Development of Drug-Induced Inverse Psoriasis in a Patient with Crohn's Disease.

ACG Case Rep J. 2018;5:e47

Authors: Darwin E, Deshpande A, Lev-Tov H

Abstract
Crohn's disease is difficult to manage and often requires multiple medications. While these drugs vastly improve quality of life, physicians must monitor for adverse events. We report a case of a flare of inverse psoriasis after 15 months of treatment with ustekinumab. This is the third reported case of a flare of drug-induced psoriasis with ustekinumab, and it is the first reported case with an inverse presentation; however, the clinical picture is confounded by concomitant use of hydroxychloroquine. Inverse psoriasis is a rare variant of drug-induced psoriasis of which physicians must be cognizant while treating patients with Crohn's disease.

PMID: 29951562 [PubMed]

Assessing the ability of the Drug-Associated Risk Tool (DART) questionnaire to stratify hospitalised older patients according to their risk of drug-related problems: a cross-sectional validation study.

BMJ Open. 2018 Jun 27;8(6):e021284

Authors: Stämpfli D, Boeni F, Gerber A, Bättig VAD, Weidmann R, Hersberger KE, Lampert ML

Abstract
OBJECTIVES: The Drug-Associated Risk Tool (DART) has been developed as a self-administered questionnaire for patients with the aim of stratifying patients according to their risk of drug-related problems (DRPs). We aimed to validate the ability of the questionnaire to distinguish between hospitalised patients showing lower and higher numbers of DRPs.
DESIGN: Cross-sectional study assessing the questionnaire's concurrent criterion validity.
SETTING: Five geriatric and the associated physical and neurological rehabilitation wards of a Swiss regional secondary care hospital with 617 beds.
PARTICIPANTS: We recruited 110 patients from a total of 437 admissions. Exclusion criteria were insufficient knowledge in spoken or written German, medical conditions preventing meaningful conversations and already receiving pharmacy services.
INTERVENTIONS: Comprehensive pharmacist-led clinical medication reviews were performed, including patient interviews, to identify potential and manifest DRPs. A cluster analysis was conducted to assess the discriminatory potential of the DART to group patients according to number (low and high) of identified DRPs. A subsequent discriminatory function analysis was performed to reduce the number of items. We determined which DART items may be used to trigger what type of medication review.
RESULTS: Recruited patients had a median age of 79 years and were prescribed a median of 11 drugs. Patients with a median DART score of 10 and a median of 3 DRPs represented one cluster, whereas patients with a median DART score of 15 and a median of 8 DRPs represented another cluster. Discriminatory function analysis reduced the questionnaire to five items with a moderate to strong correlation with the number of DRPs per patient (Spearman's rank correlation ρ=0.44). Additional items were associated with patients benefiting from interviews.
CONCLUSIONS: As a self-administered questionnaire for patients, the DART may be used to stratify hospitalised non-acute older patients in groups of having low and high likelihood of DRPs. The analyses showed that a short form of the DART can be used instead of the full tool to identify older inpatients at risk for DRPs. Additional eight items from the DART may be used to initiate additional clinical pharmacy services. The linkage between certain DART questions and type of medication review enables pharmacist resource allocation.

PMID: 29950469 [PubMed - in process]

Recent Developments in ADC Technology: Preclinical Studies Signal Future Clinical Trends.

BioDrugs. 2017 Dec;31(6):521-531

Authors: Drake PM, Rabuka D

Abstract
The antibody-drug conjugate (ADC) field is in a transitional period. Older approaches to conjugate composition and dosing regimens still dominate the ADC clinical pipeline, but preclinical work is driving a rapid evolution in how we strategize to improve efficacy and reduce toxicity towards better therapeutic outcomes. These advances are largely based upon a body of investigational studies that together offer a deeper understanding of the absorption, distribution, metabolism, and excretion (ADME) and drug metabolism and pharmacokinetics (DMPK) fates of both the intact conjugate and its small-molecule component. Knowing where the drug goes and how it is processed allows mechanistic connections to be drawn with commonly observed clinical toxicities. The field is also starting to consider ADC interactions with the immune system and potential synergistic therapeutic opportunities therein. In an indication of future directions for the field, antibody conjugates bearing non-cytotoxic small-molecule payloads are being developed to reduce side effects associated with treatment of chronic diseases. ADCs are not a magic bullet to cure disease. However, they will increasingly become valuable therapeutic tools to improve patient outcomes across a variety of indications.

PMID: 29119409 [PubMed - indexed for MEDLINE]

Assessment of drug-related problems in pediatric ward of Zewditu Memorial Referral Hospital, Addis Ababa, Ethiopia.

Int J Clin Pharm. 2017 Oct;39(5):1039-1046

Authors: Birarra MK, Heye TB, Shibeshi W

Abstract
Background Although medications play a vital role in the cure, palliation, and inhibition of disease, they also expose patients to drug-related problems (DRPs). DRPs are common in hospitalized patients. Specifically, pediatrics population are easily affected by DRPs, as dynamic and kinetic behaviors of drugs in this population are usually different than  in adults. Objectives To assess the prevalence of DRPs and associated factors in a pediatric setting in Ethiopia. Setting Pediatric ward of Zewditu Memorial Referral Hospital, Addis Abbeba, Ethiopia. Methods A cross-sectional study was conducted on 285 randomly selected patients. Data were obtained through review of physician medication orders and patient files. The prevalence and type of DRPs were studied and documented using the Pharmaceutical Care Network Europe Foundation classification system. The results were summarized using descriptive statistics including frequency, mean, and standard deviation. To identify the independent predicators of DRPs, logistic regression analysis was run and a P value ≤0.05 was considered as statistically significant. Main outcome measure DRPs, types of DRPs, drugs that are frequently involved in DRPs, and factors associated with DRPs. Main outcome measure Number of DRPs. Results Of the 1055 medication orders reviewed, a total of 106 DRPs were identified in 90 patients. This gives an overall rate of drug-related problems of 31.57%. The most frequently identified DRPs were dosing problems, with dose too low being 34.9% and dose too high being 7.5%. This was followed by drug-drug interactions (38.67%) and adverse drug reactions (8.49%). The number of prescribed drugs (AOR 2.3, 95% CI 1.3-4.3, P = 0.007) and total number of disease conditions (AOR 4.8, 95% CI 1.9, 12.1, P = 0.001) were potential risk factors for occurrence of DRPs. Conclusion The present study demonstrated that DRPs were common at the pediatric ward of Zewditu Memorial Referral Hospital and that it needs great attention. The most frequently identified DRPs were dosing problems, followed by drug-drug interactions and adverse drug reaction. Poly-pharmacy and number of disease conditions have been identified as important risk factors for occurrence of DRPs. The investigators recommend establishing a system for reporting DRPs in the pediatric ward of the hospital as it may facilitate appropriate measures for prospective interventions, such as training the healthcare team, as well as detail precautions to be followed by the practitioners. In addition to this, improving communication between the healthcare team members such as physicians, pharmacists, nurses, and other healthcare workers in the hospital is recommended.

PMID: 28689305 [PubMed - indexed for MEDLINE]

Coding for Medication-related Poisoning and Adverse Effects.

Continuum (Minneap Minn). 2017 Jun;23(3, Neurology of Systemic Disease):e17-e19

Authors: Yu M

Abstract
Accurate coding is important for proper reimbursement and documentation of care provided. This article provides an overview of coding considerations for patient encounters associated with medication use, abuse, or poisoning.

PMID: 28570335 [PubMed - indexed for MEDLINE]

Antiresorptive drug-related osteonecrosis of the jaws, literature review and 5 years of experience.

Musculoskelet Surg. 2018 Jun 14;:

Authors: Bernardi S, Di Girolamo M, Necozione S, Continenza MA, Cutilli T

Abstract
PURPOSE: Bisphosphonate drug therapy provides benefits in the case of osteoporosis and carcinomas metastasizing to the bones, but it exposes patients to important side effects. The aim of this study was to investigate the incidence and the appropriate surgical treatment of bone lesions and fractures due to antiresorptive drug-related osteonecrosis of the jaws (ARONJ).
METHODS: Patients presenting with osteonecrosis lesions of the jaw, who were referred to the Maxillo-Facial unit of the University of L'Aquila, were considered for inclusion. Grade of the lesion and treatment choice was recorded for each patient. Descriptive statistics were calculated and the data were analysed with Chi-squared tests. A representative case of a fracture reduction with a supra-periostal approach is reported.
RESULTS: Among the 165 patients with ARONJ lesions, 112 were female and 53 were male. In total, 115 patients received intra-venous bisphosphonate therapy and 50 received oral bisphosphonate therapy. Five stage 2 lesions, three stage 2 lesions and two stage 3 lesions were not a consequence of dental procedures. Eighteen surgical bone excisions were performed and four pathological fractures were reduced. In one case (the reported one), the combined use of platelet-rich plasma and the supra-periostal approach leads to a successful 1-year follow-up.
CONCLUSIONS: ARONJ lesions are a type of pathological bone disease affecting the jawbones. The pathology pathway remains a controversial and frequently discussed topic. A surgically conservative strategy seems to be the best way to assure a comfortable quality of life to those patients negatively affected by this condition.

PMID: 29948937 [PubMed - as supplied by publisher]

Adverse drug reaction monitoring in patients on antiretroviral therapy in a tertiary care hospital in Eastern India.

Indian J Pharmacol. 2017 May-Jun;49(3):223-228

Authors: Mukherjee S, Era N, Saha B, Tripathi SK

Abstract
BACKGROUND: Besides unparalleled benefits, highly active antiretroviral therapy is also associated with wide range of potential adverse drug reactions (ADRs), which hinders treatment adherence. The present study was thus designed to monitor and explore the pattern of occurrence of ADRs to various antiretroviral therapy (ART) regimens in a tertiary care ART setup.
MATERIALS AND METHODS: A prospective, observational clinical study was carried out in the outpatient setting of nodal ART center of Eastern India. A total of 610 patients on various ART regimens were studied for suspected ADRs over 12 months. Adverse event history, medication history, and other relevant details were captured. Causality and severity of each reported ADR were duly assessed.
RESULTS: 32.45% patients of total study participants presented with a total of 330 ADRs. Patients from zidovudine-based regimens presented with majority of ADRs such as anemia (up to 36%), central nervous system (CNS), and gastrointestinal (GI) side effects. Tenofovir-based regimens were, however, found to be mildly safer. The combination with Efavirenz was associated with majorly CNS side effects while that of nevirapine was associated with rash and pigmentation of nails. Atazanavir boosted second-line regimens were notably associated with increased serum lipid levels followed by other GI and CNS adverse effects. Increased liver enzymes were found in atazanavir-based second-line ART.
CONCLUSION: The study enables to obtain information on the incidence and pattern of ADRs associated with various antiretroviral regimens, thereby reducing its occurrence and protecting the patient population from avoidable harm. Need of intensive monitoring for ADRs in ARTs thus seems to be a mandate.

PMID: 29033481 [PubMed - indexed for MEDLINE]

A Pharmacoepidemiology Database System for Monitoring Risk Due to the Use of Medicines by New Zealand Primary Care Patients.

Drug Saf. 2017 Dec;40(12):1259-1277

Authors: Tomlin AM, Reith DM, Woods DJ, Lloyd HS, Smith A, Fountain JS, Tilyard MW

Abstract
INTRODUCTION: The use of large record-linked healthcare databases for drug safety research and surveillance is now accepted practice. New Zealand's standardized national healthcare datasets provide the potential to automate the conduct of pharmacoepidemiological studies to provide rapid validation of medicine safety signals.
OBJECTIVES: Our objectives were to describe the methodology undertaken by a semi-automated computer system developed to rapidly assess risk due to drug exposure in New Zealand's population of primary care patients and to compare results from three studies with previously published findings.
METHODS: Data from three national databases were linked at the patient level in the automated studies. A retrospective nested case-control design was used to evaluate risk for upper gastrointestinal bleeding (UGIB), acute kidney failure (AKF), and serious arrhythmia associated with individual medicines, therapeutic classes of medicines, and concurrent use of medicines from multiple therapeutic classes.
RESULTS: The patient cohort available for each study included 5,194,256 patients registered between 2007 and 2014, with a total of 34,630,673 patient-years at risk. An increased risk for UGIB was associated with non-steroidal anti-inflammatory drugs (NSAIDs) (adjusted odds ratio [AOR] 4.16, 95% confidence interval [CI] 3.90-4.43, p < 0.001) and selective serotonin reuptake inhibitors (AOR 1.39, 95% CI 1.20-1.62, p < 0.001); an increased risk for AKF was associated with NSAIDs (AOR 1.78, 95% CI 1.73-1.83, p < 0.001) and proton pump inhibitors (AOR 1.78, 95% CI 1.72-1.83, p < 0.001); and an increased risk for serious arrhythmia was associated with fluoroquinolones (AOR 1.38, 95% CI 1.26-151, p < 0.001) and penicillins (AOR 1.69, 95% CI 1.61-1.77, p < 0.001).
CONCLUSIONS: Automated case-control studies using New Zealand's healthcare datasets can replicate associations of risk with drug exposure consistent with previous findings. Their speed of conduct enables systematic monitoring of risk for adverse events associated with a wide range of medicines.

PMID: 28766108 [PubMed - indexed for MEDLINE]

Neurological Adverse Effects Attributable to β-Lactam Antibiotics: A Literature Review.

Drug Saf. 2017 Dec;40(12):1171-1198

Authors: Deshayes S, Coquerel A, Verdon R

Abstract
β-lactam antibiotics are commonly prescribed antibiotic drugs. To describe the clinical characteristics, risk markers and outcomes of β-lactam antibiotic-induced neurological adverse effects, we performed a general literature review to provide updated clinical data about the most used β-lactam antibiotics. For selected drugs in each class available in France (ticarcillin, piperacillin, temocillin, ceftazidime, cefepime, cefpirome, ceftaroline, ceftobiprole, ceftolozane, ertapenem and aztreonam), a systematic literature review was performed up to April 2016 via an electronic search on PubMed. Articles that reported original data, written in French, Spanish, Portuguese or English, with available individual data for patients with neurological symptoms (such as seizure, disturbed vigilance, confusional state, myoclonia, localising signs, and/or hallucinations) after the introduction of a β-lactam antibiotic were included. The neurological adverse effects of piperacillin and ertapenem are often described as seizures and hallucinations (>50 and 25% of cases, respectively). Antibiotic treatment is often adapted to renal function (>70%), and underlying brain abnormalities are seen in one in four to one in three cases. By contrast, the neurological adverse drug reactions of ceftazidime and cefepime often include abnormal movements but few hallucinations and seizures. These reactions are associated with renal insufficiency (>80%) and doses are rarely adapted to renal function. Otherwise, it appears that monobactams do not have serious neurological adverse drug reactions and that valproic acid and carbapenem combinations should be avoided. The onset of disturbed vigilance, myoclonus, and/or seizure in a patient taking β-lactam antibiotics, especially if associated with renal insufficiency or underlying brain abnormalities, should lead physicians to suspect adverse drug reactions and to consider changes in antibacterial therapy.

PMID: 28755095 [PubMed - indexed for MEDLINE]

Safety Profile of Eslicarbazepine Acetate as Add-On Therapy in Adults with Refractory Focal-Onset Seizures: From Clinical Studies to 6 Years of Post-Marketing Experience.

Drug Saf. 2017 Dec;40(12):1231-1240

Authors: Gama H, Vieira M, Costa R, Graça J, Magalhães LM, Soares-da-Silva P

Abstract
INTRODUCTION: Eslicarbazepine acetate was first approved in the European Union in 2009 as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization.
OBJECTIVE: The objective of this study was to review the safety profile of eslicarbazepine acetate analyzing the data from several clinical studies to 6 years of post-marketing surveillance.
METHODS: We used a post-hoc pooled safety analysis of four phase III, double-blind, randomized, placebo-controlled studies (BIA-2093-301, -302, -303, -304) of eslicarbazepine acetate as add-on therapy in adults. Safety data of eslicarbazepine acetate in special populations of patients aged ≥65 years with partial-onset seizures (BIA-2093-401) and subjects with moderate hepatic impairment (BIA-2093-111) and renal impairment (BIA-2093-112) are also considered. The incidences of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and serious adverse events were analyzed. The global safety database of eslicarbazepine acetate was analyzed for all cases from post-marketing surveillance from 1 October, 2009 to 21 October, 2015.
RESULTS: From a pooled analysis of four phase III studies, it was concluded that the incidence of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and adverse drug reactions were dose dependent. Dizziness, somnolence, headache, and nausea were the most common treatment-emergent adverse events (≥10% of patients) and the majority were of mild-to-moderate intensity. No dose-dependent trend was observed for serious adverse events and individual serious adverse events were reported in less than 1% of patients. Hyponatremia was classified as a possibly related treatment-emergent adverse event in phase III studies (1.2%); however, after 6 years of post-marketing surveillance it represents the most frequently (10.2%) reported adverse drug reaction, with more than half of these cases occurring with eslicarbazepine acetate at daily doses of 1200 mg. Other adverse drug reactions reported in post-marketing surveillance are seizure (5.8%), dizziness (4.1%), rash (2.6%), and fatigue (2.1%). The safety profile of eslicarbazepine acetate in renal and hepatic impairment subjects (phase I studies) and in elderly patients (phase III study) did not raise any specific concern.
CONCLUSION: After 6 years of post-marketing surveillance, eslicarbazepine acetate maintains a similar safety profile to that observed in pivotal clinical studies.

PMID: 28752473 [PubMed - indexed for MEDLINE]

Commercial Online Social Network Data and Statin Side-Effect Surveillance: A Pilot Observational Study of Aggregate Mentions on Facebook.

Drug Saf. 2017 Dec;40(12):1199-1204

Authors: Huesch MD

Abstract
INTRODUCTION: Surveillance of the safety of prescribed drugs after marketing approval has been secured remains fraught with complications. Formal ascertainment by providers and reporting to adverse-event registries, formal surveys by manufacturers, and mining of electronic medical records are all well-known approaches with varying degrees of difficulty, cost, and success. Novel approaches may be a useful adjunct, especially approaches that mine or sample internet-based methods such as online social networks.
METHODS: A novel commercial software-as-a-service data-mining product supplied by Sysomos from Datasift/Facebook was used to mine all mentions on Facebook of statins and stain-related side effects in the US in the 1-month period 9 January 2017 through 8 February 2017.
RESULTS: A total of 4.3% of all 25,700 mentions of statins also mentioned typical stain-related side effects. Multiple methodological weaknesses stymie interpretation of this percentage, which is however not inconsistent with estimates that 5-20% of patients taking statins will experience typical side effects at some time.
CONCLUSIONS: Future work on pharmacovigilance may be informed by this novel commercial tool, but the inability to mine the full text of a posting poses serious challenges to content categorization.

PMID: 28748367 [PubMed - indexed for MEDLINE]

Suspected Adverse Effects After Human Papillomavirus Vaccination: A Temporal Relationship Between Vaccine Administration and the Appearance of Symptoms in Japan.

Drug Saf. 2017 Dec;40(12):1219-1229

Authors: Ozawa K, Hineno A, Kinoshita T, Ishihara S, Ikeda SI

Abstract
INTRODUCTION: In Japan, after receiving human papillomavirus vaccination, a significant number of adolescent girls experienced various symptoms, the vast majority of which have been ascribed to chronic regional pain syndrome, orthostatic intolerance, and/or cognitive dysfunction. However, a causal link has not been established between human papillomavirus vaccination and the development of these symptoms.
OBJECTIVE: The aim of this study was to clarify the temporal relationship between human papillomavirus vaccination and the appearance of post-vaccination symptoms.
METHODS: Between June 2013 and December 2016, we examined symptoms and objective findings in 163 female patients who had received human papillomavirus vaccination. We used newly defined diagnostic criteria for accurate inclusion of patients who experienced adverse symptoms after human papillomavirus vaccination; these diagnostic criteria were created for this study, and thus their validity and reliability have not been established.
RESULTS: Overall, 43 female patients were excluded. Among the remaining 120 patients, 30 were diagnosed as having definite vaccine-related symptoms, and 42 were diagnosed as probable. Among these 72 patients, the age at initial vaccination ranged from 11 to 19 years (average 13.6 ± 1.6 years), and the age at appearance of symptoms ranged from 12 to 20 years (average 14.4 ± 1.7 years). The patients received the initial human papillomavirus vaccine injection between May 2010 and April 2013. The first affected girl developed symptoms in October 2010, and the last two affected girls developed symptoms in October 2015. The time to onset after the first vaccine dose ranged from 1 to 1532 days (average 319.7 ± 349.3 days).
CONCLUSIONS: The period of human papillomavirus vaccination considerably overlapped with that of unique post-vaccination symptom development. Based on these sequential events, it is suggested that human papillomavirus vaccination is related to the transiently high prevalence of the previously mentioned symptoms including chronic regional pain syndrome and autonomic and cognitive dysfunctions in the vaccinated patients.

PMID: 28744844 [PubMed - indexed for MEDLINE]

Analysis of safety-related regulatory actions by Japan's pharmaceutical regulatory agency.

Pharmacoepidemiol Drug Saf. 2017 Nov;26(11):1314-1320

Authors: Ishiguro C, Misu T, Iwasa E, Izawa T

Abstract
PURPOSE: To evaluate the safety-related regulatory actions implemented by Japan's Pharmaceuticals and Medical Devices Agency (PMDA) in 2012.
METHODS: We analyzed serious safety issues appended to drug package inserts (PIs) in Japan in 2012. The issues were characterized according to drug class, adverse event, years since drug approval, initiator of regulatory actions, revised section of PI, and evidence source. We also quantified the durations from signal detection to tentative decision and from tentative decision to regulatory action.
RESULTS: We identified 144 serious safety issues during the study period, and the majority of evidence originated from spontaneous reports (83.5%). The PMDA initiated regulatory actions for half of all safety issues, and the median duration from drug approval to regulatory action was 8 years (interquartile range [IQR], 3-26.5 years). The median duration was 49 days (IQR, 0-362 days) from signal detection to tentative decision and 84 days (IQR, 63-136 days) from tentative decision to regulatory action. Several safety issues involving older drugs and multiple products had protracted decision-making durations.
CONCLUSIONS: Most safety issues led to prompt regulatory actions predominantly based on spontaneous reports. Some safety issues that were not easily detected by the spontaneous reporting system were identified years after approval. In addition, several safety issues required assessments of multiple drug products, which prolonged the decision-making process.

PMID: 28722235 [PubMed - indexed for MEDLINE]

Postmarketing withdrawal of human medicinal products because of adverse reactions in animals: a systematic review and analysis.

Pharmacoepidemiol Drug Saf. 2017 Nov;26(11):1328-1337

Authors: Onakpoya IJ, Heneghan CJ, Aronson JK

Abstract
PURPOSE: We have identified human medicinal products for which animal data were used as evidence for withdrawal, determined whether the adverse reactions were reported in humans, established whether confirmatory human studies were conducted, and explored the withdrawal patterns over time.
METHODS: We searched the World Health Organization's Consolidated List of [Medicinal] Products, drug regulatory authorities' websites, PubMed, Google Scholar, and selected textbooks to identify medicinal products withdrawn from 1950 to June 2016. We included medicinal products for which animal data were specifically reported as a reason for withdrawal. We used a checklist adapted from the International Agency for Research on Cancer criteria to rate the evidence.
RESULTS: In 37 cases, evidence from animals was the reason given for withdrawal between 1963 and 2000. Evidence of carcinogenicity was cited in 23 cases (62%). Limited evidence for harms occasioned withdrawal in over 80% of cases. In 11 cases (30%), the adverse drug reactions were subsequently reported in humans. In 5 instances (14%), formal studies were conducted in humans. The median interval to withdrawal following reports of adverse reactions was 2 years (IQR = 1-9 y).
CONCLUSIONS: Regulatory authorities and drug manufacturers are likely to withdraw medicinal products quickly from the market when animal experiments suggest increased risks of cancers or congenital malformations. Human studies are seldom conducted when harms are suspected in animals. Future research should explore better methods of extrapolating harms data from animal research to humans.

PMID: 28691251 [PubMed - indexed for MEDLINE]

Drug-induced obesity and its metabolic consequences: a review with a focus on mechanisms and possible therapeutic options.

J Endocrinol Invest. 2017 Nov;40(11):1165-1174

Authors: Verhaegen AA, Van Gaal LF

Abstract
Weight gain is a common side effect of many widely used drugs. Weight gain of a few kilograms to an increase of 10% or more of initial body weight has been described. Not only the weight gain as such puts a burden on the health risks of the involved patients, the accompanying increase in the incidence of the metabolic syndrome, type 2 diabetes mellitus, and cardiovascular risk factors urges the caregiver to identify and to closely monitor the patients at risk. In this review, the different classes of drugs with significant weight gaining properties and the metabolic consequences are described. Specific attention is given to pathogenetic mechanisms underlying the metabolic effects and to potential therapeutic measures to prevent them.

PMID: 28660606 [PubMed - indexed for MEDLINE]

Effect of integrated yoga on anti-psychotic induced side effects and cognitive functions in patients suffering from schizophrenia.

J Complement Integr Med. 2018 Jun 26;:

Authors: Verma M, Bhargav H, Varambally S, Raghuram N, Bn G

Abstract
Background Twenty one (12 females) subjects, diagnosed with schizophrenia by a psychiatrist using ICD-10, in the ages 52.87 + 9.5 years and suffering since 24.0 ± 3.05 years were recruited into the study from a schizophrenia rehabilitation center in Bengaluru. Methods All subjects were taking anti-psychotic medications and were in stable state for more than a month. Psychiatric medications were kept constant during the study period. Assessments were done at three points of time: (1) baseline, (2) after one month of usual routine (pre) and (3) after five months of validated Integrated Yoga (IY) intervention (post). Validated 1 h Yoga module (consisting of asanas, pranayama, relaxation techniques and chantings) was practiced for 5 months, five sessions per week. Antipsychotic-induced side effects were assessed using Simpson Angus Scale (SAS) and Udvalg for Kliniske Undersogelser (UKU) side effect rating scale. Cognitive functions (using Trail making Test A and B), clinical symptoms and anthropometry were assessed as secondary variables. Comparisons between "pre" and "post" data was done using paired samples t-tests after subtracting baseline scores from them respectively. Results At the end of five months, significant reduction in drug-induced Parkinsonian symptoms (SAS score; p=0.001) and 38 items of UKU scale was observed along with significant improvement in processing speed, executive functions and negative symptoms of schizophrenia patients. No side effects of Yoga were reported. Conclusions The present study provides preliminary evidence for usefulness of Integrated Yoga intervention in managing anti-psychotic-induced side effects.

PMID: 29944467 [PubMed - as supplied by publisher]

Incidence of and Predictors for Early Discontinuation of Biological Therapies in Veteran Patients with Inflammatory Bowel Disease.

Inflamm Bowel Dis. 2017 Aug;23(8):1434-1439

Authors: Feagins LA, Waljee A, Hou JK, Gu P, Kanjo S, Rudrapatna V, Cipher DJ, Govani S, Gaidos J

Abstract
BACKGROUND: Biological therapies are effective for inducing and maintaining remission in inflammatory bowel disease (IBD), but patients often require changes in biological agents over the course of their illness. We sought to evaluate the rate of and reasons for discontinuing biological agents and to identify risk factors for their discontinuation.
METHODS: We performed a retrospective cohort study across 4 VA hospital systems (Dallas, TX; Houston, TX; Ann Arbor, MI; Richmond, VA). Patients with IBD who were started on biological therapy between 1998 and 2015 were identified, and their medical records were reviewed to confirm the diagnosis of IBD and to collect study data.
RESULTS: Of 1969 patients with IBD; 256 were treated with 346 courses of therapy. By 6 months after initiation of therapy, 82 (24%) had stopped the biological agent. Among patients starting their first biological agent, 21.5% had stopped by 6 months. Patients taking a concomitant thiopurine and those with ileocolonic disease or a nonpenetrating, nonstricturing phenotype were less likely to discontinue biological therapy, whereas those taking 5-ASA concomitantly were more likely to discontinue biological therapy. The most common reasons for discontinuation were primary nonresponse (40%) and adverse drug reactions (29%).
CONCLUSIONS: In conclusion, in a large multicenter VA cohort, we found that 24% of patients who are prescribed a biological stop their treatment early, most commonly for primary nonresponse or for an adverse drug reaction. Consideration should be given to treating patients with a concomitant thiopurine if at all possible, as this reduces the likelihood of early discontinuation.

PMID: 28570429 [PubMed - indexed for MEDLINE]

Effect of Opioids and Benzodiazepines on Clinical Outcomes in Patients Receiving Palliative Care: An Exploratory Analysis.

J Palliat Med. 2017 Nov;20(11):1274-1279

Authors: Boland JW, Allgar V, Boland EG, Oviasu O, Agar M, Currow DC, Johnson MJ

Abstract
BACKGROUND: Medications for symptom management in palliative care have associated, but poorly understood, harms. Drug-related harms have important clinical implications, may impact on patients' compliance and contribute to symptoms.
OBJECTIVE: To explore the longitudinal relationship between oral morphine equivalent daily dose (MEDD) and oral diazepam equivalent daily dose (DEDD) with functional, cognitive, and symptom outcomes in patients receiving palliative care.
DESIGN: Secondary longitudinal analysis of cancer decedents (n = 235) was carried out from a palliative care randomized controlled trial with multiple outcome measures. At each time point, MEDD and DEDD were calculated. Multilevel modeling was used to investigate independent associations between MEDD and DEDD, and cognitive and gastrointestinal symptoms, quality of life (QoL), performance status, and survival.
SETTING/SUBJECTS: Participants were recruited from a specialist palliative care program in southern Adelaide, were expected to live ≥48 hours, had pain in the previous 3 months, and a baseline Folstein Mini-Mental Status Examination score ≥25.
RESULTS: Cognitive and gastrointestinal symptoms, performance status, and QoL worsened over time. In the adjusted multilevel analysis, statistically significant relationships remained between MEDD/DEDD and worsening performance status (p = 0.001), DEDD and gastrointestinal effects (p < 0.001), MEDD and QoL (p < 0.022).
CONCLUSIONS: Commonly used palliative medications were associated with deteriorating performance status. The lack of association between MEDD with gastrointestinal or cognitive symptoms underlines that these associations are not inevitable with close attention. This analysis highlights the importance of including other medications as confounders when exploring medication-related harms. An understanding of the risk-benefit balance of medications is needed to maximize net benefits for patients.

PMID: 28570119 [PubMed - indexed for MEDLINE]

18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2018/06/26

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Isoniazid-induced hepatotoxicity and neurotoxicity in rats investigated by 1H NMR based metabolomics approach.

Toxicol Lett. 2018 Jun 21;:

Authors: Ruan LY, Fan JT, Hong W, Zhao H, Li MH, Jiang L, Fu YH, Xing YX, Chen C, Wang JS

Abstract
Isoniazid (INH) is a well-known therapeutic and preventive agent against tuberculosis. However, high rates of side effects with various symptoms concerning hepatotoxicity and neurotoxicity have been reported, hindering its wide and safe application in clinic. In this investigation, rats were intoxicated with INH by gavage at doses of 200 and 400 mg/kg for 7 consecutive days to develop a rat model of acute INH-induced toxicity, which was investigated by a 1H NMR-based metabolomics complemented with clinical assays, histopathological inspection and western blotting. INH decreased the weights of dosed rats and induced seizure and hepatic steatosis dose-dependently. Orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA) of the NMR profiles of rat livers, brains and serum revealed that INH dose-dependently induced oxidative stress, disorders of excitatory and inhibitory amino acid neurotransmitters, and disturbances of energy metabolism and osmotic balance, which could help clarify the mechanisms of INH-induced hepatotoxicity and neurotoxicity. This integrated metabolomics approach showcased its ability to characterize the global metabolic status of organism, providing a powerful and feasible tool to probe drug induced toxicity or side effects.

PMID: 29936297 [PubMed - as supplied by publisher]