Literature Watch
The impact of co-morbidity in childhood Cystic Fibrosis.
The impact of co-morbidity in childhood Cystic Fibrosis.
Paediatr Respir Rev. 2017 Mar 14;:
Authors: Duncan JA, Brown SM
Abstract
A number of risk factors have been identified for deterioration of lung disease in children with Cystic Fibrosis (CF), and current management strategies are based on the prevention and treatment of such elements. Further challenge ensues when a patient has co-morbid disease in addition to CF, particularly when faced with rapidly deteriorating pulmonary status. It is difficult to measure the contribution of other pathologies to this decline and optimisation of both CF care and co-morbidity is paramount. This review explores the challenges faced when treating children with CF and co-morbid conditions, focussing on gastroesophageal reflux disease pre- and post-lung transplantation.
PMID: 28400242 [PubMed - as supplied by publisher]
Highlights from the 30th North American Cystic Fibrosis Conference, Orlando 2016.
Highlights from the 30th North American Cystic Fibrosis Conference, Orlando 2016.
Paediatr Respir Rev. 2017 Mar 14;:
Authors: Shawcross A, Barry PJ
Abstract
This is a selection of papers presented at the 30th North American Cystic Fibrosis Conference held in Orlando in October 2016. The papers discussed are thought to be of particular interest to CF caregivers in the UK. We highlight the major themes covered in the conference including novel therapies, recently published and proposed guidelines and insights from registry studies.
PMID: 28400241 [PubMed - as supplied by publisher]
Biotin-thiamine responsive basal ganglia disease: Identification of a pyruvate peak on brain spectroscopy, novel mutation in SLC19A3, and calculation of prevalence based on allele frequencies from aggregated next-generation sequencing data.
Biotin-thiamine responsive basal ganglia disease: Identification of a pyruvate peak on brain spectroscopy, novel mutation in SLC19A3, and calculation of prevalence based on allele frequencies from aggregated next-generation sequencing data.
Am J Med Genet A. 2017 Apr 12;:
Authors: Ferreira CR, Whitehead MT, Leon E
Abstract
Biotin-thiamine responsive basal ganglia disease is an inborn error of metabolism caused by mutations in SLC19A3, encoding a transporter of thiamine across the plasma membrane. We report a novel mutation identified in the homozygous state in a patient with typical brain MRI changes. In addition, this patient had markedly elevated CSF pyruvate, a low lactate-to-pyruvate molar ratio, and an abnormal pyruvate peak at 2.4 ppm on brain magnetic resonance spectroscopy. Using aggregated exome sequencing data, we calculate the carrier frequency of mutations in SLC19A3 as 1 in 232 individuals in the general population, for an estimated prevalence of the disease of approximately 1 in 215,000 individuals. The disease is thus more frequent than previously recognized, and the presence of a pyruvate peak on spectroscopy could serve as an important diagnostic clue.
PMID: 28402605 [PubMed - as supplied by publisher]
LADD syndrome with glaucoma is caused by a novel gene.
LADD syndrome with glaucoma is caused by a novel gene.
Mol Vis. 2017;23:179-184
Authors: Simpson A, Avdic A, Roos BR, DeLuca A, Miller K, Schnieders MJ, Scheetz TE, Alward WL, Fingert JH
Abstract
PURPOSE: Lacrimo-auriculo-dento-digital (LADD) syndrome is an autosomal dominant disorder displaying variable expression of multiple congenital anomalies including hypoplasia or aplasia of the lacrimal and salivary systems causing abnormal tearing and dry mouth. Mutations in the FGF10, FGFR2, and FGFR3 genes were found to cause some cases of LADD syndrome in prior genetic studies. The goal of this study is to identify the genetic basis of a case of LADD syndrome with glaucoma and thin central corneal thickness (CCT).
METHODS: Whole exome sequencing was performed, and previously described disease-causing genes (FGF10, FGFR2, and FGFR3) were first evaluated for mutations. Fifty-eight additional prioritized candidate genes were identified by searching gene annotations for features of LADD syndrome. The potential pathogenicity of the identified mutations was assessed by determining their frequency in large public exome databases; through sequence analysis using the Blosum62 matrix, PolyPhen2, and SIFT algorithms; and through homology analyses. A structural analysis of the effects of the top candidate mutation in tumor protein 63 (TP63) was also conducted by superimposing the mutation over the solved crystal structure.
RESULTS: No mutations were detected in FGF10, FGFR2, or FGFR3. The LADD syndrome patient's exome data was searched for mutations in the 58 candidate genes and only one mutation was detected, an Arg343Trp mutation in the tumor protein 63 (TP63) gene. This TP63 mutation is absent from the gnomAD sequence database. Analysis of the Arg343Trp mutation with Blosum62, PolyPhen2, and SIFT all suggest it is pathogenic. This arginine residue is highly conserved in orthologous genes. Finally, crystal structure analysis showed that the Arg343Trp mutation causes a significant alteration in the structure of TP63's DNA binding domain.
CONCLUSIONS: We report a patient with no mutations in known LADD syndrome genes (FGF10, FGFR2, and FGFR3). Our analysis provides strong evidence that the Arg343Trp mutation in TP63 caused LADD syndrome in our patient and that TP63 is a fourth gene contributing to this condition. TP63 encodes a transcription factor involved in the development and differentiation of tissues affected by LADD syndrome. These data suggest that TP63 is a novel LADD syndrome gene and may also influence corneal thickness and risk for open-angle glaucoma.
PMID: 28400699 [PubMed - in process]
Ethical considerations surrounding germline next generation sequencing of children with cancer.
Ethical considerations surrounding germline next generation sequencing of children with cancer.
Expert Rev Mol Diagn. 2017 Apr 12;:
Authors: Johnson LM, Hamilton KV, Valdez JM, Knapp E, Baker JN, Nichols KE
Abstract
INTRODUCTION: The advent of next generation sequencing (NGS) has introduced an exciting new era in biomedical research. NGS forms the foundation of current genetic testing approaches, including targeted gene panel testing, as well as more comprehensive whole exome and whole genome sequencing. Together, these approaches promise to provide critical insights into the understanding of health and disease. However, with NGS testing come many ethical questions and concerns, particularly when testing involves children. These concerns are especially relevant for children with cancer, where the testing of tumor and germline tissues is increasingly being incorporated into clinical care. Areas Covered: In this manuscript, the authors explore the key ethical considerations related to conducting germline NGS testing in pediatric oncology, focusing on the four main principles of beneficence, non-maleficence, autonomy and justice. Expert Commentary: The ethical issues surrounding germline NGS testing are complex and result in part from our limited understanding of the medical relevance of many of the results obtained and poor knowledge of the impacts of testing, both beneficial and detrimental, on patients and their families. The authors discuss the risks and benefits of germline NGS testing and the arguments for and against such testing in children with cancer.
PMID: 28399664 [PubMed - as supplied by publisher]
Comparison of documentation of patient reported adverse drug reactions on both paper-based medication charts and electronic medication charts at a New Zealand hospital.
Comparison of documentation of patient reported adverse drug reactions on both paper-based medication charts and electronic medication charts at a New Zealand hospital.
N Z Med J. 2016 Oct 28;129(1444):90-96
Authors: Shen W, Wong B, Chin JY, Lee M, Coulter C, Braund R
Abstract
AIM: Known adverse drug reactions (ADRs) can have profound effects on disease states, as well as prescribing practice. Therefore, the correct and complete documentation of each individual patient's ADR history, upon hospital admission, is important in optimising that individual patient's pharmacotherapy. This study investigated the documentation of ADRs at a tertiary New Zealand hospital, on both paper-based medication charts and electronic medication charts to quantify both the number of ADRs patients self-report, as well as the differences between recording of that information in electronic and paper-based charting systems.
METHOD: Following ethical approval, inpatient medication charts on the general medical ward (electronic prescribing), or the general surgical ward (paper-based medication charts) were viewed for documented ADRs-as reported by each patient on admission. Consecutive patient charts (and electronic clinical management system) were viewed until 50 patients from each ward, each with at least one documented ADR, (in any of the information sources) were obtained. Patient demographic information, ADR history and discrepancies between information sources were determined.
RESULTS: In both wards 114 patients were reviewed in order to find 50 patients with documented ADRs. In the medical ward (electronic) 44 (90%) patients had discrepancies in ADR information between different information sources and in the surgical ward (paper) this occurred in 49 (98%) patients.
CONCLUSION: A large number of patients self-report ADRs. Full documentation of patient reported ADRs is required to adequately inform future prescribing decisions. Discrepancies between ADR information recorded in different information systems exist, but information sharing between electronic and non-electronic sources could be prioritised in order to allow full and complete information to be collected, stored and utilised; and reduce the current inadequacies.
PMID: 27806032 [PubMed - indexed for MEDLINE]
Incidence of Antipsychotic-Associated Side Effects: Impact of Clinician Versus Patient Ratings and Change Versus Absolute Scores.
Incidence of Antipsychotic-Associated Side Effects: Impact of Clinician Versus Patient Ratings and Change Versus Absolute Scores.
J Clin Psychopharmacol. 2016 Dec;36(6):593-596
Authors: Takeuchi H, Fervaha G, Remington G
Abstract
OBJECTIVE: This study aimed to compare (1) the detection rates of antipsychotic-associated side effects between clinician and patient ratings and (2) differences as a function of change and absolute score definitions.
METHODS: Data from phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (N = 1460) were analyzed. In this trial, 18 adverse events were systematically and concurrently assessed by clinicians and patients using a 4-point severity scale ranging from 0 (absent) to 3 (severe). The incidence of antipsychotic-associated side effects was calculated according to 2 definitions: change score (ie, higher score on the scale versus baseline) and absolute score (a score of 2 or 3 on the scale). In addition, patient and clinician concurrent detection rates were examined.
RESULTS: The differences in incidence of antipsychotic-associated side effects between clinician and patient ratings were as small as 5.7% across the 2 definitions. The incidence of all side effects across clinician and patient ratings was approximately 2 times higher when using the change versus absolute score definition. Among the side effects detected by patients, 11 side effects were identified more frequently by clinicians, with 14.3% to 30.2% differences when using the change versus absolute score definition. Conversely, there was no difference of 10% or greater in patient or clinician concurrent detection rate on any item when using the absolute versus change score definition.
CONCLUSIONS: Our findings suggest that patient ratings are in line with clinician ratings and that the change score definition may be superior for the assessment of antipsychotic-associated side effects in clinical studies.
PMID: 27626285 [PubMed - indexed for MEDLINE]
Polypharmacy: the challenge for nurses.
Polypharmacy: the challenge for nurses.
Nurs Stand. 2016 May 25;30(39):52-60
Authors: Kaufman G
Abstract
Polypharmacy refers to the prescribing of many medicines for one individual. Polypharmacy is increasingly common as a result of the rise in multimorbidity, use of evidence-based clinical guidelines and care pathways, and a focus on disease prevention. Polypharmacy can be justified and appropriate, but it may also be inappropriate and associated with suboptimal health outcomes and mortality. Polypharmacy is associated with adverse drug events such as drug-drug interactions and adverse drug reactions (ADRs). Taking multiple medicines can adversely affect adherence, resulting in lost opportunities for health gain and wasted medicines. Older people, and particularly those who are frail, are susceptible to the adverse effects of polypharmacy. Medication reviews should be undertaken regularly in older people with polypharmacy. Medicines management systems, research, and education are essential to improve safe practice in the management of polypharmacy.
PMID: 27224631 [PubMed - indexed for MEDLINE]
Patient Safety and End-of-Life Care: Common Issues, Perspectives, and Strategies for Improving Care.
Patient Safety and End-of-Life Care: Common Issues, Perspectives, and Strategies for Improving Care.
Am J Hosp Palliat Care. 2016 Sep;33(8):791-6
Authors: Dy SM
Abstract
The current state of the science in the fields of patient safety and palliative and end-of-life care have many issues in common. This article synthesizes recent systematic reviews and additional research on improving patient safety and end-of-life care and compares each field's perspective on common issues, both in traditional patient safety frameworks and in other areas, and how current approaches in each field can inform the other. The article then applies these overlapping concepts to a key example area: improving documentation of patient preferences for life-sustaining treatment. The synthesis demonstrates how end-of-life issues should be incorporated into patient safety initiatives. In addition, evaluating overlap and comparable issues between patient safety and end-of-life care and comparing different perspectives and improvement strategies can benefit both fields.
PMID: 25877945 [PubMed - indexed for MEDLINE]
RFP Notice: Pharmacokinetic and Pharmacodynamic Studies for Medications Development
Notice of Form Correction for PA-16-286 "Successor-in-Interest (Type 6 Parent)"
Notice of Informational Webinars for Investigators Applying for NCCIH Clinical Trials
Notice of Change in the Expiration Date for PA-15-099 "Reductions in Illicit Drug Use and Functional Outcomes (R21/R33)"
Notice of Change in the Expiration Date for PAR-14-225 Clinical Evaluation of Adjuncts to Opioid Therapies for the Treatment of Chronic Pain (R01)
Notice of Change in the Expiration Date for PA-14-084 "Neuroimmune Signaling and Function in Substance Use Disorders (R01)"
Notice of Change in the Expiration Date for PA-14-083 "Neuroimmune Signaling and Function in Substance Use Disorders (R21)"
SBIR Phase II Bridge Awards to Accelerate the Development of Cancer Therapeutics, Imaging Technologies, Interventional Devices, Diagnostics, and Prognostics toward Commercialization (R44)
Correction for AHRQ Consumer Assessment of Healthcare Providers and Systems V (U18) FOA
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Regarding the past, what is the trial you have always been dreaming of in CIDP?
Regarding the past, what is the trial you have always been dreaming of in CIDP?
Rev Neurol (Paris). 2016 Oct;172(10):620-626
Authors: Hughes RA, Lunn MP
Abstract
Chronic inflammatory demyelinating polyradiculoneuropathy is an orphan disease of poorly understood cause. While first line treatments with corticosteroids, intravenous immunoglobulin and plasma exchange have at least short-term efficacy, no trial has shown that immunosuppressants work. In our dream, we will take advantage of the recently improved EU regulations to launch a Europe wide trial which will investigate the cause of the disease. It will compare three parallel groups, the anti-B cell agent rituximab, the anti-T cell agent abatacept and usual care. The trial will not be blinded and the design will be very simple. The primary outcome measure will be improvement from baseline of the overall neuropathy limitations scale (ONLS) score by 1 or more grades at 12 weeks without increase in concomitant corticosteroids or IVIg or use of plasma exchange. There will be an option to substitute improvement in the Rasch-built overall disability scale depending on future experience with that scale as the primary outcome measure. The trial will require 3 groups of 60 participants to detect an increase from 20% in the usual care group to 30% with one of the other agents with a power of 90% and P-value of 5%. It will be larger than any trial of an immunosuppressant agent so far performed in CIDP. However, recruitment will be easier because inclusion criteria will be broad and allow randomisation of any patient in whom their neurologist wishes to introduce an immunosuppressant. Avoidance of blinding and use of simple monitoring with facetime will simplify running the trial and reduce expense. The trial will follow participants and measure outcomes at 12 months. Other outcomes will consist only of grip strength, time to walk 10 m and Euroqol, the last allowing us to estimate the cost per QALY of rituximab or abatacept. Even including central analysis of key biomarkers, the trial will only cost 3 million euros, a fraction of the cost of the usual phase III pharmaceutical company trial.
PMID: 27638135 [PubMed - indexed for MEDLINE]
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