Literature Watch
Serum Albumin and Disease Severity of Non-Cystic Fibrosis Bronchiectasis.
Serum Albumin and Disease Severity of Non-Cystic Fibrosis Bronchiectasis.
Respir Care. 2017 May 16;:
Authors: Lee SJ, Kim HJ, Kim JY, Ju S, Lim S, Yoo JW, Nam SJ, Lee GD, Cho HS, Kim RB, Cho YJ, Jeong YY, Kim HC, Lee JD
Abstract
BACKGROUND: A clinical classification system has been developed to define the severity and predict the prognosis of subjects with non-cystic fibrosis bronchiectasis (non-CF bronchiectasis). We aimed to identify laboratory parameters that are correlated with the bronchiectasis severity index (BSI) and FACED score.
METHODS: The medical records of 107 subjects with non-CF bronchiectasis for whom BSI and FACED scores could be calculated were retrospectively reviewed. The correlations between the laboratory parameters and BSI or FACED score were assessed, and multiple-linear regression analysis was performed to identify variables independently associated with BSI and FACED score. An additional subgroup analysis was performed according to sex.
RESULTS: Among all of the enrolled subjects, 49 (45.8%) were male and 58 (54.2%) were female. The mean BSI and FACED scores were 9.43 ± 3.81 and 1.92 ± 1.59, respectively. The serum albumin level (r = -0.49), bilirubin level (r = -0.31), C-reactive protein level (r = 0.22), hemoglobin level (r = -0.2), and platelet/lymphocyte ratio (r = 0.31) were significantly correlated with BSI. Meanwhile, serum albumin (r = -0.37) and bilirubin level (r = -0.25) showed a significant correlation with the FACED score. Multiple-linear regression analysis showed that the serum bilirubin level was independently associated with BSI, and the serum albumin level was independently associated with both scoring systems. Subgroup analysis revealed that the level of uric acid was also a significant variable independently associated with the BSI in male bronchiectasis subjects.
CONCLUSIONS: Several laboratory variables were identified as possible prognostic factors for non-CF bronchiectasis. Among them, the serum albumin level exhibited the strongest correlation and was identified as an independent variable associated with the BSI and FACED scores.
PMID: 28512120 [PubMed - as supplied by publisher]
High-resolution mucociliary transport measurement in live excised large animal trachea using synchrotron X-ray imaging.
High-resolution mucociliary transport measurement in live excised large animal trachea using synchrotron X-ray imaging.
Respir Res. 2017 May 16;18(1):95
Authors: Donnelley M, Morgan KS, Awadalla M, Farrow NR, Hall C, Parsons DW
Abstract
BACKGROUND: The Australian Synchrotron Imaging and Medical Beamline (IMBL) was designed as the world's widest synchrotron X-ray beam, enabling both clinical imaging and therapeutic applications for humans as well as the imaging of large animal models. Our group is developing methods for imaging the airways of newly developed CF animal models that display human-like lung disease, such as the CF pig, and we expect that the IMBL can be utilised to image airways in animals of this size.
METHODS: This study utilised samples of excised tracheal tissue to assess the feasibility, logistics and protocols required for airway imaging in large animal models such as pigs and sheep at the IMBL. We designed an image processing algorithm to automatically track and quantify the tracheal mucociliary transport (MCT) behaviour of 103 μm diameter high refractive index (HRI) glass bead marker particles deposited onto the surface of freshly-excised normal sheep and pig tracheae, and assessed the effects of airway rehydrating aerosols.
RESULTS: We successfully accessed and used scavenged tracheal tissue, identified the minimum bead size that is visible using our chosen imaging setup, verified that MCT could be visualised, and that our automated tracking algorithm could quantify particle motion. The imaging sequences show particles propelled by cilia, against gravity, up the airway surface, within a well-defined range of clearance speeds and with examples of 'clumping' behaviour that is consistent with the in vivo capture and mucus-driven transport of particles.
CONCLUSION: This study demonstrated that the wide beam at the IMBL is suitable for imaging MCT in ex vivo tissue samples. We are now transitioning to in vivo imaging of MCT in live pigs, utilising higher X-ray energies and shorter exposures to minimise motion blur.
PMID: 28511651 [PubMed - in process]
Community Acquired Burkholderia cepacia Bacteraemia Presenting as MODS in an Immunocompetent Individual: An Unusual Case.
Community Acquired Burkholderia cepacia Bacteraemia Presenting as MODS in an Immunocompetent Individual: An Unusual Case.
J Clin Diagn Res. 2017 Mar;11(3):DD01-DD02
Authors: Ranjan R, Chowdhary P, Kamra A
Abstract
Burkholderia cepacia has been recognized as a group of highly virulent organisms known as Burkholderia cepacia complex (Bcc). Bcc are ubiquitous in nature and most commonly found in moist environment, on plant roots and soil. Because of its high intrinsic antibiotic resistance, Bcc is a major cause of morbidity and mortality in hospitalized patients. It is reported most commonly in immunocompromised patients especially in patients with cystic fibrosis. Here, we report a rare case report of bacteraemia by Burkholderia cepacia in an immunocompetent male, who presented with fever and Multiple Organ Dysfunction Syndrome (MODS). Burkholderia cepacia was isolated from his blood culture, which he acquired from his work place. He was treated successfully and discharged after negative blood culture.
PMID: 28511384 [PubMed - in process]
Identification of a de novo variant in CHUK in a patient with an EEC/AEC syndrome-like phenotype and hypogammaglobulinemia.
Identification of a de novo variant in CHUK in a patient with an EEC/AEC syndrome-like phenotype and hypogammaglobulinemia.
Am J Med Genet A. 2017 May 17;:
Authors: Khandelwal KD, Ockeloen CW, Venselaar H, Boulanger C, Brichard B, Sokal E, Pfundt R, Rinne T, van Beusekom E, Bloemen M, Vriend G, Revencu N, Carels CEL, van Bokhoven H, Zhou H
Abstract
The cardinal features of Ectrodactyly, Ectodermal dysplasia, Cleft lip/palate (EEC), and Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) syndromes are ectodermal dysplasia (ED), orofacial clefting, and limb anomalies. EEC and AEC are caused by heterozygous mutations in the transcription factor p63 encoded by TP63. Here, we report a patient with an EEC/AEC syndrome-like phenotype, including ankyloblepharon, ED, cleft palate, ectrodactyly, syndactyly, additional hypogammaglobulinemia, and growth delay. Neither pathogenic mutations in TP63 nor CNVs at the TP63 locus were identified. Exome sequencing revealed de novo heterozygous variants in CHUK (conserved helix-loop-helix ubiquitous kinase), PTGER4, and IFIT2. While the variant in PTGER4 might contribute to the immunodeficiency and growth delay, the variant in CHUK appeared to be most relevant for the EEC/AEC-like phenotype. CHUK is a direct target gene of p63 and encodes a component of the IKK complex that plays a key role in NF-κB pathway activation. The identified CHUK variant (g.101980394T>C; c.425A>G; p.His142Arg) is located in the kinase domain which is responsible for the phosphorylation activity of the protein. The variant may affect CHUK function and thus contribute to the disease phenotype in three ways: (1) the variant exhibits a dominant negative effect and results in an inactive IKK complex that affects the canonical NF-κB pathway; (2) it affects the feedback loop of the canonical and non-canonical NF-κB pathways that are CHUK kinase activity-dependent; and (3) it disrupts NF-κB independent epidermal development that is often p63-dependent. Therefore, we propose that the heterozygous CHUK variant is highly likely to be causative to the EEC/AEC-like and additional hypogammaglobulinemia phenotypes in the patient presented here.
PMID: 28513979 [PubMed - as supplied by publisher]
Exome sequencing of two Italian pedigrees with non-isolated Chiari malformation type I reveals candidate genes for cranio-facial development.
Exome sequencing of two Italian pedigrees with non-isolated Chiari malformation type I reveals candidate genes for cranio-facial development.
Eur J Hum Genet. 2017 May 17;:
Authors: Merello E, Tattini L, Magi A, Accogli A, Piatelli G, Pavanello M, Tortora D, Cama A, Kibar Z, Capra V, De Marco P
Abstract
Chiari malformation type I (CMI) is a congenital abnormality of the cranio-cerebral junction with an estimated incidence of 1 in 1280. CMI is characterized by underdevelopment of the occipital bone and posterior fossa (PF) and consequent cerebellar tonsil herniation. The presence for a genetic basis to CMI is supported by many lines of evidence. The cellular and molecular mechanisms leading to CM1 are poorly understood. The occipital bone formation is dependent on complex interactions between genes and molecules with pathologies resulting from disruption of this delicate process. Whole-exome sequencing of affected and not affected individuals from two Italian families with non-isolated CMI was undertaken. Single-nucleotide and short insertion-deletion variants were prioritized using KGGSeq knowledge-based platform. We identified three heterozygous missense variants: DKK1 c.121G>A (p.(A41T)) in the first family, and the LRP4 c.2552C>G (p.(T851R)) and BMP1 c.941G>A (p.(R314H)) in the second family. The variants were located at highly conserved residues, segregated with the disease, but they were not observed in 100 unaffected in-house controls. DKK1 encodes for a potent soluble WNT inhibitor that binds to LRP5 and LRP6, and is itself regulated by bone morphogenetic proteins (BMPs). DKK1 is required for embryonic head development and patterning. LRP4 is a novel osteoblast expressed receptor for DKK1 and a WNT and BMP 4 pathways integrator. Screening of DKK1 in a cohort of 65 CMI sporadic patients identified another missense variant, the c.359G>T (p.(R120L)), in two unrelated patients. These findings implicated the WNT signaling in the correct development of the cranial mesenchyme originating the PF.European Journal of Human Genetics advance online publication, 17 May 2017; doi:10.1038/ejhg.2017.71.
PMID: 28513615 [PubMed - as supplied by publisher]
Haploinsufficiency of ZNF462 is associated with craniofacial anomalies, corpus callosum dysgenesis, ptosis, and developmental delay.
Haploinsufficiency of ZNF462 is associated with craniofacial anomalies, corpus callosum dysgenesis, ptosis, and developmental delay.
Eur J Hum Genet. 2017 May 17;:
Authors: Weiss K, Wigby K, Fannemel M, Henderson LB, Beck N, Ghali N, Study DDD, Anderlid BM, Lundin J, Hamosh A, Jones MC, Ghedia S, Muenke M, Kruszka P
Abstract
The introduction of whole-exome sequencing into the Pediatric Genetics clinic has increased the identification of novel genes associated with neurodevelopmental disorders and congenital anomalies. This agnostic approach has shed light on multiple proteins and pathways not previously known to be associated with disease. Here we report eight subjects from six families with predicted loss of function variants in ZNF462, a zinc-finger protein of unknown function. These individuals have overlapping phenotypes that include ptosis, metopic ridging, craniosynostosis, dysgenesis of the corpus callosum, and developmental delay. We propose that ZNF462 plays an important role in embryonic development, and is associated with craniofacial and neurodevelopmental abnormalities.European Journal of Human Genetics advance online publication, 17 May 2017; doi:10.1038/ejhg.2017.86.
PMID: 28513610 [PubMed - as supplied by publisher]
CAGI4 Crohn's exome challenge: Marker SNP versus exome variant models for assigning risk of Crohn disease.
CAGI4 Crohn's exome challenge: Marker SNP versus exome variant models for assigning risk of Crohn disease.
Hum Mutat. 2017 May 16;:
Authors: Pal LR, Kundu K, Yin Y, Moult J
Abstract
Understanding the basis of complex trait disease is a fundamental problem in human genetics. The CAGI Crohn's Exome challenges are providing insight into the adequacy of current disease models by requiring participants to identify which of a set of individuals has been diagnosed with the disease, given exome data. For the CAGI4 round, we developed a method that used the genotypes from exome sequencing data only to impute the status of Genome Wide Association Studies (GWAS) marker single nucleotide polymorphisms (SNPs). We then used the imputed genotypes as input to several machine learning methods that had been trained to predict disease status from marker SNP information. We achieved the best performance using Naïve Bayes and with a consensus machine learning method, obtaining an area under the curve (AUC) of 0.72, larger than other methods used in CAGI4. We also developed a model that incorporated the contribution from rare missense variants in the exome data, but this performed less well. Future progress is expected to come from the use of whole genome data rather than exomes. This article is protected by copyright. All rights reserved.
PMID: 28512778 [PubMed - as supplied by publisher]
Mutation screening in genes known to be responsible for Retinitis Pigmentosa in 98 Small Han Chinese Families.
Mutation screening in genes known to be responsible for Retinitis Pigmentosa in 98 Small Han Chinese Families.
Sci Rep. 2017 May 16;7(1):1948
Authors: Huang L, Zhang Q, Huang X, Qu C, Ma S, Mao Y, Yang J, Li Y, Li Y, Tan C, Zhao P, Yang Z
Abstract
Retinitis pigmentosa (RP) is highly heterogeneous in both clinical and genetic fields. Accurate mutation screening is very beneficial in improving clinical diagnosis and gene-specific treatment of RP patients. The reason for the difficulties in genetic diagnosis of RP is that the ethnic-specific mutation databases that contain both clinical and genetic information are largely insufficient. In this study, we recruited 98 small Han Chinese families clinically diagnosed as RP, including of 22 dominant, 19 recessive, 52 sporadic, and five X-linked. We then used whole exome sequencing (WES) analysis to detect mutations in the genes known for RP in 101 samples from these 98 families. In total, we identified 57 potential pathogenic mutations in 40 of the 98 (41%) families in 22 known RP genes, including 45 novel mutations. We detected mutations in 13 of the 22 (59%) typical autosomal dominant families, 8 of the 19 (42%) typical autosomal recessive families, 16 of the 52 (31%) sporadic small families, and four of the five (80%) X-linked families. Our results extended the mutation spectrum of known RP genes in Han Chinese, thus making a contribution to RP gene diagnosis and the pathogenetic study of RP genes.
PMID: 28512305 [PubMed - in process]
Short-term open-label chamomile (Matricaria chamomilla L.) therapy of moderate to severe generalized anxiety disorder.
Short-term open-label chamomile (Matricaria chamomilla L.) therapy of moderate to severe generalized anxiety disorder.
Phytomedicine. 2016 Dec 15;23(14):1699-1705
Authors: Keefe JR, Mao JJ, Soeller I, Li QS, Amsterdam JD
Abstract
BACKGROUND: Conventional drug treatments for Generalized Anxiety Disorder (GAD) are often accompanied by substantial side effects, dependence, and/or withdrawal syndrome. A prior controlled study of oral chamomile (Matricaria chamomilla L.) extract showed significant efficacy versus placebo, and suggested that chamomile may have anxiolytic activity for individuals with GAD.
HYPOTHESIS: We hypothesized that treatment with chamomile extract would result in a significant reduction in GAD severity ratings, and would be associated with a favorable adverse event and tolerability profile.
STUDY DESIGN: We report on the open-label phase of a two-phase randomized controlled trial of chamomile versus placebo for relapse-prevention of recurrent GAD.
METHODS: Subjects with moderate to severe GAD received open-label treatment with pharmaceutical-grade chamomile extract 1500mg/day for up to 8 weeks. Primary outcomes were the frequency of clinical response and change in GAD-7 symptom scores by week 8. Secondary outcomes included the change over time on the Hamilton Rating Scale for Anxiety, the Beck Anxiety Inventory, and the Psychological General Well Being Index. Frequency of treatment-emergent adverse events and premature treatment discontinuation were also examined.
RESULTS: Of 179 subjects, 58.1% (95% CI: 50.9% to 65.5%) met criteria for response, while 15.6% prematurely discontinued treatment. Significant improvement over time was also observed on the GAD-7 rating (β=-8.4 [95% CI=-9.1 to -7.7]). A similar proportion of subjects demonstrated statistically significant and clinically meaningful reductions in secondary outcome ratings of anxiety and well-being. Adverse events occurred in 11.7% of subjects, although no serious adverse events occurred.
CONCLUSION: Chamomile extract produced a clinically meaningful reduction in GAD symptoms over 8 weeks, with a response rate comparable to those observed during conventional anxiolytic drug therapy and a favorable adverse event profile. Future comparative effectiveness trials between chamomile and conventional drugs may help determine the optimal risk/benefit of these therapies for patients suffering from GAD.
PMID: 27912871 [PubMed - indexed for MEDLINE]
A Computer Prescribing Order Entry-Clinical Decision Support system designed for neonatal care: results of the 'preselected prescription' concept at the bedside.
A Computer Prescribing Order Entry-Clinical Decision Support system designed for neonatal care: results of the 'preselected prescription' concept at the bedside.
J Clin Pharm Ther. 2017 Feb;42(1):64-68
Authors: Gouyon B, Iacobelli S, Saliba E, Quantin C, Pignolet A, Jacqz-Aigrain E, Gouyon JB
Abstract
WHAT IS KNOWN: The neonatal intensive care units (NICUs) are at the highest risk of drug dose error of all hospital wards. NICUs also have the most complicated prescription modalities. The computerization of the prescription process is currently recommended to decrease the risk of preventable adverse drug effects (pADEs) in NICUs. However, Computer Prescribing Order Entry-Clinical Decision Support (C.P.O.E./C.D.S.) systems have been poorly studied in NICUs, and their technical compatibility with neonatal specificities has been limited.
OBJECTIVES: We set up a performance study of the preselected prescription of drugs for neonates, which limited the role of the prescriber to choosing the drugs and their indications.
METHODS: A single 29 bed neonatal ward used this neonatal C.P.O.E./C.D.S. system for all prescriptions of all hospitalized newborns over an 18-month period. The preselected prescription of drugs was based on the indication, gestational age, body weight and post-natal age. The therapeutic protocols were provided by a formulary reference (330 drugs) that had been specifically designed for newborns. The preselected prescription also gave complete information about preparation and administration of drugs by nurses. The prescriber was allowed to modify the preselected prescription but alarms provided warning when the prescription was outside the recommended range. The main clinical characteristics and all items of each line of prescription were stored in a data warehouse, thus enabling this study to take place.
RESULTS: Seven hundred and sixty successive newborns (from 24 to 42 weeks' gestation) were prescribed 52 392 lines of prescription corresponding to 65 drugs; About 30·4% of neonates had at least one out of licensed prescription; A prescription out of the recommended range for daily dose was recorded for 1·0% of all drug prescriptions. WHAT IS NEW?: The C.P.O.E./C.D.S. systems can currently provide a complete preselected prescription in NICUs according to dose rules, which are specific to newborns and also comply with local specificities (therapeutic protocols and formulation of drugs). The role of the prescriber is limited to the choice of drugs and their indications. The prescriber still retains the possibility of modifying each item of the prescription, with all other prescription items being calculated by the C.P.O.E. system. In these conditions, the prescribers rarely modified the preselected prescription and the rate of out of range prescription was low. A multicentric study is required to confirm and extend these observations.
CONCLUSIONS: This study showed the feasibility of preselected prescription in NICUs and a low rate of out of range prescriptions. The preselected prescription could play a key role in lowering the dose error rate in NICUs.
PMID: 27882560 [PubMed - indexed for MEDLINE]
Prevalence of drug-related problems associated with direct oral anticoagulants in hospitalized patients: a multicenter, cross-sectional study.
Prevalence of drug-related problems associated with direct oral anticoagulants in hospitalized patients: a multicenter, cross-sectional study.
J Clin Pharm Ther. 2017 Feb;42(1):58-63
Authors: Viprey M, Jeannin R, Piriou V, Chevalier P, Michel C, Aulagner G, Berthiller J, Armoiry X
Abstract
WHAT IS KNOWN AND OBJECTIVE: The complex dose regimens of the direct-acting oral anticoagulants (DOAC) make their appropriate prescribing highly challenging. Inappropriate prescribing of the DOAC remains poorly addressed. We studied the patterns of DOAC prescription and estimated the prevalence of drug-related problems (DRPs) associated with their use.
METHODS: A cross-sectional study was conducted using data from medical records system of the Lyon teaching hospitals. DRPs, identified among patients who received a DOAC, between 1 January 2010 and 31 July 2013, were categorized according to the Pharmaceutical Care Network Europe Classification System. The prevalence of hospital stays with a DRP was estimated, and a subgroup analysis according to DOAC and their indication for use was provided. Clinical outcomes were not assessed.
RESULTS: Of the 4154 hospital stays with at least one DOAC administration [3412 patients; median age (range): 71 years (14-98), 57% female], 70·8% were excluded from the analysis mainly due to missing information for renal function and/or patient weight. Of the 1188 hospital stays that were screened, 100 DRPs were identified (prevalence 8·4%; 95% CI, 6·8-10·0). The highest prevalence was found among patients who received rivaroxaban for atrial fibrillation (14·6%; 95% CI, 10·7-18·5). A too low drug dose was the most frequent DRP (n = 56; 4·7%), followed by a too high drug dose (n = 37; 3·1%), contraindication (n = 5; 0·4%), and pharmacokinetic problem requiring dose adjustment (n = 2; 0·2%).
WHAT IS NEW AND CONCLUSION: Drug-related problems associated with the DOACs occur quite commonly among hospitalized patients. Although these DRPs were considered to be of minor severity, prescribing protocols to support better prescribing should be disseminated to reduce the risk to patients. Renal function and body weight data should be mandatory on prescriptions to allow cross-checking.
PMID: 27778374 [PubMed - indexed for MEDLINE]
Safety and efficacy of outpatient parenteral antibiotic therapy in an academic infectious disease clinic.
Safety and efficacy of outpatient parenteral antibiotic therapy in an academic infectious disease clinic.
J Clin Pharm Ther. 2017 Feb;42(1):39-43
Authors: Suleyman G, Kenney R, Zervos MJ, Weinmann A
Abstract
WHAT IS KNOWN AND OBJECTIVE: Outpatient parenteral therapy (OPAT) has become a safe and effective modality for patients requiring intravenous or prolonged antimicrobial therapy since the 1970s. It is being increasingly utilized in various settings; however, studies evaluating the safety and efficacy of clinic-based OPAT are limited. Since 2012, patients being considered for OPAT have required an infectious disease (ID) consultation at our institution. Candidates receiving once-daily antimicrobials who were ineligible for home infusion or nursing home placement as determined by their insurance companies and those who preferred the clinic over nursing home or home infusion were referred to the ID clinic. This study assessed the safety and outcome of patients receiving OPAT in an academic inner-city ID clinic in Detroit, Michigan.
METHODS: This was a retrospective cross-sectional study of electronic medical records of patients, identified through clinic records, who received at least 2 days of OPAT from December 2012 to December 2015. Demographics, types of infections, antimicrobial regimen used, adverse events and outcome were evaluated.
RESULTS: A total of 122 cases were identified during the study period. Mean age was 62 years with 55% male; 102 (84%) of 122 patients had peripherally inserted central catheter (PICC). Fifty-five per cent of patients participated in the clinic-based OPAT programme for insurance reasons, and 43% preferred the clinic over nursing home or home infusion. The most common infections were bone and joint (36%), followed by skin and soft tissue (18%) and urinary tract infections (12%). Ertapenem (44%) and daptomycin (41%) alone or in combination were used most frequently with 40% of patients receiving at least 4 weeks of treatment. Thirteen patients (11%) experienced one or more adverse drug events on daptomycin and/or ertapenem; of these, nine (69%) patients were receiving daptomycin monotherapy. Gastrointestinal symptoms (29%), cramping and myalgias (29%) and asymptomatic creatine phosphokinase (CPK) elevation (24%) were the most common adverse events. Three (3%) of 102 patients had PICC-related complications. Fourteen (88%) of 16 patients with adverse events or PICC-related complications required changing or stopping antibiotics; two (2%) had infection-related readmission. Conversely, 113 (93%) of 122 patients who completed treatment were considered cured and none had treatment failure at the end of 30 days of treatment. No patients died as a result of treatment or infection-related complications.
WHAT IS NEW AND CONCLUSION: Outpatient parenteral therapy in our academic ID clinic was a safe and effective alternative to home infusion or skilled nursing facilities for patients requiring long-term antibiotics with few adverse events and complications.
PMID: 27747899 [PubMed - indexed for MEDLINE]
Transporters affecting biochemical test results: Creatinine-drug interactions.
Transporters affecting biochemical test results: Creatinine-drug interactions.
Clin Pharmacol Ther. 2016 Nov;100(5):437-440
Authors: Chu X, Bleasby K, Chan GH, Nunes I, Evers R
Abstract
Creatinine is eliminated by the kidneys through a combination of glomerular filtration and active transport. Drug-induced increases in serum creatinine (SCr) and/or reduced creatinine renal clearance are used as a marker for acute kidney injury. However, inhibition of active transport of creatinine can result in reversible and, therefore, benign increases in SCr levels. Herein, the transporters involved in creatinine clearance are discussed, in addition to limitations of using creatinine as a biomarker for kidney damage.
PMID: 27509262 [PubMed - indexed for MEDLINE]
Statin Intolerance: A Literature Review and Management Strategies.
Statin Intolerance: A Literature Review and Management Strategies.
Prog Cardiovasc Dis. 2016 Sep - Oct;59(2):153-164
Authors: Saxon DR, Eckel RH
Abstract
Statin intolerance is a commonly encountered clinical problem for which useful management strategies exist. Although many patients report statin-related muscle symptoms, studies indicate that the majority of these patients can tolerate a statin upon re-challenge. Alternative statin dosing strategies are an effective way to modify and reintroduce statin therapy for patients reporting adverse symptoms. Correction of vitamin D deficiency and hypothyroidism may improve statin tolerability in some patients. CoQ10 supplementation has been found to be of no benefit for statin-related muscle symptoms in most recent clinical trials. PCSK9 inhibitors are a new therapeutic option that if confirmed as safe and effective by outcomes trials may be of substantial benefit to select patients at high ASCVD risk who are unable to achieve adequate low-density lipoprotein cholesterol (LDL-C) lowering on maximally tolerated statin therapy. Other available medications to lower LDL-C in statin intolerant patients include ezetimibe, bile acid sequestrants, niacin, and fibrates.
PMID: 27497504 [PubMed - indexed for MEDLINE]
Successful Comparison of US Food and Drug Administration Sentinel Analysis Tools to Traditional Approaches in Quantifying a Known Drug-Adverse Event Association.
Successful Comparison of US Food and Drug Administration Sentinel Analysis Tools to Traditional Approaches in Quantifying a Known Drug-Adverse Event Association.
Clin Pharmacol Ther. 2016 Nov;100(5):558-564
Authors: Gagne JJ, Han X, Hennessy S, Leonard CE, Chrischilles EA, Carnahan RM, Wang SV, Fuller C, Iyer A, Katcoff H, Woodworth TS, Archdeacon P, Meyer TE, Schneeweiss S, Toh S
Abstract
The US Food and Drug Administration's Sentinel system has developed the capability to conduct active safety surveillance of marketed medical products in a large network of electronic healthcare databases. We assessed the extent to which the newly developed, semiautomated Sentinel Propensity Score Matching (PSM) tool could produce the same results as a customized protocol-driven assessment, which found an adjusted hazard ratio (HR) of 3.04 (95% confidence interval [CI], 2.81-3.27) comparing angioedema in patients initiating angiotensin-converting enzyme (ACE) inhibitors vs. beta-blockers. Using data from 13 Data Partners between 1 January 2008, and 30 September 2013, the PSM tool identified 2,211,215 eligible ACE inhibitor and 1,673,682 eligible beta-blocker initiators. The tool produced an HR of 3.14 (95% CI, 2.86-3.44). This comparison provides initial evidence that Sentinel analytic tools can produce findings similar to those produced by a highly customized protocol-driven assessment.
PMID: 27416001 [PubMed - indexed for MEDLINE]
Bivalirudin versus heparin in non-ST and ST-segment elevation myocardial infarction-a registry-based randomized clinical trial in the SWEDEHEART registry (the VALIDATE-SWEDEHEART trial).
Bivalirudin versus heparin in non-ST and ST-segment elevation myocardial infarction-a registry-based randomized clinical trial in the SWEDEHEART registry (the VALIDATE-SWEDEHEART trial).
Am Heart J. 2016 May;175:36-46
Authors: Erlinge D, Koul S, Eriksson P, Scherstén F, Omerovic E, Linder R, Östlund OP, Wallentin L, Fröbert O, James S
Abstract
BACKGROUND: The optimal anticoagulant for patients with acute coronary syndrome treated with percutaneous coronary intervention (PCI) has not been validated in current practice of radial approach and pretreatment with potent P2Y12 inhibitors. Several studies have indicated increased bleeding rate and, in some instances, even increased mortality by the routine use of heparin and glycoprotein IIb/IIIa inhibitors compared to bivalirudin. Direct comparison of bivalirudin versus heparin alone has yielded contradictory results depending on study designs.
METHODS/DESIGN: The VALIDATE-SWEDEHEART trial is a multicenter, prospective, randomized, registry-based, controlled, and open-label clinical trial in patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI undergoing PCI pretreated with ticagrelor, prasugrel, or cangrelor. We hypothesize that bivalirudin is superior to heparin alone in reducing death, myocardial infarction, and major bleeding events at 180 days (primary end point). The trial will enroll 3,000 patients with STEMI and 3,000 patients with non-STEMI undergoing PCI. The trial will use a hybrid registry-based randomized clinical trial design where inclusion, randomization, and baseline data collection are performed using The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registry. The primary composite end point (death, myocardial infarction, or major bleeding events at 180 days) will be identified through active screening after 7 and 180 days and adjudicated by a blinded central end point committee. Secondary end points and long-term outcomes will be recorded from national registries.
CONCLUSION: The VALIDATE-SWEDEHEART trial is founded on a nationwide clinical registry and uses a hybrid registry-based randomized clinical trial (RRCT) design methodology to evaluate efficacy and safety of bivalirudin as compared to heparin alone for acute coronary syndrome, in a large population receiving contemporary recommended therapies including predominantly radial invasive approach and pretreatment with potent P2Y12 inhibitors.
PMID: 27179722 [PubMed - indexed for MEDLINE]
"Rare Diseases"[Mesh] OR "orphan disease"; +7 new citations
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"Rare Diseases"[Mesh] OR "orphan disease"
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"systems biology"; +19 new citations
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Exploratory Clinical Trial Grants in Arthritis and Musculoskeletal and Skin Diseases (R21)
Silencing of HIV-1 Proviruses (R61/R33)
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