patients were classified based upon Andreasen criteria. RESULTS: The average trough concentration of CNO, N-DSMC, and CLZ were 123 ± 76.04, 171.93 ± 93.24, 229.27 ± 124.25 ng/ml, respectively. The two patient subgroups did not differ for CLZ, CNO, and N-DSMC concentrations statistically. However, clozapine nonresponse was associated with a higher CLZ/N-DSMC ratio (p = 0.03) and clozapine dose (p = 0.01). The receiver operator characteristic curve showed that the cut-off CLZ/N-DSMC ratio of 1.54 with a sensitivity of 85% and a positive predictive value of 84% for identifying nonresponders. CONCLUSION: CLZ/N-DSMC ratio and clozapine dose were identified as significant variables for future dose optimization algorithms. Pharmacometabolomics-guided clozapine therapy has the potential to revolutionize TRS management.
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Antipsicóticos , Clozapina , Esquizofrenia , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Estudos Transversais , Humanos , Esquizofrenia/tratamento farmacológico , Esquizofrenia Resistente ao TratamentoRESUMO
OBJECTIVES: To study the effectiveness, tolerability, and safety of oral nitrazepam in children with resistant West syndrome (WS). METHODS: This prospective observational study was conducted at a tertiary care hospital in North India from January 2019 to October 2020. Children with WS resistant to standard therapy were enrolled within 7 d of initiation of nitrazepam and prospectively followed-up for cessation of spasms and adverse events. RESULTS: Forty-one children with resistant WS initiated on nitrazepam therapy were evaluated. The median age at onset of spasms was 6 mo (Q1, Q3: 4, 8). There was a preponderance of male gender (71%) and structural causes (78%). More than half of the enrolled children had failed four or more antiseizure medications (ASM) for epileptic spasms. The study participants had a long lead-time-to-treatment (LTTT) for the initial standard therapy (median: 2 mo; Q1, Q3: 1, 5) and nitrazepam (median: 11 mo; Q1, Q3: 8, 16). Nitrazepam was instituted as monotherapy in 7 (17%) children and as an adjunct in the rest. Twenty-one (51%) children achieved persistent cessation of epileptic spasms. However, the electroclinical response was observed in 17 (42%) children. Drowsiness, sialorrhea, and decreased appetite were the most commonly observed adverse events. Most adverse events were mild to moderate in severity and did not require dose reduction or change of medication. There was no significant difference between the responders and nonresponders in terms of LTTT, age at onset, or etiology. CONCLUSIONS: Nitrazepam is a safe and feasible treatment alternative in children with resistant WS resulting in persistent cessation of spasms and electroclinical response in nearly half of patients.
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Nitrazepam , Espasmos Infantis , Anticonvulsivantes/efeitos adversos , Criança , Eletroencefalografia , Humanos , Lactente , Masculino , Nitrazepam/uso terapêutico , Estudos Prospectivos , Espasmo/tratamento farmacológico , Espasmos Infantis/tratamento farmacológicoRESUMO
OBJECTIVE: To determine whether high-dose, oral pyridoxine in combination with standard adrenocorticotropic hormone (ACTH) therapy has superior effectiveness than ACTH therapy alone in increasing cessation of epileptic spasms for children with West syndrome. METHODS: This study was an open-label, randomized controlled trial with masked endpoint assessments. Eligible children with West syndrome, age ranged 3-18 months, were randomized into the intervention (n = 43) and the standard arm (n = 37) of therapy. The intervention group received oral pyridoxine at 100-300 mg/kg/day in addition to standard therapy of intramuscular ACTH at 150 IU/m2/day. Primary effectiveness outcome was a complete cessation of spasms at two weeks and sustained till six weeks. RESULTS: Comparison of effectiveness measures between intervention and standard groups were : complete cessation of epileptic spasms (48.8% vs 58.3%; group difference -9.6%; 95% confidence interval [CI] -30% to 12.3%; p = 0.4), median EEG scores (Q1-Q3) by Jeavons Score at six weeks [3 (1-5) vs 3 (1-5); p = 0.6], median motor scores (Q1-Q3) by DASII (Development Assessment Scales for Indian Infants) at 12 weeks [35 (29-49) vs 42 (34.3-63.8), p = 0.04], and median mental scores (Q1-Q3) by DASII at 12 weeks [35 (29.5-46) vs 41.5 (31.3-60), p = 0.02]. Adverse events were comparable in both arms. CONCLUSIONS: There was no evidence to suggest the superiority of high-dose pyridoxine in combination with ACTH versus ACTH alone for the treatment of West syndrome, considering the limitations of the study design.
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Piridoxina , Espasmos Infantis , Administração Oral , Hormônio Adrenocorticotrópico/uso terapêutico , Quimioterapia Combinada , Humanos , Lactente , Piridoxina/uso terapêutico , Espasmos Infantis/tratamento farmacológicoRESUMO
ABSTRACT: When mycophenolic acid (MPA) was originally marketed for immunosuppressive therapy, fixed doses were recommended by the manufacturer. Awareness of the potential for a more personalized dosing has led to development of methods to estimate MPA area under the curve based on the measurement of drug concentrations in only a few samples. This approach is feasible in the clinical routine and has proven successful in terms of correlation with outcome. However, the search for superior correlates has continued, and numerous studies in search of biomarkers that could better predict the perfect dosage for the individual patient have been published. As it was considered timely for an updated and comprehensive presentation of consensus on the status for personalized treatment with MPA, this report was prepared following an initiative from members of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT). Topics included are the criteria for analytics, methods to estimate exposure including pharmacometrics, the potential influence of pharmacogenetics, development of biomarkers, and the practical aspects of implementation of target concentration intervention. For selected topics with sufficient evidence, such as the application of limited sampling strategies for MPA area under the curve, graded recommendations on target ranges are presented. To provide a comprehensive review, this report also includes updates on the status of potential biomarkers including those which may be promising but with a low level of evidence. In view of the fact that there are very few new immunosuppressive drugs under development for the transplant field, it is likely that MPA will continue to be prescribed on a large scale in the upcoming years. Discontinuation of therapy due to adverse effects is relatively common, increasing the risk for late rejections, which may contribute to graft loss. Therefore, the continued search for innovative methods to better personalize MPA dosage is warranted.
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Monitoramento de Medicamentos , Imunossupressores/administração & dosagem , Ácido Micofenólico/administração & dosagem , Transplante de Órgãos , Área Sob a Curva , Consenso , Rejeição de Enxerto/prevenção & controle , HumanosRESUMO
OBJECTIVES: This meta-analysis of randomized clinical trials (RCT) intends to evaluate the efficacy of DPP4 Inhibitors (DPP4I) compared with placebo, other antidiabetics (or DPP4I) on renal outcomes, adverse events (AEs), and all-cause mortality. METHODS: We searched relevant scientific database for RCTs with DPP4I and prespecified renal end point. The effect size (mean difference or risk ratio) was reported with its 95% confidence interval. RESULTS: Eight RCTs (n = 39040 participants) were included in the analysis. The rate of change in eGFR was not different in DPP4 inhibitor and control group. DPP4I use beyond 52 weeks did not worsen albuminuria progression (RR 0.88; 95% CI 0.80 to 0.96; high quality evidence) compared to placebo. The risk of AEs within 52 weeks (RR 0.93; 95% CI 0.80 to 1.08; moderate quality evidence), beyond 52 weeks (RR 0.98; 95% CI 0.97 to 1.00; low quality evidence), and all-cause mortality (RR 1.04; 95% CI 0.96 to 1.12; very low quality evidence) were similar to placebo. In head-to-head comparison between two DPP4I studies, no significant differences were found between alogliptin and vildagliptin for improvement in eGFR, UACR, or AE at 24 weeks. CONCLUSIONS: DPP4I do not seem to provide persuasive benefit in the renal outcomes or all-cause mortality in diabetes mellitus, though there was no evidence for increased AEs.
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BACKGROUND: Drug Information Center (DIC) with on-call evidence-based medicine service can revolutionize health-care practice and also can play a major role in health-care delivery in both developed and developing countries. OBJECTIVE: To assess the feedback received from hospital clinicians for the newly initiated DIC services in a tertiary care hospital of North India. METHODS: This is a retrospective cohort study conducted between January 1, 2016, to December 31, 2018. The clinicians approached DIC for specific pharmacotherapeutic questions for managing an index patient. After providing consultation, DIC followed up with them for the action taken and feedback on the consultation. The results of the data analyzed using Fisher Exact test and descriptive statistics. RESULTS: Of 264 encounters, more than 98% of clinicians found the service satisfactory. There was a statistically significant association between the timely answer provided to treating physicians and their level of satisfaction with the service (P < .05). There was no significant association between academic experiences and the satisfaction or dissatisfaction among the clinical fraternity colleagues. The interpretation ability of on-call pharmacology postgraduate students was a significantly associated factor with clinician's satisfaction level (P < .05). More than 96% of clinicians followed the pharmacotherapy advice recommended by DIC in their patient management. CONCLUSION: Thorough evaluation of published research needs to be taught to budding pharmacologists, pharmacists in their curriculum for an effective DIC service. DIC service has the potential to minimize the barrier of evidence-based medicine practice in developing as well as developed countries.
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Preparações Farmacêuticas , Farmacologia Clínica , Países em Desenvolvimento , Hospitais , Humanos , Centros de Informação , Encaminhamento e Consulta , Estudos RetrospectivosRESUMO
ABSTRACT: Drug-induced hematological disorders constitute up to 30% of all blood dyscrasias seen in the clinic. Hematologic toxicity from drugs may range from life-threatening marrow aplasia, agranulocytosis, hemolysis, thrombosis to mild leukopenia, and thrombocytopenia. Pathophysiologic mechanisms underlying these disorders vary from an extension of the pharmacological effect of the drug to idiosyncratic and immune-mediated reactions. Predicting these reactions is often difficult, and this makes clinical decision-making challenging. Evidence supporting the role of pharmacogenomics in the management of these disorders in clinical practice is rapidly evolving. Despite the Clinical Pharmacology Implementation Consortium and Pharmacogenomics Knowledge Base recommendations, few tests have been incorporated into routine practice. This review aims to provide a comprehensive summary of the various drugs which are implicated for the hematological adverse events, their underlying mechanisms, and the current evidence and practical recommendations to incorporate pharmacogenomic testing in clinical care for predicting these disorders.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Doenças Hematológicas , Farmacogenética , Biomarcadores , Doenças Hematológicas/induzido quimicamente , Doenças Hematológicas/genética , Humanos , Testes FarmacogenômicosRESUMO
BACKGROUND: The methanolic extract of Convolvulus pluricaulis had earlier shown lipid lowering activity in Triton induced reversible hyperlipidemia model, but, the hypolipidemic activity in irreversible models and hypoglycaemic activity are not investigated so far. OBJECTIVE: This study was designed to validate the lipid and glucose-lowering actions of C. pluricaulis methanolic extract (CPME) by using ingredients from the Indian diet for induction of hyperlipidemia and diabetes on experimental rats. MATERIALS AND METHODS: Experimental animals were divided into four groups having six animals in each group (n = 6). Animals of Group I II, III and IV received - no treatment, 0.9% NaCl, Glipizide (GPZ) 5 mg/kg and CPME 400 mg/kg once daily for two weeks respectively. Animals of all groups except group I were fed a high fat-based Indian diet for 21 days followed by a single STZ (35 mg/kg) i.p. administration in model induction phase. Afterwards, animals were sacrificed, and the pancreas was dissected for histological changes, and blood was collected for measuring lipid parameters, FBS, insulin levels, and HOMA scores. RESULTS: CPME significantly ameliorate the lipid abnormalities in HFD-STZ-treated experimental model (p < 0.001) but fails to reverse the hyperglycaemia developed in diabetic rats with no protective effect on islet architecture (p > 0.05) as compared to experimental group while, GPZ showed protective effect on both lipid abnormalities and hyperglycemia by modulating the levels of lipid parameters and insulin respectively. CONCLUSION: In conclusion, the study confirm that CPME possesses significant hypolipidemic activity but fails to reverse the hyperglycaemia developed in diabetic rats.
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BACKGROUND: Phenytoin (PHT) is a routinely prescribed prophylactic antiepileptic following aneurysmal subarachnoid hemorrhage (aSAH). However, its prophylactic use in aSAH is controversial as emerging evidence suggests worsening of the neurological and functional outcomes. In addition, there is profound damage to the blood-brain barrier (BBB) in aSAH, posing uncertainty about the permeability of PHT across BBB in these patients. This pilot study was designed to evaluate the alteration in PHT permeability across BBB in aSAH patients. MATERIALS AND METHODS: For conducting the study, 20 patients (control n = 10; aSAH (grade 3 or 4) n = 10) were recruited from a tertiary care hospital. The patients undergoing cranial surgery for pathology with intracerebral mass lesions on MRI were chosen as control for aSAH group. Both groups were administered PHT loading dose (20 mg/kg), infused in 5% dextrose, at a rate not more than 50 mg/min, followed by a maintenance dose (5 mg/kg). Quantification of PHT concentration was performed in brain tissue, plasma, and cerebrospinal fluid (CSF) by LC-MS/MS. RESULTS: The median PHT concentration in brain was found to be significantly decreased (64.8%) in aSAH group (3.78 µg/g) as compared to control (10.73 µg/g), P = 0.010. Similarly, median PHT brain concentration as fraction of plasma was significantly decreased in aSAH group (36.72%) compared to that of control (89.55%), P = 0.003. There was no significant difference in PHT concentration in plasma, CSF, and CSF as a fraction of plasma between both the groups. CONCLUSION: There is a definite decrease in the penetration of PHT to the brain in patients with grade 3 and 4 aSAH.
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Fenitoína , Hemorragia Subaracnóidea , Barreira Hematoencefálica , Cromatografia Líquida , Humanos , Permeabilidade , Projetos Piloto , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/tratamento farmacológico , Espectrometria de Massas em TandemRESUMO
OBJECTIVES: This report presents an audit of utilization of various organs from deceased donors in different states of India over a 3-year period METHODS: Data released by the various regions on their official website was analyzed from 2015 to 2017.Regions with less than 25 donations per year were excluded while calculating utilization rates. RESULTS: Total organ donation in India had increased from 570 to 843 donations from 2015 to 2017 (47.8% increase) with southern states performing exceedingly well compared with northern states. Total organs retrieved during the 3-year period were 6659 with a 54.7% increase in organ retrieval in 2017 compared with 2015 (2592 vs 1675 respectively). The net utilization rate of kidneys was 87.35%. Total liver transplants done during this period were 1894. Net liver utilization rate was 86.81% over 3 years. Total Heart transplants during this period were 641 with net utilization rate of 28.98%. An increase in utilization rates was observed from 2015 to 2017 (19.33%-34.46%). A total of 217 lung transplants were done with net utilization rate of 8.86% with an increase in yearly utilization rate from 6.5% in 2015 to 11.97% in 2017. Total pancreas transplants remained low with 48 transplants over 3 year duration with net utilization rate of 2.25% but an increase in utilization rate was observed. (0.92% in 2015 to 2.1% in 2017). CONCLUSION: There is a significant regional variability in organ utilization in India. Evaluating and addressing the cause of high variability can further increase the transplant activity.