Drug Risk Research Articles

Healthcare providers’ use of a concise summary to prescribe for lactating patients

BackgroundMost breastfeeding individuals take at least one prescription drug, yet limited data from lactation studies are available to inform the safety of these drugs during breastfeeding. As a result, healthcare providers (HCPs) rely on available information about safety of drugs used during pregnancy or on personal experiences to inform prescribing/counseling decisions for breastfeeding individuals. To improve risk communication regarding drugs used during lactation, the U.S. Food and Drug Administration published the Pregnancy and Lactation Labeling Rule (PLLR) in 2015, which added a narrative summary of available risk information to the lactation section of Prescribing Information (PI). Prior studies on labeling in PLLR format revealed that although HCPs found these details valuable, they regarded the narrative as too long to support decision-making during patient encounters. ObjectiveThis qualitative study's objective was to assess the utility of adding a concise summary to the Lactation subsection of PI to complement the narrative and succinctly communicate to busy HCPs a drug's risks when used during lactation. The concise summary consisted of a bolded headline, bulleted descriptions of available study findings and potential adverse reactions, and recommendations for risk mitigation. MethodsTwenty-five online focus groups were conducted with five segments of HCPs to obtain their feedback on the concise summary and discuss their prescribing/counseling decisions for four fictitious prescription drugs including one vaccine. ResultsHCPs utilized the concise summary to make initial prescribing/counseling decisions. Many also used the labeling narrative for a comprehensive benefit-risk assessment. ConclusionThe findings indicate a need to continue to improve communication about safety of drugs used during lactation, and that the concise summary may help facilitate this communication. The study also highlights the need to educate HCPs about PI limitations when clinical data are lacking and the need to encourage clinical studies to be conducted to support actionable recommendations about use of prescription drugs during lactation.

Active monitoring for adverse drug reactions of microtubule-damaging anti-neoplastic drug in a tertiary care hospital

Background: Cancer is a critical disease characterized by unhampered progress and metastasis of atypical aberrant cells. In India, cancer is a leading cause of increased mortality, and it is also the cause of 3 million deaths per year. Most of the anti-cancer medications originated from plants, and despite the promising anti-cancer effects of natural medications, researchers have encountered various adverse drug reactions (ADR) related to the drug. Aims and Objectives: The aims and objectives of the study are to analyze the ADR profile of cancer patients treated with microtubule-damaging anti-neoplastic and assess the preventability, severity, and causality of the documented ADR. Materials and Methods: All the cancer patients on treatment regimens containing taxanes undergoing treatment in the medical oncology department were included in this study. All the study participants were monitored for adverse effects, and any ADR reported by the patients that were diagnosed and documented in the case sheet form was recorded in the adverse reaction reporting form. The mean ± standard deviation was performed for continuous variables. Categorical variables were stated in numbers and percentages. Results: A total of sixty study participants with ADR to microtubule-damaging anticancer drugs were registered for the study and among them, 10% were males and 90% were females. The majority of adverse reactions developed in patients between 51 and 60 years of age with female dominance. A total of 114 adverse reactions were reported by the sixty study participants registered in this study, and nevertheless, more than one ADR was noticed in a greater number of patients. Conclusion: Early observation of ADR may help in either modifying the dose or changing the drug that produces adverse reactions so that damage to the organ system can be prevented.

Phototoxic drug reaction induced by hydroxychloroquine

Phototoxic drug reaction induced by hydroxychloroquine

Importance of cytochrome 3A4 and 2D6-mediated drug-drug interactions in oxycodone consumption among older adults hospitalized for hip fracture: a cross-sectional study.

Hip fracture is a common injury and represents a major health problem with an increasing incidence. In older adults, opioids such as oxycodone are often preferred to other analgesics such as tramadol because of a lower risk of delirium. Different parameters, such as inhibition of cytochrome P450 (CYP450) 2D6 and/or 3A4, can potentially lead to pharmacokinetic variations of oxycodone representing a risk of adverse drugs effects or lack of drug response. There is a risk of drug-drug interactions involving CYP450 in older adults due to the high prevalence of polypharmacy. This study sought to identify patient characteristics that influence oxycodone administration. A single-center observational study included 355 patients with a hip fracture hospitalized in a geriatric postoperative unit. Composite endpoint based on form, duration, and timing to intake separated patients into three groups: "no oxycodone", "low oxycodone ", and "high oxycodone ". CYP450 interactions were studied based on a composite variable defining the most involved CYP450 pathways between CYP2D6 and CYP3A4. CYP450 interactions with CYP2D6 pathway involved were associated with the risk of "high oxycodone" [odds ratio adjusted on age and the type of hip fracture (OR*) 4.52, 95% confidence interval (CI) 1.39-16.83, p = 0.02)], as well as serum albumin levels (OR* 1.09, 95% CI 1.02-1.17, p = 0.01). Cognitive impairment was negatively associated with the risk of "high oxycodone" (OR* 0.38, 95% CI 0.18-0.77, p = 0.02). This study showed an association between CYP2D6 interactions and higher oxycodone consumption indirectly reflecting the existence of uncontrolled postoperative pain.

A CASE STUDY ON MADHUMEHA W.S.R TO TYPE 2 DIABETES MELLITUS TREATED WITH CHANDRA KALA GUDIKA

The rising burden of Type 2 Diabetes which has occurred with modernization can be understood in the context of epidemiological transition. Irregular food habits, lack off exercise, stress and strains are some causative factors. Madhumeha leads to be a cause for blindness, renal failure etc., if it is not controlled. Rapid socio economic development and coca colonization have resulted in a life style transition from traditional to modern. As Madhumeha in modern science is compared with diabetes mellitus. Aims of Study-The present study was carried out with an objective to compare the efficacy of Chandra kala gudika in the management of Madhumeha w.s.r. to type 2 Diabetes Mellitus. Materials and Methods- The present study was Open Randomised clinical study, on 30 patients of either sex having symptoms of Madhumeha. These patients were subjective with Chandra kala gudika 500mg Bd. Result- Overall response was excellent improvement in 30%, marked improvement in 60% and mild improvement in 10% of patients. Conclusion- The Chandra kala gudika has a significant effect on both subjective and objective parameters. No adverse drugs effects were observed at the end of study.

Adverse reactions of herbal drug: a case report of hepatitis, oral mucositis, and lichenoid reactions

Herbal medicine products are widely used as a popular therapeutic option worldwide. However, it is unfounded to assume that they are entirely free from side effects. In this particular case report, we are discussing a 40-year-old male patient who was diagnosed with herbal drug-induced hepatitis and oral mucositis, along with lichenoid reactions secondary to drug reaction. The patient was advised to take oral steroids and moisturizing cream. Initially, the patient was admitted under the Department of ENT and was later transferred to the Department of Medicine due to severe thrombocytopenia. Necessary investigations were conducted, which revealed leukocytopenia, thrombocytopenia, and deranged LFT. Two pints of RDP were transfused to address the thrombocytopenia, and the platelet count gradually improved. Subsequently, the patient was shifted to the general ward. Repeated LFT results returned to normal, and the patient was discharged. By reporting such cases, healthcare professionals and the public become more aware of the potential risks associated with herbal drugs. This facilitates the identification of adverse effects, thereby aiding in the prevention of additional harm to patients.

KNOWLEDGE AND ATTITUDE OF SELF-MEDICATION AMONG HEALTHCARE AND NON-HEALTHCARE STUDENTS OF LAHORE, PAKISTAN

Introduction: Self-medication is regarded as the system of taking medicines without the consultation of licensed medical practitioner. Self-medication leads to irrational use of medical drugs which is hazardous for health. The prevalence of this crucial issue is rapidly increasing worldwide. The present study was aimed to access the pattern of self-medication trends in healthcare students and non-healthcare students of Lahore, Pakistan. Methods: A cross-sectional survey based observational study has been conducted to access the knowledge along with the attitude of medical and non-medical students regarding self-medication. The study settings included different universities and medical colleges of Lahore, Pakistan. A total of 301 students from medical department and other departments were included in the study. A validated self-medication assessment questionnaire was used to access the knowledge along with attitude pattern of self-medication among healthcare students as well as non-healthcare students. Results: The findings of the present study presented that medical students are more aware of the potential side effects and adverse reactions of the self-medicated drug as compared to the non-medical students. Whereas, trends of self-medication was observed to be slightly higher in healthcare students as compared to the non-healthcare students. Moreover, the frequency of antibiotic use was comparatively more frequent in medical students as compared to the non-medical graduates. Whereas, the use of painkillers without prescription was more prevalent in non-medical students as compare to the medical graduates. Conclusion: There has been a significant difference in knowledge of healthcare students and non-healthcare students of Lahore, Pakistan. Although both healthcare and non-healthcare students have high prevalence of self-medication but differences have been observed in case of drugs taken. Healthcare students practice self-medication more as compared to the non-health-care students. Peer Review History: Received: 10 November 2022; Revised: 18 December; Accepted: 5 January 2023, Available online: 15 January 2023 Academic Editor: Dr. Asia Selman Abdullah, Pharmacy institute, University of Basrah, Iraq, asia_abdullah65@yahoo.com Received file: Reviewer's Comments: Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Dr. A.A. Mgbahurike, University of Port Harcourt, Nigeria, amaka_mgbahurike@yahoo.com Prof. Hassan A.H. Al-Shamahy, Sana'a University, Yemen, shmahe@yemen.net.ye Similar Articles: ANTIMICROBIALS SELF MEDICATION AMONG PARAMEDICAL STUDENTS IN A NIGERIAN UNIVERSITY ANTIBIOTICS KNOWLEDGE AND THEIR USES AGAINST VARIOUS DISEASES AMONG THE DORMITORY STUDENTS OF A RESIDENTIAL UNIVERSITY IN BANGLADESH: A PILOT STUDY

PS-C10-2: POTENTIAL IMPACT OF THE 2017 AMERICA COLLEGE OF CARDIOLOGY/AMERICAN HEART ASSOCIATION HIGH BLOOD PRESSURE GUIDELINES ON SECONDARY PREVENTION POPULATION

Objective: The 2017 American College of Cardiology/American Heart Association (ACC/AHA) Hypertension Guidelines for adults have redefined blood pressure (BP) thresholds for diagnosis and treatment initiation as well as BP goals. We wanted to explore the potential impact of these recommendations on the prevalence of uncontrolled hypertension and target achievement in a secondary prevention population receiving anti-hypertensive treatment in line with the previous Guidelines. Design & Methods: This was a retrospective study in ambulatory patients attending a secondary cardiovascular disease prevention programme(mean age 62 ± 14, 77% male)using prospectively collected data from electronic medical records (Apollo Lx). Data analysed using JMP, version 7.1(SAS for Windows). Hypertension and target achieved were classified on the basis of previous International (BP < 140/90 mm Hg) as well as the new ACC/AHA Guidelines (BP < 130/80 mm Hg). Results were analysed using JMP Version 7.1(SAS for Windows). Results: Applying the new ACC/AHA cut-offs for BP, the proportion of patients with high normal BP decreased from 63% to 28% (p < 0.001), which translated into an increase in the prevalence of Stage I (39% vs. 15%, p < 0.0001) and Stage II hypertension (14.7% vs. 0.9%, p < 0.001). Overall, BP target was achieved in 75% of the patients using the old definition, compared with 43% with the new ACC/AHA Guidelines. Using the old definition, men were more likely to achieve target BP (78% vs. 72%, P < 0.0001) than women; however with the new cut-offs, BP target achieved was similar in men(42.8%) and women(43%). Using the old definition, some 84% of diabetics achieved BP control, decreasing to 52%with the new Guidelines. 71% of patients with renal impairment had BP targets achieved using the previous definition, compared with 41% in line with the new Guidelines. Conclusions: Compared with the previous European, British and American Guidelines, the new 2017 ACC/AHA recommendations resulted in a substantial increase in the prevalence of uncontrolled hypertension and reduction in patients achieving BP targets in our population. If taken up, these recommendations carry significant implications of increase in the number of anti-hypertensive drug prescribing, issues like polypharmacy, non-adherence and adverse drugs effects, with resultant escalation in health care costs.

Causality assessment of adverse drug reaction reported in patients treated with arthritis in a tertiary care hospital: A prospective study

Background: Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory condition, initially affecting smaller joints but slowly progressing to involve larger joints. Osteoarthritis (OA) is a degenerative disease affecting mainly large joints. Pain, stiffness, and loss of mobility are the cardinal features of OA. Treatment goals of RA are pain relief, slowing the progression of joint inflammation and prevention of joint disability or deformity, whereas those of OA are immediate relief of symptoms and improving joint function. Non-steroidal anti-inflammatory drugs (NSAIDS) and disease-modifying anti-rheumatic drugs (DMARDS) are used to treat above conditions. Long treatment is associated with development of ADR. The present study aimed to evaluate the prevalence of ADR patients treating for arthritis. Aims and Objectives: The objective of the study was as follows: (i) To assess the prevalence of use of drugs and drug classes in RA and OA; (ii) to assess the prevalence of adverse events (ADE) of prescribed drugs; and (iii) causality assessment of ADE. Materials and Methods: This study was an observational study of ADE of drug prescribed among 100 arthritis patients in a tertiary care teaching hospital, India. Patients diagnosed with RA or OA with or without comorbidities were enrolled in the study based on inclusion and exclusion criteria. Causality assessment severity was assessed from Hartwig and colleagues’ criteria and preventable ADE was defined by Schumock and Thornton’s criteria. Results: Out of 100 arthritis cases, the prevalence of OA was more than RA. OA was more commonly seen in males and RA in females. Arthritis was more prevalent in the age group of 36–65 years. NSAIDs were the first-choice drug in arthritis. Among NSAIDS, diclofenac was the commonly used drug for monotherapy in OA and methotrexate was commonly used in RA. Sixty-eight ADEs were detected in 51 patients. The prevalence of ADE was 35.7%. Thirty out of 68 ADEs (44.1%) were preventable. NSAIDS and DMARDS resulted in ADEs by 23 (29.6%) and 24 (34.8%) events, respectively. Common affected organs were cutaneous manifestations, gastrointestinal tract, and eyes which accounted for 20 (29.4%), 18 (26.5%), and 8 events (11.6%), respectively. Continuation of the suspected drug was noted in 42 ADEs (61.8%), classified as severity level 1 and 2a-b, and 43 ADEs (63.2%) were completely or partially resolved during the study period. Conclusion: ADEs are common in RA and OA patients with the prevalence of 35.7%. ADEs should be monitored properly and reported to prevent irrational use of drugs.

Prevalence of tuberculosis among HIV positive patients on anti-retroviral therapy with special emphasis on pattern of adverse events of first-line anti-tubercular drug

Background: Survival rates have been improved with concomitant use of anti-tubercular drugs in HIV subjects with tuberculosis. The use of anti-tubercular drugs combined with ART can lead to more drug interactions, non-compliance, toxicity, and adverse effects. Aim: To assess the pattern, severity, and prevalence of adverse drug reactions of first-line anti-tubercular drugs in HIV (Human Immunodeficiency Virus) positive subjects with tuberculosis. Methods: The present prospective, observational study included 391 subjects out of 19522 subjects who were diagnosed HIV Positive and scheduled for Anti-Retroviral therapy at the ART Centre. 102 subjects were enrolled as tuberculosis confirmation of HIV-TB Co-Infection disease during the study period. All the subjects were evaluated for adverse drug events including blurred vision, jaundice, neuropathy, skin infection, itching, blood urea, hepatotoxicity, tingling, numbness, pain, pancreatitis, diarrhea, skin rashes, and anemia. Results: The most prevalent side-effect noted was neuropathy reported in 26.13% (n=10) study participants followed by skin rashes reported in 21.05% (n=8) study subjects. Jaundice, vomiting, and body weakness were all reported in 15.78% (n=6) of study subjects each. Diarrhea, headache, hepatotoxicity, insomnia, mental confusion, and anorexia were all reported in 10.52% (n=4) of study participants each.

Effect of laparoscopic angle of His reconstruction in the treatment of patients with gastroesophageal reflux disease and hiatal hernia.

Effect of laparoscopic angle of His reconstruction in the treatment of patients with gastroesophageal reflux disease and hiatal hernia.

Study of Clinicodemographic Profile of Adverse Cutaneous Drug Reactions in Indian Perspective

Background: Cutaneous adverse drug reactions are an important group of disorders which pose considerable amount of diagnostic and therapeutic challenges. The incidence of CADRs is estimated to be 1–2% in the general population. Newer insights have been developing in the field of factors affecting CADRs and the need for studies in the Indian population regarding the newer trends in cutaneous adverse effects. Materials and Methods: A prospective and observational study was conducted in the Department of Pharmacology and Collaboration with Department of Dermatology in MGM Medical College and LSK Hospital. All cases of suspected CADRs in patients with systemically administered drugs were actively screen by a senior dermatologist. Causality assessment was done by a Pharmacologist using WHO UMC scale. Only those cases where the causality was certain probable/likely were recorded. Results: This sampling comprised of 77 CADRs over a period of 1 year from June 2012 to May 2013. The clinical pattern and spectrum of CADRs were studied in 77 subjects. A wide clinical spectrum of CADRs ranging fixed drug eruptions to serious Stevens Johnson syndrome (SJS) was observed. The predominant pattern of reactions observed was fixed drug eruptions FDE (35.1%) followed by acneiform eruptions (23.4%), erythema multiforme (9.1%), and phototoxic drug reactions (7.8%). The antimicrobials causing FDE were macrolides, cephalosporins, and fluoroquinolones. Among the NSAIDs causing FDE, most were due to diclofenac (70%). CADRs were seen most commonly in the 31–40 (26%) years age group followed by 11–20 (24.7%) years and 41–50 (19.5%) years with mean age 32.09 years. Only 5.2% patients were more than 60 years, oldest being 67 years. Antimicrobials were the most common drug group incriminated in 34% patients followed by NSAIDs in 29% cases and steroids in 25% cases. Among NSAIDs, maximum number of CADRs were caused by ibuprofen (40.9%) followed by diclofenac (36.4%), paracetamol (9%), aceclofenac (9%), and nimesulide (4.5%). Serious reactions were infrequent. Conclusion: Most of the reactions were mild (53%) to moderate (42%) requiring no major medical intervention. However, a larger and multi-centric study needs to be conducted across the state to obtain more information about CADRs among the state population.

A “Clear and Conspicuous” Distraction: Coping with Incongruent Audiovisual Content in Direct-to-Consumer Advertisements

Direct-to-consumer television advertisements for pharmaceutical medications must include a major statement disclosing the drug's most important risks and side effects. However, advertisers often pair incongruent positive visual imagery with risk information presented auditorily. Incongruence violates a principle of effective communication because it distracts from information processing. Across three studies, the authors consider how audiovisual incongruity biases perceptions of an advertised drug's risks and benefits. Using moment-to-moment measurement, Study 1 reveals that the rate of change in risk perceptions increases (i.e., accelerates) immediately after the flow of positive imagery is interrupted by a scene change during the major statement, but no such effect is observed for the advertisement in its entirety. Using post hoc measures, the latter two studies support these results. Studies 2 and 3 demonstrate that auditory risk disclosures may be enhanced by replacing distracting imagery with congruent, reinforcing text (Study 2) or by educating consumers about how distracting imagery is used as a distraction tactic (Study 3). Implications for advertising theory and recommendations for policy makers are discussed.

Severe Sunburn-Like Adverse Cutaneous Drug Reaction in a Patient on Treatment with Rifaximin: A Rare Case of Acute Phototoxic Drug Reaction

This paper describes an unreported case of a rifaximin-induced phototoxic reaction in an otherwise healthy 24-year-old female (skin type: V). The patient developed malaise, chills, and facial swelling with accompanying redness and itching that began within a day of initiating treatment with rifaximin (200 mg twice daily), and progressively increased over the next 3–4 days. The patient revealed that they had been lying in the sun for hours due to the chills they were experiencing. Over the next 10 days they developed an exaggerated, acute, sunburn-like phototoxic reaction, with blistering over the exposed skin. A skin biopsy showed no evidence of vasculopathy, endothelial damage, or extravasation of red blood cells. The patient was treated successfully with oral prednisolone (30 mg per day for a week), topical mometasone furoate (0.1%) cream applied twice daily, levocetirizine (5 mg per day taken orally), zinc oxide (20.0%) cream applied every 3 hours during daytime, and strict sun avoidance. The possible pathomechanism of rifaximin-induced sunburn is also discussed here.

Clinical Profile and Treatment Response in Section Tuberculous Meningitis- A Comparison between HIV Positive and HIV Negative Patients

Introduction: Tuberculous Meningitis (TBM) is a common infection in patients with Human Immunodeficiency Virus (HIV) and it shows significant differences in clinical profile, treatment response, and outcome compared to patients without HIV infection. Aim: To describe the clinical presentation, laboratory parameters, and radiological findings of TBM patients with and without HIV co-infection and to observe differences between them in treatment response, complications, and mortality. Materials and Methods: This was a prospective observational study, conducted on 80 TBM patients with (n=40) and without (n=40) HIV co-infection. Demographic, clinical, laboratory data, and various imaging findings were noted at the start of the study and at three and six months follow-up, for any changes from baseline to know the treatment response. Appropriate statistical tests were applied, and p-value less than 0.05 were considered statistically significant. Results: Mean age of HIV patients was 36.75 years and that of the non HIV patients was 29.35 years (p<0.05). Altered sensorium (90% in HIV and 72.5% in non HIV), seizures (50% in HIV and 20% in non HIV) were common in HIV patients, and weight loss (95% in non HIV and 87.5% in HIV) was common in non HIV patients. Common signs noted were nuchal rigidity (90% in HIV and 87.5% in the non HIV group), focal neurological deficit (50% in HIV and 22.5% in non HIV), and cranial nerve palsy (37.5% in HIV and 12.5% in non HIV). Anaemia was seen in 56.3% (87.5% in HIV and 25% in non HIV) and raised Erythrocyte Sedimentation Rate (ESR) was seen in 56.3% (25% in HIV and 87.5% in non HIV) patients. Tuberculoma was the most common (32.5%) Magnetic Resonance Imaging (MRI) brain finding. Adverse drugs reactions due to ATT (other causes ruled out) were seen in 22.5% of HIV patients (none in non HIV), and Antiretroviral Therapy (ART)-induced Adverse Drugs Effects (ADE) was noted in 10% of patients. Patient survival was better among non HIV (65%) compared to HIV (55%) patients. Multidrug-resistant Tuberculosis (MDR-TB) was more prevalent in HIV (7.5%) than non HIV (2.5%) cases. Conclusion: TBM involves a younger population, has a worse prognosis in HIV co-infection patients with more adverse reactions to treatment.

Mail-order pharmacy dispensing of mifepristone for medication abortion after in-person clinical assessment

Objective(s)To estimate the effectiveness, acceptability, and feasibility of medication abortion with mifepristone dispensed by a mail-order pharmacy after in-person clinical assessment. Study DesignThis is an interim analysis of an ongoing prospective cohort study conducted at five sites. Clinicians assessed patients in clinic and, if they were eligible for medication abortion and ≤ 63 days’ gestation, electronically sent prescriptions for mifepristone 200 mg orally and misoprostol 800 mcg buccally to a mail-order pharmacy, which shipped medications for next-day delivery. Participants completed surveys three and 14 days after enrollment, and we abstracted medical chart data. ResultsBetween January 2020 and April 2021 we enrolled 240 participants and obtained clinical outcome information for 227 (94.6%); 3 reported not taking either medication. Of those with abortion outcome information (N = 224), 216 (96.4%) completed day-3 and 212 (94.6%) day-14 surveys. Of the 224 that took medications, none reported taking past 70 days’ gestation, and complete medication abortion occurred for 217 participants (96.9%, 95% CI 93.7%-98.7%). Most received medications within three days (82.1%, 95% CI 76.5%-86.9%). In the day-3 survey, 95.4% (95% CI 91.7%-97.8%) reported being very (88.4%) or somewhat (6.9%) satisfied with receiving medications by mail. In the day-14 survey, 89.6% (95% CI 84.7%-93.4%) said they would use the mail-order service again if needed. Eleven (4.9%, 95% CI 2.5%-8.6%) experienced adverse events; two were serious (one blood transfusion, one hospitalization), and none were related to mail-order pharmacy dispensing. ConclusionsMedication abortion with mail-order pharmacy dispensing of mifepristone appears effective, feasible, and acceptable to patients. ImplicationsThe in-person dispensing requirement for mifepristone, codified in the drug's Risk Evaluation and Mitigation Strategy, should be removed.

A Database of Pediatric Drug Effects to Evaluate Ontogenic Mechanisms From Child Growth and Development

Adverse drugs effects (ADEs) in children are common and may result in disability and death. However, methodologies do not surpass event surveillance to identify and evaluate potential dynamic mechanisms from child growth and development. We generated a database of 460,837 pediatric ADEs using generalized additive models (GAMs) previously shown to identify dynamic risk estimates of adverse drug events 1 . We identified 19,438 significant drug-event risks including known pediatric drug effects exhibiting risk dynamics across child development, such as montelukast-induced psychiatric disorders within the second year of life (Odds Ratio 8.77 [2.51, 46.94]). A data-driven time-series clustering approach resulted in up to 95.2% precision and 97.8% sensitivity for categorizing risk dynamics. We found that our real-world evidence may contain biologically-relevant underpinnings. We curated this database for the research community to enable, for the first time, evaluation of real-world hypotheses of adverse drug effects across child growth and development.

Evaluating risk detection methods to uncover ontogenic-mediated adverse drug effect mechanisms in children

BackgroundIdentifying adverse drugs effects (ADEs) in children, overall and within pediatric age groups, is essential for preventing disability and death from marketed drugs. At the same time, however, detection is challenging due to dynamic biological processes during growth and maturation, called ontogeny, that alter pharmacokinetics and pharmacodynamics. As a result, methodologies in pediatric drug safety have been limited to event surveillance and have not focused on investigating adverse event mechanisms. There is an opportunity to identify drug event patterns within observational databases for evaluating ontogenic-mediated adverse event mechanisms. The first step of which is to establish statistical models that can identify temporal trends of adverse effects across childhood.ResultsUsing simulation, we evaluated a population stratification method (the proportional reporting ratio or PRR) and a population modeling method (the generalized additive model or GAM) to identify and quantify ADE risk at varying reporting rates and dynamics. We found that GAMs showed improved performance over the PRR in detecting dynamic drug event reporting across child development stages. Moreover, GAMs exhibited normally distributed and robust ADE risk estimation at all development stages by sharing information across child development stages.ConclusionsOur study underscores the opportunity for using population modeling techniques, which leverage drug event reporting across development stages, as biologically-inspired detection methods for evaluating ontogenic mechanisms.

No population left behind: Improving paediatric drug safety using informatics and systems biology.

Adverse drugs effects (ADEs) in children are common and may result in disability and death. The current paediatric drug safety landscape, including clinical trials, is limited as it rarely includes children and relies on extrapolation from adults. Children are not small adults but go through an evolutionarily conserved and physiologically dynamic process of growth and maturation. Novel quantitative approaches, integrating observations from clinical trials and drug safety databases with dynamic mechanisms, can be used to systematically identify ADEs unique to childhood. In this perspective, we discuss three critical research directions using systems biology methodologies and novel informatics to improve paediatric drug safety, namely child versus adult drug safety profiles, age‐dependent drug toxicities and genetic susceptibility of ADEs across childhood. We argue that a data‐driven framework that leverages observational data, biomedical knowledge and systems biology modelling will reveal previously unknown mechanisms of pediatric adverse drug events and lead to improved paediatric drug safety.

Drug-induced interstitial lung diseases

Pulmonary drug reactions are arelatively common factor causing interstitial pulmonary disease. Histological findings of pulmonary drug reactions can mimic other conditions such as various forms of idiopathic interstitial pneumonia such as nonspecific interstitial pneumonia, organizing pneumonia, diffuse alveolar damage, or usual interstitial pneumonia. The correct diagnosis is important since acausal therapy is possible by stopping the administration. Astringent correlation between dose/time of administration and the type of reaction exists for only afew drugs. An increased risk ofdrug side effects can arise from known reactions to that specific drug, the patient's history, the type of underlying disease, genetic polymorphisms, occupational factors, and interactions with other drugs. The identification of a pulmonary drug reaction is a difficult task that can often only be solved in an interdisciplinary manner, for which in rare cases a lung biopsy is necessary. Pathology then has to identify histomorphological reaction patterns to exclude other causes and correlate findings with clinical data. In most cases, however, the diagnosis of adrug reaction will be by exclusion.