Understanding systemic lupus erythematosus patients' desired outcomes and their perceptions of the risks and benefits of using corticosteroids.

Lupus. 2018 Mar;27(3):475-483

Authors: Ng X, dosReis S, Beardsley R, Magder L, Mullins CD, Petri M

Abstract
Introduction The use of corticosteroids in systemic lupus erythematosus (SLE) patients requires difficult trade-offs between efficacy and risk of toxicity. This qualitative study examined SLE patients' most desired outcomes and their concerns with corticosteroid use in SLE treatment. Methods SLE patients with current/past experience with using corticosteroids were recruited from the clinics at the Johns Hopkins Lupus Center and the University of Maryland Medical Center. Five in-depth interviews ( N = 5) and four focus groups ( N = 15) were conducted during which discussions were transcribed and analyzed based on a grounded theory approach. Results We identified five major themes describing SLE patients' most desired outcomes: reduction in flares, maintenance of normal activities, minimization of treatment side effects, prevention of future organ damage, and finding a cure. Further, SLE patients reported these primary concerns with the adverse effects of corticosteroids: weight gain, organ damage (particularly bone-related damage), mood swings/irritability, sleep disturbances, and dental issues. Patients appeared to be more concerned with adverse effects that immediately affected their day-to-day lives. Conclusion Knowledge gained during this study better informs how patients view the benefits and risks of corticosteroids. This can facilitate discussions between physicians and patients as they work together to determine the appropriate use of corticosteroids.

PMID: 28857718 [PubMed - indexed for MEDLINE]

A Call to Action: The Active Role Psychiatrists and the DEA Must Take to Decrease Harm from Psychotropic Drugs Acquired via the Internet.

J Clin Psychiatry. 2016 11;77(11):e1495

Authors: Goldenberg M, Hassamal S, IsHak WW, Haglund M, Miotto K, Danovitch I

PMID: 28076677 [PubMed - indexed for MEDLINE]

Period prevalence, risk factors and consequent injuries of falling among the Saudi elderly living in Riyadh, Saudi Arabia: a cross-sectional study.

BMJ Open. 2018 01 10;8(1):e019063

Authors: Almegbel FY, Alotaibi IM, Alhusain FA, Masuadi EM, Al Sulami SL, Aloushan AF, Almuqbil BI

Abstract
OBJECTIVES: Approximately 28% to 35% of people aged 65 and over fall each year. The consequent injuries of falls are considered a major public health problem. Falls account for more than half of injury-related hospitalisations among old people. The aim of this study was to measure a 1-year period prevalence of falling among old people in Riyadh, Saudi Arabia. In addition, this study described the most common risk factors and consequent injuries of falls.
SETTING AND PARTICIPANTS: A cross-sectional survey was carried out in Riyadh, using a convenient sampling. The targeted population were Saudi citizens who were 60 years or above. Over a 6-month period, 1182 individuals were sampled (545 men and 637 women).
RESULTS: The 1-year prevalence of falling among old Saudis (>=60 years) was 49.9%. Our results show that 74% of the participants who experienced falls had postfall injuries. Old participants who were uneducated and those with middle school certification were associated with falls (adjusted OR (aOR) 1.72; 95% CI 1.15 to 2.56, aOR 1.81; 95% CI 1.15 to 2.85, respectively). Those who live in rented houses had a higher risk of falls. Interestingly, having a caregiver was significantly associated with more falls (aOR 1.39; 95% CI 1.08 to 1.79). However, not using any medications was significantly related to fewer falls. In addition, old individuals using walking aids were more likely to fall than those who did not. Participants who mentioned 'not having stressors were associated with less frequent falls (aOR 0.62; 95% CI 0.39 to 0.97). Cerebrovascular accidents were strongly associated with falls with an estimated OR of 2.75 (95% CI 1.18 to 6.43). Moreover, osteoporosis, poor vision and back pain were found to be predictors for falls among the elderly.
CONCLUSION: 49.9% of elderly Saudis had experienced one or more falls during a 12-month period. Several preventable risk factors could be addressed by routine geriatric assessment. Research on the impact of these risk factors is needed.

PMID: 29326189 [PubMed - indexed for MEDLINE]

Abuse liability assessment for biologic drugs - All molecules are not created equal.

Regul Toxicol Pharmacol. 2018 Feb;92:165-172

Authors: de Zafra CLZ, Markgraf CG, Compton DR, Hudzik TJ

Abstract
The development of novel drug candidates involves the thorough evaluation of potential efficacy and safety. To facilitate the safety assessment in light of global increases in prescription drug misuse/abuse, health authorities have developed guidance documents which provide a framework for evaluating the abuse liability of candidate therapeutics. The guidances do not distinguish between small molecules and biologics/biotherapeutics; however, there are key differences between these classes of therapeutics which are important drivers of concern for abuse. An analysis of these properties, including ability to distribute to the central nervous system, pharmacokinetic properties (e.g., half-life and metabolism), potential for off-target binding, and the physiochemical characteristics of biologic drug products suggests that the potential for abuse of a biologic is limited. Many marketed antibodies and recombinant proteins have been associated with adverse effects such as headache and dizziness. However, biologics have not historically engendered the rapid-onset psychoactive effects typically present for drugs of abuse, thus further underscoring their low risk for abuse potential. The factors to be taken into consideration before conducting nonclinical abuse liability studies with biologics are described herein; importantly, the aggregate assessment of these factors leads to the conclusion that abuse liability studies are unlikely to be necessary for this class of therapeutics.

PMID: 29199066 [PubMed - indexed for MEDLINE]

Drug Interactions in Neurocritical Care.

Neurocrit Care. 2017 Oct;27(2):287-296

Authors: Spoelhof B, Farrokh S, Rivera-Lara L

Abstract
Drug-drug interactions (DDIs) are common and avoidable complications that are associated with poor patient outcomes. Neurocritical care patients may be at particular risk for DDIs due to alterations in pharmacokinetic profiles and exposure to medications with a high DDI risk. This review describes the principles of DDI pharmacology, common and severe DDIs in Neurocritical care, and recommendations to minimize adverse outcomes. A review of published literature was performed using PubMed by searching for 'Drug Interaction' and several high DDI risk and common neurocritical care medications. Key medication classes included anticoagulants, antimicrobials, antiepileptics, antihypertensives, sedatives, and selective serotonin reuptake inhibitors. Additional literature was also reviewed to determine the risk in neurocritical care and potential therapeutic alternatives. Clinicians should be aware of interactions in this setting, the long-term complications, and therapeutic alternatives.

PMID: 28054285 [PubMed - indexed for MEDLINE]

How do parents perceive adverse drug events of their children's anticonvulsant medication?

Eur J Paediatr Neurol. 2018 May;22(3):427-433

Authors: Bach VA, Neininger MP, Spindler UP, Hotopp LC, Hornemann F, Syrbe S, Merkenschlager A, Kiess W, Bernhard MK, Bertsche T, Bertsche A

Abstract
BACKGROUND: The main source of knowledge on adverse drug events (ADE) are physicians' reports in controlled clinical trials. In contrast, little is known about the parents' perception of ADE of anticonvulsants their children receive.
METHODS: After approval by the local ethics committee, we performed a survey in a neuropediatric outpatient clinic of a university hospital. Based on a structured questionnaire, we interviewed parents of children with current anticonvulsant treatment regarding (i) their fears about potential ADE, (ii) experienced ADE according to parents, and (iii) implications of ADE on the child's life.
RESULTS: Parents of 150 patients took part in the interview. (i) 95 (63.3%) parents expressed fears concerning ADE, mostly liver injury/liver failure (33 [22%]). (ii) 129 (86%) parents reported experienced ADE, mostly sedation (65 [43.3%]) and abnormal behavior (54 [36%]). (iii) Parents reported substantial implications of ADE on the child's daily life for 84 (56%) children, and 63 (42%) parents expressed a negative impact on the child's development.
CONCLUSION: We recognized a great discrepancy between those ADE that were feared and those that were experienced. Parents feared life-threatening ADE and experienced less severe ADE that nevertheless have a negative impact on the child's daily life.

PMID: 29475820 [PubMed - indexed for MEDLINE]

HLA Association with Drug-Induced Adverse Reactions.

J Immunol Res. 2017;2017:3186328

Authors: Fan WL, Shiao MS, Hui RC, Su SC, Wang CW, Chang YC, Chung WH

Abstract
Adverse drug reactions (ADRs) remain a common and major problem in healthcare. Severe cutaneous adverse drug reactions (SCARs), such as Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) with mortality rate ranges from 10% to more than 30%, can be life threatening. A number of recent studies demonstrated that ADRs possess strong genetic predisposition. ADRs induced by several drugs have been shown to have significant associations with specific alleles of human leukocyte antigen (HLA) genes. For example, hypersensitivity to abacavir, a drug used for treating of human immunodeficiency virus (HIV) infection, has been proposed to be associated with allele 57:01 of HLA-B gene (terms HLA-B∗57:01). The incidences of abacavir hypersensitivity are much higher in Caucasians compared to other populations due to various allele frequencies in different ethnic populations. The antithyroid drug- (ATDs- ) induced agranulocytosis are strongly associated with two alleles: HLA-B∗38:02 and HLA-DRB1∗08:03. In addition, HLA-B∗15:02 allele was reported to be related to carbamazepine-induced SJS/TEN, and HLA-B∗57:01 in abacavir hypersensitivity and flucloxacillin induced drug-induced liver injury (DILI). In this review, we summarized the alleles of HLA genes which have been proposed to have association with ADRs caused by different drugs.

PMID: 29333460 [PubMed - indexed for MEDLINE]

Evaluation of a medication intensity screening tool used in malignant hematology and bone marrow transplant services to identify patients at risk for medication-related problems.

J Oncol Pharm Pract. 2018 Jun;24(4):243-252

Authors: Lucena M, Bondarenka C, Luehrs-Hayes G, Perez A

Abstract
Background In 2014, a screening tool was implemented at Medical University of South Carolina (MUSC) Health to identify patients who are at risk for medication-related events. Patients are classified as high-risk if they meet one of the following criteria: receiving anticoagulation therapy, taking more than 10 scheduled medications upon admission, or readmission within the past 30 days. The goal of this study was to determine risk criteria specific to the malignant hematology (MH) and bone marrow transplant (BMT) patients. Methods A retrospective chart review of 114 patients admitted and discharged from the MH/BMT services between 1 September 2015 and 31 October 2015 was performed. A pharmacist-conducted medication history was completed and documented, and all interventions at admission and throughout hospitalization were categorized by severity and by value of service. The primary objective was to evaluate if patients in the MH/BMT services have more medication-related interventions documented upon admission compared with patients who are not screened as high risk. The secondary objectives were to evaluate the different types and severities of interventions made by pharmacists during the entire hospital stay, and to determine if there are certain characteristics that can help identify hematology/oncology high-risk patients. Results More interventions documented upon admission in the high-risk group as a whole when compared with the not high-risk group (73 vs. 31), but when normalized per patients in each group, there was an equal number of interventions (1.0). The most common interventions were to modify regimen (36%) and discontinue therapy (16%). The patient characteristics associated with high-risk included neutropenia, lower average platelet counts on admission, and longer length of stay. Conclusion The screening tool does not further differentiate an already complex MH/BMT patient population. Pharmacists may be more useful at capturing errors or changes during a patient's hospital stay instead of upon admission. Thrombocytopenia, neutropenia, and active infections may correlate with higher-risk status.

PMID: 29284343 [PubMed - indexed for MEDLINE]

Ameliorative Effect of Gallic Acid in Doxorubicin-Induced Hepatotoxicity in Wistar Rats Through Antioxidant Defense System.

J Diet Suppl. 2018 Mar 04;15(2):183-196

Authors: Omobowale TO, Oyagbemi AA, Ajufo UE, Adejumobi OA, Ola-Davies OE, Adedapo AA, Yakubu MA

Abstract
Hepatotoxicity has been found to be one of the main side effects associated with doxorubicin (Dox) administration in cancer therapy. The aim of the present study was to examine the ameliorative effect of gallic acid (GA) in Dox-induced hepatotoxicity. Sixty male Wistar rats of 10 rats per group were used in this study and were randomly divided into 6 experimental groups (A-F). Rats in Group A served as the control group and received distilled water orally for 7 days; Group B was given Dox at 15 mg/kg body weight intraperitoneally (IP) on Day 8. Group C was given GA at 60 mg/kg body weight orally for 7 days + Dox at 15 mg/kg IP on Day 8. Group D was given GA at 120 mg/kg body weight orally for 7 days + Dox at 15 mg/kg IP on day 8. Rats in Groups E and F were administered GA alone at 60 and 120 mg/kg body weight orally for 7 days, respectively. Dox administration led to a significant reduction in hepatic reduced glutathione and nonprotein thiol (NPT) together with significant increase in hepatic malondialdehyde, hydrogen peroxide generation, superoxide dismutase, and catalase activity; hepatic glutathione peroxidase and glutathione-S-transferase activity were significantly inhibited in Dox-treated rats. The serum alanine aminotransferase (ALT), alkaline phosphatase, and total bilirubin concentrations were significantly elevated following Dox administration. Pretreatment with GA ameliorated Dox-induced hepatotoxicity and oxidative stress. The results suggest that GA may offer protection against hepatic damage in Dox cancer chemotherapy.

PMID: 28718673 [PubMed - indexed for MEDLINE]

Proton pump inhibitors use; beware of side-effects.

J Pak Med Assoc. 2016 12;66(12):1672

Authors: Noman ul Haq, Riaz S, Nasim A

PMID: 27924970 [PubMed - indexed for MEDLINE]

[Lead compound optimization strategy(5) – reducing the hERG cardiac toxicity in drug development].

Yao Xue Xue Bao. 2016 10;51(10):1530-9

Authors: Zhou SB, Wang J, Liu H

Abstract
The potassium channel encoded by the human ether-a-go-go related gene(hERG) plays a very important role in the physiological and pathological processes in human. hERG potassium channel determines the outward currents which facilitate the repolarization of the myocardial cells. Some drugs were withdrawn from the market for the serious side effect of long QT interval and arrhythmia due to blockade of hERG channel. The strategies for lead compound optimization are to reduce inhibitory activity of hERG potassium channel and decrease cardiac toxicity. These methods include reduction of lipophilicity and basicity of amines, introduction of hydroxyl and acidic groups, and restricting conformation.

PMID: 29932317 [PubMed - indexed for MEDLINE]

Lack of effect of azithromycin on QT interval in children: a cohort study.

Arch Dis Child. 2016 Nov;101(11):1079

Authors: Espadas D, Castillo S, Moreno M, Escribano A

PMID: 27515186 [PubMed - indexed for MEDLINE]

A new paediatric formulation of valaciclovir: development and bioequivalence assessment.

Arch Dis Child. 2016 10;101(10):971-2

Authors: Bastiaans DE, Bartels-Wilmer CM, Colbers AP, Heijens CA, Velthoven-Graafland K, Smeets OS, Vink N, Harbers VE, Warris A, Burger DM

PMID: 27162003 [PubMed - indexed for MEDLINE]

The Efficacy and Safety of Apatinib Treatment for Patients with Unresectable or Relapsed Liver Cancer: a retrospective study.

J Cancer. 2018;9(16):2773-2777

Authors: Zhen L, Jiali C, Yong F, Han X, Hongming P, Weidong H

Abstract
Purpose: Liver cancer is insensitive to chemotherapy. Sorafenib is currently the standard treatment for patients with advanced diseases, with mild survival extension and several intolerable drug-related side effects. The establishment of new treatments is an unmet clinical need. The aim of our study was to assess the efficacy and safety of apatinib, a novel antiangiogenic drug, in the treatment of patients with liver cancer. Materials and Methods: Patients with unresectable or relapsed liver cancer were included in a single center, retrospective, observational study and treated with apatinib until progressive disease or unacceptable toxicity. Results: 32 patients were reviewed from January 2015 to March 2017. No complete response (CR) occurred, 5 patients (16%) showed partial response (PR), 14 patients (44%) had stable disease (SD), 13 patients (41%) had progressive disease (PD), with disease control rate of 60%. Median progression-free survival (PFS) was 5 months (95% confidence interval [CI]: 4.3-6.1 months) for hepatocellular carcinoma (HCC) and 3 months (95% CI: 2.5-4.2 months) for intrahepatic cholangiocarcinoma (ICC). The median overall survival (OS) was 13 months (95% CI: 12.4-14.1 months) for HCC and 5 months (95% CI: 4.5-6.2 months) for ICC, respectively. The most common adverse effects (AEs) were proteinuria (31%), secondary hypertension (28%) and liver dysfunction (13%). Conclusion: Apatinib treatment was an effective for patients with liver cancer. The toxicities were mild and tolerable.

PMID: 30123344 [PubMed]

Usefulness of Pharmacogenetic Analysis in Psychiatric Clinical Practice: A Case Report.

Clin Psychopharmacol Neurosci. 2018 Aug 31;16(3):349-357

Authors: Franco-Martin MA, Sans F, García-Berrocal B, Blanco C, Llanes-Alvarez C, Isidoro-García M

Abstract
There are many factors involved in the effectiveness and efficiency of psychiatric drug treatment. One of them is psychotropic drug metabolism, which takes place mostly in the liver through the P450 enzyme system. However, there are genotypic variants of this system's enzymes that can directly affect both the efficacy and the onset of side effects of a given therapeutic regimen. These genotypic changes could partly explain the lack of efficacy of treatment in certain patients. We report the case of a patient diagnosed with bipolar type I disorder that presented multiple and frequent manic episodes in which the efficacy and tolerability of several pharmacological regimens with mood stabilizers and antipsychotics was scarce. The choice of medical treatment should be based on its efficacy and side effect profile. This decision can be made more accurately using the information provided by pharmacogenetic analysis. This case illustrates the importance of pharmacogenetic studies in clinical practice. The results of pharmacogenetic analysis helped to decide on a better treatment plan to achieve clinical improvement and reduce drug-induced adverse effects.

PMID: 30121988 [PubMed]

Successful Management of Clozapine-induced Akathisia with Gabapentin Enacarbil: A Case Report.

Clin Psychopharmacol Neurosci. 2018 Aug 31;16(3):346-348

Authors: Takeshima M, Ishikawa H, Kikuchi Y, Kanbayashi T, Shimizu T

Abstract
The management of clozapine (CLZ)-induced adverse events affects patient prognoses. Akathisia is a relatively rare adverse event related to CLZ administration and thus the management of this syndrome is not well established. Here, we report a case of treatment-resistant schizophrenia wherein CLZ-induced akathisia was successfully managed with gabapentin enacarbil (GE). The patient was a 39-year-old woman who had been treated with atypical antipsychotics other than CLZ for three years with poor tolerability. Initiation of CLZ (400 mg/day) attenuated her psychotic symptoms, but was followed by moderate akathisia. Neither benzodiazepines nor biperiden improved the akathisia; however, akathisia was finally diminished with co-administration of GE. GE facilitated a dosage increase in CLZ (450 mg/day) for the improved management of pyschotic symptoms, and thus indirectly contributed to treatment of the patient's schizophrenia. We suggest that GE is a useful candidate for the management of CLZ-induced akathisia. The improved management of treatment-induced akathisia and other adverse events can extend the potential application of CLZ for treatment-resistant schizophrenia.

PMID: 30121987 [PubMed]

Plasma alpha-1-acid glycoprotein as a potential predictive biomarker for non-haematological adverse events of docetaxel in breast cancer patients.

Biomarkers. 2018 Mar;23(2):142-146

Authors: Jabir RS, Ho GF, Annuar MABA, Stanslas J

Abstract
CONTEXT: Rash and oral mucositis are major non-haematological adverse events (AEs) of docetaxel, in addition to fatigue, nausea, vomiting and diarrhoea, which restrict the use of the drug in cancer therapy. Alpha-1-acid glycoprotein (AAG) is an acute phase reactant glycoprotein and is a primary carrier of docetaxel in the blood. Docetaxel has extensive binding (>98%) to plasma proteins such as AAG, lipoproteins and albumin.
OBJECTIVE: To study the association between plasma AAG level and non-haematological AEs of docetaxel in Malaysian breast cancer patients of three major ethnic groups (Malays, Chinese and Indians).
MATERIALS AND METHODS: One hundred and twenty Malaysian breast cancer patients receiving docetaxel as single agent chemotherapy were investigated for AAG plasma level using enzyme-linked immunosorbent assay technique. Toxicity assessment was determined using Common Terminology Criteria of Adverse Events v4.0. The association between AAG and toxicity were then established.
RESULTS: There was interethnic variation of plasma AAG level; it was 182 ± 85 mg/dl in Chinese, 237 ± 94 mg/dl in Malays and 240 ± 83 mg/dl in Indians. It was found that low plasma levels of AAG were significantly associated with oral mucositis and rash.
CONCLUSIONS: This study proposes plasma AAG as a potential predictive biomarker of docetaxel non-haematological AEs namely oral mucositis and rash.

PMID: 28554261 [PubMed - indexed for MEDLINE]

Are Idiopathic Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Related to Drugs in Food? The Example of Phenylbutazone.

J Invest Dermatol. 2017 05;137(5):1179-1181

Authors: Haddad C, Chosidow O, Valeyrie-Allanore L, Ghaleh B, Legrand T, Mockenhaupt M, Barau C, Khoudour N, Sekula P, Wolkenstein P, Hulin A

PMID: 28108296 [PubMed - indexed for MEDLINE]

Proton pump inhibitors use; beware of side-effects.

J Pak Med Assoc. 2016 10;66(10):1314-1318

Authors: Asim Syed IA, Abbas Naqvi SH

Abstract
Proton pump inhibitors are most widely prescribed medicines all over the world. Since their introduction in pharmacy, life of millions of people has changed completely. Their ability to inhibit acid secretion in stomach has changed the natural history of many once-dreaded conditions like peptic ulcer and gastroesophageal reflux disease. Operation like gastrectomy and partial gastrectomy are carried out very rarely. These medicines are considered very cost-effective, have excellent safety profile, and provide prompt symptomatic relief. However, they are not without side effects, and several warnings have been issued by the Food and Drug Agency of the United States about the risk of hypomagnesaemia, possibility of increased fracture risk, and reduction in efficacy of clopidogrel by concomitant use of proton pump inhibitors. But despite all these warnings, their use is still on the rise. This Review was planned to highlight side effects and drug interactions so that a practising physician may keep the rare but potentially devastating effects in mind while prescribing the pumps.

PMID: 27686311 [PubMed - indexed for MEDLINE]

Multi-disciplinary proactive follow-up algorithm for patients with advanced NSCLC receiving afatinib.

Support Care Cancer. 2018 Aug 16;:

Authors: Cheema PK, Thawer A, Leake J, Cheng SY, Khanna S, Charles Victor J

Abstract
PURPOSE: Afatinib is a standard first-line therapy for advanced EGFR-positive NSCLC. We implemented a pharmacist-led proactive follow-up algorithm to identify and manage early afatinib-related adverse events (AEs).
METHODS: We conducted a retrospective chart review of all patients treated with afatinib after implementation of the algorithm at the Sunnybrook Odette Cancer Centre (Toronto, ON, Canada) from April 1, 2015 to July 31, 2016. Our in-house algorithm involved consultations in person and proactive pharmacist-led callbacks on days 5, 10, and 17. All AEs were graded and documented in real time and management based on toxicity grade was standardized. This study evaluated the impact of our algorithm on real-world AEs.
RESULTS AND DISCUSSION: Thirty-three patients were identified and reviewed. Median follow-up was 248 days. All patients experienced at least one drug-related AE; 18.2% were grade 3/4. The most common AEs were diarrhea 87.9%, rash 81.8%, stomatitis 57.6%, and paronychia 45.5%. Median dose of afatinib was 40 mg daily; 51.5% of patients had ≥ 1 dose reduction and 6.3% discontinued afatinib due to AEs. Proactive calls by the pharmacist identified 36.5% of all drug-related AEs, 33.3% of grade 3/4 AEs, 58.1% of first drug-related AEs and identified two patients that were non-compliant. Only 3.2% of AEs were identified by an emergency room/urgent clinic visit.
CONCLUSIONS: This proactive multi-disciplinary AE management algorithm resulted in a low rate of urgent assessments and discontinuation due to toxicity while maintaining afatinib at ideal dose, thus providing a useful tool for centers prescribing afatinib.

PMID: 30116943 [PubMed - as supplied by publisher]