Symptoms Of Adverse Drug Reactions Research Articles

Patients' Identification, Management and Prevention of Adverse Drug Reactions: A Cross-Sectional Survey of Patients with Severe Adverse Drug Reactions.

Background: Few studies have been conducted on how patients identify, manage, and prevent severe adverse drug reactions (ADRs). This study aimed to explore the reasoning that patients use to identify symptoms of severe ADRs and the methods they employ to manage and prevent them. Methods: A cross-sectional survey using structured telephone interviews was administered to patients with a self-assessed severe ADR and to patients with serious skin ADRs from a hospital medical record database (in-patient and out-patient) from 1 September 2016 to 1 September 2019. Patients identified via the medical records were asked to assess their ADR for severity, and only patients that rated their ADR as severe were followed up with a telephone interview. Structured telephone interviews were conducted with respondents by a research pharmacist and audio-recorded. Results: A total of 722 patients with a severe ADR were identified, with 300 completing the interview (41.6%). The most frequently cited reasons for classifying ADRs as severe was worsening ADR symptoms (58.3%), severe ADR symptoms (44.4%), and ADR symptoms interfering with their life (36.4%). Only severe ADR symptoms were significantly different between the questionnaire and the medical records database groups (p = 0.007). The most frequent method of ADR management was discontinuation of drug by physicians (88.3%). About 79.0% of patients stated that they increased their carefulness when using other drugs after experiencing ADRs. The main method patients used to prevent ADRs was informing healthcare professionals (HCPs) about their drug allergy history (65.7%). Conclusions: Worsening ADR symptoms were often used to identify severe ADRs. However, HCPs were mainly responsible for the management and prevention of severe ADRs. Increasing awareness of ADRs by HCPs, and providing additional drug information, may improve patient safety.

Spontaneously reported adverse drug reaction pattern in a tertiary care teaching hospital: A cross-sectional study

Background: Adverse drug reactions (ADRs) are unintended and harmful reactions to medications that occur at doses normally used for therapeutic purposes. The reporting of ADRs is essential for the identification and prevention of ADRs. Aims and Objectives: The aim of the study was to estimate the frequency and distribution of spontaneously reported ADRs in the tertiary care teaching hospital. Materials and Methods: A retrospective cross-sectional study was conducted from July 2020 to June 2023, from spontaneously reported ADRs by the ADR Monitoring Centre, MGM Medical College, Kishanganj, Bihar. Distribution of age, gender, department, medication groups, and systems involved were examined. Utilizing certain scales, causality, severity, and preventability were evaluated. Results: Total 47 ADRs were reported during the study period. The most common ADRs were cutaneous ADRs (n = 19,40.43%) followed by the central nervous system (CNS) (n = 12, 25.53%), gastrointestinal system (GI) (n = 9, 19.15%), musculoskeletal (n = 4, 8.51%) and others. The most commonly implicated drugs were Antibiotics (21.28%) followed by analgesics (12.77%), DMARD (12.77%), antihypertensive (12.77%), and others shown in the study. The severity assessment of ADRs was done by Modified Hartwig et al. severity assessment scale and was found mild (87%), followed by moderate (8.5%) and severe (4.3%). Using the modified Schumock and Thronton preventability scale preventability assessment of ADRs was done and was found 51.06% of ADRs were definitely preventable, 38.30% were probably preventable and 12.77% of ADRs were not preventable. Conclusion: The findings of this study emphasize the significance of pharmacovigilance and the requirement that medical personnel be knowledgeable about the indications and symptoms of ADRs.

Comparing patient reported and medical record data of adverse drug reactions to anti-seizure drugs.

Anti-seizure drugs (ASDs) can potentially cause serious adverse drug reactions (ADRs). Patient self-reporting can increase the rate of ADR detection, but studies examining patient self-reporting of ADRs caused by ASDs are lacking. To determine the characteristics of ADRs reported by patients receiving ASDs, assess laboratory data and medical record confirmation of patient-reported ADRs, and explore factors associated with laboratory data and medical record confirmation. A self-reporting questionnaire was distributed to patients prescribed ASDs at outpatient clinics. Patients assessed the causality of suspected ADRs using Causality Assessment Tool. Naranjo's algorithm was used by researchers for causality assessment. Medical records were used to gather information on ADR symptoms, ASD medication, and abnormal laboratory data. From 478 distributed questionnaires, 93.1% completed the questionnaire and 67.4% of respondents reported at least one ADR. The most common ADRs were drowsiness (50.7%), dizziness (9.7%), and ataxia (4.3%). For causality, suspected ADRs were classified as possible in 52.3% of cases and probable in 46.3% of cases by patients, and possible in 64.7% of cases and probable in 25.7% of cases by researchers. Only 12.7% of patients had laboratory data and/or medical record confirmation of suspected ADRs. The psychiatry clinic was less likely to confirm suspected ADRs compared to the epilepsy clinic (OR = 0.412, p = 0.022). Confirmation of patient-reported ADRs with either laboratory data or medical records was uncommon. Recording patient-reported ADRs in patients' medical history and monitoring laboratory tests related to patient-reported symptoms should be promoted to increase the safety of ASD treatment.

Adverse drug reactions due to linezolid in the programmatic management of drug-resistant tuberculosis in India: A retrospective multicenter study

BackgroundMonitoring and managing adverse drug reactions (ADR) are critical for treating drug-resistant tuberculosis (TB). ObjectiveTo study symptomatic, linezolid-attributable ADRs in TB patients initiated on all oral longer bedaquiline-based treatment regime for multidrug-resistant/rifampicin-resistant (MDR/RR)-TB under programmatic conditions. MethodsIt was a multicenter, retrospective study of people with MDR/RR-TB in nine TB units in Nagpur, India, from March 2020 to April 2022. ResultsThe study consisted of a sample size of 106 individuals with multidrug-resistant and rifampicin-resistant tuberculosis out of a total of 110 individuals with the disease. Of these, 45 (42.45%) experienced linezolid ADRs, with an incidence of 11.37 cases per 1000 person-weeks. These patients were significantly younger (31.24 ± 11.13 years) and more likely to be female (27, 50%) than those without ADRs. ADR severity was mild in 20 (44.45%), moderate in 15 (33.33%), and severe in 10 (22.22%) patients. The most common ADR was peripheral neuropathy (42, 93.33%), followed by lactic acidosis (3, 6.67%), anemia (2, 4.44%), and optic neuritis (2, 4.44%). Dosing was reduced in 17 (37.78%) patients, and linezolid was withdrawn entirely in 19 (42.22%) patients. Only 9 (20%) patients continued linezolid unmodified. For mild to moderate linezolid-associated symptomatic peripheral neuropathy, symptom management with or without dose reduction is an effective strategy; however, immediate linezolid withdrawal is necessary in severe or life-threatening peripheral neuropathy cases. After a mean follow-up of 41 ± 21.33 weeks, ADR symptoms resolved completely in 4 (6.67%) patients and decreased in 42 (93.33%) patients. ConclusionLinezolid ADRs, often neuropathy, frequently occur in patients on an all-oral bedaquiline-based treatment regime for MDR/RR-TB. Women and younger patients are more likely to experience these ADRs, usually mild to moderate in severity. Management of symptomatic linezolid-associated peripheral neuropathy should be based on ADR severity. These ADRs often affect linezolid dosing, so it is important to identify and manage them early.

The effect of clinical pharmacists’ intervention in adverse drug reaction reporting: a retrospective analysis with a 9-year interrupted time series

BackgroundIn China, 85.4% of adverse drug reactions (ADRs) are spontaneously reported by healthcare facilities. As a result, many ADRs are not reported due to lack of mandatory reporting requirements. As healthcare professionals, clinical pharmacists (CPhs) serve as a bridge between clinical work and medication and ensure rational drug use. In China, A team of CPhs implemented an intervention for ADRs reporting, with the goal of improving the number of ADRs reports, the number of unreported ADRs, and the standardized reporting rate.MethodsOn June 01, 2015, a team of CPhs implemented an intervention for ADRs reporting at a Grade A, Class 3 hospital in China. The drug review catalogue (DRC) was used to screen physician orders for having visible symptoms of ADRs across departments, pooled the ADRs, and submitted them to the Center for Advanced Drug Monitoring (CNCAM). We retrospectively analysed the effect of a CPhs ADRs reporting intervention on the number of clinical ADRs reports, the number of unreported ADRs, and the standardized reporting rate over a 9-year period by interrupted time series (ITS). The method was implemented at the hospital on June 1, 2015, and a segmented regression model was used to analyse the data from January 1, 2010, to December 31, 2019.ResultsAfter the CPhs ADRs reporting intervention, the number of inpatient ADRs reports submitted to the CNCAM immediately increased by approximately 63 (62.658, P < 0.01) and then decreased by approximately 1 (0.701, P = 0.000151 < 0.01) per month afterward; the number of unreported ADRs was immediately reduced by approximately 44 (44.091, P < 0.01) and remained largely unchanged over time (P > 0.05); the standardized ADRs reporting rate per month immediately increased by 63.634% (P < 0.01) and remained largely unchanged over time (P > 0.05).ConclusionThe CPhs ADRs reporting intervention had an immediate effect on improving ADRs reporting, which highlights the severity of ADRs underreporting in Chinese hospitals. The method is practical and should be used more widely in clinical practice. For example, the method can adjust and establish a DRC catalog that meets the actual situation of the implementing hospital based on the hospital's drug use habits and has the characteristics of good adaptability. However, it does have some limitations; for example, it may be difficult to detect early ADRs without visible symptoms.

Explainable detection of adverse drug reaction with imbalanced data distribution.

Analysis of health-related texts can be used to detect adverse drug reactions (ADR). The greatest challenge for ADR detection lies in imbalanced data distributions where words related to ADR symptoms are often minority classes. As a result, trained models tend to converge to a point that strongly biases towards the majority class and then ignores the minority class. Since the most used cross-entropy criteria is an approximation to accuracy, the model focuses more readily on the majority class to achieve high accuracy. To address this issue, existing methods apply either oversampling or down-sampling strategies to balance the data distribution and exploit the most difficult samples of the minority class. However, increasing or reducing the number of individual tokens alone in sequence labeling tasks will result in the loss of the syntactic relations of the sentence. This paper proposes a weighted variant of conditional random field (CRF) for data-imbalanced sequence labeling tasks. Such a weighting strategy can alleviate data distribution imbalances between majority and minority classes. Instead of using softmax in the output layer, the CRF can capture the relationship of labels between tokens. The locally interpretable model-agnostic explanations (LIME) algorithm was applied to investigate performance differences between models with and without the weighted loss function. Experimental results on two different ADR tasks show that the proposed model outperforms previously proposed sequence labeling methods.

Evaluating Drug Risk Using GAN and SMOTE Based on CFDA's Spontaneous Reporting Data.

Adverse drug reactions (ADRs) pose health threats to humans. Therefore, the risk re-evaluation of post-marketing drugs has become an important part of the pharmacovigilance work of various countries. In China, drugs are mainly divided into three categories, from high-risk to low-risk drugs, namely, prescription drugs (Rx), over-the-counter drugs A (OTC-A), and over-the-counter drugs B (OTC-B). Until now, there has been a lack of automated evaluation methods for the three status switch of drugs. Based on China Food and Drug Administration's (CFDA) spontaneous reporting database (CSRD), we proposed a classification model to predict risk level of drugs by using feature enhancement based on Generative Adversarial Networks (GAN) and Synthetic Minority Over-Sampling Technique (SMOTE). A total of 985,960 spontaneous reports from 2011 to 2018 were selected from CSRD in Jiangsu Province as experimental data. After data preprocessing, a class-imbalance data set was obtained, which contained 887 Rx (accounting for 84.72%), 113 OTC-A (10.79%), and 47 OTC-B (4.49%). Taking drugs as the samples, ADRs as the features, and signal detection results obtained by proportional reporting ratio (PRR) method as the feature values, we constructed the original data matrix, where the last column represents the category label of each drug. Our proposed model expands the ADR data from both the sample space and the feature space. In terms of feature space, we use feature selection (FS) to screen ADR symptoms with higher importance scores. Then, we use GAN to generate artificial data, which are added to the feature space to achieve feature enhancement. In terms of sample space, we use SMOTE technology to expand the minority samples to balance three categories of drugs and minimize the classification deviation caused by the gap in the sample size. Finally, we use random forest (RF) algorithm to classify the feature-enhanced and balanced data set. The experimental results show that the accuracy of the proposed classification model reaches 98%. Our proposed model can well evaluate drug risk levels and provide automated methods for status switch of post-marketing drugs.

Symptom experience of adverse drug reaction among male and female patients with newly diagnosed pulmonary tuberculosis in Thailand.

Patients with newly diagnosed pulmonary tuberculosis often suffer from adverse drug reaction symptoms, which leads to the automatic discontinuation of anti-tuberculosis drugs. Thus, understanding symptom experience of adverse drug reactions is necessary. This study aimed to examine differences in symptoms experienced in four dimensions: presence, frequency, severity, and distress of adverse drug reactions, between male and female patients. This was a quantitative survey with a cross-sectional design, with data collected between January and April 2020. A total of 394 patients with newly diagnosed pulmonary tuberculosis was selected through a purposive sampling technique. The symptom experiences of adverse drug reactions were measured using a validated instrument. Data were analyzed using mean, standard deviation, and independent t-test. The most commonly reported symptom was itchiness (24.1% in males and 34.9% in females). Vomiting occurred as the most frequent symptom among males (x̄ ± SD = 2.73 ± .88), and fatigue was found to be the most severe and distressing symptom across male patients (x̄ ± SD = 2.50 ± 1.61 and 2.06 ± 1.30, respectively). In contrast, yellowing of the eyes and skin was most frequent and severe among females (x̄ ± SD = 3.17 ± .75 and 3.83 ± 1.47, respectively). In addition, flu-like symptoms were evaluated as the most distressing symptom for female patients (x̄ ± SD = 2.80 ± 1.09). The symptom burdens of the females ranged significantly and reached higher than those of the male patients at a p-value of .05 (t = 3.33). Females taking anti-tuberculosis drugs should be carefully monitored to deal with adverse drug reaction symptoms. This finding would help to decrease the severity of disease and improve their quality of life.

CYP2D6 in the Brain: Potential Impact on Adverse Drug Reactions in the Central Nervous System-Results From the ADRED Study.

Cytochrome P450 (CYP) 2D6 is a polymorphic enzyme expressed in the central nervous system (CNS), important in drug metabolism and with a potentially constitutive role in CNS function such as vigilance. This study aimed to analyze variability in CYP2D6 activity linked to vigilance-related adverse drug reactions (ADRs) in the CNS. A dataset of N = 2939 ADR cases of the prospective multicenter observational trial in emergency departments (EDs) (ADRED; trial registration: DRKS-ID: DRKS00008979) was analyzed. Dizziness as the most frequent reported CNS ADR symptom (12.7% of patients, n = 372) related to vigilance was chosen as the outcome. The association of dizziness with CYP2D6 activity markers was analyzed. The number of CYP2D6 substrates taken, a CYP2D6 saturation score (no, moderate, and strong saturation), a CYP2D6 saturation/inhibition score (no, weak, moderate, and strong), and composed CYP2D6 activity using a genotyped subsample (n = 740) calculating additive effects of genotype and CYP2D6 saturation by drug exposure were used as CYP2D6 activity markers. Effects were compared to other frequent nonvigilance-related CNS ADR symptoms (syncope and headache). Secondary analyses were conducted to control for other ADR symptoms frequently associated with dizziness (syncope, nausea, and falls). The majority of all patients (64.5%, n = 1895) took at least one drug metabolized by CYP2D6. Around a third took a CNS drug (32.5%, n = 955). The chance to present with drug-related dizziness to the ED increased with each CYP2D6 substrate taken by OR 1.11 [1.01–1.23]. Presenting with drug-related dizziness was more likely with CYP2D6 saturation and saturation/inhibition (both OR 1.27 [1.00–1.60]). The composed CYP2D6 activity was positively associated with dizziness (p = 0.028), while poorer activity affected patients more often with dizziness as an ADR. In contrast, nonvigilance-related ADR symptoms such as syncope and nausea were not consistently significantly associated with CYP2D6 activity markers. This study shows an association between the number of CYP2D6 substrates, the predicted CYP2D6 activity, and the occurrence of dizziness as a CNS ADR symptom. As dizziness is a vigilance-related CNS symptom, patients with low CYP2D6 activity might be more vulnerable to drug-related dizziness. This study underlines the need for understanding individual drug metabolism activity and individual risks for ADRs.

Assessing the prevalence and effect of adverse drug reactions among patients receiving first line anti-tubercular medicines in the Tamale Teaching Hospital, Ghana.

Introductiontuberculosis (TB) remains a global major health problem, especially in developing countries. Although treatment regimen for TB has been highly effective, treatment-related adverse effects account for significant morbidity leading to reduced effectiveness of therapy and high default rate. This study evaluated the nature and occurrence of Adverse Drug Reactions (ADRs) in patients receiving first line antitubercular therapy (ATT) in Tamale Teaching Hospital (TTH) and its effects on adherence.Methodsthe study was a cross-sectional study for a period of six months. A total of 66 participants who were on first line antituberculotic therapy consented for the study. Data was collected using a questionnaire and analysed using SPSS version 22.0.Resultsabout 77% (n=51) of the participants had experienced ADRs. Gastrointestinal symptoms were the most commonly reported symptoms of ADR (80%, n=41). Regarding adherence, over half (51.0%, n=26) said the occurrence of the Adverse Drug Reaction had affected the manner in which they take their medications. Of these, 84.6% (n=22) of the participants indicated that they skipped/missed their medications and 15.4% stopped the medication entirely. About 39.2% (n=20) reported ADRs to a healthcare practitioner and 60.8% did not. All the reported cases were managed by a health practitioner using another medication.Conclusionthe study showed that ADRs are common among patients receiving first line ATT. Gastrointestinal tract (GIT) related ADRs were the most common. Adherence to first line antitubercular therapy is poor as a result of adverse drugs reaction.

Adverse Drug Reactions in the Emergency Department: Is There a Role for Pharmacogenomic Profiles at Risk?-Results from the ADRED Study.

Individual differences in required drug dosages exist based on the pharmacogenomic (PGx) profiles. This study aimed to assess associations between PGx profiles and adverse drug reactions (ADR) that lead to admissions to the emergency department (ED). ADR cases of the prospective multi-center observational trial in EDs (ADRED study) were analyzed (n = 776) together with the relevant PGx phenotypes of the enzymes CYP2D6, CYP2C19, CYP2C9, and VKORC1. Overall, the allele frequency distribution in this cohort did not differ from the population frequencies. We compared the frequencies of phenotypes in the subgroups with the drugs suspected of certain ADR, in the remaining cases. The frequency distribution of CYP2C19 differed for the ADR bleeding cases suspected of clopidogrel (p = 0.020). In a logistic regression analysis, higher CYP2C19 activity (OR (95% CI): 4.97 (1.73−14.27)), together with age (1.05 (1.02−1.08)), showed an impact on the clopidogrel-suspecting ADRs, when adjusting for the clinical parameters. There was a trend for an association of phenprocoumon-risk profiles (low VKORC1 or CYP2C9 activity) with phenprocoumon-suspecting ADRs (p = 0.052). The PGx impact on serious ADRs might be highest in drugs that cannot be easily monitored or those that do not provoke mild ADR symptoms very quickly. Therefore, patients that require the intake of those drugs with PGx variability such as clopidogrel, might benefit from PGx testing.

The phenotype of adverse drug effects: Do emergency visits due to adverse drug reactions look different in older people? Results from the ADRED study.

AimsOlder patients in particular suffer from adverse drug reactions (ADR) when presenting in the emergency department. We aimed to characterise the phenotype of those ADRs, to be able to recognise an ADR in older patients.MethodsCases of ADRs in emergency departments collected within the multicentre prospective observational study (ADRED) were analysed (n = 2215). We analysed ADR‐associated diagnoses, symptoms and their risk profiles. We present frequencies and odds ratios (OR) with 95% confidence intervals for adults (18–64 years) compared to older adults (≥65 years; young–old 65–79, old–old ≥80 years) and regression coefficients (B) for each year of age.ResultsMost prominent differences were seen for drug‐associated confusion, dehydration, and bradycardia (OR 6.70 [1.59–28.27], B .054; OR 6.02 [2.41–15.03], B .081, and 4.82 [2.21–10.54], B .040), more likely seen in older adults. Bleedings were reported in all age groups, but gastrointestinal bleedings occurred with more than doubled chance in older adults (OR 2.46 [1.77–3.41], B .030), likewise did other bleedings such as haemorrhage from respiratory passages (OR 2.89 [1.37–6.11], B.036). Falls were more likely in older adults (OR 2.84 [1.77–4.53], B .030), while dizziness was frequent in both age groups.ConclusionOur data point to differences in symptoms of ADRs between adults and older individuals, with dangerous drug‐associated phenomena in the older adult such as bleedings or falls. Physicians should consider drug‐associated origins of symptoms in older adults with an increased risk for serious health problems.

Risk factors for adverse drug reactions in older inpatients of geriatric wards at admission: Multicenter study.

To investigate the characteristics of adverse drug reactions (ADR) and their risk factors among very old patients in five geriatric wards in Japan. A retrospective observational multicenter study was carried out to investigate factors related to ADR in older inpatients from geriatric wards of five university hospitals in Japan. Data including drugs profile and short-form comprehensive geriatric assessment were obtained from medical charts. ADR were identified from geriatrician's reports. For each ADR, symptoms and causal drugs were clarified, and factors associated with ADR were analyzed statistically. In 1155 patients (52.5% women, mean age 82.8 ± 7.0 years), the proportion with ADR was 15.4%. There was a great variety of signs and symptoms of ADR, and a great variety of drugs suspected to be the cause of ADR. On multiple logistic regression analysis, ADR was significantly associated with an increase in drugs (odds ratio 1.11, 95% CI 1.07-1.16) and emergency admission (odds ratio 2.76, 95% CI 1.82-4.15). Receiver operating characteristic curve analysis showed that the optimal cut-off number of drugs for predicting ADR was ≥7. In geriatric inpatients, polypharmacy (especially ≥7 drugs) and emergency admission were associated with ADR. Because there was a great variety of ADR in the study, clinicians must consider reviewing all drugs to prevent adverse drugs reactions during admission in this vulnerable population. Geriatr Gerontol Int 2019; ••: ••-••. Geriatr Gerontol Int 2020; 20: 144-149.

Can the lower rate of CT- or MRI-related adverse drug reactions to contrast media due to stricter limitations on patients undergoing contrast-enhanced CT or MRI?

The aim of this study was to examine whether a decreased occurrence rate of adverse drug reactions (ADRs) to contrast media in contrast-enhanced CT and MRI was attributable to appropriate criteria for patients with some diseases. A secondary aim was to elucidate safety profiles for contrast media and factors influencing the occurrence of ADRs. Clinical data of patients who underwent contrast-enhanced CT (5576 cases) or MRI (3357 cases) were retrospectively analyzed to evaluate rates of ADRs to contrast media, symptoms of ADRs, treatments for ADRs, and differences in medical history, blood test results, and other factors between patients with and without ADRs in a dental hospital. The rate of ADRs to contrast media was 0.54% for CT and 0.09% for MRI. The most frequent ADRs in contrast-enhanced CT or MRI were nausea and vomiting as physiologic reactions. Two serious reactions were seen for CT, but none for MRI. Significant differences between patients with and without ADRs were seen in liver function according to blood tests for CT, and in digestive disorders elicited from medical interviews for MRI. The lower occurrence rate of ADRs to contrast media in dental hospitals could be due to the adoption of appropriate criteria for patients with some diseases undergoing enhanced CT or MRI. Complete suppression of ADRs to contrast media for CT or MRI is unrealistic, so attention is warranted for patients with decreased liver function when performing enhanced CT, and for patients with digestive disorders when performing enhanced MRI.

Named entity recognition from Chinese adverse drug event reports with lexical feature based BiLSTM-CRF and tri-training.

The Adverse Drug Event Reports (ADERs) from the spontaneous reporting system are important data sources for studying Adverse Drug Reactions (ADRs) as well as post-marketing pharmacovigilance. Apart from the conventional ADR information contained in the structured section of ADERs, more detailed information such as pre- and post- ADR symptoms, multi-drug usages and ADR-relief treatments are described in the free-text section, which can be mined through Natural Language Processing (NLP) tools. The goal of this study was to extract ADR-related entities from free-text section of Chinese ADERs, which can act as supplements for the information contained in structured section, so as to further assist in ADR evaluation. Three models of Conditional Random Field (CRF), Bidirectional Long Short-Term Memory-CRF (BiLSTM-CRF) and Lexical Feature based BiLSTM-CRF (LF-BiLSTM-CRF) were constructed to conduct Named Entity Recognition (NER) tasks in free-text section of Chinese ADERs. A semi-supervised learning method of tri-training was applied on the basis of the three established models to give un-annotated raw data with reliable tags. Among the three basic models, the LF-BiLSTM-CRF achieved the highest average F1 score of 94.35%. After the process of tri-training, almost half of the un-annotated cases were tagged with labels, and the performances of all the three models improved after iterative training. The LF-BiLSTM-CRF model that we constructed could achieve a comparatively high F1 score, and the fusion of CRF, while BiLSTM-CRF and LF-BiLSTM-CRF in tri-training might further strengthen the reliability of predicted tags. The results suggested the usefulness of our methods in developing the specialized NER tools for identifying ADR-related information from Chinese ADERs.

Phytopharmacovigilance in the Elderly: Highlights from the Brazilian Amazon.

Practices described as traditional medicine may coexist with formalized, science-based medicine. In this context, the present study aimed to verify the profile of the elderly who consumed herbal medicines concomitantly with medications and to identify suspected adverse drug reactions (ADRs) in the Brazilian Amazon (Macapá, Amapá). The study was carried out in two steps: a cross-sectional study (structured questionnaire) and a clinical study (pharmacotherapeutic follow-up). Out of 208 participants, 78.8% were female with age between 60 and 69 years (58.7%), 59.1% used herbal medicines concurrently with medications, and 40.9% did not report use of herbal medicine. Losartan was the most used medication, and Lippia alba (Mill.) N.E. Br was the most common herbal medicine used. The total prevalence of suspected ADRs, among the elderly who answered the structured questionnaire, was 41.3%, with 27.4% being in the elderly who used herbal medicines and medications, and 13.9% being in the elderly who used only medications. Meanwhile, the total prevalence of suspected ADRs was 71.0% among the elderly patients who underwent pharmacotherapeutic follow-up, 60.5% in elderly who used herbal medicines and medications, and 10.5% in elderly who used only medications. The most reported ADR symptoms were related to disorders that affect the nervous system (38.4%) in the structured questionnaire and related to digestive disorders (36.4%) in the pharmacotherapeutic follow-up. The probability associated with the occurrence of a given ADR in the face of a set of demographic, socioeconomic, and clinical variables was estimated; the results showed that, in the studied population, only sex (p = 0.030) had an influence on the occurrence of ADR. The prevalence of ADRs with probable causality was high in this study population, but it was only sex-related, although more prevalent in the elderly who consume herbal medicines.

Efficacy of the HLA-B∗58:01 Screening Test in Preventing Allopurinol-Induced Severe Cutaneous Adverse Reactions in Patients with Chronic Renal Insufficiency—A Prospective Study

Thus far, human leukocyte antigen (HLA)-B∗58:01 has been recognized as the most important risk factor for allopurinol induced severe cutaneous adverse reactions (SCARs). To determine the usefulness of prospective screening for the HLA-B∗58:01 allele to identify Korean individuals at risk for SCARs induced by allopurinol treatment. We prospectively enrolled 542 patients with chronic renal insufficiency (CRI) from 10 hospitals nationwide and performed DNA genotyping to determine whether they carried the HLA-B∗58:01 allele. Of these, 503 HLA-B∗58:01-negative patients (92.8% of total) were treated with allopurinol, and 39 HLA-B∗58:01-positive patients (7.2%) were treated with febuxostat, an alternative drug. The patients then were followed up biweekly for 90 days using a telephone survey to monitor symptoms of adverse drug reactions, including SCARs. As a control, we used the historical incidence rate of allopurinol-induced SCARs in 4002 patients with CRI from the same hospitals who were enrolled retrospectively. Nineteen patients in the prospective cohort developed mild and transient adverse reactions but none showed allopurinol-induced SCARs. By contrast, we identified 38 patients with allopurinol-induced SCARs (0.95%) in the historical control. The difference in the incidence of allopurinol-induced SCARs between the prospective cohort and historical control was statistically significant (0% vs 0.95%, respectively; P= .029). The present study demonstrated the clinical usefulness of the HLA-B∗58:01 screening test before allopurinol administration to prevent allopurinol-induced SCARs in patients with CRI.

Adverse drug reactions to integrase strand transfer inhibitors.

To describe and compare integrase strand transfer inhibitor (INSTI) adverse drug reactions (ADRs) for raltegravir, elvitegravir-cobicistat, and dolutegravir. Population-based, retrospective cohort. Antiretroviral-experienced and naive persons at least 19 years old were included if they received their first prescription for raltegravir, elvitegravir-cobicistat, or dolutegravir in British Columbia, Canada, in 2012-2014, and were followed for 2 years until 31 December 2016. The primary outcome was an ADR resulting in INSTI discontinuation. ADR rates and 95% confidence intervals (95% CIs) were calculated by Poisson method. Cox proportional-hazards regression estimated the hazard ratio for ADR-related INSTI discontinuation, adjusted for confounders. ADR symptoms were compared across INSTIs. There were 1344 persons contributing 1464 person-INSTI exposures. The cohort was predominantly male (79%) and antiretroviral therapy-experienced (85%). ADR events and unadjusted ADR rates (95% CI) per 100 person-years were raltegravir 24 of 551 (4.4%), 2.91 (1.95, 4.35); elvitegravir-cobicistat 38 of 394 (9.6%), 5.94 (4.32, 8.16); and dolutegravir 27 of 519 (5.2%), 2.96 (2.03, 4.31). The ADR rate for elvitegravir-cobicistat was double that of dolutegravir (adjusted hazard ratio 2.24, 95% CI 1.13, 4.44), but not significantly different for either dolutegravir or elvitegravir versus raltegravir. Elvitegravir-cobicistat-treated persons had a significantly higher proportion of gastrointestinal and general (fatigue, malaise) ADRs. Neuropsychiatric ADRs were more frequent with dolutegravir, but not significantly different between INSTIs. Among those switching between INSTIs, there was no apparent relationship between experiencing an ADR to one INSTI and subsequent intolerance to another. This study affirms INSTIs are well tolerated during routine clinical use. Consideration of differences in side effect profiles can inform antiretroviral therapy individualization.

Physicians’ and pharmacists’ information provision and patients’ psychological distress

ABSTRACTProviding information related to medication has many benefits for patients. However, patients’ conflicting perceptions about medical information provided by physicians and pharmacists may be associated with their psychological distress regarding treatment and medication. This study investigated associations between patients’ perceptions of agreement between physicians and pharmacists about medical information and improvements in their psychological distress. It also clarified the specific relationships of their perceptions with psychological distress. A cross-sectional survey was conducted in Japanese community pharmacy settings. Pharmacists approached 1,500 patients visiting community pharmacies and provided them with questionnaire packages. Patients completed the questionnaires at home and returned them to the researchers by mail. Multivariate logistic regression analysis and signal detection analysis were conducted to examine associations of patients’ perceptions of information agreement with improvement in psychological distress. Measures of improvement in worry and anxiety about disease, improvement in worry and anxiety about medication, and improvement in depressive mood were used to assess alleviation of psychological distress. A total of 645 patients returned the questionnaires; 628 contributed to the data. Multivariate logistic regression analyses clarified that patients’ perceptions of agreement in information regarding need for medication, methods for adverse drug reaction reduction, adverse drug reaction symptoms, coping with forgetting to take medication, and advice for daily life were significantly associated with improvements in psychological distress. Furthermore, signal detection analysis showed that several combinations of patients’ perceptions of agreement between physicians and pharmacists about specific medical information were also significantly associated with improvement in psychological distress. Consistent information provision by physicians and pharmacists could contribute to decreased psychological distress in patients, and consequently to adherence to treatment and taking medication.

Protocol of intensive hospital monitoring with long follow up and large sample: Diemailing Kudiezi injection as example

This is a protocol of intensive hospital monitoring with long follow up and large sample of Diemailing Kudiezi injection, which aims to identify adverse drug reactions(ADRs) of Diemailing Kudiezi injection, including known incidence of adverse reactions, the incidence of new adverse reactions, the incidence of various ADR symptoms and the incidence of ADR among the sub populations; clarify the clinical features of ADRs of Diemailing Kudiezi injection; explore risk factors for ADRs; and analyze their usage in real world. After all, no existing experience about active surveillance on safety issues for postmarkeing traditional Chinese medicine injections could be used for us to learn. On the basis of references to related domestic policies and regulations as well as the design points for observational studies, we extensively solicited opinions from experts in the industry to develop this implementation protocol on monitoring research.