Literature Watch
Sinus hypoplasia in the cystic fibrosis rat resolves in the absence of chronic infection.
Sinus hypoplasia in the cystic fibrosis rat resolves in the absence of chronic infection.
Int Forum Allergy Rhinol. 2017 Jun 08;:
Authors: Grayson J, Tipirneni KE, Skinner DF, Fort M, Cho DY, Zhang S, Prince AC, Lim DJ, Mackey C, Woodworth BA
Abstract
BACKGROUND: Sinus hypoplasia is a hallmark characteristic in cystic fibrosis (CF). Chronic rhinosinusitis (CRS) is nearly universal from a young age, impaired sinus development could be secondary to loss of the cystic fibrosis transmembrane conductance regulator (CFTR) or consequences of chronic infection during maturation. The objective of this study was to assess sinus development relative to overall growth in a novel CF animal model.
METHODS: Sinus development was evaluated in CFTR(-/-) and CFTR(+/+) rats at 3 stages of development: newborn; 3 weeks; and 16 weeks. Microcomputed tomography (microCT) scanning, cultures, and histology were performed. Three-dimensional sinus and skull volumes were quantified.
RESULTS: At birth, sinus volumes were decreased in CFTR(-/-) rats compared with wild-type rats (mean ± SEM: 11.3 ± 0.85 mm(3) vs 14.5 ± 0.73 mm(3) ; p < 0.05), despite similar weights (8.4 ± 0.46 gm vs 8.3 ± 0.51 gm; p = 0.86). CF rat weights declined by 16 weeks (378.4 ± 10.6 gm vs 447.4 ± 15.9 gm; p < 0.05), sinus volume increased similar to wild-type rats (201.1 ± 3.77 gm vs 203.4 ± 7.13 gm; p = 0.8). The ratio of sinus volume to body weight indicates hypoplasia present at birth (1.37 ± 0.12 vs 1.78 ± 0.11; p < 0.05) and showed an increase compared with CFTR(+/+) animals by 16 weeks (0.53 ± 0.02 vs 0.46 ± 0.02; p < 0.05). Rats did not develop histologic evidence of chronic infection.
CONCLUSION: CF rat sinuses are smaller at birth, but develop volumes similar to wild-type rats with maturation. This suggests that loss of CFTR may confer sinus hypoplasia at birth, but normal development ensues without chronic sinus infection. ©2017 ARSAAOA, LLC.
PMID: 28597597 [PubMed - as supplied by publisher]
Factors associated with changes in health-related quality of life in children with cystic fibrosis during 1-year follow-up.
Factors associated with changes in health-related quality of life in children with cystic fibrosis during 1-year follow-up.
Eur J Pediatr. 2017 Jun 09;:
Authors: van Horck M, Winkens B, Wesseling G, de Winter-de Groot K, de Vreede I, Jöbsis Q, Dompeling E
Abstract
There are limited data on health-related quality of life (HRQoL) changes over time in children with cystic fibrosis (CF). We investigated associations between clinical and treatment variables with changes in HRQoL during 1 year. Forty-nine children with CF aged 6-18 years were followed in this multicentre, observational cohort study during 1 year. HRQoL was measured by the validated disease specific cystic fibrosis questionnaire-revised (CFQ-R). The CFQ-R total score as well as most domain scores improved significantly (8.0 points and [3.3-31.7] points respectively) during the one-year follow-up. Age at baseline demonstrated a strong longitudinal association with the change of CFQ-R total score (2.853 points decrease of CFQ-R total score per year increase in age) and several domain scores. Below 12 years of age, CFQ-R total score improved in most children, whereas a deterioration was observed in most children above 12 years. The number of PEx was associated with an increase of treatment burden score (4.466 points decrease per extra PEx).
CONCLUSION: In the group as a whole, HRQoL improved significantly over time. However, changes over time were significantly influenced by age: below 12 years of age, HRQoL improved in most patients whereas a deterioration was observed in most children >12 years. Strategies how to preserve or ideally to improve HRQoL in adolescence should be developed. What is known: • Quality of life in patient with CF is diminished • Although CF is a chronic disease, longitudinal data on QoL in children with CF are scarce. What is new: • Below 12 years of age, quality of life improved in most children during the 1-year follow-up whereas a deterioration in quality of life was observed in most children above 12 years. • the treatment burden score of QoL correlated with the exacerbation rate.
PMID: 28597092 [PubMed - as supplied by publisher]
Long Persistence of a Streptococcus pneumoniae 23F Clone in a Cystic Fibrosis Patient.
Long Persistence of a Streptococcus pneumoniae 23F Clone in a Cystic Fibrosis Patient.
mSphere. 2017 May-Jun;2(3):
Authors: Rieger M, Mauch H, Hakenbeck R
Abstract
Streptococcus pneumoniae isolates of serotype 23F with intermediate penicillin resistance were recovered on seven occasions over a period of 37 months from a cystic fibrosis patient in Berlin. All isolates expressed the same multilocus sequence type (ST), ST10523. The genome sequences of the first and last isolates, D122 and D141, revealed the absence of two phage-related gene clusters compared to the genome of another ST10523 strain, D219, isolated earlier at a different place in Germany. Genomes of all three strains carried the same novel mosaic penicillin-binding protein (PBP) genes, pbp2x, pbp2b, and pbp1a; these genes were distinct from those of other penicillin-resistant S. pneumoniae strains except for pbp1a of a Romanian S. pneumoniae isolate. All PBPs contained mutations that have been associated with the penicillin resistance phenotype. Most interestingly, a mosaic block identical to an internal pbp2x sequence of ST10523 was present in pbp2x of Streptococcus mitis strain B93-4, which was isolated from the same patient. This suggests interspecies gene transfer from S. pneumoniae to S. mitis within the host. Nearly all genes expressing surface proteins, which represent major virulence factors of S. pneumoniae and are typical for this species, were present in the genome of ST10523. One exception was the hyaluronidase gene hlyA, which contained a 12-nucleotide deletion within the promoter region and an internal stop codon. The lack of a functional hyaluronidase might contribute to the ability to persist in the host for an unusually long period of time. IMPORTANCEStreptococcus pneumoniae is a common resident in the human nasopharynx. However, carriage can result in severe diseases due to a unique repertoire of pathogenicity factors that are rare in closely related commensal streptococci. We investigated a penicillin-resistant S. pneumoniae clone of serotype 23F isolated from a cystic fibrosis patient on multiple occasions over an unusually long period of over 3 years that was present without causing disease. Genome comparisons revealed an apparent nonfunctional pneumococcus-specific gene encoding a hyaluronidase, supporting the view that this enzyme adds to the virulence potential of the bacterium. The 23F clone harbored unique mosaic genes encoding penicillin resistance determinants, the product of horizontal gene transfer involving the commensal S. mitis as donor species. Sequences identical to one such mosaic gene were identified in an S. mitis strain from the same patient, suggesting that in this case S. pneumoniae played the role of donor.
PMID: 28596991 [PubMed - in process]
Review: Quality of Life in Children with Non-cystic Fibrosis Bronchiectasis.
Review: Quality of Life in Children with Non-cystic Fibrosis Bronchiectasis.
Front Pediatr. 2017;5:84
Authors: Nathan AM, de Bruyne JA, Eg KP, Thavagnanam S
Abstract
Non-cystic fibrosis bronchiectasis (NCFB) has gained renewed interest, due to its increasing health-care burden. Annual mortality statistics in England and Wales showed that under 1,000 people die from bronchiectasis each year, and this number is increasing by 3% yearly. Unfortunately, there is a severe lack of well-powered, randomized controlled trials to guide clinicians how to manage NCFB effectively. Quality-of-life (QOL) measures in NCFB are an important aspect of clinical care that has not been studied well. Commonly used disease-specific questionnaires in children with NCFB are the St George's Respiratory Questionnaire, Short Form-36, the Leicester Cough Questionnaire, and the Parent Cough-Specific Quality of Life questionnaire (PC-QOL). Of these, only the PC-QOL can be used in young children, as it is a parent-proxy questionnaire. We reviewed pediatric studies looking at QOL in children with NCFB and cystic fibrosis. All types of airway clearance techniques appear to be safe and have no significant benefit over each other. Number of exacerbations and hospitalizations correlated with QOL scores, while symptom subscales correlated with lung function, worse QOL, frequent antibiotic requirements, and duration of regular follow-up in only one study. There was a correlation between QOL and age of diagnosis in children with primary ciliary dyskinesia. Other studies have shown no relationship between QOL scores and etiology of NCFB as well as CT changes. As for treatments, oral azithromycin and yoga have demonstrated some improvement in QOL scores. In conclusion, more studies are required to accurately determine important factors contributing to QOL.
PMID: 28596950 [PubMed - in process]
The challenge of defining exacerbation in bronchiectasis.
The challenge of defining exacerbation in bronchiectasis.
Eur Respir J. 2017 Jun;49(6):
Authors: Martínez-García MÁ, Máiz-Carro L
PMID: 28596429 [PubMed - in process]
Patient-specific molecular alterations are associated with metastatic clear cell renal cell cancer progressing under tyrosine kinase inhibitor therapy.
Patient-specific molecular alterations are associated with metastatic clear cell renal cell cancer progressing under tyrosine kinase inhibitor therapy.
Oncotarget. 2017 May 23;:
Authors: Dietz S, Sültmann H, Du Y, Reisinger E, Riediger AL, Volckmar AL, Stenzinger A, Schlesner M, Jäger D, Hohenfellner M, Duensing S, Grüllich C, Pahernik S
Abstract
The availability of tyrosine kinase inhibitors (TKI) during the past ten years has led to improved response and overall survival of patients suffering from metastatic clear cell renal cell carcinoma (ccRCC). However, most of these tumors will eventually progress due to resistance evolving under therapy. The objective of this pilot study was to determine whether molecular alterations in ccRCC tissues sampled over the course of the disease might be suggestive of potential therapies. We performed whole exome sequencing of nine samples from four patients in the MORE (Molecular Renal Cancer Evolution) trial. We analyzed the mutational patterns in the tissues at baseline and compared them to those detectable in biopsy samples after progression under TKI therapy. We found limited genetic concordance between primary and secondary tumor sites with private mutations in FLT4, MTOR, ITGA5, SETD2, PBRM1, and BRCA1 on progression. One patient who showed an increased mutational load in the metastasis responded to nivolumab treatment. Our data provide evidence for clonal evolution and diverse pathways leading to acquired TKI resistance of ccRCC. Acquired resistance to TKI in metastatic ccRCC is due to intra-tumor heterogeneity and clonal evolution of resistant subclones. Mutations occurring under progression might be informative for alternative targeted therapies.
PMID: 28598822 [PubMed - as supplied by publisher]
Genetic epidemiology of Familial Mediterranean Fever through integrative analysis of whole genome and exome sequences from Middle East and North Africa.
Genetic epidemiology of Familial Mediterranean Fever through integrative analysis of whole genome and exome sequences from Middle East and North Africa.
Clin Genet. 2017 Jun 09;:
Authors: Koshy R, Sivadas A, Scaria V
Abstract
Familial Mediterranean fever (FMF), an autosomal recessive and rare autoinflammatory disease is caused by genetic mutations in the MEFV gene and is highly prevalent in the Mediterranean basin. Though the carrier frequency of specific disease variants in the MEFV gene has been reported from isolated studies, a comprehensive view of variants in the Mediterranean region has not been possible due to paucity of data. The recent availability of whole-genome and whole-exome datasets prompted us to study the genetic epidemiology of MEFV variants in the region. We assembled data from five datasets encompassing whole-genome and whole-exome datasets for 2115 individuals from multiple subpopulations in the region and also created a compendium for MEFV genetic variants, which were further systematically annotated as per the ACMG guidelines. Our analysis points to significant differences in allele frequencies in the subpopulations, and the carrier frequency for MEFV genetic variants in the population to be about 8%. The MEFV gene appears to be under natural selection from our analysis. To the best of our knowledge, this is the most comprehensive study and analysis of population epidemiology of MEFV gene variants in the Middle East and North African populations.
PMID: 28597968 [PubMed - as supplied by publisher]
Postmortem Whole Exome Sequencing Identifies Novel EIF2B3 Mutation With Prenatal Phenotype in 2 Siblings.
Postmortem Whole Exome Sequencing Identifies Novel EIF2B3 Mutation With Prenatal Phenotype in 2 Siblings.
J Child Neurol. 2017 Jan 01;:883073817712588
Authors: Song H, Haeri S, Vogel H, van der Knaap M, Van Haren K
Abstract
OBJECTIVE: We describe 2 male siblings with a severe, prenatal phenotype of vanishing white matter disease and the impact of whole exome sequencing on their diagnosis and clinical care.
METHODS: The 2 children underwent detailed clinical characterization, through clinical and laboratory testing, as well as prenatal and postnatal imaging. Biobanked blood from the 2 siblings was submitted for whole exome sequencing at Baylor Laboratories.
RESULTS: Both male children had abnormal prenatal neuroimaging and suffered precipitous, fatal neurologic decline. Neuropathologic findings included subependymal pseudocysts, microcalcifications, and profound lack of brain myelin and sparing of peripheral nerve myelin. A novel homozygous mutation in the EIF2B3 gene (c.97A>G [p.Lys33Glu]) was found in both children; both parents were heterozygous carriers. The family subsequently conceived a healthy child via in vitro fertilization with preimplantation mutation screening.
CONCLUSION: These histories expand the prenatal phenotype of eIF2b-related disorders and poignantly illustrate the impact that unbiased genomic sequencing can have on the diagnosis and medical decision making for families affected by childhood neurodegenerative disorders.
PMID: 28597716 [PubMed - as supplied by publisher]
Identification and description of three families with familial Alzheimer disease that segregate variants in the SORL1 gene.
Identification and description of three families with familial Alzheimer disease that segregate variants in the SORL1 gene.
Acta Neuropathol Commun. 2017 Jun 09;5(1):43
Authors: Thonberg H, Chiang HH, Lilius L, Forsell C, Lindström AK, Johansson C, Björkström J, Thordardottir S, Sleegers K, Van Broeckhoven C, Rönnbäck A, Graff C
Abstract
Alzheimer disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. The majority of AD cases are sporadic, while up to 5% are families with an early onset AD (EOAD). Mutations in one of the three genes: amyloid beta precursor protein (APP), presenilin 1 (PSEN1) or presenilin 2 (PSEN2) can be disease causing. However, most EOAD families do not carry mutations in any of these three genes, and candidate genes, such as the sortilin-related receptor 1 (SORL1), have been suggested to be potentially causative. To identify AD causative variants, we performed whole-exome sequencing on five individuals from a family with EOAD and a missense variant, p.Arg1303Cys (c.3907C > T) was identified in SORL1 which segregated with disease and was further characterized with immunohistochemistry on two post mortem autopsy cases from the same family. In a targeted re-sequencing effort on independent index patients from 35 EOAD-families, a second SORL1 variant, c.3050-2A > G, was found which segregated with the disease in 3 affected and was absent in one unaffected family member. The c.3050-2A > G variant is located two nucleotides upstream of exon 22 and was shown to cause exon 22 skipping, resulting in a deletion of amino acids Gly1017- Glu1074 of SORL1. Furthermore, a third SORL1 variant, c.5195G > C, recently identified in a Swedish case control cohort included in the European Early-Onset Dementia (EU EOD) consortium study, was detected in two affected siblings in a third family with familial EOAD. The finding of three SORL1-variants that segregate with disease in three separate families with EOAD supports the involvement of SORL1 in AD pathology. The cause of these rare monogenic forms of EOAD has proven difficult to find and the use of exome and genome sequencing may be a successful route to target them.
PMID: 28595629 [PubMed - in process]
Preclinical data on the combination of cisplatin and anti-CD70 therapy in non-small cell lung cancer as an excellent match in the era of combination therapy.
Preclinical data on the combination of cisplatin and anti-CD70 therapy in non-small cell lung cancer as an excellent match in the era of combination therapy.
Oncotarget. 2017 May 23;:
Authors: Jacobs J, Deschoolmeester V, Rolfo C, Zwaenepoel K, den Bossche JV, Deben C, Silence K, Haard H, Hermans C, Rottey S, Vangestel C, Lardon F, Smits E, Pauwels P
Abstract
In contrast to the negligible expression of the immunomodulating protein CD70 in normal tissue, we have demonstrated constitutive overexpression of CD70 on tumor cells in a subset of primary non-small cell lung cancer (NSCLC) biopsies. This can be exploited by CD70-targeting antibody-dependent cellular cytotoxicity (ADCC)-inducing antibodies. Early clinical trials of these antibodies have already shown promising results in CD70-positive malignancies.In this study, we explored the potential of cisplatin to induce CD70 expression in NSCLC. Using real-time measurement tools, we also assessed the efficacy of a combination regimen with cisplatin and anti-CD70 therapy under normoxia and hypoxia. We identified an induction of CD70 expression on lung cancer cells upon low doses of cisplatin, independent of oxygen levels. More importantly, the use of cisplatin resulted in an enhanced ADCC-effect of anti-CD70 therapy. As such, this combination regimen led to a significant decrease in lung cancer cell survival cell survival, broadening the applicability the applicability of CD70-targeting therapy.This is the first study that proves the potential of a combination therapy with cisplatin and CD70-targeting drugs in NSCLC. Based on our data, we postulate that this combination strategy is an interesting approach to increase tumor-specific cytotoxicity and reduce drug-related side effects.
PMID: 28598823 [PubMed - as supplied by publisher]
Phase I study of oral ridaforolimus in combination with paclitaxel and carboplatin in patients with solid tumor cancers.
Phase I study of oral ridaforolimus in combination with paclitaxel and carboplatin in patients with solid tumor cancers.
BMC Cancer. 2017 Jun 08;17(1):407
Authors: Chon HS, Kang S, Lee JK, Apte SM, Shahzad MM, Williams-Elson I, Wenham RM
Abstract
BACKGROUND: Ridaforolimus is a mammalian target of rapamycin inhibitor that has activity in solid tumors. Paclitaxel and carboplatin have broad antineoplastic activity in many cancers. This phase I trial was conducted to determine the safety profile, maximal tolerated dose, and recommended phase II dose and schedule of oral ridaforolimus combined with paclitaxel and carboplatin in patients with solid tumor cancers.
METHODS: Eligible patients with advanced solid tumor cancers received oral 10 to 30 mg ridaforolimus daily for 5 consecutive days per week combined with intravenous paclitaxel (175 mg/m(2)) and carboplatin (area under the curve [AUC] 5-6 mg/mL/min) in 3-week cycles. A standard 3 + 3 design was used to escalate doses, with predefined changes to an alternate dosing schedule and/or changes in carboplatin AUC doses based on dose-limiting toxicity (DLT). Secondary information was collected regarding response and time to progression. Patients were continued on treatment if therapy was tolerated and if stable disease or better was demonstrated.
RESULTS: Thirty-one patients were consented, 28 patients were screened, and 24 patients met eligibility requirements and received treatment. Two patients were replaced for events unrelated to drug-related toxicity, resulting in 22 DLT-evaluable patients. Two grade 4 DLTs due to neutropenia were observed at dose level 1. The next cohort was changed to a predefined alternate dosing schedule (days 1-5 and 8-12). DLTs were neutropenia, sepsis, mucositis, and thrombocytopenia. The most common adverse events were neutropenia, anemia, thrombocytopenia, fatigue, alopecia, nausea, pain, and leukopenia. Twenty-four patients received a median of 4 cycles (range, 1-12). Evaluable patients for response (n = 18) demonstrated a median tumor measurement decrease of 25%. The best response in these 18 patients included 9 patients with partial response (50%), 6 with stable disease (33%), and 3 with progressive disease (17%). Thirteen of these patients received treatment for 4 or more cycles.
CONCLUSIONS: Treatment with ridaforolimus combined with paclitaxel and carboplatin had no unanticipated toxicities and showed antineoplastic activity. The recommended phase II dose and schedule is ridaforolimus 30 mg (days 1-5 and 8-12) plus day 1 paclitaxel (175 mg/m(2)) and carboplatin (AUC 5 mg/mL/min) on a 21-day cycle.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01256268 (trial registration date: December 1, 2010).
PMID: 28595616 [PubMed - in process]
Neuroprotective effects of drug-induced therapeutic hypothermia in central nervous system diseases.
Neuroprotective effects of drug-induced therapeutic hypothermia in central nervous system diseases.
Curr Drug Targets. 2017 Jun 06;:
Authors: Ma J, Wang Y, Wang Z, Li H, Wang Z, Chen G
Abstract
Cerebrovascular diseases often cause neurological deficits. Experimental studies have shown that drug-induced hypothermia alleviates brain damage and plays a neuroprotective role, thereby reducing mortality and ameliorating neurological deficits. Therefore, drug-induced hypothermia has an important research value and is further considered in the clinical setting. However, drug-induced hypothermia is also associated with side effects, such as ventricular tachycardia, ventricular fibrillation, suppressed immune function, infection, electrolyte imbalance, glucose metabolism disorders, and skeletal muscle tremor. Existing drugs with cooling effects belong to the following categories: (1) dopamine receptor agonists; (2) cannabis; (3) opioid receptors; (4) vanilloid receptors; (5) vasopressins (potent neurotensin receptor agonists); (6) thyroid drugs; (7) adenosine drugs; and (8) purine drugs. This review article focuses on the neuroprotective effect of drug-induced hypothermia in cerebrovascular diseases and discusses its related side effects.
PMID: 28595536 [PubMed - as supplied by publisher]
Dilemma of first line regimens in metastatic pancreatic adenocarcinoma.
Dilemma of first line regimens in metastatic pancreatic adenocarcinoma.
World J Gastroenterol. 2016 Dec 14;22(46):10124-10130
Authors: Ghosn M, Ibrahim T, Assi T, El Rassy E, Kourie HR, Kattan J
Abstract
Pancreatic cancer is one of the deadliest cancers, ranking fourth among cancer-related deaths. Despite all the major molecular advances and treatment breakthroughs, mainly targeted therapies, the cornerstone treatment of metastatic pancreatic cancer (mPC) remains cytotoxic chemotherapy. In 2016, more than 40 years after the introduction of gemcitabine in the management of mPC, the best choice for first-line treatment has not yet been fully elucidated. Two main strategies have been adopted to enhance treatment efficacy. The first strategy is based on combining non-cross resistant drugs, while the second option includes the development of newer generations of chemotherapy. More recently, two new regimens, FOLFIRINOX and gemcitabine/nab-paclitaxel (GNP), have both been shown to improve overall survival in comparison with gemcitabine alone, at the cost of increased toxicity. Therefore, the best choice for first line therapy is a matter of debate. For some authors, FOLFIRINOX should be the first choice in patients with an Eastern Cooperative Oncology Group score (0-1) given its lower hazard ratio. However, others do not share this opinion. In this paper, we review the main comparison points between FOLFIRINOX and GNP. We analyze the two pivotal trials to determine the similarities and differences in study design. In addition, we compare the toxicity profile of the two regimens as well as the impact on quality of life. Finally, we present studies revealing real life experiences and review the advantages and disadvantages of possible second-line therapies including their cost effectiveness.
PMID: 28028360 [PubMed - indexed for MEDLINE]
Immunizing Patients With Adverse Events After Immunization and Potential Contraindications to Immunization: A Report From the Special Immunization Clinics Network.
Immunizing Patients With Adverse Events After Immunization and Potential Contraindications to Immunization: A Report From the Special Immunization Clinics Network.
Pediatr Infect Dis J. 2016 Dec;35(12):e384-e391
Authors: Top KA, Billard MN, Gariepy MC, Rouleau I, Pernica JM, Pham-Huy A, Quach C, Tran D, Vaudry W, Dobson S, Boucher FD, Carignan A, Jadavji T, McConnell A, McNeil SA, Halperin SA, De Serres G, Canadian Immunization Research Network’s (CIRN) Special Immunization Clinics Network investigators
Abstract
BACKGROUND: For patients who have experienced adverse events following immunization (AEFI) or who have specific medical conditions, there is limited evidence regarding the best approach to immunization. The Special Immunization Clinics (SICs) Network was established to standardize patient management and assess outcomes after reimmunization. The study objective was to describe the first 2 years of the network's implementation.
METHODS: Twelve SICs were established across Canada by infectious diseases specialists and allergists. Inclusion criteria were as follows: local reaction ≥ 10 cm, allergic symptoms < 24 hours postimmunization, neurologic symptoms and other AEFI or medical conditions of concern. Eligible patients underwent a standardized evaluation, causality assessment was performed, immunization recommendations were made by expert physicians and patients were followed up to capture AEFI. After individual consent, data were transferred to a central database for analysis.
RESULTS: From June 2013 to May 2015, 151 patients were enrolled. Most were referred for prior AEFI (132/151, 87%): 42 (32%) for allergic-like reactions, 31 (23%) for injection-site reactions, 20 (15%) for neurologic symptoms and 39 (30%) for other systemic symptoms. Nineteen patients (13%) were seen for underlying conditions that complicated immunization. Reimmunization was recommended for 109 patients, 60 of whom (55%) were immunized and followed up. Eleven patients (18%) experienced recurrence of their AEFI; none were serious (eg, resulting in hospitalization, permanent disability or death).
CONCLUSIONS: The most frequent reasons for referral to a SIC were allergic-like events and injection site reactions. Reimmunization was safe in most patients. Larger studies are needed to determine outcomes for specific types of AEFI.
PMID: 27626920 [PubMed - indexed for MEDLINE]
Ambulatory Computerized Prescribing and Preventable Adverse Drug Events.
Ambulatory Computerized Prescribing and Preventable Adverse Drug Events.
J Patient Saf. 2016 Jun;12(2):69-74
Authors: Overhage JM, Gandhi TK, Hope C, Seger AC, Murray MD, Orav EJ, Bates DW
Abstract
BACKGROUND: Adverse drug events (ADEs) represent a significant cause of injury in the ambulatory care setting. Computerized physician order entry reduces rates of serious medication errors that can lead to ADEs in the inpatient setting, but few studies have evaluated whether computerized prescribing in the ambulatory setting reduces preventable ADE rates in ambulatory care.
OBJECTIVE: To determine the rates of preventable ADEs before and after the implementation of computerized prescribing with basic clinical decision support for ordering medications.
DESIGN: Before-after study of ADE rates in practices implementing computer order entry.
PARTICIPANTS: Adult patients seeking care in primary care practices at academic medical centers in Boston, Massachusetts (n = 41,819), and Indianapolis, Indiana (n = 9128).
MAIN MEASURES: We attempted to standardize the medication-related decision support knowledge base provided at the 2 sites, although the electronic records and presentation layers used at the 2 sites differed. The primary outcome was preventable ADEs identified based on structured results or symptoms defined by extracting symptom concepts from provider notes; potential ADEs were a secondary outcome.
RESULTS: Computerized prescribing did not significantly change the rate of preventable ADEs at either site. Compared with Boston practices, the rate of potential ADEs was more than seven-fold greater at Indianapolis (6.4/10,000 patient-months vs. 49.5/10,000 patient-months, P < 0.001). Computerized prescribing was associated with a 56% decrease in the potential ADE rate at Indianapolis (49.5 to 21.9/10,000 patient-months, P < 0.001) but a 104% increase at Boston (6.4 to 13.0/10,000 patient-months, P < 0.001). Preventable ADEs that occurred after computerized prescribing was implemented were due to patient education issues, physicians ignoring feedback from CDSS, and incomplete computerized knowledge base was incomplete (34%, 33%, and 33% in Indianapolis and 44%, 28%, and 28% in Boston).
CONCLUSIONS: The implementation of computerized prescribing in the ambulatory setting was not associated with any change in preventable ADEs but was associated with a decrease in potential ADEs at Indianapolis but an increase at Boston, although the absolute rate of ADEs was much lower in Boston.
PMID: 26001546 [PubMed - indexed for MEDLINE]
Root Cause Analysis of Ambulatory Adverse Drug Events That Present to the Emergency Department.
Root Cause Analysis of Ambulatory Adverse Drug Events That Present to the Emergency Department.
J Patient Saf. 2016 Sep;12(3):119-24
Authors: Gertler SA, Coralic Z, López A, Stein JC, Sarkar U
Abstract
BACKGROUND: Adverse drug events (ADEs) among patients self-administering medications in home/community settings are a common cause of emergency department (ED) visits, but the causes of these ambulatory ADEs remain unclear. Root cause analysis, rarely applied in outpatient settings, may reveal the underlying factors that contribute to adverse events.
STUDY OBJECTIVES: To elicit patient and provider perspectives on ambulatory ADEs and apply root cause analysis methodology to identify cross-cutting themes among these events.
METHODS: Emergency department clinical pharmacists screened, identified, and enrolled a convenience sample of adult patients 18 years or older who presented to a single, urban, academic ED with symptoms or diagnoses consistent with suspected ADEs. Semistructured phone interviews were conducted with the patients and their providers. We conducted a qualitative analysis. We applied a prespecified version of the injury prevention framework (deductive coding), identifying themes relating to the agent (drug), host (patient), and environment (social and health systems). These themes were used to construct a root cause analysis for each ADE.
RESULTS: From 18 interviews overall, we identified the following themes within the injury prevention framework. Agent factors included high-risk drugs, narrow therapeutic indices, and uncommon severe effects. Host factors included patient capacity or understanding of how to use medications, awareness of side effects, mistrust of the medical system, patients with multiple comorbidities, difficult risk-benefit assessments, and high health-care users. Environmental factors included lack of social support, and health systems issues included access to care, encompassing medication availability, access to specialists, and a lack of continuity and communication among prescribing physicians. Root cause analysis revealed multiple underlying factors relating to agent, host, and environment for each event.
CONCLUSION: Patient and physician perspectives can inform a root cause analysis of ambulatory ADEs. Such methodology may be applied to understand the factors that contribute to ambulatory ADEs and serve as the formative work for future interventions improving home/community medication use.
PMID: 24583958 [PubMed - indexed for MEDLINE]
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