Drug Reactions In Patients Research Articles

An Unusual Case of Drug-Induced Linear IgA Bullous Disease

An Unusual Case of Drug-Induced Linear IgA Bullous Disease

Cost effectiveness analysis of HLA-B*58:01 genotyping prior to initiation of allopurinol for gout.

To determine whether prospective testing for HLA-B*58:01, as a strategy to prevent serious adverse reactions to allopurinol in patients with gout, is cost-effective from the perspective of the National Health Service in the UK. A systematic review and meta-analysis for the association of HLA-B*58:01 with cutaneous and hypersensitivity adverse drug reactions informed a decision analytic and Markov model to estimate lifetime costs and outcomes associated with testing vs standard care (with febuxostat prescribed for patients who test positive). Scenario analyses assessed alternative treatment assumptions and patient populations. The number of patients needed to test to prevent one case of adverse drug reaction was 11 286 (95% central range (CR): 2573, 53 594). Cost and quality-adjusted life-year (QALY) gains were small, £103 (95% CR: £98, £106) and 0.0023 (95% CR: -0.0006, 0.0055), respectively, resulting in an incremental cost-effectiveness ratio (ICER) of £44 954 per QALY gained. The probability of testing being cost-effective at a threshold of £30 000 per QALY was 0.25. Reduced costs of testing or febuxostat resulted in an ICER below £30 000 per QALY gained. The ICER for patients with chronic renal insufficiency was £38 478 per QALY gained. Routine testing for HLA-B*58:01 in order to reduce the incidence of adverse drug reactions in patients being prescribed allopurinol for gout is unlikely to be cost-effective in the UK; however testing is expected to become cost-effective with reductions in the cost of genotyping, and with the future availability of cheaper, generic febuxostat.

Pharmacodynamic genetic polymorphisms affect adverse drug reactions of haloperidol in patients with alcohol-use disorder.

BackgroundAntipsychotic action of haloperidol is due to blockade of D2 receptors in the mesolimbic dopamine pathway, while the adverse drug reactions are associated with striatal D2 receptor blockade. Contradictory data concerning the effects of genetic polymorphisms of genes encoding these receptors and associated structures (catechol-O-methyltransferase [COMT], glycine transporter and gene encoding the density of D2 receptors on the neuronal membrane) are described.ObjectiveThe objectives of this study were to evaluate the correlation between DRD2, SLC6A3 (DAT) and COMT genetic polymorphisms and to investigate their effect on the development of adverse drug reactions in patients with alcohol-use disorder who received haloperidol.Patients and methodsThe study included 64 male patients (average age 41.38 ± 10.14 years, median age 40 years, lower quintile [LQ] 35 years, upper quintile [UQ] 49 years). Bio-Rad CFX Manager™ software and “SNP-Screen” sets of “Syntol” (Russia) were used to determine polymorphisms rs4680, rs1800497, rs1124493, rs2242592, rs2298826 and rs2863170. In every “SNP-Screen” set, two allele-specific hybridizations were used, which allowed to determine two alleles of studied polymorphism separately on two fluorescence channels.ResultsResults of this study detected a statistically significant difference in the adverse drug reaction intensity in patients receiving haloperidol with genotypes 9/10 and 10/10 of polymorphic marker SLC6A3 rs28363170. In patients receiving haloperidol in tablets, the increases in the UKU Side-Effect Rating Scale (UKU) score of 9.96 ± 2.24 (10/10) versus 13 ± 2.37 (9/10; p < 0.001) and in the Simpson-Angus Scale (SAS) score of 5.04 ± 1.59 (10/10) versus 6.41 ± 1.33 (9/10; p = 0.006) were revealed.ConclusionPolymorphism of the SCL6A3 gene can affect the safety of haloperidol, and this should be taken into account during the choice of drug and its dosage regimen.

A demographic study on gender related differences in adverse drug reactions of a tertiary care teaching hospital

Background: As a part of pharmacovigilance program of India (PvPI) adverse drug reactions (ADRs) are cause of mortality and morbidity in patients unnoticed, which is a part of WHO program for International Drug Safety Monitoring across world. ADRs are considered to be among top 10 causes for mortality. The reason for sex difference in medication response is multi factorial with wide range of aspects like steroid hormones, organ physiology to psychology and socio-cultural factors. The aim was to study on gender related differences in adverse drug reactions in patients attending tertiary care teaching hospital at Nandyal.Methods: ADR cases were collected from multicenter health care units from tertiary care teaching hospital. ADRs were reported in ADR notification forms or yellow form, CDSCO forms are used to report ADR to Regional pharmacovigilance center. Causality assessment of the ADRs was done based on WHO-UMC causality assessment scale using modified Hartwig and Seigel scale.Results: In the 30 ADR reports collected 21 reports (70%) are of female patients and 9 reports (30%) are of male patients. According to WHO-UMC scale 20 (70%) of Adverse drug reactions were falling into PROBABLE, while 10 (30%) ADR’s are CERTAIN. In 21 females, ADR reports were due to 15(76.43%) Antibiotics, 2 (9.52%) NSAID’s, 2 (9.52%) proton pump inhibitors, 2 (9.52%) anti-convulsants. In 9 males, ADR reports were due to 5 (55.5%) Antibiotics, 2 (22.22%) NSAID’s, 2 (22.22%) anti-convulsants.Conclusions: ADRs are the common occurrences but ADR monitoring helps in prevention of morbidity and mortality in patients. The most commonly affected gender is among female patients, as they are more exposed to drugs starting their journey right from the childhood, pregnancy till their adult menopausal stage.

Monitoring cutaneous adverse drug reactions in patients on TDF+3TC+EFV: a single centre experience

Background: HIV-infected patients initiating antiretroviral therapy may manifest a wide variety of ADRs ranging from trivial manifestation, such as rashes, pigmentation, to severe life‑threatening reactions, such as Steven–Johnson syndrome, toxic epidermal necrolysis. The present study thus monitored cutaneous adverse drug reactions in patients on first line antiretroviral regimen comprising of tenofovir disoproxil fumerate, lamivudine and efavirenz as a three drug-combination.Methods: A prospective observational clinical study was carried out for a period of one year among PLHIV receiving TDF+3TC+EFV as first line regimen in the outpatient setting of a nodal ART centre of eastern India.Results: The major regimen induced dermatological complications presenting in our study set up included rashes, itching, SJS, pigmentation of nails, skin Hyperpigmentation. The morbilliform eruption, often referred to as a maculopapular rash, is the most common type of reaction occurring after treatment initiation.Conclusions: Adverse drug reactions are one of the most common public health concerns, which influence patients' treatment options along with health care costs.

Comparative evaluation of adverse drug reactions in patients of acne prescribed with either topical benzyl peroxide or retinoic acid in a tertiary care teaching hospital

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; To evaluate and compare the profile of adverse drug reaction, its causality, severity and preventability in patients of acne prescribed with either topical benzyl peroxide or topical retinoic acid in a tertiary care teaching hospital.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; Two hundred patients attending to dermatology department with acne and prescribed with either topical benzyl peroxide or topical retinoic acid were observed for occurrence of adverse drug events (ADEs). ADEs were either spontaneously reported or elucidated from personal interviews and analyzed.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Out of total 200 patients, 110 (55%) were given benzoyl peroxide gel (2.5%) and remaining 90 (45%) were given retinoic acid cream (0.025%). Total 54 adverse events were reported in 47 (23.5%) patients. Highest number of patients having ADR was from 16-20 years (35, 74.46%) with male predominance (59.57%). Number of adverse events reported was significantly higher (p &amp;lt;0.05) in retinoic acid group (34, 62.96%) as compare to benzyl peroxide group (20, 37.03%). Most common ADRs were exfoliation (14, 25.92%) and burning sensation (13, 24.07%). Most of the ADRs fell in category of ‘probable’ and ‘possible’ in causality assessment by both WHO-UMC method and Narenjo’s scale. All the ADRs were of mild (44, 81.48%) and moderate (10, 18.52%) severity. Majority of ADRs were not preventable (24, 44.44%) followed by definitely preventable 22(40.74%) and 8 (14.81%) probably preventable.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; ADRs is a common problem associated with topically used medications for acne and its occurrence is significantly higher with retinoic acid as compare to benzyl peroxide. Early diagnosis and proper education about use of topical drugs can prevent some of the ADRs. &lt;/p&gt;

Efficacy and safety of combination therapy with tamsulosin, dutasteride and imidafenacin for the management of overactive bladder symptoms associated with benign prostatic hyperplasia: A multicenter, randomized, open-label, controlled trial (DIrecT Study)

To evaluate the efficacy and safety of a combination therapy with dutasteride and imidafenacin in patients with benign prostatic hyperplasia and persistent overactive bladder symptoms. A total of 163 patients presenting an enlarged prostate (volume >30 mL) and persistent overactive bladder symptoms despite at least 8 weeks of tamsulosin were randomized to receive tamsulosin and dutasteride, or tamsulosin, dutasteride and imidafenacin at a 1:1 ratio. The primary end-point was the mean change from baseline to week 24 in total overactive bladder symptom score. The mean change in total overactive bladder symptom score from baseline at week 24 was -1.99 (95% confidence interval -2.57 to -1.41) in the tamsulosin and dutasteride group, and -3.12 (95% confidence interval -3.72 to -2.52) in the tamsulosin, dutasteride and imidafenacin group. The tamsulosin, dutasteride and imidafenacin group significantly improved total overactive bladder symptom score at week 24 as compared with the tamsulosin and dutasteride group; the mean difference was -1.18 (-2.02 to -0.34). The between-group difference was statistically significant as early as week 4. The total International Prostate Symptom Score, storage subscore, quality of life index, and benign prostatic hyperplasia impact index also significantly improved in the tamsulosin, dutasteride and imidafenacin group. Tamsulosin, dutasteride and imidafenacin combination therapy improves overactive bladder symptoms and quality of life without causing serious adverse drug reactions in patients with enlarged prostate not responding to tamsulosin. This combination therapy seems to represent a promising therapeutic option in these patients.

Economic impact and severity of adverse drug reactions in patients with mental illness: A prospective observational study

INTRODUCTION: Psychotropic medications are the mainstay in the management of psychiatric disorders but they are not devoid of side effects. The occurrence of adverse drug reactions (ADRs) in Indian psychiatry populace varies from 5.9% to 45%. The cost associated with the management of ADRs in general settings ranges from Rs. 412.76 to 1080/- per ADR. MATERIALS AND METHODS: A prospective observational study was conducted for a period of 1 year. The ADRs were assessed for causality by the World Health Organization probability scale and severity by modified Hartwig and Siegel scale. The direct costs in the management of ADRs were calculated. RESULTS: A total of 494 ADRs were reported and evaluated from 300 patients. Of the total reported ADRs, 3.44% (n = 17) lead to hospital admissions and 2.83% (n = 14) prolonged the hospital stay. The gastrointestinal system 25.10% (n = 125) and central and peripheral nervous system 20.64% (n = 102) were the most common system organ class affected by ADRs. The drug classes mainly implicated with ADRs were antipsychotics 53.03% (n = 262) and antidepressants 23.88% (n = 118). Majority (24.29%) of the reactions that lead to cost impact was moderate in severity. Total cost incurred for the management of 131 reported ADRs was Rs. 57,891.33/- with an average cost of Rs. 117.18/- per ADR. CONCLUSION: In 131 cost impact ADRs, 114 patients had a cost impact of Rs. 57,891.33/- A directly proportionate relationship was observed between the severity and cost incurred for the management of ADRs. Hence, it is necessary to identify and prevent these reactions as they cause burden to the patients.

Pharmacovigilance by World Health Organisation Uppsala Monitoring Center Causality Assessment Algorithm in Medicine Ward of Tertiary Care Hospital of New Delhi

Introduction Pharmacovigilance is not new to India and has in fact been going on since 1998. Adverse drugs reaction (ADRs) are important causes of morbidity and mortality all over the world. They account for approximately 10-20% of all hospitalized patients. The overall incidence of serious ADRs is 6.7% and that of fatal is 0.32%.Objective The objectives of the study was to find the pattern of adverse drug reactions in patients attending medicine ward of a tertiary care center of New Delhi.Methodology A prospective study was conducted from March 2013 to December 2013. On the basis of WHO-UMC causality assessment algorithm, the incidence and pattern of ADRs were assessed from 300 patients of 18 to 70 years of age. The collected data was entered in Microsoft Excel, Common Terminology Criteria for Adverse Events (CTCAE) and analysed by SPSS.Results The incidence of ADRs was found to be 13.67%. More than one ADRs has been reported from some patients. The gender of the patients has no significance in the occurance of ADRs (p=0.194). Highest number of ADRs were found in gastrointestional system followed by central nervous system. Gastrointestional ADRs were must commonly associated with the uses of antimicrobials. The most frequently seen ADRs were diarrhea, gastritis, abdominal pain followed by nausea and vomiting. Decreased level of consciousness (sedation, drowsiness) followed by dizziness and tremors were the frequent ADRs related to the central nervous systems. Based on WHO-UMC causality assessment algorithm, it was observed that a total of 57 ADRs were possible and 2 were probable. No other causality assessment category was observed.Conclusion The ADRs incidence was common even in a tertiary care center. The Gastrointestional and central nervous system disorder were common. The concern of Pharmacovigilance should be initiated.Birat Journal of Health Sciences 2016 1(1): 61-64

Ocular Toxoplasmosis: Therapy-Related Adverse Drug Reactions and Their Management.

Background There are different treatment options for ocular toxoplasmosis (OT). "Classic" therapy consists of pyrimethamine, sulfadiazine and folinic acid combined with systemic steroids and is still widely used. However, potentially severe side effects of this therapy have been reported. The aim of this retrospective study was to evaluate the incidence and types of adverse drug reactions in patients treated for OT. Clinical management of each adverse drug reaction was assessed. Patients and Methods In this retrospective analysis, we reviewed data of patients with OT, who were consecutively examined between December 2011 and December 2015 at the Department of Ophthalmology, University Hospital Zurich. Results In total, 49 patients had at least one episode of active OT. In 54 (83.0 %) of 65 treated episodes, the classic regimen was used. Of the 37 patients who received classic treatment, 9 (24.3 %) developed at least one adverse drug reaction which led to drug discontinuation, including elevated creatinine (5.4 %), elevated liver enzymes (5.4 %), vomiting (5.4 %), rash (5.4 %) and facial swelling (2.7 %). In 5 patients, treatment was switched to another drug, while in the other 4 patients, therapy was stopped. In these 9 patients, inflammation was well controlled 8 weeks after onset of therapy. No patient suffered from severe side effects, such as potentially life-threatening allergic reactions or pancytopenia. Conclusions In OT patients who were treated with classic therapy, adverse drug reactions are common. Therefore, clinical and laboratory monitoring is mandatory. Adverse drug reactions may require interdisciplinary management.

Potential Mechanisms of Hematological Adverse Drug Reactions in Patients Receiving Clozapine in Combination With Proton Pump Inhibitors.

Clozapine is a second-generation antipsychotic which has proven efficacy in treating the symptoms of schizophrenia. Although clozapine therapy is associated with a number of adverse drug reactions, it is frequently used. One of the most common adverse drug reactions is gastroesophageal reflux disease which is an indication for treatment with proton pump inhibitors (PPIs). Coadministration of clozapine and PPIs increases the risk of hematological adverse drug reactions, including neutropenia and agranulocytosis. The mechanism in idiosyncratic agranulocytosis is not dose related and involves either a direct toxic or an immune-allergic effect. It is suspected that the clozapine metabolites nitrenium ion and N-desmethylclozapine may cause apoptosis or impair growth of granulocytes. Formation of N-desmethylclozapine is correlated with activity of the cytochrome P450 enzymes 1A2 and 3A4 (CYP1A2 and CYP3A4). Nitrenium ion is produced by the flavin-containing monooxygenase system of leukocytes. A drug interaction between clozapine and a PPI is a consequence of the induction of common metabolic pathways either by the PPI or clozapine. Findings to date suggest that indirect induction of flavin-containing monooxygenase by omeprazole through the aryl hydrocarbon receptor increases the expression of the enzyme mRNA and in the long term may cause the increase in activity. Moreover, induction of CYP1A2, especially by omeprazole and lansoprazole, may increase the serum concentration of N-desmethylclozapine, which can accumulate in lymphocytes and may achieve toxic levels. Another hypothesis that may explain hematological adverse drug reactions is competitive inhibition of CYP2C19, which may contribute to increased serum concentrations of toxic metabolites.

Study of adverse drug reactions in patients with diabetes attending a tertiary care hospital in New Delhi, India.

The present prospective observational study was carried out in a tertiary care hospital in New Delhi, India from May 2014 to June 2015 to report adverse drug reactions (ADRs) in patients with type 2 diabetes mellitus (T2DM) using antidiabetic drugs. A total of 220 patients (121 males, 99 females) were enrolled. ADRs were recorded on the prescribed form. Causality and severity assessment was done using Naranjo's probability scale and modified Hartwig and Siegel's severity scale, respectively. Commonly prescribed drugs were biguanides, peptide hormone and sulphonylurea. A total of 26 ADRs were recorded (16 in males and 10 in females). Most commonly observed ADRs were related to endocrine and gastrointestinal system. Severity assessment of ADRs showed seven (26.9%) ADRs as moderate, and 19 (73.1%) as mild. No severe reactions were observed. ADRs were mostly related to endocrine and gastrointestinal system. More information on prescribed drugs and their side effects is required for ensuring patient safety.

A study of adverse drug reactions in patients receiving treatment for multi-drug resistant tuberculosis

Background: A high frequency of adverse drug reactions (ADRs) is one of the major challenges in the treatment of Multi-drug resistant tuberculosis (MDR-TB). Patients may refuse to continue treatment if ADRs are not properly addressed, drugs may be stopped unnecessarily and treatment may be terminated prematurely by inexperienced health workers, resulting in a high proportion of failure.Methods: Patients diagnosed for MDR-TB and registered in Drug Resistant TB centre (DR-TB) of tertiary care hospital during period of July 2014 to June 2015 were enrolled in the study. Data of patients hospitalized for the complaints of ADR in DR-TB centre during study period was collected.Results: Out of 468 patients, 60 (12.82%) patients developed at least one adverse reaction and were hospitalised for the same. Among 109 reported ADRs, Gastrointestinal upset was the most common ADR reported (5.98%) followed by psychosis (4.91%) and ototoxicity (2.99%).Conclusions: The health providers, the patients and their relatives should be sensitised about these ADRs for early detection and treatment. It can also be suggested that the setup of DR-TB centre should be integrated with psychiatry and ENT specialities, with all the provisions of early detection of ADR and treatment.

Pharmacotherapeutic Considerations for Individuals with Down Syndrome.

Down syndrome (DS; trisomy 21) is the most common survivable disorder due to aneuploidy. Individuals with DS may experience multiple comorbid health problems including congenital heart defects, endocrine abnormalities, skin and dental problems, seizure disorders, leukemia, dementia, and obesity. These associated conditions may necessitate pharmacotherapeutic management with various drugs. The complex pathobiology of DS may alter drug disposition and drug response in some individuals. For example, reports have documented increased rates of adverse drug reactions in patients with DS treated for leukemia and dementia. Intellectual disability resulting from DS may impact adherence to medication regimens. In this review, we highlight literature focused on pharmacotherapy for individuals with DS. We discuss reports of altered drug disposition or response in patients with DS and explore social factors that may impact medication adherence in the DS setting. Enhanced monitoring during drug therapy in individuals with DS is justified based on reports of altered drug disposition, drug response, and other characteristics present in this population.

A Prospective Study of Adverse Drug Reactions in Patients with Bipolar Disorder in Psychiatry Outpatient Department of a Tertiary Care Hospital.

Bipolar disorder is a chronic, debilitating psychiatric disorder. Mood stabilizers and atypical antipsychotics are first line drugs for bipolar disorder. They have significant adverse effects. The study was conducted with an aim to evaluate the pattern of occurrence of Adverse Drug Reactions (ADRs) in the patients with bipolar disorder and to assess their causality, severity and preventability. A prospective and observational study - carried out in the psychiatry outpatient department of New Civil Hospital, Surat for 15 months. All patients diagnosed with bipolar disorder and receiving pharmacotherapy were included. Udvalg for Kliniske Undersøgelser (UKU) side effect rating scale and Abnormal Involuntary Movement Scale (AIMS) were used for documenting ADRs and tardive dyskinesia, respectively. Assessment of causality, severity and preventability of recorded ADRs was done using Naranjo's algorithm and WHO-UMC scale, modified Hartwig and Seigel Scale and modified Schumock and Thornton scale, respectively. Descriptive statistics was used (percentage, mean±standard deviation) for presentation of demographics and other numerical data; Chi Square test and Fisher's exact test were used to assess association between variables. A p-value < 0.05 was considered significant. A total of 703 ADRs were recorded from 175 patients. The most common ADRs observed were asthenia (11.95%) and sedation (10.24%). Majority of ADRs were mild on assessment with UKU scale. Mood stabilizers (59.46%) were most frequently associated with ADRs and lithium was most common single drug responsible. Upon causality assessment, majority of the reactions were probable (54.77% with WHO-UMC scale, and 56.33% with Naranjo's algorithm). The association of results between the two scales was statistically significant (p<0.001). Majority of ADRs (70.27%) were assessed as mild and 64.30% of the ADRs were not preventable. ADRs are a frequent occurrence in patients with bipolar disorder which are mild in most cases. Incidence of ADRs can be decreased and compliance as well as quality of life of patient can be improved by early detection and management.

Causality, severity and preventability assessment of adverse drug reactions in patients received anti-retroviral therapy in a tertiary care hospital: A retrospective study

Background: The cornerstone of management of patients with human immunodeficiency virus/acquired immunodeficiency syndrome (AIDS) infection is highly active antiretroviral therapy (HAART). However, antiretroviral drugs are highly toxic and are associated with various adverse drug reactions (ADRs). Therefore, many patients require the withdrawal of the drug or even discontinue the treatment resulting in the treatment failure. Aims and Objectives: To study the demographic details and type of ADRs in patients receiving ART and to do causality, severity, and preventability assessment of the spontaneously reported ADRs. Materials and Methods: This was a retrospective cross-sectional observational study conducted for 18 months from January 2015 to June 2016 in Rajendra Institute of Medical Sciences, Ranchi. Spontaneously reported ADR data were evaluated for the patient demography, type of ADRs, drugs/regimes responsible, and body system affected. ADRs were assessed for their causality, severity, and preventability as per the standard scales. Results: Out of 356 patients given ART 197 ADR reports received which showed slight male predominance. 86.80% cases fell in 25-54 years age group with a mean age of 38.38 ± 10.74 years. The majority were neuropsychiatric (29.44%) and gastrointestinal-hepatobiliary (24.87%) followed by hematologic, dermatologic, and metabolic ADRs. Regimen containing tenofovir, lamivudine, and efavirenz were responsible for maximum number of ADRs (49.23%) followed by zidovudine, lamivudine, nevirapine (23.85%). 88.85% of ADRs were possible, 9.14% probable, and 2.03% certain according to the World health organization-Upsala monitoring centre causality assessment. 67.51% ADRs were mild followed by 29.44% moderate and 3.04% severe. 21.82% ADRs were definitely preventable, 37.06% probably preventable, and 41.12% not preventable. Conclusion: Although HAART is effective in decreasing AIDS-related deaths, it is associated with a number of ADRs. To maintain the patient compliance judicious use of ART and continuous monitoring of ADRs and their effective treatment prevention is advocated.

113P Chemotherapy administration safety standards for preventing medication errors and adverse drug reactions in patients with breast cancers

113P Chemotherapy administration safety standards for preventing medication errors and adverse drug reactions in patients with breast cancers

113P Chemotherapy administration safety standards for preventing medication errors and adverse drug reactions in patients with breast cancers

113P Chemotherapy administration safety standards for preventing medication errors and adverse drug reactions in patients with breast cancers

Learning approaches to improve prediction of drug sensitivity in breast cancer patients.

Predicting drug response to cancer disease is an important problem in modern clinical oncology that attracted increasing recent attention from various domains such as computational biology, machine learning, and data mining. Cancer patients respond differently to each cancer therapy owing to disease diversity, genetic factors, and environmental causes. Thus, oncologists aim to identify the effective therapies for cancer patients and avoid adverse drug reactions in patients. By predicting the drug response to cancer, oncologists gain full understanding of the effective treatments on each patient, which leads to better personalized treatment. In this paper, we present three learning approaches to improve the prediction of breast cancer patients' response to chemotherapy drug: the instance selection approach, the oversampling approach, and the hybrid approach. We evaluate the performance of our approaches and compare them against the baseline approach using the Area Under the ROC Curve (AUC) on clinical trial data, in addition to testing the stability of the approaches. Our experimental results show the stability of our approaches giving the highest AUC with statistical significance.

Development of a prediction system for anti-tuberculosis drug-induced liver injury in Japanese patients.

Drug-induced liver injury (DILI) is a common adverse drug reaction in patients receiving antituberculosis (anti-TB) treatment. Among the anti-TB agents, isoniazid (INH) is the primary drug that causes hepatotoxicity in TB patients with DILI. Previous reports in several populations have consistently demonstrated an association between polymorphisms in the N-acetyltransferase 2 (NAT2) gene, which is responsible for INH hepatic metabolism, and a risk of DILI in TB patients. In this study, the genetic and baseline clinical data from 366 Japanese patients with TB (73 patients with DILI and 293 without DILI) were used to develop a system to predict DILI risk due to anti-TB agents. The distribution of the NAT2 acetylator status among the TB patients with DILI was 31 (42.5%), 29 (39.7%), and 13 (17.8%) for rapid, intermediate, and slow acetylators, respectively. A significant association was observed between NAT2 slow acetylators and DILI risk (odds ratio 4.32, 95% confidence interval 1.93–9.66, P value=5.56×10−4). A logistic regression model based on age and NAT2 genotype revealed that the area under the curve for the receiver-operating characteristic curve was 0.717. The findings demonstrated that slow NAT2 acetylator status is a significant predictor of the risk of DILI by anti-TB agents, and a personalized anti-TB treatment approach may aid in making treatment decisions and reducing the incidence of DILI.