Characterization of Thermally Activated Metalloenediyne Cytotoxicity in Human Melanoma Cells.

Radiat Res. 2018 May 15;:

Authors: Keller EJ, Porter M, Garrett JE, Varie M, Wang H, Pollok KE, Turchi JJ, Zaleski JM, Dynlacht JR

Abstract
Enediynes are a highly cytotoxic class of compounds. However, metallation of these compounds may modulate their activation, and thus their cytotoxicity. We previously demonstrated that cytotoxicity of two different metalloenediynes, including (Z)-N,N'-bis[1-pyridyl-2-yl-meth-(E)-ylidene]octa-4-ene-2,6-diyne-1,8-diamine] (PyED), is potentiated when the compounds are administered to HeLa cells during hyperthermia treatment at concentrations that are minimally or not cytotoxic at 37°C. In this study, we further characterized the concentration, time and temperature dependence of cytotoxicity of PyED on human U-1 melanoma cells. We also investigated the potential mechanisms by which PyED cytotoxicity is enhanced during hyperthermia treatment. Cell killing with PyED was dependent on concentration, temperature during treatment and time of exposure. Potentiation of cytotoxicity was observed when cells were treated with PyED at temperatures ≥39.5°C, and enhancement of cell killing increased with temperature and with increasing time at a given temperature. All cells treated with PyED were shown to have DNA damage, but substantially more damage was observed in cells treated with PyED during heating. DNA repair was also inhibited in cells treated with the drug during hyperthermia. Thus, potentiation of PyED cytotoxicity by hyperthermia may be due to enhancement of drug-induced DNA lesions, and/or the inhibition of repair of sublethal DNA damage. While the selective thermal activation of PyED supports the potential clinical utility of metalloenediynes as cancer thermochemotherapeutic agents, therapeutic gain could be optimized by identifying compounds that produce minimal toxicity at 37°C but which become activated and show enhancement of cytotoxicity within a tumor subjected to localized hyperthermic or thermal ablative treatment, or which might act as bifunctional agents. We thus also describe the development and initial characterization of a novel cofactor complex of PyED, platinated PyED (Pt-PyED). Pt-PyED binds to DNA-like cisplatin, and much like PyED, cytotoxicity is greatly enhanced after treatment with the drug at elevated temperatures. However, in contrast to PyED, Pt-PyED is only minimally cytotoxic at 37°C, at concentrations at which cytotoxicity is enhanced by hyperthermia. Further development of cisplatin-based enediynes may result in compounds which, when activated, will possess multiple DNA binding modalities similar to cisplatin, but produce less side effects in tissues at normothermic temperatures.

PMID: 29763378 [PubMed - as supplied by publisher]

Efficacy, safety and quality of life in patients receiving subcutaneous IgG treatment: experience in Bogotá, Colombia.

Immunotherapy. 2018 May 15;:

Authors: Ortega-López MC, Garay J, Pinilla ML

Abstract
AIM: Investigate efficacy, safety and quality of life of gammanorm® 16.5% (subcutaneous immunoglobulin [SCIG]) in patients with primary immunodeficiencies (PIDs) and safety and to lesser extent efficacy in autoimmune diseases.
PATIENTS & METHODS: Medical records were extracted from 31 pediatric and 12 adult patients who received SCIG as part of the Personalized Program at University Children's Hospital, Bogotá, Colombia.
RESULTS: Mean SCIG dose was 28.7 g/month. Serious bacterial infections were observed in 7/33 patients in the PID group, most often bacterial pneumonia (3/33). There were no serious adverse events related to SCIG treatment. Drug-related adverse reactions were reported in 2/43 patients.
CONCLUSION: Self-administration of SCIG provided effective protection, favorable tolerability and improved quality of life in patients with PIDs and autoimmune diseases from Colombia.

PMID: 29761739 [PubMed - as supplied by publisher]

[Pharmacological action and clinical outcome of newly developed NSAIDs patch, "LOQOA® tape"].

Nihon Yakurigaku Zasshi. 2018;151(5):221-227

Authors: Otsuka N, Yataba I

Abstract
Topical non-steroidal anti-inflammatory drugs (NSAIDs) patches are indispensable for the treatment of musculoskeletal diseases, while they are considered less effective than oral NSAIDs. LOQOA® tape is a tape-type patch containing esflurbiprofen (SFP) as a major active ingredient with potent cyclooxygenase inhibition and sufficient skin permeability. SFP patch (SFPP) showed higher percutaneous absorption rate, rapid pain relief, and potent anti-inflammatory efficacy comparing with existing NSAIDs patches in rat. SFPP showed dramatically higher synovial fluid and tissue concentration on SFP than that of flurbiprofen (FP) patch after single application to knee osteoarthritis (OA) patients. On the other hand, clinical dosage of SFPP was determined as not more than two patches a day from the estimation of systemic exposure to SFP of SFPP and oral FP. SFPP showed statistically significant differences in pain relief and all the other efficacy end points compared to inactive placebo or FP patch in knee OA patients. Efficacy on OA other than knee joint was also observed. In long-term study of SFPP, using up to two patches a day, a total of 201 patients was included and 161 patients achieved 52-week application. Among drug-related side effects, skin reaction at the application sites was observed in 46.8% and discontinued in 4.3%. Although gastro-intestinal reaction and abnormal changes in laboratory tests related to kidney function were observed as systemic drug-related side effects, most of them were mild in severity. SFPP, the new generation NSAIDs patch, would be one of effective options for the treatment of symptomatic OA patients.

PMID: 29760367 [PubMed - in process]

A content analysis of the representation of statins in the British newsprint media.

BMJ Open. 2017 Aug 21;7(8):e012613

Authors: Chisnell J, Marshall T, Hyde C, Zhelev Z, Fleming LE

Abstract
OBJECTIVE: This study reviewed the news media coverage of statins, seeking to identify specific trends or differences in viewpoint between media outlets and examine common themes.
DESIGN: The study is a content analysis of the frequency and content of the reporting of statins in a selection of the British newsprint media. It involved an assessment of the number, timing and thematic content of articles followed by a discourse analysis examining the underlying narratives. The sample was the output of four UK newspapers, covering a broad-spectrum readership, over a six month timeframe 1 October 2013 to 31 March 2014.
RESULTS: A total of 67 articles included reference to statins. The majority (39, 58%) were reporting or responding to publication of a clinical study. The ratio of negative to positive coverage was greater than 2:1 overall. In the more politically right-leaning newspapers, 67% of coverage was predominantly negative (30/45 articles); 32% in the more left-leaning papers (7/22 articles). Common themes were the perceived 'medicalisation' of the population; the balance between lifestyle modification and medical treatments in the primary prevention of heart disease; side effects and effectiveness of statins; pharmaceutical sponsorship and implications for the reliability of evidence; trust between the public and government, institutions, research organisations and the medical profession.
CONCLUSIONS: Newsprint media coverage of statins was substantially influenced by the publication of national guidance and by coverage in the medical journals of clinical studies and comment. Statins received a predominantly negative portrayal, notably in the more right-leaning press. There were shared themes: concern about the balance between medication and lifestyle change in the primary prevention of heart disease; the adverse effects of treatment; and a questioning of the reliability of evidence from research institutions, scientists and clinicians in the light of their potential allegiances and funding.

PMID: 28827228 [PubMed - indexed for MEDLINE]

Short-term treatment with taurolidine is associated with liver injury.

BMC Pharmacol Toxicol. 2017 Aug 11;18(1):61

Authors: Fahrner R, Möller A, Press AT, Kortgen A, Kiehntopf M, Rauchfuss F, Settmacher U, Mosig AS

Abstract
BACKGROUND: Taurolidine has been used for peritonitis, oncological and catheter-lock treatment because of its anti-inflammatory properties. It has been suggested that taurolidine has no severe side-effects, but after long-term use morphological and functional changes of the liver were reported. The aim of this study was to investigate the effect of short-term use of taurolidine on the liver.
METHODS: In HepaRG cell cultures and on a novel liver biochip dose-dependent effects of taurolidine treatment on hepatocyte adherence and cell viability was investigated. Furthermore, liver enzymes and interleukin- (IL-) 6 were measured in supernatants. Male rats were treated with low- or high-dose taurolidine, respectively, and compared to controls with physiological saline solution administration regarding blood serum parameters and histology.
RESULTS: In HepaRG cell cultures, hepatocyte adherence was significantly decreased, cell death and cleaved caspase-3 were significantly increased after administration of taurolidine in a dose-dependent manner. High-dose application of taurolidine led to elevated liver enzymes and IL-6 secretion in hepatic organoid. After 24 h a significant increase of serum GLDH and ASAT was observed in rats treated with high-dose taurolidine treatment.
CONCLUSIONS: Our results suggest that taurolidine caused liver injury after short-term use in in vitro and in vivo models probably due to direct toxic effects on hepatocytes. Therefore, the taurolidine dose should be titrated in further investigations regarding liver injury and inflammation.

PMID: 28800748 [PubMed - indexed for MEDLINE]

11 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 2018/05/15

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.

11 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 2018/05/15

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.

Long-term safety and efficacy of the novel β3 -adrenoreceptor agonist vibegron in Japanese patients with overactive bladder: A phase III prospective study.

Int J Urol. 2018 May 11;:

Authors: Yoshida M, Kakizaki H, Takahashi S, Nagai S, Kurose T

Abstract
OBJECTIVES: To evaluate the long-term safety and efficacy of vibegron 50 mg and 100 mg, a novel β3 -adrenoreceptor agonist, in Japanese patients with overactive bladder.
METHODS: This was a 1-year, multicenter, open-label, non-controlled study. After a 1-week observation phase, patients were treated with vibegron for 52 weeks. When the efficacy was insufficient after an 8-week treatment with 50 mg, the dose was increased to 100 mg and maintained for an additional 44 weeks.
RESULTS: Among a total of 169 patients receiving one or more doses of vibegron, 118 (69.8%) received vibegron 50 mg for 52 weeks, and the dose was increased to 100 mg in 51 (30.2%) patients. The incidence of drug-related adverse events was 18.1% (21/116) in the vibegron 50 mg group and 11.8% (6/51) in the vibegron 100 mg group. Most frequent drug-related adverse events were dry mouth (3.0%), residual urine volume increased (3.0%), constipation (2.4%) and cystitis (1.8%). Statistically significant changes in overactive bladder symptom variables (daily means of micturitions, urgency episodes, urgency incontinence episodes, incontinence episodes and night-time frequency) from baseline were observed at week 4 and maintained until week 52. The condition of patients who did not respond well to vibegron 50 mg was much improved by increasing the dose to 100 mg. Vibegron improved the quality of life, and the proportion of patients' satisfaction after the treatment with vibegron was high.
CONCLUSIONS: Long-term (52-week) treatment with vibegron is safe, well-tolerated and effective in patients with overactive bladder.

PMID: 29752752 [PubMed - as supplied by publisher]

Linezolid-Containing Treatment Regimens for Tuberculosis in Children.

Pediatr Infect Dis J. 2018 May 10;:

Authors: Prieto LM, Santiago B, Del Rosal T, Carazo B, Jiménez AB, Pérez-Gorricho B, Rubio F, Tagarro A, Blázquez D, Moreno-Pérez D, Mellado MJ, Baquero-Artigao F, Spanish Paediatric TB Research Network (pTBred)

Abstract
BACKGROUND: In recent years there is an increasing interest in the use of linezolid for the treatment of tuberculosis (TB).
METHODS: Patients under 18 years of age who received linezolid within the Spanish Pediatric TB Network (pTBred) from 2001 to 2016 were retrospectively included. Treatment characteristics, adverse events (AEs) and outcomes were analyzed.
RESULTS: Fifteen children were included (53% male) with a median age of 3.6 years (IQR: 1.6-6.2). Median follow up was 54 months (IQR: 38-76). The reasons for linezolid use were drug-resistant TB (DR-TB) in eight (53%) patients, drug-induced liver injury (DILI) in five (33%) patients and chronic liver disease (CLD) in two (13%) patients. Four children (26%) were on immunosuppressive therapy when TB was diagnosed. Five children (33%) were diagnosed with extrapulmonary TB. The median duration of linezolid treatment was 13 months (IQR: 7.5-17). Nine patients had 13 linezolid-related AEs. Hematologic toxicity was observed in eight patients (53%) and gastrointestinal intolerance in 3 patients (20%). In two patients linezolid dose was reduced and in two patients linezolid was discontinued because of AEs. A 2- year-old girl went back to her country of birth and was lost to follow-up. No relapses were observed among the other 14 patients (93%).
CONCLUSIONS: Linezolid may be considered when treating children with drug resistant TB but also in the cases of patients with chronic liver disease or drug induced liver injury. However, AEs should be closely monitored. Further studies are needed to determine the optimum dosage and the optimal duration of linezolid treatment in children.

PMID: 29750764 [PubMed - as supplied by publisher]

A phase I study of nintedanib combined with cisplatin/gemcitabine as first-line therapy for advanced squamous non-small cell lung cancer (LUME-Lung 3).

Lung Cancer. 2018 Jun;120:27-33

Authors: Forster M, Hackshaw A, De Pas T, Cobo M, Garrido P, Summers Y, Dingemans AC, Flynn M, Schnell D, von Wangenheim U, Loembé AB, Kaiser R, Lee SM

Abstract
BACKGROUND: There are limited treatment options for squamous non-small cell lung cancer (sqNSCLC) and prognosis remains poor. The safety and pharmacokinetics (PK) of nintedanib, a triple angiokinase inhibitor, plus cisplatin/gemcitabine as first-line treatment for advanced sqNSCLC patients, were evaluated.
MATERIALS AND METHODS: A phase I, dose-escalation study administering drugs in a 21-day cycle: cisplatin (75 mg/m2, Day 1), gemcitabine (1250 mg/m2, Days 1 and 8) and nintedanib (Days 2-7, 9-21) were given for 4-6 cycles, followed by monotherapy until disease progression or adverse events (AEs). Two nintedanib doses were tested, 150 mg twice daily (bid) and 200 mg bid, to determine maximum tolerated dose (MTD) based on occurrence of dose-limiting toxicities (DLTs) during Cycle 1. DLTs were primarily defined as drug-related non-hematologic (Grade ≥3) or hematologic (Grade 4) AEs.
RESULTS: Sixteen patients were treated with nintedanib; n = 4 for 150 mg bid, n = 12 for 200 mg bid. No DLTs were observed in Cycle 1; therefore, the MTD was 200 mg bid. In subsequent cycles, two patients had DLTs: renal failure and reduced blood magnesium levels. The most common AEs were gastrointestinal. Three patients discontinued last study medication due to AEs and one had a nintedanib dose reduction. No relevant PK interactions were observed. Five patients had partial responses (31.3%) and eight had stable disease (50.0%); disease control rate was 81.3%. There were three long-term survivors (17-35 months).
CONCLUSIONS: The safety profile of nintedanib 200 mg bid plus cisplatin/gemcitabine was manageable, with AEs consistent with previous observations. PK data demonstrated no interaction, and preliminary antitumor activity was observed.

PMID: 29748012 [PubMed - in process]

Comparison of lacosamide versus sodium valproate in status epilepticus: A pilot study.

Epilepsy Behav. 2017 Nov;76:110-113

Authors: Misra UK, Dubey D, Kalita J

Abstract
PURPOSE: The purpose of this study was to compare the efficacy and safety of lacosamide (LCM) and sodium valproate (SVA) in lorazepam (LOR)-resistant SE.
METHODS: Patients with LOR-resistant SE were randomized to intravenous LCM 400mg at the rate of 60mg/kg/min or SVA 30mg/kg at the rate of 100mg/min. The SE severity score (STESS), duration of SE and its etiology, and MRI findings were noted. Primary outcome was seizure cessation for 1h, and secondary outcomes were 24h seizure remission, in-hospital death, and severe adverse events (SAE).
RESULTS: Sixty-six patients were included, and their median age was 40 (range 18-90) years. Thirty-three patients each received LCM and SVA. Their demographic, clinical, STESS, etiology, and MRI findings were not significantly different. One-hour seizure remission was not significantly different between LCM and SVA groups (66.7% vs 69.7%; P=0.79). Twenty-four-hour seizure freedom was insignificantly higher in SVA (20, 66.6%) compared with LCM group (15, 45.5%). Death (10 vs 12) and composite side effects (4 vs 6) were also not significantly different in LCM and SVA groups. LCM was associated with hypotension and bradycardia (1 patient), and SVA with liver dysfunction (6).
CONCLUSION: In patients with LOR-resistant SE, both LCM and SVA have comparable efficacy and safety.

PMID: 28919386 [PubMed - indexed for MEDLINE]

[Cross sectional study of comorbidities and concomitant medications in a cohort of human immunodeficiency virus-infected patients].

Aten Primaria. 2017 May;49(5):286-293

Authors: García Gonzalo MA, Santamaría Mas MI, Pascual Tomé L, Ibarguren Pinilla M, Rodríguez-Arrondo F

Abstract
AIM: To assess the prevalence of comorbidities, concomitant therapies and adverse effects associated with the medication in a cohort of patients with HIV infection.
DESIGN: Multicentre cross-sectional study.
SETTINGS: Infectious Diseases or Internal Medicine outpatient Clinics of 3 hospitals in the Basque Country.
PARTICIPANTS: During a 3 month period, patients with the following inclusion criteria were randomly selected: HIV infection, age>18years, antiretroviral treatment (ART) for at least 6months, and no changes in ART in the previous 4weeks. A total of 224 patients (of the 225 expected) were included.
MEASUREMENTS: Data were collected using a form, and include, epidemiological and anthropometric data, data related to HIV infection, comorbidities, current therapies, and adverse effects.
RESULTS: Of the 224 patients, 95.5% had at least one comorbidity, the most common being HCV infection (51.3%), dyslipidaemia (37.9%), diabetes mellitus or impaired fasting glucose (21.9%), and hypertension (21.9%). A total of 155 patients (69.2%) were taking concomitant medication: anxiolytics (21.4%), antihypertensives (19.6%), proton pump inhibitors (17.9%), statins (17%), and antidepressants (16.5%). Adverse effects (AE) were observed in 62.9% of subjects, the most common being, changes in body fat distribution (32.6%) and gastrointestinal (24.1%).
CONCLUSIONS: Patients with HIV infection are getting older, with more comorbidities, with very frequent use of concomitant treatments, and high number of adverse effects. This requires a multidisciplinary approach and a coordinated effort within the Primary Care setting.

PMID: 27720238 [PubMed - indexed for MEDLINE]

11 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 2018/05/11

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.

Adverse reactions associated with first-line regimens in patient initiating antiretroviral therapy.

Eur J Clin Pharmacol. 2018 May 08;:

Authors: Mendes JC, Bonolo PF, Ceccato MDGB, Costa JO, Reis AMM, Dos Santos H, Silveira MR

Abstract
OBJECTIVE: To evaluate the prevalence of adverse drug reactions (ADR) and associated factors during the use of Highly Active Antiretroviral Therapy (HAART) in patients initiating treatment.
METHODS: This is a cross-sectional analysis of a prospective study conducted in three public referral services specialized in HIV/AIDS care in Belo Horizonte, Brazil. Self-reported ADR and explanatory variables were obtained from face-to-face interview and from Information Systems. Associated factors with ADR were evaluated by logistic regression in SPSS software v.22.
RESULTS: We included 399 patients, of which 85.5% reported at least one and 72.7% up to 5 ADRs after HAART initiation. Neurological reactions were the most frequent, with self-reported ADRs being distinct according to HAART regimen used. The global model showed higher chance of ADRs among females (OR = 3.52) and illicit drug users (OR = 2.28). Lower chance of ADRs was found for patients aged > 33 years (OR = 0.37), DTG/TDF/3TC users (OR = 0.41), and higher physical domain of quality of life (OR = 0.78). The model restricted to patients using the single-tablet regimen EFV/TDF/3TC showed lower ADRs among patients with CD4+ T lymphocyte count > 200 cells/mm3 (OR = 0.23) and higher independence domain of quality of life (OR = 0.74). The model restricted to DTG/TDF/3TC and to other regimens showed lower ADRs with higher physical domain of quality of life (OR = 0.74 and OR = 0.55, respectively).
CONCLUSIONS: The prevalence of self-reported ADRs to first-line antiretroviral regimens was high and patients using DTG/TDF/3TC had a smaller number of ADRs. In addition to HAART regimen, sociodemographic, clinical, and quality of life characteristics were associated with ADRs.

PMID: 29740676 [PubMed - as supplied by publisher]

Optimal nonvitamin K antagonist oral anticoagulant therapy in a warfarin-sensitive patient after left atrial appendage closure: A case report.

Medicine (Baltimore). 2018 May;97(18):e0683

Authors: Shen L, Fang SS, Ge H, Qiao ZQ, Gu ZC

Abstract
RATIONALE: Developing an optimal medication strategy poses a challenging task in fragile patients after left atrial appendage closure (LAAC). We report an optimal nonvitamin K antagonist oral anticoagulant (NOAC) therapy in a warfarin-sensitive patient after LAAC.
PATIENT CONCERNS: A 77-year-old nonvalvular atrial fibrillation (NVAF) male carrying 2 warfarin-sensitive alleles experienced 2 gum-bleeding with the international normalized ratio (INR) around 3.
DIAGNOSES: Persistent NVAF with a history of subtotal gastrectomy and moderate renal insufficiency.
INTERVENTIONS: Warfarin was discontinued and vitamin K1 was immediately administrated via intravenous infusion. LAAC was regarded as a preferable option, and rivaroxaban 15 mg daily was managed after LACC.
OUTCOMES: Complete endothelialization on the surface of device was detected via transoesophageal echocardiography (TEE), and no peridevice spillage and adverse event occurred.
LESSONS: A post-LAAC treatment with NOAC may be a viable regimen in patients intolerant to warfarin.

PMID: 29718897 [PubMed - indexed for MEDLINE]

Visual field defects following different resective procedures for mesiotemporal lobe epilepsy.

Epilepsy Behav. 2017 Nov;76:39-45

Authors: Schmeiser B, Daniel M, Kogias E, Böhringer D, Egger K, Yang S, Foit NA, Schulze-Bonhage A, Steinhoff BJ, Zentner J, Lagrèze WA, Gross NJ

Abstract
INTRODUCTION: One of the most common side effects of mesiotemporal lobe resection in patients with medically intractable epilepsy are visual field defects (VFD). While peripheral defects usually remain unnoticed by patients, extended VFD influence daily life activities and can, in particular, affect driving regulations. This study had been designed to evaluate frequency and extent of VFD following different surgical approaches to the mesiotemporal area with respect to the ability to drive.
MATERIALS AND METHODS: This study comprises a consecutive series of 366 patients operated at the Epilepsy Center in Freiburg for intractable mesiotemporal lobe epilepsy from 1998 to 2016. The following procedures were performed: standard anterior temporal lobectomy (ATL: n=134; 37%), anterior temporal or keyhole resection (KH: n=53; 15%), and selective amygdalohippocampectomy via the transsylvian (tsAHE: n=145; 40%) and the subtemporal (ssAHE: n=34; 9%) approach. Frequency and extent of postoperative VFD were evaluated in relation to different surgical procedures. According to the German driving guidelines, postoperative VFD were classified as driving-relevant VFD with the involvement of absolute, homonymous central scotoma within 20° and driving-irrelevant VFD with either none or exclusively minor VFD sparing the center.
RESULTS: Postoperative visual field examinations were available in 276 of 366 cases. Postoperative VFD were observed in 202 of 276 patients (73%) and were found to be driving-relevant in 133 of 276 patients (48%), whereas 69 patients (25%) showed VFD irrelevant for driving. Visual field defects were significantly less likely following ssAHE compared with other temporal resections, and if present, they were less frequently driving-relevant (p<0.05), irrespective of the side of surgery.
CONCLUSION: Subtemporal sAHE (ssAHE) caused significantly less frequently and less severely driving-relevant VFD compared with all other approaches to the temporal lobe, irrespective of the side of surgery.

PMID: 28954709 [PubMed - indexed for MEDLINE]

Psychiatric and behavioral side effects of antiepileptic drugs in adults with epilepsy.

Epilepsy Behav. 2017 Nov;76:24-31

Authors: Chen B, Choi H, Hirsch LJ, Katz A, Legge A, Buchsbaum R, Detyniecki K

Abstract
PURPOSE: Psychiatric and behavioral side effects (PBSEs) are common, undesirable effects associated with antiepileptic drug (AED) use. The objective of the study was to compare the PBSE profiles of older and newer AEDs in a large specialty practice-based sample of patients diagnosed with epilepsy.
METHODS: As part of the Columbia and Yale AED Database Project, we reviewed patient records including demographics, medical history, AED use, and side effects for 4085 adult patients (age: 18 years) newly started on an AED regimen. Psychiatric and behavioral side effects were determined by patient or physician report in the medical record, which included depressive mood, psychosis, anxiety, suicidal thoughts, irritability, aggression, and tantrum. Significant non-AED predictors of PBSE rate were first determined from 83 variables using logistic regression. Predictors were then controlled for in the comparison analysis of the rate of PBSEs and intolerable PBSEs (PBSEs that led to dosage reduction or discontinuation) between 18 AEDs.
RESULTS: Psychiatric and behavioral side effects occurred in 17.2% of patients and led to intolerability in 13.8% of patients. History of psychiatric condition(s), secondary generalized seizures, absence seizures, and intractable epilepsy were associated with increased incidence of PBSE. Levetiracetam (LEV) had the greatest PBSE rate (22.1%). This was statistically significant when compared with the aggregate of the other AEDs (P<0.001, OR=6.87). Levetiracetam was also significantly (P<0.001) associated with higher intolerability rate (17.7%), dose decreased rate (9.4%), and complete cessation rate (8.3%), when compared with the aggregate of the other AEDs. Zonisamide (ZNS) was also significantly associated with a higher rate of PBSE (9.7%) and IPBSE (7.9%, all P<0.001). On the other hand, carbamazepine (CBZ), clobazam (CLB), gabapentin (GBP), lamotrigine (LTG), oxcarbazepine (OXC), phenytoin (PHT), and valproate (VPA) were significantly associated with a decreased PBSE rates (P<0.001). Carbamazepine, GBP, LTG, PHT, and VPA were also associated with lower IPBSE rates when compared individually with the aggregate of other AEDs. All other AEDs were found to have intermediate rates that were not either increased or decreased compared with other AEDs. When each AED was compared to LTG, only CBZ had a significantly lower PBSE rate. The main limitations of this study were that the study design was retrospective and not blinded, and the AEDs were not randomly assigned to patients.
CONCLUSIONS: Psychiatric and behavioral side effects occur more frequently in patients taking LEV and ZNS than any other AED and led to higher rates of intolerability. Lower PBSE rates were seen in patients taking CBZ, CLB, GBP, LTG, OXC, PHT, and VPA. Our findings may help facilitate the AED selection process.

PMID: 28931473 [PubMed - indexed for MEDLINE]

Factors contributing to antiretroviral drug adherence among adults living with HIV or AIDS in a Kenyan rural community.

Afr J Prim Health Care Fam Med. 2017 Jul 31;9(1):e1-e7

Authors: Kioko MT, Pertet AM

Abstract
BACKGROUND: Antiretroviral (ARV) adherence of ≥ 95% is recommended for suppressing HIV. However, studies have shown that the ≥ 95% recommended level is rarely achieved.
OBJECTIVE: This cross-sectional community-based study sought to assess factors contributing to ARV drug adherence among adults living with HIV or AIDS.
SETTING: The study was conducted in a rural community in Machakos County, Kenya.
METHODS: The questions used for the study were adapted from the Patient Medicine Adherence Questionnaire (PMAQ), a tool grounded in the Health Belief Model. Adherence to ARV was measured using self-reports and pill counts. The perception social support was measured with a 5-point Likert scale, whereas the type and the number of side effects experienced were recorded using 'yes' and 'no' questions. We used the chi-square test to test associations and binary logistic regression to assess factors explaining dose adherence to ARV.
RESULTS: The levels of adherence of 86% using self-reports were significantly higher (p &lt; 0.001) than the pill count of 58.6%. The immediate family was rated high in providing social support (3.7 ± 0.6) followed by social support groups (3.1 ± 0.8). A binary logistic regression analysis was conducted to predict ARV adherence (adherent, non-adherent) using social support, side effects and marital status as explanatory variables. The Wald criterion demonstrated that marital status (p = 0.019) and burden of side effects (p ≤ 0.001) made a significant contribution to the prediction of ARV adherence.
CONCLUSION: The burden of side effects and being a divorcee are primary predictors of ARV adherence.

PMID: 28828875 [PubMed - indexed for MEDLINE]

Pharmacogenomics of off-target adverse drug reactions.

Br J Clin Pharmacol. 2017 Sep;83(9):1896-1911

Authors: Garon SL, Pavlos RK, White KD, Brown NJ, Stone CA, Phillips EJ

Abstract
Off-target adverse drug reactions (ADRs) are associated with significant morbidity and costs to the healthcare system, and their occurrence is not predictable based on the known pharmacological action of the drug's therapeutic effect. Off-target ADRs may or may not be associated with immunological memory, although they can manifest with a variety of shared clinical features, including maculopapular exanthema, severe cutaneous adverse reactions (SCARs), angioedema, pruritus and bronchospasm. Discovery of specific genes associated with a particular ADR phenotype is a foundational component of clinical translation into screening programmes for their prevention. In this review, genetic associations of off-target drug-induced ADRs that have a clinical phenotype suggestive of an immunologically mediated process and their mechanisms are highlighted. A significant proportion of these reactions lack immunological memory and current data are informative for these ADRs with regard to disease pathophysiology, therapeutic targets and biomarkers which may identify patients at greatest risk. Although many serious delayed immune-mediated (IM)-ADRs show strong human leukocyte antigen associations, only a small subset have successfully been implemented in screening programmes. More recently, other factors, such as drug metabolism, have been shown to contribute to the risk of the IM-ADR. In the future, pharmacogenomic targets and an understanding of how they interact with drugs to cause ADRs will be applied to drug design and preclinical testing, and this will allow selection of optimal therapy to improve patient safety.

PMID: 28345177 [PubMed - indexed for MEDLINE]

Hydralazine-associated adverse events: a report of two cases of hydralazine-induced ANCA vasculitis.

J Bras Nefrol. 2018 May 07;:

Authors: Zuckerman R, Patel M, Costanzo EJ, Dounis H, Haj RA, Seyedali S, Asif A

Abstract
Hydralazine is a direct-acting vasodilator, which has been used in treatment for hypertension (HTN) since the 1950s. While it is well known to cause drug-induced lupus (DIL), recent reports are indicating the emergence of the drug-induced anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (DIV). Herein, we describe two patients (aged 57 and 87 years) who presented with severe acute kidney injury (AKI), proteinuria, and hematuria. Both were receiving hydralazine for the treatment of hypertension. ANCA serology was positive in both patients along with anti-histone antibodies (commonly seen in drug-induced vasculitis). Renal biopsy revealed classic crescentic (pauci-immune) glomerulonephritis in these patients and hydralazine was discontinued. During the hospital course, the 57-year-old patient required dialysis therapy and was treated with steroids and rituximab for the ANCA disease. Renal function improved and the patient was discharged (off dialysis) with a serum creatinine of 3.6 mg/dL (baseline = 0.9 mg/dL). At a follow-up of 2 years, the patient remained off dialysis with advanced chronic kidney disease (CKD) (stage IIIb). The 87-year-old patient had severe AKI with serum creatinine at 10.41 mg/dL (baseline = 2.27 mg/dL). The patient required hemodialysis and was treated with steroids, rituximab, and plasmapheresis. Unfortunately, the patient developed catheter-induced bacteremia and subsequently died of sepsis. Hydralazine can cause severe AKI resulting in CKD or death. Given this extremely unfavorable adverse-event profile and the widespread availability of alternative anti-hypertensive agents, the use of hydralazine should be carefully considered.

PMID: 29738027 [PubMed - as supplied by publisher]