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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
    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: The Journal of Allergy and Clinical Immunology, July 2012, Vol.130(1), pp.162-168
    Description: Venom immunotherapy can be initiated by different schedules, but randomized comparisons have not been performed. We aimed to compare the safety of 2 initiation schedules. Patients of any age with prior immediate generalized reactions to jack jumper ant stings were randomized to venom immunotherapy initiation by a semirush schedule over 10 visits (9 weeks) or an ultrarush schedule over 3 visits (2 weeks). In a concurrent treatment efficacy study, the target maintenance dose was randomized to either 50 μg or 100 μg. The primary outcome was the occurrence of 1 or more objective systemic reactions during venom immunotherapy initiation. Analyses were by intention to treat. We also assessed outcomes in patients who declined randomization. Of 213 eligible patients, 93 were randomized to semirush (44 patients) or ultrarush (49 patients) initiation. Objective systemic reactions were more likely during ultrarush initiation (65% vs 29%;  〈 .001), as were severe reactions (12% vs 0%;  = .029). Times to maximal increases in venom-specific IgG were no different between treatments, whereas the maximal increase in venom-specific IgE occurred earlier with ultrarush treatment. Similar differences between methods were observed in patients who declined randomization. One hundred seventy-eight patients were randomized to maintenance doses of either 50 μg (90 patients) or 100 μg (88 patients). The target maintenance dose had no effect on the primary outcome, but multiple-failure-per-subject analysis found that the 50 μg dose reduced the likelihood of reactions. Ultrarush initiation increases the risk of systemic reactions. A lower maintenance dose reduces the risk of repeated reactions, but the effect on treatment efficacy is unknown.
    Keywords: Insect Sting Allergy ; Anaphylaxis ; Immunotherapy ; Venom Immunotherapy ; Randomized Controlled Trial ; Medicine
    ISSN: 0091-6749
    E-ISSN: 1097-6825
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  • 5
    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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  • 6
    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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  • 7
    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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  • 8
    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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  • 9
    In: British Journal of Clinical Pharmacology, June 2016, Vol.81(6), pp.1046-1057
    Description: Byline: Jessica Wojciechowski, Michael D. Wiese, Susanna M. Proudman, David J. R. Foster, Richard N. Upton Keywords: disease activity; disease modifying anti-rheumatic drugs; population modelling; rheumatoid arthritis Aims Composite indices for quantifying rheumatoid arthritis (RA) disease activity such as the 28-joint disease activity score (DAS28) are comprised of single parameters ('metrics') in various combinations. Population modelling methods were used to evaluate single metrics for their ability to reflect changes in disease activity with a view to understanding and improving composite indices. Methods A total of 11 single metrics of RA disease activity (tender and swollen joint counts, acute phase reactants and global health, pain and physical function assessments) were obtained from 203 patients with recent onset RA. Participants received combination disease-modifying anti-rheumatic drugs (DMARDs) according to a treat-to-target approach with a pre-defined protocol for treatment intensification. Models describing each metric's magnitude and variability of change from baseline to a single 'treated' state in the population were developed using nonmem.sub.[R]. Measures that displayed uniformly large changes between states across the population were ranked higher in terms of discriminatory capacity. Results Joint counts demonstrated a greater ability to discriminate changes in RA disease activity than others. Correlations between metrics demonstrated that erythrocyte sedimentation rate (ESR) had limited relationships with others for baseline scores and changes in RA disease activity (r generally 〈0.2). However it appeared to be important in describing changes for those individuals where ESR levels were initially elevated. Conclusion It appears unlikely that a single group of metrics may be suitable to capture disease activity changes across all RA patients and defining the most appropriate metric(s) for individual patients will be an important area of future research. CAPTION(S): Supporting Information Supporting Information Supporting Information
    Keywords: Disease Activity ; Disease Modifying Anti‐Rheumatic Drugs ; Population Modelling ; Rheumatoid Arthritis
    ISSN: 0306-5251
    E-ISSN: 1365-2125
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  • 10
    Language: English
    In: Journal of Agromedicine, 01 October 2016, Vol.21(4), pp.373-379
    Description: Dimethyl disulfide (DMDS) is a new soil fumigant that is considered a replacement for methyl bromide. In 2014, the Florida Department of Health (FDOH) received several complaints of illness following a strong DMDS odor in Hillsborough County. Public health investigation of DMDS-related illness...
    Keywords: Acute Poisonings ; Dimethyl Disulfide ; Paladin ; Pesticides ; Soil Fumigant ; Surveillance ; Medicine
    ISSN: 1059-924X
    E-ISSN: 1545-0813
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