Literature Watch
Evaluating performance in sweat testing in medical biochemistry laboratories in Croatia.
Evaluating performance in sweat testing in medical biochemistry laboratories in Croatia.
Biochem Med (Zagreb). 2017 Feb 15;27(1):122-130
Authors: Aralica M, Krleza JL
Abstract
INTRODUCTION: Sweat test has a diagnostic role in evaluation of cystic fibrosis. Its performance includes sweat stimulation, collection and analysis. All listed may be sources of inconsistencies in everyday practice. The aim of this study was an evaluation of external quality assessment (EQA) of sweat chloride measurement including sweat test performance in medical biochemistry laboratories in Croatia.
MATERIALS AND METHODS: EQA for sweat chloride measurement was provided by Croatian Centre for Quality Assessment in Laboratory Medicine (CROQALM) in five consecutive exercises to medical biochemistry laboratories (MBL) that offered sweat testing. A questionnaire regarding all phases of testing was mailed to involved MBL (N = 10). Survey results were compared to current guidelines for sweat test performance.
RESULTS: Reported results of EQA in 2015 exercises showed coefficients of variation (CV) from 28.9%, 29.0% to 35.3%, respectively. An introduction of uniform sweat chloride measurement protocol resulted in CV of 15.5% and 14.7% reported in following two exercises in 2016. All MBL included in this study replied to the questionnaire. Results reported by MBL indicated: lack of patient information policy (7/10), use of unacceptable electrodes (6/9), misuse of minimum of acceptable sweat weight (6/9), lack of internal quality assessment (5/9) and recommended reference ranges (5/9 and 4/9). Agreements to guidelines were found in approach to unsuitable patients (9/10) and sweat collection (8/9).
CONCLUSION: Presented results indicate major weak points of current practice in sweat test performance in Croatian MBL and stress the need for its standardization on a national level.
PMID: 28392735 [PubMed - in process]
An empirical method to cluster objective nebulizer adherence data among adults with cystic fibrosis.
An empirical method to cluster objective nebulizer adherence data among adults with cystic fibrosis.
Patient Prefer Adherence. 2017;11:631-642
Authors: Hoo ZH, Campbell MJ, Curley R, Wildman MJ
Abstract
BACKGROUND: The purpose of using preventative inhaled treatments in cystic fibrosis is to improve health outcomes. Therefore, understanding the relationship between adherence to treatment and health outcome is crucial. Temporal variability, as well as absolute magnitude of adherence affects health outcomes, and there is likely to be a threshold effect in the relationship between adherence and outcomes. We therefore propose a pragmatic algorithm-based clustering method of objective nebulizer adherence data to better understand this relationship, and potentially, to guide clinical decisions.
METHODS TO CLUSTER ADHERENCE DATA: This clustering method consists of three related steps. The first step is to split adherence data for the previous 12 months into four 3-monthly sections. The second step is to calculate mean adherence for each section and to score the section based on mean adherence. The third step is to aggregate the individual scores to determine the final cluster ("cluster 1" = very low adherence; "cluster 2" = low adherence; "cluster 3" = moderate adherence; "cluster 4" = high adherence), and taking into account adherence trend as represented by sequential individual scores. The individual scores should be displayed along with the final cluster for clinicians to fully understand the adherence data.
THREE ILLUSTRATIVE CASES: We present three cases to illustrate the use of the proposed clustering method.
CONCLUSION: This pragmatic clustering method can deal with adherence data of variable duration (ie, can be used even if 12 months' worth of data are unavailable) and can cluster adherence data in real time. Empirical support for some of the clustering parameters is not yet available, but the suggested classifications provide a structure to investigate parameters in future prospective datasets in which there are accurate measurements of nebulizer adherence and health outcomes.
PMID: 28392678 [PubMed - in process]
Active-Site Flexibility and Substrate Specificity in a Bacterial Virulence Factor: Crystallographic Snapshots of an Epoxide Hydrolase.
Active-Site Flexibility and Substrate Specificity in a Bacterial Virulence Factor: Crystallographic Snapshots of an Epoxide Hydrolase.
Structure. 2017 Mar 31;:
Authors: Hvorecny KL, Bahl CD, Kitamura S, Lee KS, Hammock BD, Morisseau C, Madden DR
Abstract
Pseudomonas aeruginosa secretes an epoxide hydrolase with catalytic activity that triggers degradation of the cystic fibrosis transmembrane conductance regulator (CFTR) and perturbs other host defense networks. Targets of this CFTR inhibitory factor (Cif) are largely unknown, but include an epoxy-fatty acid. In this class of signaling molecules, chirality can be an important determinant of physiological output and potency. Here we explore the active-site chemistry of this two-step α/β-hydrolase and its implications for an emerging class of virulence enzymes. In combination with hydrolysis data, crystal structures of 15 trapped hydroxyalkyl-enzyme intermediates reveal the stereochemical basis of Cif's substrate specificity, as well as its regioisomeric and enantiomeric preferences. The structures also reveal distinct sets of conformational changes that enable the active site to expand dramatically in two directions, accommodating a surprising array of potential physiological epoxide targets. These new substrates may contribute to Cif's diverse effects in vivo, and thus to the success of P. aeruginosa and other pathogens during infection.
PMID: 28392259 [PubMed - as supplied by publisher]
Obstetric care in women with genetic disorders.
Obstetric care in women with genetic disorders.
Best Pract Res Clin Obstet Gynaecol. 2017 Mar 18;:
Authors: Chetty S, Norton ME
Abstract
The management of pregnant women who are themselves affected with genetic diseases is an increasingly relevant and important issue. Improvements in early diagnosis and management of genetic disease, as well as advances in assisted reproductive technology have impacted pregnancy rates in a cohort of women who may not have otherwise been able to conceive. A multidisciplinary approach is key to the management of pregnant women with complex health conditions, including genetic diseases. Pertinent issues should be addressed in the preconception, antepartum, intrapartum and postpartum periods to optimize maternal and fetal health. Additionally, counseling regarding risk of inheritance in offspring and options for prenatal diagnosis should be reviewed if available. This reviews aims to help provide background and insight into the management strategies for various commonly encountered and complex genetic conditions in the setting of pregnancy.
PMID: 28392223 [PubMed - as supplied by publisher]
Modeling cystic fibrosis disease progression in patients with the rare CFTR mutation P67L.
Modeling cystic fibrosis disease progression in patients with the rare CFTR mutation P67L.
J Cyst Fibros. 2017 Apr 05;:
Authors: MacKenzie IE, Paquette V, Gosse F, George S, Chappe F, Chappe V
Abstract
BACKGROUND: The progression of cystic fibrosis (CF) in patients with the rare mutation P67L was examined to determine if it induced a milder form of CF compared to the common severe ΔF508 mutation.
METHODS: Parameters of lung function, level of bacterial infection, nutritional status and hospitalization were used to represent CF progression. Age at diagnosis and pancreatic status were used to assess CF presentation. Analysis of data from the CF Canada Registry collected over a 15-year period included 266 ΔF508/ΔF508 homozygote patients from CF clinics in Atlantic Canada and 26 compound heterozygote patients with the rare P67L mutation from clinics across Canada.
RESULTS: Late age at diagnosis, high incidence of pancreatic sufficiency, maintained Body Mass Index (BMI) with age, delayed life-threatening bacterial infection, and fewer days in hospital were observed for P67L heterozygote patients included in this study. Although the decline of lung function did not differ from ΔF508 homozygotes, the fact that a greater proportion of P67L heterozygotes live to an older age suggests that lung function is not the primary factor determining CF progression for P67L heterozygote patients.
CONCLUSION: The P67L mutation is associated with a mild disease, even when combined with the severe ΔF508 mutation.
PMID: 28392015 [PubMed - as supplied by publisher]
A treatment evaluator tool to monitor the real-world effectiveness of inhaled aztreonam lysine in cystic fibrosis.
A treatment evaluator tool to monitor the real-world effectiveness of inhaled aztreonam lysine in cystic fibrosis.
J Cyst Fibros. 2017 Apr 06;:
Authors: Plant BJ, Downey DG, Eustace JA, Gunaratnam C, Haworth CS, Jones AM, McKone EF, Peckham DG, Ketchell RI, Bilton D
Abstract
BACKGROUND: Studies are required that evaluate real-world outcomes of inhaled aztreonam lysine in patients with cystic fibrosis (CF).
METHODS: Our treatment-evaluator tool assessed the effectiveness of inhaled aztreonam in routine practice in 117 CF patients across four time periods (6-12 (P2) and 0-6months (P1) pre-initiation, and 0-6 (T1) and 6-12months (T2) post-initiation). Outcomes were: changes in %-predicted forced expiratory volume in 1s (FEV1), body-mass index (BMI), hospitalisation days and intravenous antibiotic usage.
RESULTS: Median FEV1% predicted for each 6-month period was 38.9%, 34.6%, 37.1% and 36.5%; median change was -2.0% between P2 and P1, increasing to +0.6% (p<0.001) between P1 and T1. Annualised hospital bed-days was reduced (p=0.05) post-initiation, as was intravenous antibiotics days (p=0.001). BMI increased over 6months post-initiation (p≤0.001).
CONCLUSIONS: In patients with CF in routine practice, inhaled aztreonam lysine is associated with improved lung function and weight, and reduced hospitalisation and intravenous antibiotic use.
PMID: 28392014 [PubMed - as supplied by publisher]
Does clinical indication play a role in CT radiation dose in pediatric patients?
Does clinical indication play a role in CT radiation dose in pediatric patients?
Phys Med. 2017 Apr 05;:
Authors: Triantopoulou S, Tsapaki V
Abstract
PURPOSE: The purpose of this study was to identify the main pathologies for which CT is applied on pediatric patients and the related radiation doses as reported in the literature in order to facilitate justification and CT optimization.
METHODS: A critical analysis of a literature review was performed. Different search engines were used such as PubMed, Google Scholar and Science Direct. Various terms and keywords were used to locate pertinent articles such as Pediatric, Computed tomography, Radiation Dose, Organ dose, Effective dose.
RESULTS: The results showed that the main pathologies for which CT is applied are: Crohn's disease, hydrocephalus, cystic fibrosis and pediatric malignancies-mainly lymphoma. The related radiation dose data are extremely scarce and are in the range of 3.48-17.56, 0.2-15.3mSv, 0.14-6.20mSv, and 2.8-518.0mSv, respectively. The radiation doses reported are high especially in pediatric oncology.
CONCLUSIONS: Pediatric patients with malignancies are those exposed to the higher levels of radiation during CT imaging. Literature is lacking reporting of dose in Pediatric CT imaging. More studies need to be realized for the determination of radiation dose in those patients. Special protocols need to be recommended in order to reduce the exposure of children in radiation.
PMID: 28391959 [PubMed - as supplied by publisher]
Long-Term NSAIDs and Acetaminophen Linked to Hearing Loss in Women.
Long-Term NSAIDs and Acetaminophen Linked to Hearing Loss in Women.
Am J Nurs. 2017 Apr;117(4):16
Authors: Zolot J
Abstract
Duration of aspirin use, however, doesn't affect hearing.
PMID: 28333727 [PubMed - indexed for MEDLINE]
Current evidence supports use of lipid rescue therapy in local anaesthetic systemic toxicity.
Current evidence supports use of lipid rescue therapy in local anaesthetic systemic toxicity.
Acta Anaesthesiol Scand. 2017 04;61(4):365-368
Authors: Weinberg G
PMID: 28251603 [PubMed - indexed for MEDLINE]
Open letter on access to the BIA 10-2474 clinical trial data.
Open letter on access to the BIA 10-2474 clinical trial data.
Lancet. 2017 01 14;389(10065):156
Authors: Brøsen K, Funck-Brentano C, Kroemer HK, Pirmohamed M, Schwab M
PMID: 27955829 [PubMed - indexed for MEDLINE]
Role of Oxidative Stress in Drug-Induced Kidney Injury.
Role of Oxidative Stress in Drug-Induced Kidney Injury.
Int J Mol Sci. 2016 Nov 01;17(11):
Authors: Hosohata K
Abstract
The kidney plays a primary role in maintaining homeostasis and detoxification of numerous hydrophilic xenobiotics as well as endogenous compounds. Because the kidney is exposed to a larger proportion and higher concentration of drugs and toxins than other organs through the secretion of ionic drugs by tubular organic ion transporters across the luminal membranes of renal tubular epithelial cells, and through the reabsorption of filtered toxins into the lumen of the tubule, these cells are at greater risk for injury. In fact, drug-induced kidney injury is a serious problem in clinical practice and accounts for roughly 20% of cases of acute kidney injury (AKI) among hospitalized patients. Therefore, its early detection is becoming more important. Usually, drug-induced AKI consists of two patterns of renal injury: acute tubular necrosis (ATN) and acute interstitial nephritis (AIN). Whereas AIN develops from medications that incite an allergic reaction, ATN develops from direct toxicity on tubular epithelial cells. Among several cellular mechanisms underlying ATN, oxidative stress plays an important role in progression to ATN by activation of inflammatory response via proinflammatory cytokine release and inflammatory cell accumulation in tissues. This review provides an overview of drugs associated with AKI, the role of oxidative stress in drug-induced AKI, and a biomarker for drug-induced AKI focusing on oxidative stress.
PMID: 27809280 [PubMed - indexed for MEDLINE]
Interpretation of the evidence for the efficacy and safety of statin therapy.
Interpretation of the evidence for the efficacy and safety of statin therapy.
Lancet. 2016 11 19;388(10059):2532-2561
Authors: Collins R, Reith C, Emberson J, Armitage J, Baigent C, Blackwell L, Blumenthal R, Danesh J, Smith GD, DeMets D, Evans S, Law M, MacMahon S, Martin S, Neal B, Poulter N, Preiss D, Ridker P, Roberts I, Rodgers A, Sandercock P, Schulz K, Sever P, Simes J, Smeeth L, Wald N, Yusuf S, Peto R
Abstract
This Review is intended to help clinicians, patients, and the public make informed decisions about statin therapy for the prevention of heart attacks and strokes. It explains how the evidence that is available from randomised controlled trials yields reliable information about both the efficacy and safety of statin therapy. In addition, it discusses how claims that statins commonly cause adverse effects reflect a failure to recognise the limitations of other sources of evidence about the effects of treatment. Large-scale evidence from randomised trials shows that statin therapy reduces the risk of major vascular events (ie, coronary deaths or myocardial infarctions, strokes, and coronary revascularisation procedures) by about one-quarter for each mmol/L reduction in LDL cholesterol during each year (after the first) that it continues to be taken. The absolute benefits of statin therapy depend on an individual's absolute risk of occlusive vascular events and the absolute reduction in LDL cholesterol that is achieved. For example, lowering LDL cholesterol by 2 mmol/L (77 mg/dL) with an effective low-cost statin regimen (eg, atorvastatin 40 mg daily, costing about £2 per month) for 5 years in 10 000 patients would typically prevent major vascular events from occurring in about 1000 patients (ie, 10% absolute benefit) with pre-existing occlusive vascular disease (secondary prevention) and in 500 patients (ie, 5% absolute benefit) who are at increased risk but have not yet had a vascular event (primary prevention). Statin therapy has been shown to reduce vascular disease risk during each year it continues to be taken, so larger absolute benefits would accrue with more prolonged therapy, and these benefits persist long term. The only serious adverse events that have been shown to be caused by long-term statin therapy-ie, adverse effects of the statin-are myopathy (defined as muscle pain or weakness combined with large increases in blood concentrations of creatine kinase), new-onset diabetes mellitus, and, probably, haemorrhagic stroke. Typically, treatment of 10 000 patients for 5 years with an effective regimen (eg, atorvastatin 40 mg daily) would cause about 5 cases of myopathy (one of which might progress, if the statin therapy is not stopped, to the more severe condition of rhabdomyolysis), 50-100 new cases of diabetes, and 5-10 haemorrhagic strokes. However, any adverse impact of these side-effects on major vascular events has already been taken into account in the estimates of the absolute benefits. Statin therapy may cause symptomatic adverse events (eg, muscle pain or weakness) in up to about 50-100 patients (ie, 0·5-1·0% absolute harm) per 10 000 treated for 5 years. However, placebo-controlled randomised trials have shown definitively that almost all of the symptomatic adverse events that are attributed to statin therapy in routine practice are not actually caused by it (ie, they represent misattribution). The large-scale evidence available from randomised trials also indicates that it is unlikely that large absolute excesses in other serious adverse events still await discovery. Consequently, any further findings that emerge about the effects of statin therapy would not be expected to alter materially the balance of benefits and harms. It is, therefore, of concern that exaggerated claims about side-effect rates with statin therapy may be responsible for its under-use among individuals at increased risk of cardiovascular events. For, whereas the rare cases of myopathy and any muscle-related symptoms that are attributed to statin therapy generally resolve rapidly when treatment is stopped, the heart attacks or strokes that may occur if statin therapy is stopped unnecessarily can be devastating.
PMID: 27616593 [PubMed - indexed for MEDLINE]
A systematic review of the prevalence and incidence of prescribing errors with high-risk medicines in hospitals.
A systematic review of the prevalence and incidence of prescribing errors with high-risk medicines in hospitals.
J Clin Pharm Ther. 2016 Jun;41(3):239-45
Authors: Alanazi MA, Tully MP, Lewis PJ
Abstract
WHAT IS KNOWN: Prescribing errors are the most common type of error in the medication use process. However, there is a paucity of literature regarding the prevalence or incidence of prescribing errors in high-risk medicines (HRMs). HRMs bear a heightened risk of causing significant patient harm when they are used in error.
OBJECTIVE: The aim of this research was to systematically investigate the literature regarding the prevalence and incidence of prescribing errors in HRMs in inpatient settings.
METHODS: A search strategy was developed based on four categories of keywords: prescribing errors, HRMs, hospital inpatients, and prevalence or incidence. All keywords were searched for in Medline, Embase, Cochrane and the International Pharmaceutical Abstracts. The search was limited to English quantitative studies that reported the incidence or prevalence of prescribing errors by medical prescribers, whether they were seniors or juniors, since 1985.
RESULTS: Of the 3507 records identified, nine studies met the review criteria. The most frequent denominator in the included studies was medication orders, in eight studies, ranged from 0·24 to 89·6 errors per 100 orders of HRMs. Two studies reported 107 and 218 errors per 100 admissions prescribed HRMs, and one study reported 27·2 errors per 100 prescriptions with a HRM. The incidence of prescribing errors could not be calculated.
WHAT IS NEW AND CONCLUSION: The prevalence of prescribing errors in HRMs in the inpatient setting has a very wide range that reflects the different data collection methods used within the included studies. Future studies in prescribing errors should use standardized approaches to enable comparison.
PMID: 27167088 [PubMed - indexed for MEDLINE]
Bundle interventions used to reduce prescribing and administration errors in hospitalized children: a systematic review.
Bundle interventions used to reduce prescribing and administration errors in hospitalized children: a systematic review.
J Clin Pharm Ther. 2016 Jun;41(3):246-55
Authors: Bannan DF, Tully MP
Abstract
WHAT IS KNOWN AND OBJECTIVE: Bundle interventions are becoming increasingly used as patient safety interventions. The objective of this study was to describe and categorize which bundle interventions are used to reduce prescribing errors (PEs) and administration errors (AEs) in hospitalized children and to assess the quality of the published literature.
METHODS: Articles published in English and Arabic between 1985 and September 2015 were sought in MEDLINE, EMBASE and CINHAL. Bibliographies of included articles were screened for additional studies. We included any study with a comparator group reporting rates of PEs and AEs. Two authors independently extracted data, classified interventions in each bundle and assessed the studies for potential risk of bias. Constituent interventions of the bundles were categorized using both the Cochrane Effective Practice and Organization of Care Group (EPOC) taxonomy of intervention and the Behavioural Change Wheel (BCW).
RESULTS AND DISCUSSION: Seventeen studies met the inclusion criteria. All bundles contained interventions that were either professional, organizational or a mixture of both. According to the BCW, studies used interventions with functions delivering environmental restructuring (17/17), education (16/17), persuasion (4/17), training (3/17), restriction (3/17), incentivization (1/17), coercion (1/17), modelling (1/17) and enablement (1/17). Nine studies had bundles with two intervention functions, and eight studies had three or more intervention functions. All studies were low quality before/after studies. Selection bias varied between studies. Performance bias was either low or unclear. Attrition bias was unclear, and detection bias was rated high in most studies. Ten studies described the interventions fairly well, and seven studies did not adequately explain the interventions used.
WHAT IS NEW AND CONCLUSION: This novel analysis in a systematic review showed that bundle interventions delivering two or more intervention functions have been investigated but that the study quality was too poor to assess impact.
PMID: 27145467 [PubMed - indexed for MEDLINE]
Ameliorative effect of berberine against gentamicin-induced nephrotoxicity in rats via attenuation of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction.
Ameliorative effect of berberine against gentamicin-induced nephrotoxicity in rats via attenuation of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction.
Ren Fail. 2016 Jul;38(6):996-1006
Authors: Adil M, Kandhare AD, Dalvi G, Ghosh P, Venkata S, Raygude KS, Bodhankar SL
Abstract
BACKGROUND: Gentamicin (GM) is the commonly used antibiotics against Gram-negative infection, but the nephrotoxic potential of drug limit its clinical interest. The aim of this study was to investigate the protective effect of berberine (BER) against GM-induced nephrotoxicity and possible underlying mechanisms.
MATERIAL AND METHODS: The rats were divided into various group, namely normal, GM-control, GM + BER (10, 20, and 40 mg/kg). Nephrotoxicity was induced by intraperitoneal administration of GM (120 mg/kg) for 7 consecutive days. BER (10, 20, and 40 mg/kg; p.o.) was also administered for the 7 days. Various biochemical, molecular, and histological parameters were assessed in serum and kidney.
RESULTS: GM-administration significantly increased (p < 0.001) the serum creatinine and blood urea nitrogen (BUN) as well as renal malonaldehyde (MDA), nitric oxide (NO) along with Kidney Injury Molecule-1 (KIM-1), Neutrophil gelatinase-associated lipocalin (NGAL), and nuclear factor-kappa B (NF-KB) renal mRNA expressions. In addition, GM also significantly decreased (p < 0.001) the renal superoxide dismutase (SOD), reduced glutathione (GSH), B-cell lymphoma 2 (Bcl-2) mRNA expression, and mitochondrial enzymes (NADH dehydrogenase and cytochrome c oxidase) activities. Rats treated with BER (20 and 40 mg/kg; p.o.) significantly and dose-dependently (p < 0.05 and p < 0.01) restore the altered levels of antioxidant, inflammatory, apoptosis, AKI markers as well as depleted mitochondrial enzymes. Histopathological abbreviations were also ameliorated by BER administration.
CONCLUSION: Berberine exerts renoprotective effects through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.[Formula: see text].
PMID: 27056079 [PubMed - indexed for MEDLINE]
Advancing Conformance with the Voluntary National Retail Food Regulatory Program Standards (VNRFRPS) (U18)
Expanding Medication Assisted Treatment for Opioid Use Disorders in the Context of the SAMHSA Opioid STR Grants (R21/R33)
NINDS Program Project Grant (P01)
Integrative Computational Biology for Analysis of NHLBI TOPMed Data
Notice of Pre-application Webinar for PAR-16-131 Emerging Questions in Cancer Systems Biology (U01)
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