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  • 1
    In: Journal of the American Geriatrics Society, September 2013, Vol.61(9), pp.1508-1514
    Description: Byline: Emily Reeve, Michael D. Wiese, Ivanka Hendrix, Michael S. Roberts, Sepehr Shakib Keywords: elderly; polypharmacy; deprescribing; potentially inappropriate medications; discontinuation Objectives To capture people's attitudes, beliefs, and experiences regarding the number of medications they are taking and their feelings about stopping medications. Design Administration of a validated questionnaire. Setting Multidisciplinary ambulatory consulting service at the Royal Adelaide Hospital. Participants Participants were individuals aged 18 and older (median 71.5) taking at least one regular prescription medication; 100 participants completed all items of the questionnaire, 65 of whom were aged 65 and older. Measurements Participants were administered the 15-item Patients' Attitudes Towards Deprescribing (PATD) questionnaire. Results Participants were taking an average of 10 different prescription and nonprescription (including complementary), regular and as-needed medications. More than 60% felt that they were taking a "large number" of medications, and 92% stated that they would be willing to stop one or more of their current medications if possible. Number of regular medications, age, and number of medical conditions were not found to be correlated with willingness to stop a medication. The findings were similar in older and younger participants. Conclusion This study has shown that a cohort of mostly older adults were largely accepting of a trial of cessation of medication(s) that their prescriber deemed to be no longer required. Because few factors were associated with willingness to cease medications, all patients should be individually evaluated for deprescribing. CAPTION(S): Figure S1. Distribution of propensity score for Intervention and Control participants. Table S1. List of Exclusionary Comorbidities, ICD-9 Codes, and CPT Codes. Table S2. Control county selection criteria. Table S3. ICD-9-CM diagnosis codes for disease classification of participants. Table S4. Regression specifications. Table S1. Comparison of frailty components for Men in the Cardiovascular Health Study (CHS) and Men in the Osteoporotic Fractures in Men (MrOS) Study.
Table S2. Association between Cystatin C and frailty status among 1,257 Subjects with eGFRCr 〉60 ml/min/1.73 m2. Table S1. Adjusted* odds ratios (95% CI) from logistic regression analyses for cognitive impairment (lowest 10% performance within ethnic group) on individual cognitive tests per 10 mmHg increment in each listed blood pressure measurement.
    Keywords: Elderly ; Polypharmacy ; Deprescribing ; Potentially Inappropriate Medications ; Discontinuation
    ISSN: 0002-8614
    E-ISSN: 1532-5415
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  • 2
    In: Medical Journal of Australia, July 2011, Vol.195(2), pp.69-73
    Description: To determine the Australian native ant species associated with ant sting anaphylaxis, geographical distribution of allergic reactions, and feasibility of diagnostic venom‐specific IgE (sIgE) testing. Descriptive clinical, entomological and immunological study of Australians with a history of ant sting anaphylaxis, recruited in 2006–2007 through media exposure and referrals from allergy practices and emergency physicians nationwide. We interviewed participants, collected entomological specimens, prepared reference venom extracts, and conducted serum sIgE testing against ant venom panels relevant to the species found in each geographical region. Reaction causation attributed using a combination of ant identification and sIgE testing. 376 participants reported 735 systemic reactions. Of 299 participants for whom a cause was determined, 265 (89%; 95% CI, 84%–92%) had reacted clinically to species and 34 (11%; 95% CI, 8%–16%) to green‐head ant (). Of those with reactions to species, 176 reacted to jack jumper ant ( species complex), 18 to other jumper ants (15 to , three to ) and 56 to a variety of bulldog ants, with some participants reacting to more than one type of bulldog ant. Variable serological cross‐reactivity between bulldog ant species was observed, and sera from patients with bulldog ant allergy were all positive to one or more venoms extracted from , and . Four main groups of Australian ants cause anaphylaxis. Serum sIgE testing enhances the accuracy of diagnosis and is a prerequisite for administering species‐specific venom immunotherapy.
    Keywords: Emergency Medicine ; Immune System Diseases
    ISSN: 0025-729X
    E-ISSN: 1326-5377
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  • 3
    In: Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 2016, Vol. 71(6), pp.831-837
    Description: Background: Adverse drug events are a leading cause of hospitalization among older people. Up to half of all medication-related hospitalizations are potentially preventable. The objective of this study was to investigate and compare the association between medication regimen complexity and number of medications with unplanned hospitalizations over a 3-year period. Methods: Data were analyzed for 3,348 participants aged 60 years or older in Sweden. Regimen complexity was assessed using the 65item Medication Regimen Complexity Index (MRCI) and number of medications was assessed as a continuous variable. Cox proportional hazard models were used to compute unadjusted and adjusted hazard ratios with 95% confidence intervals (CIs) for associations between regimen complexity and number of medications with unplanned hospitalizations over a 3-year period. Receiver operating characteristics curves with corresponding areas under the curve were calculated for regimen complexity and number of medications in relation to unplanned hospitalizations. The population attributable fraction of unplanned hospitalizations was calculated for MRCI and number of medications. Results: In total, 1,125 participants (33.6%) had one or more unplanned hospitalizations. Regimen complexity (hazard ratio 1.22; 95% CI 1.14-1.34) and number of medications (hazard ratio 1.07; 95% CI 1.04-1.09) were both associated with unplanned hospitalizations and had similar sensitivity and specificity (area under the curve 0.641 for regimen complexity and area under the curve 0.644 for number of medications). The population attributable fraction was 14.08% (95% CI 9.62-18.33) for MRCI and 17.61% (95% CI 12.59- 22.35) for number of medications. Conclusions: There was no evidence that using a complex tool to assess regimen complexity was better at predicting unplanned hospitalization than number of medications. Keywords: Medication regimen complexity--Polypharmacy--Hospitalization--Aged--Inappropriate prescribing doi: 10.1093/gerona/glv219
    Keywords: Medication Regimen Complexity ; Polypharmacy ; Hospitalization ; Aged ; Inappropriate Prescribing
    ISSN: 1079-5006
    E-ISSN: 1758-535X
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  • 4
    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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  • 5
    In: Journal of the American Geriatrics Society, April 2017, Vol.65(4), pp.747-753
    Description: Byline: Barbara C Wimmer, Amanda J Cross, Natali Jokanovic, Michael D Wiese, Johnson George, Kristina Johnell, Basia Diug, J. Simon Bell Keywords: medication regimen complexity; aged; adherence; systematic review Objectives To systematically review clinical outcomes associated with medication regimen complexity in older people. Design Systematic review of EMBASE, MEDLINE, International Pharmaceutical Abstracts, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane library. Setting Hospitals, home, and long-term care. Participants English-language peer-reviewed original research published before June 2016 was eligible if regimen complexity was quantified using a metric that considered number of medications and at least one other parameter, regimen complexity was calculated for participants' overall regimen, at least 80% of participants were aged 60 and older, and the study investigated a clinical outcome associated with regimen complexity. Measurements Quality assessment was conducted using an adapted version of the Joanna Briggs Institute critical appraisal tool. Results Sixteen observational studies met the inclusion criteria. Regimen complexity was associated with medication nonadherence (2/6 studies) and higher rates of hospitalization (2/4 studies). One study found that participants with less-complex medication administration were more likely to stop medications when feeling worse. One study each identified an association between regimen complexity and higher ability to administer medications as directed, medication self-administration errors, caregiver medication administration hassles, hospital discharge to non-home settings, postdischarge potential adverse drug events, all-cause mortality, and lower patient knowledge of their medication. Regimen complexity had no association with postdischarge medication modification, change in medication- and health-related problems, emergency department visits, or quality of life as rated by nursing staff. Conclusion Research into whether medication regimen complexity is associated with nonadherence and hospitalization has produced inconsistent results. Moderate-quality evidence from four studies (two each for nonadherence and hospitalization) suggests that medication regimen complexity is associated with nonadherence and higher rates of hospitalization. CAPTION(S): Figure S1. Adapted Joanna Briggs Institute Critical Appraisal Checklist for Comparable Cohort/Case Control5 Table S1. Characteristics of Included Studies Table S2. Quality Assessment of Included Studies (Based on an Adapted Version of the Joanna Briggs Institute Critical Appraisal Tool)10 Table S3. Clinical Outcomes Associated with Regimen Complexity
    Keywords: Medication Regimen Complexity ; Aged ; Adherence ; Systematic Review
    ISSN: 0002-8614
    E-ISSN: 1532-5415
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  • 6
    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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  • 7
    Language: English
    In: Pharmacogenomics, September 2012, Vol.13(12), pp.1427-34
    Description: Leflunomide is a disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis. Not all patients respond to leflunomide and, as it has potentially serious side effects, targeting only those most likely to benefit would address a clinical need. We aimed to determine whether variations in the gene encoding DHODH, the molecular target of leflunomide, might include biomarkers that could be used to rationalize provision of this drug. We analyzed six haplotype-tagging SNPs in DHODH in 56 patients with rheumatoid arthritis treated with leflunomide. Clinical response was determined by assessing the change in 28 joint disease activity score over the first 3 months of treatment. Carriage of a six-marker DHODH haplotype was associated with a reduced treatment response (p = 0.008). This suggests that a functional variant in strong linkage disequilibrium with this haplotype may predispose to reduced leflunomide efficacy.
    Keywords: Antirheumatic Agents -- Therapeutic Use ; Arthritis, Rheumatoid -- Drug Therapy ; Isoxazoles -- Therapeutic Use ; Oxidoreductases Acting on Ch-Ch Group Donors -- Genetics
    ISSN: 14622416
    E-ISSN: 1744-8042
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  • 8
    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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  • 9
    Language: English
    In: The Lancet, 22 March 2003, Vol.361(9362), pp.1001-1006
    Description: The jack jumper ant is responsible for about 90% of ant venom anaphylaxis in southeastern Australia. We aimed to establish whether venom immunotherapy (VIT) prevents lifethreatening sting anaphylaxis in otherwise healthy adults. We did a double-blind, placebo-controlled crossover trial of VIT. Participants were randomly allocated either immunotherapy, in accordance with the semirush hyposensitisation regimen, or placebo. The primary endpoint was systemic reaction after a deliberate sting challenge. Analysis was per protocol. We randomly allocated 68 healthy volunteers (aged 20–63 years) who were allergic to venom to placebo (33) and VIT (35). Four on placebo were stopped early and 12 on VIT had their treatment allocations revealed before the sting challenge, thus 29 on placebo and 23 on VIT were included in the primary analysis. Objectively defined systemic reactions to sting challenges arose in 21 of 29 participants (72%) on placebo (8 reactions were associated with hypotension) and none of 23 on VIT (p〈0·0001). Of the remaining 12 on VIT who underwent sting challenges after treatment allocations were revealed, only one reacted to sting challenge with transient urticaria that did not require treatment. After crossover of the placebo group to VIT, one of 26 had a reaction to sting challenge (transient urticaria). In all patients who had VIT, we recorded objective systemic reactions in 22 of 64 (34%) during VIT; two of which were hypotensive. In well motivated, highly allergic, but otherwise healthy adults, VIT is highly effective in prevention of sting anaphylaxis. The risk of systemic reactions during VIT means that treatment should be given where there is immediate access to resuscitation facilities.
    Keywords: Medicine
    ISSN: 0140-6736
    E-ISSN: 1474-547X
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  • 10
    Language: English
    In: Annals of Pharmacotherapy, January 2015, Vol.49(1), pp.29-38
    Description: Background: Proton pump inhibitors (PPIs) are inappropriately prescribed in up to 50% of users. Systematic medication review and cessation of inappropriate medications or deprescribing may improve patient outcomes and reduce costs. Objective: The aim of this study was to assess the feasibility of a patient-centered deprescribing process in a population of adults with complex polypharmacy. Methods: This was a prospective feasibility study. Participants were recruited from hospital outpatient clinics. The patient-centered deprescribing process consisted of 5 steps: comprehensive medication history, identification of potentially inappropriate medications, determining if the medication can be ceased, planning the withdrawal regimen (eg, tapering where necessary), and provision of monitoring, support, and documentation. Feasibility was determined by assessing time taken to complete the different steps of the deprescribing process and participant feedback. Results: In all, 57 PPI users were recruited; participants were 70 ± 14 years old and took 14 ± 6 medications. The indication for PPI use was verified in 43 participants and judged as potentially inappropriate in 19 (44%); 8 were suitable for trial withdrawal, and 6 consented. All 6 successfully ceased (n = 3) or reduced (n = 3) their PPI use, and this was sustained at 6 months postintervention in 4 participants. Conclusions: The patient-centered deprescribing process can safely reduce inappropriate PPI prescribing in a small proportion of people. Although the process was acceptable to participants, difficulties in accessing complete medical histories, time limitations, and minimal evidence to support effectiveness in certain indications were barriers to implementation of the process in clinical practice.
    Keywords: Deprescribing ; Inappropriate Medication Use ; Medication Withdrawal ; Older Adults ; Polypharmacy ; Proton Pump Inhibitors ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 1060-0280
    E-ISSN: 1542-6270
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