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  • Springer (CrossRef)  (44)
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  • 1
    Language: English
    In: Drugs & Aging, 2012, Vol.29(11), pp.925-926
    Keywords: Female–Prevention & Control ; Humans–Statistics & Numerical Data ; Inappropriate Prescribing–Methods ; Male–Therapeutic Use ; Patient Education As Topic–Therapeutic Use ; Proton Pump Inhibitors–Therapeutic Use ; Proton Pump Inhibitors;
    ISSN: 1170-229X
    E-ISSN: 1179-1969
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  • 2
    Language: English
    In: Pharmaceutical Research, 2017, Vol.34(8), pp.1544-1550
    Description: Pharmacogenetic testing aims to personalize drug therapy with a view to optimising drug efficacy and minimise toxicity. However, despite the potential benefits, pharmacogenetic testing is mostly confined to specialised medical areas, laboratories and centres. Widespread integration into routine clinical practice has been limited by a complex set of issues including regulatory and reimbursement frameworks, evidence of clinical utility and clinician perspectives, practices and education. Here we assess the current barriers to widespread clinical uptake and identify the key issue necessary to address to accelerate routine testing.
    Keywords: biomarkers ; clinical uptake ; diagnostic tests ; personalized medicine
    ISSN: 0724-8741
    E-ISSN: 1573-904X
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  • 3
    Language: English
    In: Journal of Cancer Research and Clinical Oncology, 2013, Vol.139(2), pp.259-267
    Description: PURPOSETo assign functional properties to gene expression profiles of cervical cancer stages and identify clinically relevant biomarker genes. EXPERIMENTAL DESIGNMicroarray samples of 24 normal and 102 cervical cancer biopsies from four publicly available studies were pooled and evaluated. High-quality microarrays were normalized using the CONOR package from the Bioconductor project. Gene expression profiling was performed using variance-component analysis for accessing most reliable probes, which were subsequently processed by gene set enrichment analysis. RESULTSOf 22.277 probes that were subject to variance-component analysis, eleven probes had low heterogeneity, that is, a W/T ratio between 0.18 and 0.38. Seven of these probes are induced in all cervical cancer stages: they are GINS1, PAK2, DTL, AURKA, PRKDC, NEK2 and CEP55. The other four probes are induced in normal cervix: P11, EMP1, UPK1A and HSPC159. We performed GSEA of 9.873 probes exhibiting less variability, that is, having a W/T ratio of 〈0.75. Repeatedly, significant gene expression signatures were found that are related to treatment using angiocidin and darapladib. Additionally, expression signatures from immunological disease signatures were found, for example graft versus host disease and acute kidney rejection. Another finding comprises a gene expression signature in stage IB2 that refers to MT1-MMP-dependent migration and invasion. This gene signature is accompanied by gene expression signatures which refer to ECM receptor-mediated interactions. CONCLUSIONAnalysis of cervical cancer patient gene expression data reveals a novel perspective on HPV-mediated transcription processes. This novel point of view contains a better understanding and even might provide improvements to cancer therapy.
    Keywords: Darapladib ; Angiocidin ; Cervical cancer ; AURKA
    ISSN: 0171-5216
    E-ISSN: 1432-1335
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  • 4
    Language: English
    In: International Journal of Clinical Pharmacy, 2014, Vol.36(1), pp.26-29
    Description: Deprescribing is a holistic process of medication cessation that encompasses gaining a comprehensive medication list, identifying potentially inappropriate medications, deciding if the identified medication can be ceased, planning the withdrawal regimen and monitoring, support and follow-up. It is currently being investigated as a mechanism to reduce unnecessary or redundant medications. However, given the systematic and patient-centred nature of the deprescribing process, it is possible that it may also confer additional benefits such as improving adherence to medications, even if there is no net reduction in overall medication use. Specifically, deprescribing may improve adherence via reducing polypharmacy, reducing the financial costs associated with medication taking, increasing the patient’s medication knowledge through education, increasing patient engagement in medication management and resolution of adverse drug reactions. More research into deprescribing must be conducted to establish if these potential benefits can be realised, in addition to establishing any negative consequences.
    Keywords: Adherence ; Deprescribing ; Inappropriate medication use ; Medication withdrawal
    ISSN: 2210-7703
    E-ISSN: 2210-7711
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  • 5
    Language: English
    In: PharmacoEconomics, 2013, Vol.31(5), pp.377-391
    Description: Hypercholesterolaemia is a highly prevalent condition that has major health and cost implications for society. Pharmacotherapy is an important and effective treatment modality for hypercholesterolaemia, with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (‘statins’) the most commonly used class of drugs. Over the past decade, there has been intensive research to identify pharmacogenetic markers to guide treatment of hypercholesterolaemia. This study aimed to review the evidence of incremental cost, effect and cost effectiveness of pharmacogenetic-guided treatment of hypercholesterolaemia. Three cost-effectiveness analyses (CEAs) were identified that studied the value of screening for genotypes of angiotensin I converting enzyme ( ACE ), cholesteryl ester transfer protein ( CETP ), and kinesin family member 6 ( KIF6 ) prior to initiating statin therapy. For all three CEAs, a major limitation identified was the reproducibility of the evidence supporting the clinical effect of screening for the pharmacogenetic marker. Associated issues included the uncertain value of pharmacogenetic markers over or in addition to existing approaches for monitoring lipid levels, and the lack of evidence to assess the effectiveness of alternative therapeutic options for individuals identified as poor responders to statin therapy. Finally, the economic context of the market for diagnostic tests (is it competitive or is there market power?) and the practicality of large-scale screening programmes to inform prescribing in a complex and varied market may limit the generalizability of the results of the specific CEAs to policy outcomes. The genotype of solute carrier organic anion transporter family member 1B1 ( SLCO1B1 ) has recently been associated with increased risk of muscle toxicity with statin therapy and the review identified that exploration of cost effectiveness of this pharmacogenetic marker is likely warranted.
    Keywords: Anticholesteremic Agents–Economics ; Anticholesteremic Agents–Therapeutic Use ; Cholesterol Ester Transfer Proteins–Genetics ; Cost-Benefit Analysis–Economics ; Genotype–Therapeutic Use ; Humans–Drug Therapy ; Hydroxymethylglutaryl-Coa Reductase Inhibitors–Economics ; Hydroxymethylglutaryl-Coa Reductase Inhibitors–Genetics ; Hypercholesterolemia–Genetics ; Hypercholesterolemia–Genetics ; Hypercholesterolemia–Genetics ; Kinesin–Genetics ; Organic Anion Transporters–Genetics ; Peptidyl-Dipeptidase A–Genetics ; Pharmacogenetics–Genetics ; Reproducibility of Results–Genetics ; United Kingdom–UK ; Pharmacology ; Health Care Expenditures ; Patient Care Planning ; Effectiveness ; Health Care Industry ; Medical Treatment ; Health Care Industry ; Western Europe ; Anticholesteremic Agents ; Cholesterol Ester Transfer Proteins ; Hydroxymethylglutaryl-Coa Reductase Inhibitors ; Organic Anion Transporters ; Slco1b1 Protein, Human ; Peptidyl-Dipeptidase A ; Kif6 Protein, Human ; Kinesin;
    ISSN: 1170-7690
    E-ISSN: 1179-2027
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  • 6
    Language: English
    In: International journal of clinical pharmacy, February 2013, Vol.35(1), pp.51-6
    Description: There is a large amount of research into and promotion of rational prescribing, but there is a comparative lack of investigation into deprescribing. The success of deprescribing is likely to be dependent on both medical and patient factors. The aim of this study was to develop and validate a tool to capture the views and beliefs of patients regarding cessation of medications. Setting Participants were recruited from a multidisciplinary clinic at the Royal Adelaide Hospital and Hampstead Rehabilitation Centre. The patients' attitudes towards deprescribing (PATD) questionnaire was developed through expert opinion and piloting. Psychometric testing included face, content and criterion validity, sensitivity and test-retest reliability. A final 15 item questionnaire was produced. Through piloting, expert review and gamma rank correlation with the previously validated beliefs about medicines questionnaire, the PATD was determined to be valid. Test-retesting resulted in a total concordance of 71.3 % (95 % confidence interval, 64.1-78.5 %). The PATD has acceptable psychometric properties and has potential for future use in research and practice to not only determine patients' willingness towards deprescribing, but also uncover what beliefs may influence this.
    Keywords: Attitude ; Polypharmacy ; Surveys and Questionnaires
    ISSN: 22107703
    E-ISSN: 2210-7711
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  • 7
    Language: English
    In: Drugs & Aging, 2013, Vol.30(10), pp.793-807
    Description: BACKGROUNDInappropriate medication use is common in the elderly and the risks associated with their use are well known. The term deprescribing has been utilised to describe the complex process that is required for the safe and effective cessation of inappropriate medications. Given the primacy of the consumer in health care, their views must be central in the development of any deprescribing process. OBJECTIVESThe aim of this study was to identify barriers and enablers that may influence a patient's decision to cease a medication. DATA SOURCESA systematic search of MEDLINE, International Pharmaceutical Abstracts, EMBASE, CINAHL, Informit and Scopus was conducted and augmented with a manual search. Numerous search terms relating to withdrawal of medications and consumers' beliefs were utilised. STUDY ELIGIBILITY CRITERIAArticles were included if the barriers or enablers were directly patient/carer reported and related to long-term medication(s) that they were currently taking or had recently ceased. STUDY APPRAISAL AND SYNTHESIS METHODSDetermination of relevance and data extraction was performed independently by two reviewers. Content analysis with coding was utilised for synthesis of results. RESULTSTwenty-one articles met the criteria and were included in the review. Three themes, disagreement/agreement with 'appropriateness' of cessation, absence/presence of a 'process' for cessation, and negative/positive 'influences' to cease medication, were identified as both potential barriers and enablers, with 'fear' of cessation and 'dislike' of medications as a fourth barrier and enabler, respectively. The most common barrier/enabler identified was 'appropriateness' of cessation, with 15 studies identifying this as a barrier and 18 as an enabler. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGSThe decision to stop a medication by an individual is influenced by multiple competing barriers and enablers. Knowledge of these will aid in the development of a deprescribing process, particularly in approaching the topic of cessation with the patient and what process should be utilised. However, further research is required to determine if the proposed patient-centred deprescribing process will result in improved patient outcomes.
    Keywords: Decision Making–Statistics & Numerical Data ; Humans–Statistics & Numerical Data ; Inappropriate Prescribing–Statistics & Numerical Data ; Patient Safety–Statistics & Numerical Data ; Withholding Treatment–Statistics & Numerical Data;
    ISSN: 1170-229X
    E-ISSN: 1179-1969
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  • 8
    Language: English
    In: European Journal of Clinical Pharmacology, 2015, Vol.71(9), pp.1099-1108
    Description: Byline: Barbara Caecilia Wimmer (1), Kristina Johnell (2), Johan Fastbom (2), Michael David Wiese (3), J. Simon Bell (1,3) Keywords: Medication regimen complexity; Polypharmacy; Aged; Inappropriate prescribing; Population-based study Abstract: Purpose There is a lack of population-based research about factors associated with medication regimen complexity. This study investigated factors associated with medication regimen complexity in older people, and whether factors associated with regimen complexity were similar to factors associated with number of medications. Methods This cross-sectional population-based study included 3348 people aged a[yen]60 years. Medication regimen complexity was computed using the validated 65-item Medication Regimen Complexity Index (MRCI). Multinomial logistic regression was used to compute unadjusted and adjusted odds ratios (ORs) with 95 % confidence intervals (CIs) for factors associated with regimen complexity. Multivariable quantile regression was used to compare factors associated with regimen complexity and number of medications. Results In adjusted analyses, participants in the highest MRCI quintile (MRCI〉20) were older (OR=1.04, 95 % CI 1.02 1.05), less likely to live at home (OR=0.35, 95 % CI 0.15 0.86), had greater comorbidities (OR=2.17, 95 % CI 1.89 2.49), had higher cognitive status (OR=1.06, 95 % CI 1.01 1.11), a higher prevalence of self-reported pain (OR=2.85, 95 % CI 2.16 3.76), had impaired dexterity (OR=2.39, 95 % CI 1.77 3.24) and were more likely to receive help to sort their medications (OR=4.43 95 % CI 2.39 8.56) than those with low regimen complexity (MRCI 〉0--5.5). Similar factors were associated with both regimen complexity and number of medications. Conclusion Older people with probable difficulties managing complex regimens, including those with impaired dexterity and living in institutional settings, had the most complex medication regimens even after adjusting for receipt of help to sort medications. The strong correlation between regimen complexity and number of medications suggests that clinicians could use a person's number of medications to target interventions to reduce complexity. Author Affiliation: (1) Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, Australia (2) Aging Research Center, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden (3) Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia (4) 381 Royal Parade, Parkville, VIC, 3052, Australia Article History: Registration Date: 02/06/2015 Received Date: 16/04/2015 Accepted Date: 02/06/2015 Online Date: 14/06/2015
    Keywords: Medication regimen complexity ; Polypharmacy ; Aged ; Inappropriate prescribing ; Population-based study
    ISSN: 0031-6970
    E-ISSN: 1432-1041
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  • 9
    Language: English
    In: Breast Cancer Research and Treatment, 2012, Vol.135(1), pp.307-318
    Description: Identification and characterization of tumor subtypes using gene expression profiles of triple negative breast cancer patients. Microarray data of four breast cancer studies were pooled and evaluated. Molecular subtype classification was performed using random forest and a novel algorithm for feature extraction via composite scoring and voting. Biological and clinical properties were evaluated via GSEA, functional annotation clustering and clinical endpoint analysis. The subtype signatures are highly predictive for distant metastasis free survival of tamoxifen-treated patients. Consensus clustering and the novel algorithm proposed three triple negative subtypes. One subtype shows low E2F4 gene expression and is predictive for survival of ER negative breast cancer patients. The other two subtypes share commonalities with luminal B tumors. Classification of breast cancer expression profiles may reveal novel tumor subtypes, possessing clinical impact. Furthermore, subtype characterizing gene signatures might hold potential for novel strategies in cancer therapy.
    Keywords: Classification ; Machine learning ; Triple negative breast cancer ; Tumor subtypes ; E2F4
    ISSN: 0167-6806
    E-ISSN: 1573-7217
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  • 10
    Language: English
    In: Rheumatology International, 2017, Vol.37(6), pp.897-904
    Description: Medication adherence is believed to be a major contributor to treatment outcomes yet studies quantifying this relationship as rare in rheumatoid arthritis (RA). To determine the association of adherence to DMARD therapy with treatment outcomes among new and existing DMARD users over 2 years. Relevant clinical parameters were obtained from a longitudinal cohort of RA patients, most of who were treated with combination therapy. Patients were classified as adherent if the proportion of days covered for each DMARD was ≥80%. Outcome measures were the change in the disease activity score in 28 joints (DAS28), simplified disease activity index (SDAI), modified health assessment questionnaires (mHAQ) and proportion of patients who achieved response criteria. An inverse propensity-score weighting method was used to estimate the association of adherence with each outcome. Of 194 patients invited, a total of 111 patients (new = 45 and existing = 66 DMARD users) met study eligibility. DMARD-naive patients demonstrated relatively higher rates of adherence compared to existing users. After controlling for confounding variables, adherence was significantly associated with reduction in DAS28 ( β  = −1.5, 95% CI of β  = − 2.17 to −0.83, p  〈 0.0001), SDAI ( β  = −9.44, 95% CI of β  = −15.53 to −3.35, p  = 0.002) and mHAQ ( β  = −0.269, 95% CI of β , −0.462 to −0.077, p  = 0.017) over 2 years among new patients and adherent patients were more likely to achieve most response criteria compared to non-adherent patients. Such associations were not replicated among existing DMARD users. Adherence to combination DMARD therapy was associated with improvements in disease activity and functional outcomes in the first 2 years of therapy.
    Keywords: Medication adherence ; Treatment outcomes ; Rheumatoid arthritis ; Propensity scores ; Clinical outcomes
    ISSN: 0172-8172
    E-ISSN: 1437-160X
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