Proportion Of Adverse Drug Reactions Research Articles

DNA methylation inhibitors adverse reaction characteristic analysis: a descriptive analysis from WHO-VigiAccess

IntroductionDNA methylation inhibitors (azacitidine, decitabine) have revolutionized the treatment dilemma of myelodysplastic syndromes (MDS), a group of malignant hematopoietic disorders. This study evaluates the adverse drug reactions (ADRs) following the use of DNA methylation inhibitors in the World Health Organization (WHO) VigiAccess database and compares the characteristics of ADRs between the two drugs to select the drug with the minimum individualized risk for patients.MethodsThis study employed a retrospective descriptive analysis method. We compiled ADR reports for two marketed DNA methylation inhibitors for the treatment of MDS from WHO-VigiAccess. Data collected included demographic data such as age groups, gender, and regions of global patients covered by ADR reports, as well as data on the disease systems and symptoms caused by ADRs recorded in the annual reports and reports received by WHO. By calculating the proportion of ADRs reported for each drug, we compared the similarities and differences in ADRs between the two drugs.ResultsOverall, 23,763 adverse events (AEs) related to the two DNA methylation inhibitors were reported in VigiAccess. The results showed that the top 10 most common AEs were febrile neutropenia, bone marrow suppression, neutropenia, anemia, pancytopenia, leukopenia, thrombocytopenia, bone marrow failure, agranulocytosis, and hematotoxicity. The top five common types of DNA methylation inhibitor AEs were blood and lymphatic system disorders (11,178 cases, 47.0%), cardiac organ diseases (1,488 cases, 6.3%), various congenital familial genetic diseases (49 cases, 0.2%), ear and labyrinth diseases (100, 4.2%), and endocrine system diseases (57, 2.4%).ConclusionThere is no Strong correlation between DNA methylation inhibitors and ADRs. Current comparative observational studies of these inhibitors show that there are common and specific adverse reactions in the ADR reports received by WHO for these drugs. Clinicians should improve the rational use of these drugs based on the characteristics of ADRs.

Exploring the Link Between Exogenous Thyroid Hormones and Dementia Symptoms: A Real-World Disproportionality Analysis of FDA Adverse Event Reporting System.

A growing body of evidence indicates a strong association between exogenous thyroid hormone (ETH) and brain health. Establishing the potential relationship between ETH therapy and dementia symptoms is crucial for patients with thyroid disorders. In this study, we investigate the potential association between ETH therapy and dementia symptoms by exploring the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Disproportionality analysis (DPA) was conducted using postmarketing data from the FAERS repository (Q1 2004 to Q4 2023). Cases of dementia symptoms associated with ETH therapy were identified and analyzed through DPA using reporting odds ratios and information component methods. Dose and time-to-onset analyses were performed to assess the association between ETH therapy and dementia symptoms. A total of 9889 cases of ETH-associated symptoms were identified in the FAERS database. Dementia accounted for a consistent proportion of adverse drug reactions each year (3.4%-6.3%). The DPA indicated an association between ETH therapy and dementia symptoms, which remained significant even across sex, age, and indications. The median time-to-onset of dementia symptoms was 7.5 days, and the median treatment time was 40.5 days. No significant dose-response relationship was observed. This study provides evidence for a link between ETH therapy and dementia. Clinicians are therefore advised to exercise vigilance, conduct comprehensive monitoring, and consider individualized dosing to mitigate potential reactions to ETH drug administration.

Prevalence of urgent hospitalizations caused by adverse drug reactions: a cross-sectional study

Adverse drug reactions account for a substantial portion of emergency hospital admissions. However, in the last decade, few studies have been conducted to determine the prevalence of hospitalization due to adverse drug reactions. Therefore, this cross-sectional study was conducted to determine the proportion of adverse drug reactions leading to emergency hospital admission and to evaluate the risk factors for these reactions. A total of 5707 consecutive patients aged > 18 years who were emergently hospitalized due to acute medical illnesses between June 2018 and May 2021 were included. Causality assessment for adverse drug reactions was performed by using the World Health Organization-Uppsala Monitoring Centre criteria. The median patient age was 78 years (IQR 63–87), and the proportion of women was 47.9%. Among all the hospitalizations, 287 (5.0%; 95% confidence interval (CI) 4.5–5.6%) were caused by 368 adverse drug reactions. The risk factors independently associated with hospitalization due to adverse drug reactions were polypharmacy (OR 2.66), age ≥ 65 years (OR 2.00), and ambulance use (OR 1.41). Given that the population is rapidly aging worldwide, further efforts are needed to minimize hospitalizations caused by adverse drug reactions.

Pearls for practice from the 2022 joint task force drug allergy practice parameter.

To review updated recommendations in the 2022 Drug Allergy Practice Parameters for the evaluation and management of drug hypersensitivity reactions. Adverse drug reactions have become increasingly prominent with the advent of new and emerging pharmacologic therapies. Hypersensitivity reactions encompass a significant proportion of adverse drug reactions and negatively impact both the individual patient and overall health system. Reactions are heterogeneous in presentation and may be immediate (onset of symptoms ≤6 h) or delayed (onset of symptoms >6 h to months) after drug exposure. The 2022 Drug Allergy Practice Parameter provides consensus-based statements for evaluation of hypersensitivity reactions to antibiotics, NSAIDs, cancer chemotherapies, immune checkpoint inhibitors, biologics, and excipients. In general, the guideline highlights the importance of patient history in elucidating the phenotype and severity of the index reaction. Drug challenge remains the gold standard for diagnosis and is increasingly favored over skin testing in patients with nonsevere, nonanaphylactic drug reaction histories. The 2022 Drug Allergy Practice Parameter provides an updated framework for physicians to reference in clinical practice when managing patients with drug hypersensitivity reactions.

Toxic reactions of non-steroidal anti-inflammatory drugs in the Russian Federation, analysis of the national database “Pharmacovigilance”

Non-steroidal anti-inflammatory drugs are widely used by patients and medical workers, both in the Russian Federation and abroad. Despite the well-established public opinion about the safety of this group of drugs, their use is associated with toxic reactions. This study analyzed the download of the national database “Pharmacovigilance” for 11 years (for the period 2010 to 2020) with the identification of the main representatives of this class of drugs that cause adverse reactions. To compare several independent samples of patients who received different groups of NSAIDs, Kruskel-Wallis ANOVA rank analysis of variations was used using Microsoft Excel 2013, STATISTICA 10.0 packages. Based on the results obtained, it can be concluded that the main proportion of adverse drug reactions (ADR) is associated with the female sex and the use of metamizole sodium. In addition, fatal AEs have been reported, most of which are associated with the use of paracetamol.

Evaluation of Adverse Drug Reactions Due to Fixed-dose Combinations at a Tertiary Care Hospital: An Observational Retrospective Study

Introduction: The mushrooming of Fixed-dose Combinations (FDCs) has been observed in the past decade in the Indian market. The majority of these FDCs are irrational and put patient safety at risk. Aim: To evaluate Adverse Drug Reactions (ADRs) due to rational as well as irrational FDCs available in India. Materials and Methods: This was an observational, retrospective study where recorded data of ADRs reported over a period of 10 years (January 2011-December 2021) at the Regional Training Centre and ADR Monitoring Centre (B.J. Medical College and Civil Hospital, Ahmedabad, Gujarat, India) was analysed. The data evaluation was carried out from May 1, 2022, to December 15, 2022. Any ADR where FDC(s) was the suspected causal drug was included in the analysis. Out of a total of 8,218 reported ADRs in the ten-year duration, 1,575 ADRs were reported to have occurred due to FDCs. The data were analysed for age, gender, System Organ Class (SOC), suspected drug, seriousness of the ADRs, causality assessment, and outcome of ADRs, and presented in terms of numbers or percentages. Results: A total of 1,575 ADRs occurred due to 1,649 FDC(s). The most common SOC class of ADRs was Gastrointestinal (GI) disorders in 359 (23%) cases, followed by skin and subcutaneous disorders in 317 (20%). The common suspected groups were Anti-Retroviral (ARV) drugs in 787 (50%) ADRs, followed by antitubercular drugs in 298 (19%). Out of a total of 1,649 FDCs as the suspected drug, 1,551 (94%) were rational, and 98 (6%) were irrational. A total of 169 (11%) serious ADRs were reported, of which seven ADRs were due to irrational FDCs (prescribed for cold and cough). Causality assessment using the World Health Organisation-Upsala Monitoring Centre (WHO UMC) classification showed a possible causal association with the suspect FDCs for 1,385 (84%) ADRs. Conclusion: FDCs contribute to a significant proportion of ADRs, which could be prevented by avoiding the use of irrational FDCs and monitoring the patients for the possible development of ADRs.

The Impact of Pharmacist-Led Medication Management Services on the Quality of Life and Adverse Drug Reaction Occurrence.

The aim of this research was to assess the impact of comprehensive medication management (CMM) services on patients’ health-related quality of life (HRQoL) and frequency of adverse drug reactions (ADRs) in older patients with cardiovascular diseases (CVDs). A prospective, pre- and post-intervention study with a one-year follow-up was conducted at the Health Care Centre Zagreb—Centre (HCZC). The Euro-Quality of Life Questionnaire 5 Dimensions 5 Levels (EQ-5D-5L) was used to measure the HRQoL at baseline (initial visit at the HCZC) and 12 months following CMM services. The ADRs collected at the initial assessment of the CMM services and throughout follow-up consultations were analyzed according to the occurrence mechanism, seriousness, expectedness and distribution of the Preferred Term according to the System Organ Class. Following the CMM intervention, 65 patients reported significant improvement in dimensions “self-care” (p = 0.011) and “usual activities” (p = 0.003), whereas no significant change was found in the “mobility” (p = 0.203), “pain/discomfort” (p = 0.173) and “anxiety/depression” (p = 0.083) dimensions and the self-rated VAS scale (p = 0.781). A total of 596 suspected ADR reports were found, the majority at patients’ initial assessment (67.3%), with a mean ± SD of 9.2 ± 16.9 per patient. The CMM services significantly reduced the rate of suspected ADRs, namely 2.7 ± 1.7 ADRs per patient at the initial assessment vs. 1.0 ± 1.5 ADRs per patient at the last consultation (p < 0.001). The obtained results indicate that CMM services may improve patients’ HRQoL. Additionally, as CMM services diminished the proportion of ADRs following 1-year patient follow-up, they may serve as a viable solution for safety management.

Incidence and risk factors of adverse drug reactions in patients with coronavirus disease 2019: A pharmacovigilance experience utilizing an ADR trigger tool

BackgroundSince the World Health Organization declared coronavirus disease (COVID-19) as a pandemic, most countries started treating their patients with various therapies. However, the data regarding their safety and effectiveness is still lacking. ObjectivesWe aimed to evaluate the adverse drug reactions (ADRs) incidence and their predisposing factors among COVID-19 patients. MethodsA retrospective observational study that was conducted at a tertiary academic hospital from March – June 2020. Patients were included if they were ≥ 18 years old, inpatient, had a reverse transcriptase-polymerase chain reaction (PCR) positive for COVID-19, and were treated with; (lopinavir-ritonavir, hydroxychloroquine, chloroquine, favipiravir, ribavirin, or interferon-ß) either as monotherapy or combination therapy for three days or longer. The data of eligible patients were retrieved from the electronic medical records. A standardized data collection form was designed to collect patient demographics, COVID-19 severity based on the Saudi Ministry of Health management protocols, antiviral therapies, duration of therapy, and length of stay (LOS). The ADRs were identified via conducting a comprehensive review using predefined triggers and were evaluated using Naranjo Score. ResultsA total of 155 patients were included of which 123 (79.4%) were males. In our sample, the incidence proportion of ADRs per patient was 72.3%. A total of 287 ADRs were identified most of them were hepatic (n = 101, 35.2%), gastrointestinal (n = 59, 20.6%), hematological (n = 47, 16%), and endocrine (n = 45, 15%). Hydroxychloroquine was the most common drug associated with ADRs (n = 155). The length of stay (10 – 20 days) was the only statistically significant with the ADR incidence (p-value = 0.008; 95 %CI 1.216:3.568). ConclusionsThe ADRs are prevalent among COVID-19 patients, which assure the importance of implementing active hospital-based pharmacovigilance systems.

Adverse drug reaction profile of daily regimen antituberculosis treatment.

The objective was to estimate the proportion of adverse drug reactions (ADRs) to daily regimen antituberculosis treatment (ATT) among the ADRs received in the ADR monitoring center (AMC) of the institution and to describe its pattern. This was a descriptive study conducted in the Department of Pharmacology of a Government Medical College in Central Kerala and the period under study was October 2017-June 2020. The data on ADR were entered into a structured pro forma and data were analyzed using SPSS for Windows Version 16.0 (SPSS Inc., Chicago, USA). Of the 643 ADRs, 98 (15.24%) were suspected to be due to the daily regimen of ATT. The most common organ system affected was hepatobiliary 46 (46.9%) namely hepatitis in 35 and asymptomatic elevated liver enzymes in 11 followed by eye with 26 reports of decreased vision. In 96 (97.95%), the suspected ADR had probable causality and in 2 (2.04%) it was possible. Seventy-seven (78.6%) ADR reports were serious as well as moderate-level 4b in severity and 57 (58.16%) were probably preventable. The mean days of onset of ADR after starting the ATT regimen were 56.40 ± 58.29 days (range 1-180). Decrease in vision with a mean duration of 125.23 ± 55.46 days had the longest latency in onset among all the ADRs. Of all the ADRs reported to AMC 15.24% were due to the daily regimen of ATT. Hepatitis was the most common ADR encountered followed by decrease in vision. The majority of the ADRs were probable in causality, serious, moderate-level 4b in severity, and probably preventable.

Adverse Drug Reactions Reporting among Health Professionals in Government Hospitals in Katsina State, Nigeria

Medicines have the potential to cause Adverse Drug Reactions (ADRs) and therefore the need for health professionals to detect and spontaneously report to the National Agency for Food and Drug Administration and Control (NAFDAC) for further actions to ensure patients and public safety. The study was conducted to ascertain the proportion and reporting procedures of ADRs reported by health professionals in the Government Hospitals in Katsina State, Nigeria. This was a cross-sectional survey of 392 health professionals randomly selected from the 19 secondary hospitals in Katsina state. Data were collected through a self-administered structured questionnaire from 18th January to 19th February 2021 with a 98.7% and 1.3% response rate. Data were analyzed using STATA software Version 15.0. Descriptive statistics were used to describe the background characteristics of respondents, and the outcome, such as the proportion of ADR reported summarized in percentages, frequencies, and charts. There was only a 28.3% ADRs reporting rate, and 25.1% of health professionals who saw an ADRs case reported it by completing the ADRs form. The level of knowledge on ADRs reporting procedures was 58.3% among respondents. The main systemic challenge with ADRs reporting was the lack of access to the reporting form for ADRs. Therefore, there is a need to improve access to the reporting form in all the hospitals. Keywords: Adverse Drug Reaction Reporting, Government Hospitals, Health Professionals, Katsina state, Nigeria, Reporting Rate.

Assessment of drug interactions and their associated factors among patients with cardiovascular diseases: a cross-sectional study from the occupied Palestinian territory

BackgroundCardiovascular diseases (CVDs) are the leading cause of death in the West Bank and worldwide. Potential drug–drug interactions (pDDIs) contribute to a significant proportion of adverse drug reactions, which have been shown to be a major cause of morbidity and mortality. Patients with CVD require more attention regarding these interactions owing to the complexity of their conditions and therapeutic regimens. The purpose of this study was to assess the prevalence and types of pDDIs, and their associated factors in patients with CVD. MethodsA cross-sectional study was conducted at two large referral hospitals for patients with CVD in the northern West Bank. Inpatients who were diagnosed with any CVD during the period of the study (from Sept 1, 2016, to Feb 28, 2017) were selected by convenience sampling. Data were collected from patients’ medical records and in a face-to-face interview with each of the patients (by use of a standardised data collection form). The sample size was calculated using the Raosoft calculator. pDDIs between medications prescribed at discharge were identified using the Lexicomp interaction checker. Data were analysed with SPSS version 16. FindingsThe study included 400 patients with CVDs. According to the Lexicomp interaction checker, 94% (375 of 400) of the patients were discharged with medications with pDDIs. Patients had an average of 3·14 (SD 1·41) diseases, and were prescribed 1–16 medications on discharge (mean 7·08, SD 2·76). The most common comorbid disease was diabetes (in 51% of patients; 205 of 400), followed by chronic kidney disease (in 14% of patients; 56 of 400). Aspirin was the most frequently prescribed medication. The most frequent pDDI was furosemide and aspirin, which were prescribed simultaneously for 37% of patients (148 of 400), followed by angiotensin-converting-enzyme inhibitor and aspirin, which were prescribed simultaneously for 33% of patients (131 of 400), and statins and proton pump inhibitors, which were prescribed simultaneously for 32% of patients (129 of 400). The number of pDDIs was associated with the number of diseases (p<0·0001), the total number of discharge medications (p<0·0001), and the length of hospital stay (p=0·0012). InterpretationThe prevalence of pDDIs is very high among discharge medications for patients with CVDs. These interactions were associated with the number of diseases, the number of medications prescribed, and the length of hospital stay. Monitoring for pDDIs should be performed regularly. To prevent the risks of pDDIs, work is required to raise awareness, and clinical pharmacists should be involved in reviewing medications at discharge. FundingNone.

Ambispective study of adverse drug reactions in multi-drug resistant tuberculosis patients in Warangal, Telangana.

Background:Multidrug-resistant tuberculosis (MDR-TB) has become a global threat concerning to a risk of high mortality with the potential to cause adverse drug reactions (ADRs) which if not managed properly may affect patient compliance, resulting in below par treatment outcome.Aim:The aim of the study was to study, assess, and report the ADRs of patients diagnosed with MDR-TB.Subjects and Methods:An ambispective, observational study was conducted among confirmed cases of MDR-TB patients without any comorbidities during the period of January 2015–December 2018 in patients of age 15 years and above.Statistical Analysis:Data were analyzed descriptively using MS-Excel sheet 2013 and Chi-square test in GraphPad Prism 8.2.1. Results were expressed as either frequency, percentage, or mean ± standard deviation. ADRs were evaluated for causality, severity, and preventability attributes.Results:In the sample size of 400 patients, 236 (ADRs) were reported among 136 patients. The proportion of ADRs was higher in males (P = 0.0001) and in the age group of 36–75 years (P = 0.0211). Most commonly encountered ADRs include nausea and vomiting (35.31%) and arthralgia (14.04%), followed by peripheral neuropathy (8.93%) and giddiness (8.93%). Overall, 53% were of possible category and 60% of moderate level severity and 85% were unpreventable ADRs.Conclusion:Our study included 13 types of ADRs, of which most commonly reported were nausea and vomiting, arthralgia, and peripheral neuropathy and least common were psychosis, nephrotoxicity, and gynecomastia with a higher incidence in males. Majority of ADRs were moderate, unpreventable ADRs and had a possible relationship with the suspected drugs.

Estimation of adverse drug reaction reporting in Iran: Correction for underreporting.

Underreporting of Adverse Drug Reactions (ADRs) reduces the sensitivity of pharmacovigilance systems. We described ADR reporting and its trend from 1999 to 2017 and estimated the ADR underreporting in the Iranian Pharmacovigilance Center. We expressed the number of ADR reporting per inhabitants and admissions and their possible trends. Finally, ADR underreporting percentages were estimated by three approaches: prospective studies, literature review, stratification of the country; and the trend of the proportion of ADR per inhabitants was corrected. The proportion of ADR reporting was 15.3 per 100 000 inhabitants (95% CI: 15.2, 15.8) and 10.0 per 100 000 admissions (95% CI: 9.8, 10.2) in 2017, and its trend was increasing with 16.3% average change per annum during 19 years. The median of estimated percentages of underreporting was 76.0% (IQR: 64.32-81.35). After the correction, the mean proportion of ADR reporting for 19 years reached from 5.87 to 10.33 per 100 000 inhabitants. The trend of ADRs reporting has been increasing over the 19 years but is still low. This study showed a considerable underreporting of ADR, and about one of four detected ADRs were reported to the pharmacovigilance center from 1999 to 2017.

Adverse drug reactions reported to a provincial public health sector pharmacovigilance programme in South Africa.

There are limited data in South Africa (SA) on adverse drug reaction (ADR) patterns and common causative medicines, outside of HIV and tuberculosis treatment programmes. In SA, Western Cape Province has a pharmacovigilance programme that collects spontaneous reports of suspected ADRs from public sector healthcare facilities. To describe reports received by the pharmacovigilance programme over a 4-year period (excluding those ascribed to medicines used to treat HIV and tuberculosis), as well as challenges faced in the implementation of such a system. Reports of suspected ADRs and deaths possibly related to ADRs received between January 2015 and December 2018 were reviewed. Causality was assessed by a pharmacist, with multidisciplinary team involvement for all deaths and complicated cases. Causality was categorised according to the World Health Organization-Uppsala Monitoring Centre system. Preventability was assessed using Schumock and Thornton criteria. Observations on preventability and challenges faced in the operation of a spontaneous reporting system were also noted. We received 5 346 reports containing 6 023 suspected ADRs. There were 5 486 ADRs confirmed after causality assessment, in 5 103 reports. Cough, angio-oedema, movement disorders and uterine bleeding disorders were the most common ADRs. Enalapril, etonogestrel, amlodipine and hydrochlorothiazide were the most commonly implicated drugs. Seven deaths were reported; 3 of these reports of deaths had confirmed ADRs, and these ADRs were assessed as contributing to the deaths. Approximately 3.8% of commonly reported ADRs were preventable. Enalapril and etonogestrel were responsible for a significant proportion of ADRs reported to this provincial programme. Future work should include quantification of preventability aspects to better inform gaps in healthcare worker knowledge that can be addressed in order to improve patient care.

Adverse drug reactions to anti-diabetic drugs are commonest in patients whose treatment do not adhere to diabetes management clinical guidelines: cross-sectional study in a tertiary care service in sub-Saharan Africa.

The study aimed to identify and describe adverse drug reactions and adherence to clinical guidelines in patients receiving treatment for type 2 diabetes mellitus (T2DM) in Cameroon. The method used was a cross-sectional study at a tertiary diabetes care service in Yaoundé, Cameroon. Adult T2DM patients attending the diabetes clinic were interviewed using a pre-structured data collection form. Adverse drug reactions (ADRs) were self-reported by the patients. Naranjo's algorithm and Hartwig and Siegel's scale were used for assessment of causality and severity of ADRs, respectively. A blinded senior endocrinologist assessed whether treatment pattern of patients was "adherent" or not to local clinical guidelines for the management of diabetes. Of a total of 350 patients enrolled into the study 61.1% were on oral hypoglycaemic agents only, 24.9% were on both oral hypoglycaemic agents and insulin, while 13.4% were on insulin alone. Metformin was used by 96.3% of the patients. Ninety patients reported 101 suspected ADRs. The proportion of ADRs among patients with poor adherence to clinical guidelines was higher than ADRs reported among adherent patients (Chi-square test = 7.3273; p= 0.007). Hypoglycaemia was more frequent ADR among non-adherent (25.7% of the suspected ADR) than adherent participants (11.6%). In the participants whose treatment pattern did not adhere to local clinical guidelines, ADRs were definite in 63.9%, probable in 16.6%, doubtful in 13.9% and possible in 5.6% of the cases. ADRs were moderate in 61.1% and severe in 19.4% of cases whose treatment pattern was non-adherent to clinical guidelines. Adverse drug reactions may be frequent in type 2 diabetes patients whose treatment pattern does not adhere to local clinical guidelines in Cameroon. Therefore, the promotion of active pharmacovigilance and the design of training activities to promote the appropriate use of medicines at hospital level in Cameroon could help to improve the management of diabetes and reduce the incidence of avoidable ADRs in the future.

A non-randomized interventional study to promote the knowledge, attitude and practices of community pharmacists towards pharmacovigilance

Pharmacovigilance promotes the safe and effective use of medicines and thereby optimizes the treatment quality. However, lack of awareness among community pharmacists towards pharmacovigilance decreases the proportion of adverse drug reactions reported and impairs the signal detection process. Hence this study was designed to assess and promote the awareness and attitude of community pharmacists towards pharmacovigilance. This educational interventional study was carried out with 102 community pharmacists across Chennai. A pre-validated three domain-containing questionnaire, 20 items was used to assess the knowledge, attitude and practice before and after the educational intervention. Knowledge, attitude and practices of community pharmacists towards pharmacovigilance was significantly increased after the educational intervention (P&lt;0.05, 95%CI). Median difference in an overall score of knowledge and practice was observed to be 4 and 4.5, respectively. Though the frequency of ADR reporting was not found to be greatly increased in our study, mass educational programs with adequate sampling intervals are needed to strengthen the signal generation process.

A prospective pharmacovigilance study in the infectious diseases unit of a tertiary care hospital.

The frequency, causality, severity, preventability and risk factors of ADRs (adverse drug reactions) in infectious disease units are not well defined in the literature. Thus, the aim of this study was to determine the characteristics of the ADRs encountered in an infectious disease unit of a tertiary teaching hospital. The patients who were admitted to the infectious disease unit of a tertiary teaching hospital longer than 24 hours between January and December of 2016 were followed prospectively. Patients were observed and questioned for any sign of ADRs. The proportion of ADRs and patient characteristics were investigated. Causality was evaluated by the Naranjo algorithm, severity was determined using the Hartwig classification, and preventability was assessed using the Schumock and Thornton scale. 210 patients were admitted to the unit during the study period, of whom 44 patients (20.9%) experienced 51 ADRs. 5.9% of ADRs were found to be serious according to the Hartwig severity classification. In addition, 88.1% of ADRs were not preventable. The most frequently detected ADR was skin and subcutaneous tissue reactions (33.3%), and systemic antimicrobials were the most common type of drugs that caused an ADR. Prolonged hospitalization (p < 0.001) and usage of an increased number of drugs (p < 0.001) were found to be significant risk factors for ADR development. Prolonged hospital stay and polypharmacy are significant risk factors that increase the incidence of ADRs in infectious disease units. The likelihood of unavoidable ADRs should arouse the attention of clinicians when prescribing antimicrobials.

Effectiveness of daily directly observed treatment, short-course regimen among patients registered for treatment at an urban primary health center in Bengaluru

Background: Tuberculosis (TB) is a major public health problem in India with high morbidity and mortality. As per the World Health Organization guidelines, the Revised National Tuberculosis Control Program introduced daily directly observed treatment, short-course (DOTS) regimen with a fixed-dose combination with weight bands. This study was undertaken to compare the effectiveness of daily DOTS regimen with intermittent regimen and to assess the proportion of adverse drug reactions in both groups. Materials and Methods: A descriptive study was conducted at a peripheral health institute under one of the TB Units in South Bengaluru. Participants registered for treatment during the third and fourth quarter of 2017 were selected using continuous sampling. Data were collected by case record analysis, structured interviews, and telephonic follow-up. Results: The study included 81 participants, with the mean age of 40 ± 16.1 years. Majority of the study participants 55 (67.9%) were male, and majority (38 [46.9%]) belonged to the upper-lower class. Forty-two (51.8%) of the study participants were on intermittent regimen, and 39 (48.1%) were on daily DOTS regimen. There was 100% sputum conversion at the end of treatment under both treatment regimens. A total of 36 (85.7%) participants under intermittent regimen and nine (23%) under daily regimen developed one or the other adverse drug reactions. The treatment success for participants under intermittent regimen was 38 (90.47%) and that for daily regimen was 35 (89.74%). However, there was no statistically significant difference between the two groups. Conclusion: Both daily and intermittent DOTS regimens are equally effective in TB treatment, but adverse drug reactions were more common with the intermittent regimen.

An Expandable Mechanopharmaceutical Device (2): Drug Induced Granulomas Maximize the Cargo Sequestering Capacity of Macrophages in the Liver.

Drug-induced liver injuries (DILI) comprise a significant proportion of adverse drug reactions leading to hospitalizations and death. One frequent DILI is granulomatous inflammation from exposure to harmful metabolites that activate inflammatory pathways of immune cells of the liver, which may act as a barrier to isolate the irritating stimulus and limit tissue damage. Paralleling the accumulation of CFZ precipitates in the liver, granulomatous inflammation was studied to gain insight into its effect on liver structure and function. A structural analog that does not precipitate within macrophages was also studied using micro-analytical approaches. Depleting macrophages was used to inhibit granuloma formation and assess its effect on drug bioaccumulation and toxicity. Granuloma-associated macrophages showed a distinct phenotype, differentiating them from non-granuloma macrophages. Granulomas were induced by insoluble CFZ cargo, but not by the more soluble analog, pointing to precipitation being a factor driving granulomatous inflammation. Granuloma-associated macrophages showed increased activation of lysosomal master-regulator transcription factor EB (TFEB). Inhibiting granuloma formation increased hepatic necrosis and systemic toxicity in CFZ-treated animals. Granuloma-associated macrophages are a specialized cell population equipped to actively sequester and stabilize cytotoxic chemotherapeutic agents. Thus, drug-induced granulomas may function as drug sequestering "organoids" -an induced, specialized sub-compartment- to limit tissue damage.

CYP2D6 genotypes in revolving door patients with bipolar disorders: A case series.

In psychiatric disorders, interindividual differences in cytochrome P450 (CYP)2D6 (CYP2D6) enzymatic activity could be responsible of adverse drug reactions (ADRs) and therapeutic failures (TFs) for CYP2D6-metabolized drugs, contributing to the periodical hospital readmissions of the revolving door (RD) condition. We investigated CYP2D6 genotypes in a controlled series of 5 consecutive RD patients with Bipolar Disorder (BD). Psychiatric patients affected by Bipolar Disorder. We defined TFs as a difference at the Brief Psychiatric Rating Scale score ΔBPRS < 25% at each 1-week of stable treatment, and ADRs as the onset of extrapyramidal symptoms and/or metabolic impairment with weight gain. At 3 months, a mean number of 2.75 ± 1.26 ADR and a mean ΔBPRS score of 16.07 ± 0.05% were observed. At 6 months of follow-up, compared to the only patient without BD (ΔBPRS < 32.10%), BD patients (n = 4) showed TFs (ΔBPRS < 25%). CYP2D6 genotyping revealed intermediate metabolizer phenotypes for BD patients and an extensive metabolizer phenotype for the patient without BD. In BD patients, the ratio of drugs maintained/discontinued for TFs or ADRs was 1.75 for non-CYP2D6 versus 0.33 for CYP2D6 interacting drugs, while the proportion of ADR:TF was 0:4 versus 6:3. Our findings may suggest that CYP2D6 clinically relevant genotypes may be involved in the unwanted outcomes observed in RD patients with BD.