Adverse Events Associated with Treatment of Multidrug-Resistant Tuberculosis in China: An Ambispective Cohort Study.

Med Sci Monit. 2017 May 18;23:2348-2356

Authors: Zhang Y, Wu S, Xia Y, Wang N, Zhou L, Wang J, Fang R, Sun F, Chen M, Zhan S

Abstract
BACKGROUND Adverse events are under-appreciated negative consequences that are significant clinical problems for patients undergoing anti-MDR-TB treatment due to longer duration of treatment and more need for concurrent use of multiple second-line drugs. The aim of this study was to determine the incidence of adverse events and their impact on MDR-TB therapy and treatment outcome, and to identify possible drug-event pairs in China. MATERIAL AND METHODS An ambispective cohort study was conducted based on hospital medical records, which included a retrospective study that enrolled 751 MDR-TB patients receiving standardized regimen between May 2009 and July 2013, and a follow-up investigation of treatment outcome conducted in December 2016 in China. Adverse events were determined according to laboratory results or clinical criteria. Cox's proportional hazards regression models were used for evaluating associations. RESULTS There were 681(90.7%) patients experienced at least 1 type of adverse event and 55.2% of them required a changed MDR-TB treatment; 51(6.8%) patients required permanent discontinuation of the offending drug due to adverse events. The occurrence of adverse events was associated with poor treatment outcome (adjusted hazard ratio, 1.54; 95% CI 1.21, 1.87). A total of 10 different drug-event pairs were identified. CONCLUSIONS Adverse events occurred commonly during MDR-TB treatment in China, and often resulted in MDR-TB treatment change. The occurrence of adverse events affected MDR-TB poor outcome after treatment.

PMID: 28520704 [PubMed - indexed for MEDLINE]

Estimation of the prevalence of adverse drug reactions from social media.

Int J Med Inform. 2017 Jun;102:130-137

Authors: Nguyen T, Larsen ME, O'Dea B, Phung D, Venkatesh S, Christensen H

Abstract
This work aims to estimate the degree of adverse drug reactions (ADR) for psychiatric medications from social media, including Twitter, Reddit, and LiveJournal. Advances in lightning-fast cluster computing was employed to process large scale data, consisting of 6.4 terabytes of data containing 3.8 billion records from all the media. Rates of ADR were quantified using the SIDER database of drugs and side-effects, and an estimated ADR rate was based on the prevalence of discussion in the social media corpora. Agreement between these measures for a sample of ten popular psychiatric drugs was evaluated using the Pearson correlation coefficient, r, with values between 0.08 and 0.50. Word2vec, a novel neural learning framework, was utilized to improve the coverage of variants of ADR terms in the unstructured text by identifying syntactically or semantically similar terms. Improved correlation coefficients, between 0.29 and 0.59, demonstrates the capability of advanced techniques in machine learning to aid in the discovery of meaningful patterns from medical data, and social media data, at scale.

PMID: 28495341 [PubMed - indexed for MEDLINE]

Review Article: The Role of Molecular Pathological Epidemiology in the Study of Neoplastic and Non-neoplastic Diseases in the Era of Precision Medicine.

Epidemiology. 2016 Jul;27(4):602-11

Authors: Ogino S, Nishihara R, VanderWeele TJ, Wang M, Nishi A, Lochhead P, Qian ZR, Zhang X, Wu K, Nan H, Yoshida K, Milner DA, Chan AT, Field AE, Camargo CA, Williams MA, Giovannucci EL

Abstract
Molecular pathology diagnostics to subclassify diseases based on pathogenesis are increasingly common in clinical translational medicine. Molecular pathological epidemiology (MPE) is an integrative transdisciplinary science based on the unique disease principle and the disease continuum theory. While it has been most commonly applied to research on breast, lung, and colorectal cancers, MPE can investigate etiologic heterogeneity in non-neoplastic diseases, such as cardiovascular diseases, obesity, diabetes mellitus, drug toxicity, and immunity-related and infectious diseases. This science can enhance causal inference by linking putative etiologic factors to specific molecular biomarkers as outcomes. Technological advances increasingly enable analyses of various -omics, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics, microbiome, immunomics, interactomics, etc. Challenges in MPE include sample size limitations (depending on availability of biospecimens or biomedical/radiological imaging), need for rigorous validation of molecular assays and study findings, and paucities of interdisciplinary experts, education programs, international forums, and standardized guidelines. To address these challenges, there are ongoing efforts such as multidisciplinary consortium pooling projects, the International Molecular Pathological Epidemiology Meeting Series, and the Strengthening the Reporting of Observational Studies in Epidemiology-MPE guideline project. Efforts should be made to build biorepository and biobank networks, and worldwide population-based MPE databases. These activities match with the purposes of the Big Data to Knowledge (BD2K), Genetic Associations and Mechanisms in Oncology (GAME-ON), and Precision Medicine Initiatives of the United States National Institute of Health. Given advances in biotechnology, bioinformatics, and computational/systems biology, there are wide open opportunities in MPE to contribute to public health.

PMID: 26928707 [PubMed - indexed for MEDLINE]

Blockade of histone deacetylase 6 protects against cisplatin-induced acute kidney injury.

Clin Sci (Lond). 2018 Jan 22;:

Authors: Tang J, Shi Y, Liu N, Xu L, Zang X, Li P, Zhang J, Zheng X, Qiu A, Zhuang S

Abstract
Histone deacetylase 6 (HDAC6) has been shown to be involved in various pathological conditions, including cancer, neurodegenerative disorders and inflammatory diseases. Nonetheless, its specific role in drug-induced nephrotoxicity is poorly understood. Cisplatin (dichlorodiamino platinum) belongs to an inorganic platinum-fundamental chemotherapeutic drug utilized in the therapy of various solid malignant tumors. However, the use of cisplatin is limited by obvious side effects. In this study, we utilized a murine model of cisplatin-induced acute kidney injury (AKI) and a highly selective inhibitor of HDAC6, tubastatin A (TA), to assess the role of HDAC6 in nephrotoxicity and its associated mechanisms. Cisplatin-induced AKI was accompanied by increased expression and activation of HDAC6; blocking HDAC6 with TA lessened renal dysfunction, attenuated renal pathological changes, reduced expression of neutrophil gelatinase-associated lipocalin and Kim-1, and decreased tubular cell apoptosis. In cultured human epithelial cells, TA or HDAC6 siRNA treatment also inhibited cisplatin-induced apoptosis. Mechanistic studies demonstrated that cisplatin induced phosphorylation of AKT and loss of E-cadherin in the nephrotoxic kidney, and administration of TA enhanced AKT phosphorylation and preserved E-cadherin expression. HDAC6 inhibition also potentiated autophagy as evidenced by increased expression of Atg7, Beclin-1, and decreased renal oxidative stress as demonstrated by upregulation of superoxide dismutase activity and downregulation of malondialdehyde levels. Moreover, TA was effective in inhibiting NF-κB phosphorylation and suppressing the expression of tumor necrosis factor-a and interleukin-6. Collectively, these data provide strong evidence that HDAC6 inhibition is protective against cisplatin-induced AKI and suggest that HDAC6 may be a potential therapeutic target for AKI treatment.

PMID: 29358506 [PubMed - as supplied by publisher]

Drug-induced liver and skin reactions: In need of a consensus definition.

Hepatology. 2017 01;65(1):391

Authors: Medina-Cáliz I, Robles-Díaz M, Lucena MI, Andrade RJ

PMID: 27618725 [PubMed - indexed for MEDLINE]

Detrimental Side Effects of Repeated Ketamine Infusions in the Brain.

Am J Psychiatry. 2016 10 01;173(10):1044-1045

Authors: Hashimoto K

PMID: 27690555 [PubMed - indexed for MEDLINE]

Trends in the Concomitant Prescribing of Opioids and Benzodiazepines, 2002-2014.

Am J Prev Med. 2016 Aug;51(2):151-160

Authors: Hwang CS, Kang EM, Kornegay CJ, Staffa JA, Jones CM, McAninch JK

Abstract
INTRODUCTION: Although many clinical guidelines caution against the combined use of opioids and benzodiazepines, overdose deaths and emergency department visits involving the co-ingestion of these drugs are increasing.
METHODS: In this ecologic time series study, the IMS Health Total Patient Tracker was used to describe nationally projected trends of patients receiving opioids and benzodiazepines in the U.S. outpatient retail setting between January 2002 and December 2014. The IMS Health Data Extract Tool was used to examine trends in the concomitant prescribing of these two medication classes among 177 million individuals receiving opioids during this period. The annual proportion of opioid recipients who were prescribed benzodiazepines concomitantly was calculated and stratified by gender, age, duration of opioid use, immediate-release versus extended-release/long-acting opioids, and benzodiazepine molecule. The proportion of patients with concomitancy receiving opioids and benzodiazepines from the same prescriber was also analyzed. Analyses were conducted from April to June 2015.
RESULTS: The nationally projected number of patients receiving opioids and benzodiazepines increased by 8% and 31%, respectively, from 2002 to 2014. During this period, the annual proportion of opioid recipients dispensed a benzodiazepine concomitantly increased from 6.8% to 9.6%, which corresponded to a relative increase of 41%. Approximately half of these patients received both prescriptions from the same prescriber on the same day. Concomitancy was more common in patients receiving opioids for ≥90 days, women, and the elderly.
CONCLUSIONS: Concomitant prescribing of opioids and benzodiazepines is increasing and may play a growing role in adverse patient outcomes related to these medications.

PMID: 27079639 [PubMed - indexed for MEDLINE]

Synergy evaluation of anti-Herpes Simplex Virus type 1 and 2 compounds acting on different steps of virus life cycle.

Antiviral Res. 2018 Jan 18;:

Authors: Criscuolo E, Clementi N, Mancini N, Burioni R, Miduri M, Castelli M, Clementi M

Abstract
Despite the clinical need of novel and safe anti-herpetic compounds effective for treating both primary infections and reactivations of Herpes Simplex Virus type 1 (HSV-1) and type 2 (HSV-2), the development of novel antivirals approved for clinical administration has been limited in the last decades to improvements of nucleoside analogues compounds. In this context, targeting different steps of the herpesvirus life cycle, including entry and cell-to-cell infection, can represent an important starting point for obtaining more efficient infection inhibition, and for overcoming both drug resistance and toxicity. Under these perspectives, testing possible synergy between drugs currently in clinical use and novel immunotherapeutics, such as neutralizing human monoclonal antibodies, represents a fascinating option. In the study here described we tested for the first-time possible combinations of inhibitors of Herpesvirus DNA synthesis and a human neutralizing IgG able to block also cell-to-cell infection, by analysing experimental results with different mathematical models. The present study clearly highlights the synergism between all anti-herpetic drugs tested in combination with the mAb; this strongly suggests possible reduction of anti-herpetic drugs combined with the IgG for overcoming drug-related side effects, as indicated by Drug Reduction Index.

PMID: 29357297 [PubMed - as supplied by publisher]

Moxifloxacin in Pediatric Patients with Complicated Intra-Abdominal Infections: Results of the MOXIPEDIA Randomized Controlled Study.

Pediatr Infect Dis J. 2018 Jan 18;:

Authors: Wirth S, Emil SGS, Engelis A, Digtyar V, Criollo M, DiCasoli C, Stass H, Willmann S, Nkulikiyinka R, Grossmann U, MOXIPEDIA Study Group

Abstract
BACKGROUND: This study was designed to evaluate primarily the safety and also the efficacy of moxifloxacin (MXF) in children with complicated intra-abdominal infections (cIAIs).
METHODS: In this multicenter, randomized, double-blind, controlled study, 451 pediatric patients aged 3 months to 17 years with cIAIs were treated with intravenous/oral MXF (N = 301) or comparator (COMP, intravenous ertapenem followed by oral amoxicillin/clavulanate; N = 150) for 5 to 14 days. Doses of MXF were selected based on the results of a Phase 1 study in pediatric patients (NCT01049022). The primary endpoint was safety, with particular focus on cardiac and musculoskeletal safety; clinical and bacteriological efficacy at test of cure were also investigated.
RESULTS: The proportion of patients with adverse events (AEs) was comparable between the two treatment arms (MXF: 58.1% and COMP: 54.7%). The incidence of drug-related AEs was higher in the MXF arm than the COMP arm (14.3% and 6.7%, respectively). No cases of QTc interval prolongation-related morbidity or mortality were observed. The proportion of patients with musculoskeletal AEs was comparable between treatment arms; no drug-related events were reported. Clinical cure rates were 84.6% and 95.5% in the MXF and COMP arms, respectively, in patients with confirmed pathogen(s) at baseline.
CONCLUSIONS: MXF treatment was well tolerated in children with cIAIs. However, a lower clinical cure rate was observed with MXF treatment compared with COMP. This study does not support a recommendation of MXF for children with cIAIs when alternative more efficacious antibiotics with better safety profile are available.

PMID: 29356761 [PubMed - as supplied by publisher]

Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer.

J Clin Oncol. 2018 Jan 20;:JCO2017769901

Authors: Overman MJ, Lonardi S, Wong KYM, Lenz HJ, Gelsomino F, Aglietta M, Morse MA, Van Cutsem E, McDermott R, Hill A, Sawyer MB, Hendlisz A, Neyns B, Svrcek M, Moss RA, Ledeine JM, Cao ZA, Kamble S, Kopetz S, André T

Abstract
Purpose Nivolumab provides clinical benefit (objective response rate [ORR], 31%; 95% CI, 20.8 to 42.9; disease control rate, 69%; 12-month overall survival [OS], 73%) in previously treated patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC); nivolumab plus ipilimumab may improve these outcomes. Efficacy and safety results for the nivolumab plus ipilimumab cohort of CheckMate-142, the largest single-study report of an immunotherapy combination in dMMR/MSI-H mCRC, are reported. Patients and Methods Patients received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks. Primary end point was investigator-assessed ORR. Results Of 119 patients, 76% had received ≥ two prior systemic therapies. At median follow-up of 13.4 months, investigator-assessed ORR was 55% (95% CI, 45.2 to 63.8), and disease control rate for ≥ 12 weeks was 80%. Median duration of response was not reached; most responses (94%) were ongoing at data cutoff. Progression-free survival rates were 76% (9 months) and 71% (12 months); respective OS rates were 87% and 85%. Statistically significant and clinically meaningful improvements were observed in patient-reported outcomes, including functioning, symptoms, and quality of life. Grade 3 to 4 treatment-related adverse events (AEs) occurred in 32% of patients and were manageable. Patients (13%) who discontinued treatment because of study drug-related AEs had an ORR (63%) consistent with that of the overall population. Conclusion Nivolumab plus ipilimumab demonstrated high response rates, encouraging progression-free survival and OS at 12 months, manageable safety, and meaningful improvements in key patient-reported outcomes. Indirect comparisons suggest combination therapy provides improved efficacy relative to anti-programmed death-1 monotherapy and has a favorable benefit-risk profile. Nivolumab plus ipilimumab provides a promising new treatment option for patients with dMMR/MSI-H mCRC.

PMID: 29355075 [PubMed - as supplied by publisher]

Estimating causal log-odds ratio using the case-control sample and its application in the pharmaco-epidemiology study.

Stat Methods Med Res. 2018 Jan 01;:962280217750175

Authors: Zhu A, Zeng D, Zhang P, Li L

Abstract
One important goal in pharmaco-epidemiology studies is to understand the causal relationship between drug exposures and their clinical outcomes, including adverse drug events. In order to achieve this goal, however, we need to resolve several challenges. Most of pharmaco-epidemiology data are observational and confounding is largely present due to many co-medications. The pharmaco-epidemiology study data set is often sampled from large medical record databases using a matched case-control design, and it may not be representative of the original patient population in the medical record databases. Data analysis method needs to handle a large sample size that cannot be handled using existing statistical analysis packages. In this paper, we tackle these challenges both methodologically and computationally. We propose a conditional causal log-odds ratio (OR) definition to characterize causal effects of drug exposures on a binary adverse drug event adjusting for individual level confounders. Using a case-control design, we present a propensity score estimation using only case samples and we provide sufficient conditions for the consistency of the estimation of the causal log-odds ratio using case-based propensity scores. Computationally, we implement a principle component analysis to reduce high-dimensional confounders. Extensive simulation studies are performed to demonstrate superior performance of our method to existing methods. Finally, we apply the proposed method to analyze drug-induced myopathy data sampled from a de-identified subset of medical record database (close to 5 million patient records), The Indiana Network for Patient Care. Our method identified 70 drug-induced myopathy ( p < 0.05) out 72 drugs, which have myoathy side effects on their FDA drug labels. These 70 drugs include three statins who are known for their myopathy side effects.

PMID: 29355073 [PubMed - as supplied by publisher]

Preventing drug-related adverse events following hospital discharge: the role of the pharmacist.

Integr Pharm Res Pract. 2017;6:61-69

Authors: Nicholls J, MacKenzie C, Braund R

Abstract
Transition of care (ToC) points, and in particular hospital admission and discharge, can be associated with an increased risk of adverse drug events (ADEs) and other drug-related problems (DRPs). The growing recognition of the pharmacist as an expert in medication management, patient education and communication makes them well placed to intervene. There is evidence to indicate that the inclusion of pharmacists in the health care team at ToC points reduces ADEs and DRPs and improves patient outcomes. The objectives of this paper are to outline the following using current literature: 1) the increased risk of medication-related problems at ToC points; 2) to highlight some strategies that have been successful in reducing these problems; and 3) to illustrate how the role of the pharmacist across all facets of care can contribute to the reduction of ADEs, particularly for patients at ToC points.

PMID: 29354552 [PubMed]

The effect of prescriber education on medication-related patient harm in the hospital: a systematic review.

Br J Clin Pharmacol. 2017 May;83(5):953-961

Authors: Bos JM, van den Bemt PMLA, de Smet PAGM, Kramers C

Abstract
AIMS: Educating prescribers is a strategy to reduce prescription errors in hospitals. The present systematic review gives an overview of original research papers on the education of prescribers and reporting outcomes on (potential) patient harm.
METHODS: A search of the databases Embase and Medline, using the Ovid interface, was performed. Research on the effect of physician education in order to prevent medication-related problems in inpatients, and on reporting original data and outcomes on prescribing errors and/or (potential) patient harm, was included. The assessment of methodological quality and risk of bias was performed using the Methodological Index for Non-Randomized studies (MINORS) checklist and the suggested risk of bias criteria for Effective Practice and Organization of Care (EPOC) reviews.
RESULTS: Eight studies investigated an intervention on education alone, and in seven studies education was the main part of a multifaceted intervention. All studies were small and had short follow-up periods. The educational programmes varied and were given to physicians of different specialties and levels of experience. Most studies reported intermediate process parameters as the outcome. The risk of performance and reporting bias were high.
CONCLUSION: All included studies suffered from poor methodology. The majority, especially studies in which education was part of a multifaceted intervention, reported effectiveness on intermediate outcome markers as prescription errors and potential adverse drug events. However, we found no firm evidence that educating prescribers in the hospital leads to a decrease in patient harm. Further work is needed to develop educational programmes, accompanied by more high-quality research with outcomes on the improvement of patient care.

PMID: 27918623 [PubMed - indexed for MEDLINE]

QT-interval prolongation due to medication found in the preoperative evaluation.

J Dent Anesth Pain Med. 2017 Dec;17(4):323-327

Authors: Seto M, Koga S, Kita R, Kikuta T

Abstract
QT prolongation is an electrocardiographic change that can lead to lethal arrhythmia. Acquired QT prolongation is known to be caused by drugs and electrolyte abnormalities. We report three cases in which the prolonged QT interval was improved at the time of operation by briefly discontinuing the drugs suspected to have caused the QT prolongation observed on preoperative electrocardiography. The QTc of cases 1, 2, and 3 improved from 518 to 429 ms, 463 to 441 ms, and 473 to 443 ms on discontinuing the use of a gastrointestinal prokinetic agent, a proton pump inhibitor, and a molecular targeted drug, respectively. These cases were considered to have drug-induced QT prolongation. We reaffirmed that even drugs administered for conditions unrelated to cardiac diseases can have adverse side effect of QT prolongation. In conclusion, our cases indicate that dental surgeons should be aware of the dangerous and even potentially lethal side effects of QT prolongation. For safe oral and maxillofacial surgery, cooperation with medical departments in various fields is important.

PMID: 29349356 [PubMed]

A Personalized and Learning Approach for Identifying Drugs with Adverse Events.

Yonsei Med J. 2017 Nov;58(6):1229-1236

Authors: Shin SK, Hur H, Cheon EK, Oh OH, Lee JS, Ko WJ, Kim BS, Kwon Y

Abstract
PURPOSE: Adverse drug events (ADEs) are associated with high health and financial costs and have increased as more elderly patients treated with multiple medications emerge in an aging society. It has thus become challenging for physicians to identify drugs causing adverse events. This study proposes a novel approach that can improve clinical decision making with recommendations on ADE causative drugs based on patient information, drug information, and previous ADE cases.
MATERIALS AND METHODS: We introduce a personalized and learning approach for detecting drugs with a specific adverse event, where recommendations tailored to each patient are generated using data mining techniques. Recommendations could be improved by learning the associations of patients and ADEs as more ADE cases are accumulated through iterations. After consulting the system-generated recommendations, a physician can alter prescriptions accordingly and report feedback, enabling the system to evolve with actual causal relationships.
RESULTS: A prototype system is developed using ADE cases reported over 1.5 years and recommendations obtained from decision tree analysis are validated by physicians. Two representative cases demonstrate that the personalized recommendations could contribute to more prompt and accurate responses to ADEs.
CONCLUSION: The current system where the information of individual drugs exists but is not organized in such a way that facilitates the extraction of relevant information together can be complemented with the proposed approach to enhance the treatment of patients with ADEs. Our illustrative results show the promise of the proposed system and further studies are expected to validate its performance with quantitative measures.

PMID: 29047249 [PubMed - indexed for MEDLINE]

Preventivt arbete kan minska läkemedelsbiverkningar.

Lakartidningen. 2017 Jul 14;114:

Authors: Hallberg P, Collin S, Wadelius M

PMID: 28718862 [PubMed - indexed for MEDLINE]

Consumer reporting of adverse drug reactions: Systems that allow patients to report side effects of the drugs they are taking have yielded valuable information for improving drugs safety and health care.

EMBO Rep. 2016 07;17(7):949-52

Authors: Weigmann K

PMID: 27198546 [PubMed - indexed for MEDLINE]

Bioinformatics Approaches to Predict Drug Responses from Genomic Sequencing.

Methods Mol Biol. 2018;1711:277-296

Authors: Madhukar NS, Elemento O

Abstract
Fulfilling the promises of precision medicine will depend on our ability to create patient-specific treatment regimens. Therefore, being able to translate genomic sequencing into predicting how a patient will respond to a given drug is critical. In this chapter, we review common bioinformatics approaches that aim to use sequencing data to predict sample-specific drug susceptibility. First, we explain the importance of customized drug regimens to the future of medical care. Second, we discuss the different public databases and community efforts that can be leveraged to develop new methods for identifying new predictive biomarkers. Third, we cover the basic methods that are currently used to identify markers or signatures of drug response, without any prior knowledge of the drug's mechanism of action. We further discuss how one can integrate knowledge about drug targets, mechanisms, and predictive markers to better estimate drug response in a diverse set of samples. We begin this section with a primer on popular methods to identify targets and mechanism of action for new small molecules. This discussion also includes a set of computational methods that incorporate other drug features, which do not relate to drug-induced genetic changes or sequencing data such as drug structures, side-effects, and efficacy profiles. Those additional drug properties can aid in gaining higher accuracy for the identification of drug target and mechanism of action. We then progress to discuss using these targets in combination with disease-specific expression patterns, known pathways, and genetic interaction networks to aid drug choice. Finally, we conclude this chapter with a general overview of machine learning methods that can integrate multiple pieces of sequencing data along with prior drug or biological knowledge to drastically improve response prediction.

PMID: 29344895 [PubMed - in process]

Levetiracetam-Induced Skin Hyperpigmentation: An Extremely Rare Undesirable Side Effect.

J Epilepsy Res. 2017 Dec;7(2):106-108

Authors: Algahtani H, Marghalani S, Satti M, Shirah B

Abstract
Levetiracetam is one of the newer second-generation antiepileptic drugs with multiple mechanisms of action. Cutaneous side effects due to levetiracetam are rarely reported in the literature. In this article, we describe a patient with skin hyperpigmentation due to the treatment with levetiracetam with complete resolution after discontinuation of the medication. In addition, we review the topic and hypothesize the mechanism behind this rare complication. To the best of our knowledge, this is the first report of skin hyperpigmentation as a side effect of levetiracetam in the literature. The prescribing physicians should inform the patients about all potential side effect of levetiracetam including skin hyperpigmentation. Similar to many undiagnosed conditions, increased awareness of their existence is the key to diagnosis. Early recognition and timely cessation of therapy are important to reverse this effect. Further studies should be conducted to explore the pathophysiology of this rare side effect.

PMID: 29344468 [PubMed]

Safety of yellow fever vaccine in Indian travellers: A prospective observational study.

Indian J Med Res. 2016 Nov;144(5):778-780

Authors: Tiwari P, Ahlawat R, Gupta G

PMID: 28361832 [PubMed - indexed for MEDLINE]