Disparities in Mortality of Hispanic Cystic Fibrosis Patients in the United States: A National and Regional Cohort Study.

Am J Respir Crit Care Med. 2018 May 09;:

Authors: Rho J, Ahn C, Gao A, Sawicki GS, Keller A, Jain R

Abstract
RATIONALE: Cystic Fibrosis (CF) patients of Hispanic origin are the largest growing minority, representing 8.5% of CF patients in the United States. No national survival analysis of this group has ever been undertaken.
OBJECTIVE: We aimed to determine whether Hispanic ethnicity within the CF population is associated with worse outcomes and whether any geographic differences exist.
METHODS: Using U.S. CF Foundation Patient Registry data from 2010-2014, we performed a retrospective cohort analysis comparing survival rates between Hispanics and non-Hispanics using Kaplan-Meier and Cox regression analysis. A subject's residence was categorized into geographic regions based on U.S. Census Bureau data: Northeast, Midwest, West and South.
MAIN RESULTS: 29,637 patients were included in the study; 2,493 identified themselves as Hispanic. Hispanics had a lower survival probability overall, with a mean age of death of 22.4 ± 9.9 years compared to non-Hispanics of 28.1 ± 10.0 years (p < 0.0001). Multivariate cox proportional hazards modeling revealed that Hispanic CF patients had a 1.27 times higher rate of death compared to non-Hispanics (95% CI: 1.05 - 1.53) after adjusting for covariates including age, sex, genetic mutations, bacterial cultures, lung function, body mass index, use of CF respiratory therapies, low socioeconomic status, pancreatic enzyme use, and CF-related diabetes. When analyzed by region, Hispanics in the Midwest, Northeast, and West had shorter median survivals compared to Non-Hispanics, which was not demonstrated in the South.
CONCLUSIONS: CF patients of Hispanic origin have a higher mortality rate than non-Hispanic CF patients. This pattern was seen in the Midwest, Northeast, and West but not in the South.

PMID: 29742360 [PubMed - as supplied by publisher]

Influenza A non-H1N1 associated with acute respiratory failure and acute renal failure in a previously vaccinated cystic fibrosis patient.

Rev Bras Ter Intensiva. 2018 Mar;30(1):127-130

Authors: Penteado LP, Osório CS, Balbinotto A, Dalcin PTR

Abstract
In the 2014 - 2015 season, most influenza infections were due to A (H3N2) viruses. More than two-thirds of circulating A (H3N2) viruses are antigenically and genetically different (drifted) from the A (H3N2) vaccine component of 2014 - 2015 northern and southern Hemisphere seasonal influenza vaccines. The purpose of this paper is to report a case of seasonal influenza A non-H1N1 infection that occurred in June 2015 in an adult cystic fibrosis patient with severe lung disease previously vaccinated with the anti-flu trivalent vaccine. The patient evolved to respiratory and renal failure (without rhabdomyolysis) and was placed under mechanical ventilation and hemodialysis. The clinical outcome was positive after 39 days of hospital stay. In addition, the patient was clinically stable after 18 months of follow-up. With the recent advances in critical care medicine and in cystic fibrosis treatment, survival with advanced pulmonary disease in cystic fibrosis presents new questions and potential problems, which are still being formulated.

PMID: 29742226 [PubMed - in process]

Effect of backpack carrying on forced vital capacity in cystic fibrosis: A randomized crossover-controlled trial.

PLoS One. 2018;13(5):e0196750

Authors: Combret Y, Medrinal C, Prieur G, Robledo Quesada A, Le Roux P, Reychler G

Abstract
BACKGROUND: Backpack carrying impacts lung function in healthy children but the effect in children with cystic fibrosis (CF) is unknown.
METHODS: Three backpack positions were tested: no backpack (NB), a 12.5% body-weight backpack carried bilaterally (BB) or unilaterally (UB), at rest and during a 10 minute walk. Primary outcome was forced vital capacity (FVC). Secondary outcomes included comparison of cardio-respiratory variables within and between groups.
RESULTS: Nine children with CF (13.3±2.6 years; FEV1 66±22%) and 18 healthy children (13.8±1.8 years; FEV1 107±30%) were included. FVC was reduced with UB compared to NB (68.5±23.3% vs 72.1±24.3%, p = 0.024) in children with CF. FEV1, MIP and MEP decreased more with UB in children with CF than in healthy peers. Increases in VO2, VCO2 and minute ventilation with UB were greater in the CF group during walking.
CONCLUSIONS: Unilateral backpack wearing affects FVC in children with CF and requires greater cardio-respiratory adjustments compared to healthy peers.

PMID: 29742145 [PubMed - in process]

Frontline Science: Pathological conditioning of human neutrophils recruited to the airway milieu in cystic fibrosis.

J Leukoc Biol. 2018 May 09;:

Authors: Forrest OA, Ingersoll SA, Preininger MK, Laval J, Limoli DH, Brown MR, Lee FE, Bedi B, Sadikot RT, Goldberg JB, Tangpricha V, Gaggar A, Tirouvanziam R

Abstract
RATIONALE: Recruitment of neutrophils to the airways, and their pathological conditioning therein, drive tissue damage and coincide with the loss of lung function in patients with cystic fibrosis (CF). So far, these key processes have not been adequately recapitulated in models, hampering drug development. Here, we hypothesized that the migration of naïve blood neutrophils into CF airway fluid in vitro would induce similar functional adaptation to that observed in vivo, and provide a model to identify new therapies.
METHODS: We used multiple platforms (flow cytometry, bacteria-killing, and metabolic assays) to characterize functional properties of blood neutrophils recruited in a transepithelial migration model using airway milieu from CF subjects as an apical chemoattractant.
MAIN FINDINGS: Similarly to neutrophils recruited to CF airways in vivo, neutrophils migrated into CF airway milieu in vitro display depressed phagocytic receptor expression and bacterial killing, but enhanced granule release, immunoregulatory function (arginase-1 activation), and metabolic activities, including high Glut1 expression, glycolysis, and oxidant production. We also identify enhanced pinocytic activity as a novel feature of these cells. In vitro treatment with the leukotriene pathway inhibitor acebilustat reduces the number of transmigrating neutrophils, while the metabolic modulator metformin decreases metabolism and oxidant production, but fails to restore bacterial killing. Interestingly, we describe similar pathological conditioning of neutrophils in other inflammatory airway diseases.
CONCLUSIONS: We successfully tested the hypothesis that recruitment of neutrophils into airway milieu from patients with CF in vitro induces similar pathological conditioning to that observed in vivo, opening new avenues for targeted therapeutic intervention.

PMID: 29741792 [PubMed - as supplied by publisher]

Vestibulotoxicity: strategies for clinical diagnosis and rehabilitation.

Int J Audiol. 2018 May 09;:1-9

Authors: Handelsman JA

Abstract
OBJECTIVE: The purpose of this article is to discuss the most commonly prescribed vestibulotoxic medications and their impact on the vestibular system, to describe the clinical features of vestibular ototoxicity including symptoms reported by patients, and to describe assessment tools that may be used in a monitoring programme, including the functional impact of vestibular loss. Recently published data from a cohort of patients exposed to systemic aminoglycosides (AGS) are summarised, which highlight the importance of monitoring. The role and importance of vestibular rehabilitation in treating affected individuals is discussed.
DESIGN: This is a descriptive article.
STUDY SAMPLE: Recently published data from 71 patients with cystic fibrosis with AGS exposure are summarised.
RESULTS: Recently published data from a cohort of patients exposed to systemic AGS reveal a high prevalence of vestibular system involvement.
CONCLUSIONS: Evidence suggests that including assessment of vestibular function in a programme to monitor for ototoxic damage is essential. While suggestions about possible components of a monitoring programme are made, the need for further study in order to determine an ideal protocol for assessing vestibular system function during and following exposure to toxic agents is stressed.

PMID: 29741128 [PubMed - as supplied by publisher]

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High prevalence of diabetes before and after lung transplantation: Target for improving outcome?

Intern Med J. 2018 May 09;:

Authors: Fazekas-Lavu M, Reyes M, Malouf M, Plit M, Havryk A, Campbell LV, Center JR, Glanville AR, Greenfield JR

Abstract
BACKGROUND: Diabetes increases morbidity and mortality of lung transplantation. However, the reported prevalence of diabetes varies post-transplantation partly due to lack of detection protocols.
AIMS: We determined the prevalence of diabetes in patients (i) waitlisted for lung transplant and (ii) early post-transplantation.
METHODS: We analyzed patients on the St Vincent's Heart Lung database from 1/4/14 to 30/9/15 on the waitlist (Study 1) and those transplanted (Study 2). Standard of care required all non-diabetic patients to have an oral glucose tolerance test (OGTT) (modified for patients with cystic fibrosis [CF] to screen for CF-related hyperglycemia (CFRH) (plasma glucose ≥ 8.2 mmol/L at 60 or 90 minutes).
RESULTS: Study 1 included 114 patients (32 with CF, 82 without CF). Twenty-seven of 30 CF patients (90%) with glycemic data had abnormal glucose metabolism: 18 had diabetes and 9 had CFRH. In 50 patients without CF, 20 (40%) had abnormal glucose metabolism; 8 had diabetes and 12 had impaired fasting glucose and/or impaired glucose tolerance. Study 2 included 78 transplanted patients (25 with CF, 53 without CF). Fourteen CF patients had pre-existing diabetes and 7 had pre-existing CFRH. All but 1 patient were diagnosed with diabetes post-transplantation. Hence, diabetes prevalence in CF patients post-transplantation was 96%. Among 53 transplanted patients without CF, 7 (13%) had abnormal glucose metabolism but thirty (57%) were diagnosed with post-transplant diabetes.
CONCLUSION: There is a high prevalence of diabetes in lung transplant patients. Earlier endocrine participation in lung transplant services is likely to lower diabetes-related morbidity and mortality further.

PMID: 29740976 [PubMed - as supplied by publisher]

A case report of heterozygous TINF2 gene mutation associated with pulmonary fibrosis in a patient with dyskeratosis congenita.

Medicine (Baltimore). 2018 May;97(19):e0724

Authors: Du H, Guo Y, Ma D, Tang K, Cai D, Luo Y, Xie C

Abstract
RATIONALE: Dyskeratosis congenita (DC) is a rare inherited disease characterized by the classical mucocutaneous triad. Pulmonary fibrosis, bone marrow failure, and solid tumors are the main causes of mortality in DC. Pathogenic variants in TERT, TERC, and DKC1 have been identified in individuals with familial pulmonary fibrosis. Mutations in TINF2 gene have been reported to be associated with bone marrow failure in most cases. However, the relationship between TINF2 mutation and pulmonary fibrosis is not yet clear.
PATIENT CONCERNS: Here, we report the case of a 32-year-old woman presented with irritating cough for 2 years and progressive breathlessness for 6 months.
DIAGNOSES: The patient was diagnosed with DC based on the following clinical evidences. Along with some family members, she had the typical mucocutaneous triad and pulmonary fibrosis. A heterozygous mutation (c.844C>T), located in exon 6 of TINF2 gene, that changed arginine to cysteine (Arg282Cys) was identified in this proband by whole exome sequencing.
INTERVENTIONS: The patient received corticosteroid therapy but refused to receive lung transplantation.
OUTCOMES: The proband died of respiratory failure 4 months after the diagnosis. The missense mutation was located in the conserved region of TINF2 gene and predicted to be deleterious by altering the protein structure.
LESSONS: Lung transplantation should be considered for improved survival of patients with DC, and pulmonary fibrosis. Whole exome and whole genome sequencing should be widely used in the identification of such rare genetic variants for clinical diagnosis. The study of DC with pulmonary fibrosis can provide a more appropriate means of clinical research and therapy to the unfortunate patients who suffer from this rare disorder.

PMID: 29742735 [PubMed - in process]

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Gain-of-function mutations in DNMT3A in patients with paraganglioma.

Genet Med. 2018 May 08;:

Authors: Remacha L, Currás-Freixes M, Torres-Ruiz R, Schiavi F, Torres-Pérez R, Calsina B, Letón R, Comino-Méndez I, Roldán-Romero JM, Montero-Conde C, Santos M, Pérez LI, Pita G, Alonso MR, Honrado E, Pedrinaci S, Crespo-Facorro B, Percesepe A, Falcioni M, Rodríguez-Perales S, Korpershoek E, Ramón-Maiques S, Opocher G, Rodríguez-Antona C, Robledo M, Cascón A

Abstract
PURPOSE: The high percentage of patients carrying germline mutations makes pheochromocytomas/paragangliomas the most heritable of all tumors. However, there are still cases unexplained by mutations in the known genes. We aimed to identify the genetic cause of disease in patients strongly suspected of having hereditary tumors.
METHODS: Whole-exome sequencing was applied to the germlines of a parent-proband trio. Genome-wide methylome analysis, RNA-seq, CRISPR/Cas9 gene editing, and targeted sequencing were also performed.
RESULTS: We identified a novel de novo germline mutation in DNMT3A, affecting a highly conserved residue located close to the aromatic cage that binds to trimethylated histone H3. DNMT3A-mutated tumors exhibited significant hypermethylation of homeobox-containing genes, suggesting an activating role of the mutation. CRISPR/Cas9-mediated knock-in in HeLa cells led to global changes in methylation, providing evidence of the DNMT3A-altered function. Targeted sequencing revealed subclonal somatic mutations in six additional paragangliomas. Finally, a second germline DNMT3A mutation, also causing global tumor DNA hypermethylation, was found in a patient with a family history of pheochromocytoma.
CONCLUSION: Our findings suggest that DNMT3A may be a susceptibility gene for paragangliomas and, if confirmed in future studies, would represent the first example of gain-of-function mutations affecting a DNA methyltransferase gene involved in cancer predisposition.

PMID: 29740169 [PubMed - as supplied by publisher]

Related Articles

Exome sequencing revealed C1Q homozygous mutation in Pediatric Systemic Lupus Erythematosus.

Allergol Immunopathol (Madr). 2018 May 05;:

Authors: Zoghi S, Ziaee V, Hirschmugl T, Jimenez-Heredia R, Krolo A, Boztug K, Rezaei N

Abstract
INTRODUCTION AND OBJECTIVES: Pediatric Systemic Lupus Erythematosus (pSLE) is an autoimmune disorder of children. Early disease onset raises the probability of genetic etiology and it is more severe than adult SLE.
PATIENTS AND METHODS: Herein an eight-year-old girl with pSLE from consanguineous parents is reported.
RESULTS: Although she was diagnosed as pSLE since the age of two years, Whole Exome Sequencing (WES) revealed a rare stop-gained C>T mutation in C1QA gene. The variant was validated and segregated in patient and the family. Furthermore, serum levels of the C1q protein were measured and found to be much lower than normal ranges.
CONCLUSIONS: This study indicated that C1Q deficiency should be considered as a differential diagnosis of pSLE. Therefore, measurement of C1q should be recommended in all cases with pSLE.

PMID: 29739689 [PubMed - as supplied by publisher]

Related Articles

Case report of a novel homozygous splice site mutation in PLA2G6 gene causing infantile neuroaxonal dystrophy in a Sudanese family.

BMC Med Genet. 2018 May 08;19(1):72

Authors: Elsayed LEO, Mohammed IN, Hamed AAA, Elseed MA, Salih MAM, Yahia A, Siddig RA, Amin M, Koko M, Elbashir MI, Ibrahim ME, Brice A, Ahmed AE, Stevanin G

Abstract
BACKGROUND: Infantile neuroaxonal dystrophy (INAD) is a rare hereditary neurological disorder caused by mutations in PLA2G6. The disease commonly affects children below 3 years of age and presents with delay in motor skills, optic atrophy and progressive spastic tetraparesis. Studies of INAD in Africa are extremely rare, and genetic studies from Sub Saharan Africa are almost non-existent.
CASE PRESENTATION: Two Sudanese siblings presented, at ages 18 and 24 months, with regression in both motor milestones and speech development and hyper-reflexia. Brain MRI showed bilateral and symmetrical T2/FLAIR hyperintense signal changes in periventricular areas and basal ganglia and mild cerebellar atrophy. Whole exome sequencing with confirmatory Sanger sequencing were performed for the two patients and healthy family members. A novel variant (NM_003560.2 c.1427 + 2 T > C) acting on a splice donor site and predicted to lead to skipping of exon 10 was found in PLA2G6. It was found in a homozygous state in the two patients and homozygous reference or heterozygous in five healthy family members.
CONCLUSION: This variant has one very strong (loss of function mutation) and three supporting evidences for its pathogenicity (segregation with the disease, multiple computational evidence and specific patients' phenotype). Therefore this variant can be currently annotated as "pathogenic". This is the first study to report mutations in PLA2G6 gene in patients from Sudan.

PMID: 29739362 [PubMed - in process]

Related Articles

Clinical genetics of craniosynostosis.

Curr Opin Pediatr. 2017 12;29(6):622-628

Authors: Wilkie AOM, Johnson D, Wall SA

Abstract
PURPOSE OF REVIEW: When providing accurate clinical diagnosis and genetic counseling in craniosynostosis, the challenge is heightened by knowledge that etiology in any individual case may be entirely genetic, entirely environmental, or anything in between. This review will scope out how recent genetic discoveries from next-generation sequencing have impacted on the clinical genetic evaluation of craniosynostosis.
RECENT FINDINGS: Survey of a 13-year birth cohort of patients treated at a single craniofacial unit demonstrates that a genetic cause of craniosynostosis can be identified in one quarter of cases. The substantial contributions of mutations in two genes, TCF12 and ERF, is confirmed. Important recent discoveries are mutations of CDC45 and SMO in specific craniosynostosis syndromes, and of SMAD6 in nonsyndromic midline synostosis. The added value of exome or whole genome sequencing in the diagnosis of difficult cases is highlighted.
SUMMARY: Strategies to optimize clinical genetic diagnostic pathways by combining both targeted and next-generation sequencing are discussed. In addition to improved genetic counseling, recent discoveries spotlight the important roles of signaling through the bone morphogenetic protein and hedgehog pathways in cranial suture biogenesis, as well as a key requirement for adequate cell division in suture maintenance.

PMID: 28914635 [PubMed - indexed for MEDLINE]

Related Articles

Epithelioid Trophoblastic Tumor Around an Abdominal Cesarean Scar: A Pathologic and Molecular Genetic Analysis.

Int J Gynecol Pathol. 2017 Nov;36(6):562-567

Authors: Hsiue EH, Hsu C, Tseng LH, Lu TP, Kuo KT

Abstract
Epithelioid trophoblastic tumor (ETT) is a rare chemoresistant gestational trophoblastic neoplasm that typically presents as an intrauterine lesion. To our knowledge, no isolated abdominal wall ETT around a Cesarean scar has been reported. Here we describe a 54-yr-old woman with a complex obstetric history who presented with a solitary abdominal wall tumor adjacent to the abdominal Cesarean section scar. The tumor demonstrated typical morphologic and immunophenotypic features of ETT. The gestational origin of the tumor was confirmed by microsatellite genotyping. The tumor enlarged despite the patient undergoing multiagent chemotherapy. Whole-exome sequencing was performed to explore the mechanisms underlying chemoresistance. The ATP-binding cassette subfamily B member 1 (ABCB1) 3435CC genotype, and a putative deleterious x-ray cross-complementing group 4 (XRCC4) Ala73Pro mutations were found. In conclusion, ETT may present as a solitary abdominal wall lesion and microsatellite genotyping could facilitate the determination of its gestational origin. More studies are required to provide mechanistic insights into the chemoresistance of ETT.

PMID: 28134666 [PubMed - indexed for MEDLINE]

Related Articles

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]

Related Articles

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]

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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]

Related Articles

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]

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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]

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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]

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Funding Opportunity RFA-CA-18-014 from the NIH Guide for Grants and Contracts. The purpose of the funding opportunity announcement (FOA) is to advance our understanding of the modes of transmission of Kaposi sarcoma-associated herpesvirus (KSHV), also called human herpesvirus-8 (HHV-8); the biology of the initial steps of infection; and risk factors for infection to inform efforts to prevent KSHV transmission and thus prevent Kaposi sarcoma (KS), KSHV-associated multicentric Castleman disease (MCD), primary effusion lymphoma (PEL), and other KSHV-induced diseases in populations living with HIV or at high risk of developing HIV.