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Neural circuit plasticity and sensory response dynamics depend on forming new synaptic connections. Despite recent advances toward understanding the consequences of circuit plasticity, the mechanisms driving circuit plasticity are unknown. Adult-born neurons within the olfactory bulb have proven to be a powerful model for studying circuit plasticity, providing a broad and accessible avenue into neuron development, migration, and circuit integration. We and others have shown that efficient adult-born neuron circuit integration hinges on presynaptic activity in the form of diverse signaling peptides. Here, we demonstrate a novel oxytocin-dependent mechanism of adult-born neuron synaptic maturation and circuit integration. We reveal spatial and temporal enrichment of oxytocin receptor expression within adult-born neurons in the murine olfactory bulb, with oxytocin receptor expression peaking during activity-dependent integration. Using viral labeling, confocal microscopy, and cell type-specific RNA-seq, we demonstrate that oxytocin receptor signaling promotes synaptic maturation of newly integrating adult-born neurons by regulating their morphological development and expression of mature synaptic AMPARs and other structural proteins.
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Ocitocina , Receptores de Ocitocina , Camundongos , Animais , Ocitocina/metabolismo , Receptores de Ocitocina/genética , Receptores de Ocitocina/metabolismo , Neurônios/fisiologia , Bulbo Olfatório/metabolismo , NeurogêneseRESUMO
OBJECTIVES: Antibiotic resistance in gonorrhoea is of significant public health concern with the emergence of resistance to last-line therapies such as ceftriaxone. Despite around half of Neisseria gonorrhoeae isolates tested in the UK being susceptible to ciprofloxacin, very little ciprofloxacin is used in clinical practice. Testing for the S91F mutation associated with ciprofloxacin resistance is now available in CE-marked assays and may reduce the requirement for ceftriaxone, but many patients are treated empirically, or as sexual contacts, which may limit any benefit. We describe the real-world impact of such testing on antimicrobial use and clinical outcomes in people found to have gonorrhoea in a large urban UK sexual health clinic. METHODS: Molecular ciprofloxacin resistance testing (ResistancePlus GC assay (SpeeDx)) was undertaken as an additional test after initial diagnosis (m2000 Realtime CT/NG assay (Abbott Molecular)) in those not already known to have had antimicrobial treatment. Data from a 6-month period (from March to September 2022) were analysed to determine treatment choice and treatment outcome. RESULTS: A total of 998 clinical samples tested positive for N.â¯gonorrhoeae in 682 episodes of infection. Of the 560 (56%) samples eligible for resistance testing, 269 (48.0%) were reported as wild-type, 180 (32.1%) were predicted to be resistant, 63 (11.3%) had an indeterminate resistance profile, and in 48 (8.6%) samples, N.â¯gonorrhoeae was not detected. Ciprofloxacin was prescribed in 172 (75%) of 228 episodes in which the wild-type strain was detected. Four (2%) of those treated with ciprofloxacin had a positive test-of-cure sample by NAAT, with no reinfection risk. All four had ciprofloxacin-susceptible infection by phenotypic antimicrobial susceptibility testing. CONCLUSIONS: In routine practice in a large UK clinic, molecular ciprofloxacin resistance testing led to a significant shift in antibiotic use, reducing use of ceftriaxone. Testing can be targeted to reduce unnecessary additional testing. Longer term impact on antimicrobial resistance requires ongoing surveillance.
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Antibacterianos , Ciprofloxacina , Farmacorresistência Bacteriana , Gonorreia , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae , Humanos , Ciprofloxacina/uso terapêutico , Ciprofloxacina/farmacologia , Gonorreia/tratamento farmacológico , Gonorreia/diagnóstico , Gonorreia/microbiologia , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/genética , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Masculino , Feminino , Adulto , Reino Unido , Ceftriaxona/uso terapêutico , Ceftriaxona/farmacologia , Mutação , Adulto Jovem , Pessoa de Meia-IdadeRESUMO
Between December 2021 and June 2022, 10 cases of ceftriaxone-resistant Neisseria gonorrhoeae (ST8123;â¯nâ¯=â¯8) were detected in the United Kingdom, compared with nine cases during the previous 6 years. Most of these cases were associated with travel from the Asia-Pacific region; all were heterosexual people, with most in their 20s. Although all cases were successfully treated, not all partners of cases could be traced, and there is a risk of further transmission of ceftriaxone-resistant gonococcal infection within the UK.
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Gonorreia , Neisseria gonorrhoeae , Humanos , Neisseria gonorrhoeae/genética , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Testes de Sensibilidade Microbiana , Gonorreia/diagnóstico , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Reino Unido/epidemiologiaRESUMO
Science funders, publishers, and data archives make decisions about how to responsibly allocate resources to maximize the reuse potential of research data. This paper introduces a dataset developed to measure the impact of archival and data curation decisions on data reuse. The dataset describes 10,605 social science research datasets, their curation histories, and reuse contexts in 94,755 publications that cover 59 years from 1963 to 2022. The dataset was constructed from study-level metadata, citing publications, and curation records available through the Inter-university Consortium for Political and Social Research (ICPSR) at the University of Michigan. The dataset includes information about study-level attributes (e.g., PIs, funders, subject terms); usage statistics (e.g., downloads, citations); archiving decisions (e.g., curation activities, data transformations); and bibliometric attributes (e.g., journals, authors) for citing publications. This dataset provides information on factors that contribute to long-term data reuse, which can inform the design of effective evidence-based recommendations to support high-impact research data curation decisions.
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BACKGROUND: Growing evidence suggests that intensive lowering of systolic blood pressure (BP) may prevent mild cognitive impairment (MCI) and dementia. However, current guidelines provide inconsistent recommendations regarding optimal BP targets, citing safety concerns of excessive BP lowering in the diverse population of older adults. We are conducting a pragmatic trial to determine if an implementation strategy to reduce systolic BP to <130 and diastolic BP to <80 mmHg will safely slow cognitive decline in older adults with hypertension when compared to patients receiving usual care. METHODS: The Preventing Cognitive Decline by Reducing BP Target Trial (PCOT) is an embedded randomized pragmatic clinical trial in 4000 patients from two diverse health-systems who are age ≥ 70 years with BP >130/80 mmHg. Participants are randomized to the intervention arm or usual care using a permuted block randomization within each health system. The intervention is a combination of team-based care with clinical decision support to lower home BP to <130/80 mmHg. The primary outcome is cognitive decline as determined by the change in the modified Telephone Interview for Cognitive Status (TICS-m) scores from baseline. As a secondary outcome, patients who decline ≥3 points on the TICS-m will complete additional cognitive assessments and this information will be reviewed by an expert panel to determine if they meet criteria for MCI or dementia. CONCLUSION: The PCOT trial will address the effectiveness and safety of hypertension treatment in two large health systems to lower BP targets to reduce risk of cognitive decline in real-world settings.
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Disfunção Cognitiva , Demência , Hipertensão , Hipotensão , Idoso , Humanos , Pressão Sanguínea , Disfunção Cognitiva/prevenção & controle , Demência/prevenção & controle , Hipertensão/terapiaRESUMO
Purpose: This study aimed to measure the frequency of high-quality and transparent sexual orientation and gender identity (SOGI) data collection and reporting in highly cited current alcohol use research, using the extant literature to identify community-informed priorities for the measurement of these variables. Methods: A single search to identify alcohol use literature was conducted on PubMed with results restricted to primary research articles published between 2015 and 2022. The 200 most highly cited studies from each year were identified and their titles and abstracts reviewed against inclusion criteria after deduplication. After full-text review, study characteristics and data indicating quality of SOGI reporting were extracted. The fidelity of the results was verified with a random sample before analyses. Results: The final sample comprised 580 records. Few studies reported gender identity (n = 194; 33.4%) and, of these, 7.2% reported the associated gender identity measure. A two-stage approach to measure gender was adopted in 3 studies, one study used an open-ended question with a free-text response option, and 13 studies recorded nonbinary gender identities (reported by 0.9% of the whole sample). Nineteen (3.3%) studies reported sexual orientation and more than half of these provided the sexual orientation measure. Eight of the 20 studies that reported sexual orientation and/or gender identity measures were classified as sexual and gender minority specialist research. Conclusions: Culturally competent SOGI reporting is lacking in highly cited current alcohol research. SOGI measures should be disclosed in future research and should provide free-text response options.
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Interpreting chemical information and translating it into ethologically relevant output is a common challenge of olfactory systems across species. Are computations performed by olfactory circuits conserved across species to overcome these common challenges? To understand this, we compared odor responses in the locust antennal lobe (AL) and mouse olfactory bulb (OB). We found that odors activated nearly mutually exclusive neural ensembles during stimulus presentation ('ON response') and after stimulus termination ('OFF response'). Strikingly, ON and OFF responses evoked by a single odor were anticorrelated with each other. 'Inverted' OFF responses enhanced contrast between odors experienced close together in time. Notably, OFF responses persisted long after odor termination in both AL and OB networks, indicating a form of short-term memory. Taken together, our results reveal key neurodynamic features underlying olfactory computations that are conserved across insect and mammalian olfactory systems.
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Co-transmission of multiple neurotransmitters from a single neuron increases the complexity of signaling information within defined neuronal circuits. Superficial short-axon cells in the olfactory bulb release both dopamine and γ-aminobutyric acid (GABA), yet the specific targets of these neurotransmitters and their respective roles in olfaction have remained unknown. Here, we implement intersectional genetics in mice to selectively block GABA or dopamine release from superficial short-axon cells to identify their distinct cellular targets, impact on circuit function, and behavioral contribution of each neurotransmitter toward olfactory behaviors. We provide functional and anatomical evidence for divergent superficial short-axon cell signaling onto downstream neurons to shape patterns of mitral cell firing that contribute to olfactory-related behaviors.
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Bulbo Olfatório , Olfato , Camundongos , Animais , Bulbo Olfatório/fisiologia , Olfato/fisiologia , Dopamina , Interneurônios/fisiologia , Ácido gama-Aminobutírico , NeurotransmissoresRESUMO
Background Pharmacy fill data are a practical tool for assessing medication nonadherence. However, previous studies have not compared the accuracy of pharmacy fill data to measurement of plasma drug levels, or chemical adherence testing (CAT). Methods and Results We performed a cross-sectional study in patients with uncontrolled hypertension in outpatient clinics in a safety net health system. Plasma samples were obtained for measurement of common cardiovascular drugs, including calcium channel blockers, thiazide diuretics, beta blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and statins, using liquid chromatography mass spectrometry. Proportion of days covered (PDC), a method for tracking pharmacy fill data, was calculated via linkages with Surescripts, and its diagnostic test characteristics were compared with CAT. Among 77 patients with uncontrolled hypertension, 13 (17%) were nonadherent to at least 1 antihypertensive drug and 23 (37%) were nonadherent to statins by CAT. PDC was significantly lower in the nonadherent versus the adherent group by CAT only among patients prescribed an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker or statin (all P<0.05) but not in patients prescribed other drug classes. The sensitivity and specificity of PDC in detecting nonadherence to angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and statin drugs by CAT were 75% to 82% and 56% to 79%, respectively. The positive predictive value of PDC in detecting nonadherence was only 11% to 27% for antihypertensive drugs and 45% for statins. Conclusions PDC is useful in detecting nonadherence to angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and statins but has limited usefulness in detecting nonadherence to calcium channel blockers, beta blockers, or thiazide diuretics and has a low positive predictive value for all drug classes.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Hipertensão , Farmácia , Antagonistas Adrenérgicos beta/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Estudos Transversais , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipertensão/tratamento farmacológico , Adesão à Medicação , Provedores de Redes de Segurança , Inibidores de Simportadores de Cloreto de Sódio/uso terapêuticoRESUMO
Environmental cues and internal states such as mood, reward, or aversion directly influence feeding behaviors beyond homeostatic necessity. The hypothalamus has been extensively investigated for its role in homeostatic feeding. However, many of the neural circuits that drive more complex, non-homeostatic feeding that integrate valence and sensory cues (such as taste and smell) remain unknown. Here, we describe a basal forebrain (BF)-to-lateral habenula (LHb) circuit that directly modulates non-homeostatic feeding behavior. Using viral-mediated circuit mapping, we identified a population of glutamatergic neurons within the BF that project to the LHb, which responds to diverse sensory cues, including aversive and food-related odors. Optogenetic activation of BF-to-LHb circuitry drives robust, reflexive-like aversion. Furthermore, activation of this circuitry suppresses the drive to eat in a fasted state. Together, these data reveal a role of basal forebrain glutamatergic neurons in modulating LHb-associated aversion and feeding behaviors by sensing environmental cues.
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Prosencéfalo Basal , Habenula , Habenula/fisiologia , Prosencéfalo Basal/fisiologia , Afeto , Hipotálamo/fisiologia , Comportamento Alimentar , Vias Neurais/fisiologiaRESUMO
Low socioeconomic status (SES) is associated with greater morbidity and increased healthcare resource utilization (HRU) in IBD. We examined whether a financial assistance program (FAP) to improve healthcare access affected outcomes and HRU in a cohort of indigent IBD patients requiring biologics. IBD patients (>18 years) receiving care at a 'safety-net' hospital who initiated biologics as outpatients between 1 January 2010 and 1 January 2019 were included. Patients were divided by FAP status. Patients without FAP had Medicare, Medicaid, or commercial insurance. Primary outcomes were steroid-free clinical remission at 6 and 12 months. Secondary outcomes were surgery, hospitalization, and ED utilization. Multivariate logistic regression was used to calculate odds ratio (OR) and 95% confidence interval (CI). Decision tree analysis (DTA) was also performed. We included 204 patients with 258 new biologic prescriptions. FAP patients had less complex Crohn's disease (50.7% vs. 70%, p = 0.033) than non-FAP patients. FAP records indicated fewer prior surgeries (19.6% vs. 38.4% p = 0.003). There were no statistically significant differences in remission rates, disease duration, or days between prescription and receipt of biologics. In multivariable logistic regression, adjusting for baseline demographics and disease severity variables, FAP patients were less likely to undergo surgery (OR: 0.28, 95% CI [0.08−0.91], p = 0.034). DTA suggests that imaging utilization may shed light on surgical differences. We found FAP enrollment was associated with fewer surgeries in a cohort of indigent IBD patients requiring biologics. Further studies are needed to identify interventions to address healthcare disparities in IBD.
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PURPOSE: To determine whether the beneficial effects of acetazolamide (ACZ) in improving vision at 6 months continues to month 12 in participants of the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). DESIGN: Nonrandomized clinical study. METHODS: In the IIHTT, subjects were randomly assigned to placebo-plus-diet or maximally tolerated dosage of acetazolamide-plus-diet. At 6 months subjects transitioned from study drug to ACZ. This resulted in the following groups: (1) ACZ to ACZ; n = 34; (2) placebo to ACZ; n = 35; (3) ACZ to no treatment; n = 16; and (4) placebo to no treatment; n = 11. Ninety-six IIHTT subjects had evaluations at 6 and 12 months. Our main outcome measure was change from month 6 to month 12 in visual field mean deviation (MD) with secondary measures being change in papilledema grade, ETDRS scores, and quality-of-life (QoL) measures. RESULTS: The ACZ to ACZ group improved 0.35 dB, P = .05; placebo subjects with no ACZ improved 0.81 dB MD, P = .07 at 12 months. The other groups improved 0.35-0.46 dB MD. Mean improvements in papilledema grade occurred most markedly in the group that exchanged placebo for ACZ (0.91 units, P < .001). QoL and headache disability scores showed significant improvements in the placebo group with added ACZ. CONCLUSION: Improvements in MD continued from month 6 to month 12 of the IIHTT in all treatment groups, most marked in the placebo group tapered off study drug. Adding ACZ to the placebo group significantly improved papilledema grade, headache, and QoL measures.
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Acetazolamida/administração & dosagem , Papiledema/etiologia , Pseudotumor Cerebral/tratamento farmacológico , Campos Visuais/fisiologia , Administração Oral , Adulto , Inibidores da Anidrase Carbônica/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Masculino , Papiledema/fisiopatologia , Papiledema/prevenção & controle , Pseudotumor Cerebral/complicações , Pseudotumor Cerebral/fisiopatologia , Qualidade de Vida , Fatores de Tempo , Resultado do TratamentoRESUMO
Premature clopidogrel discontinuation is an important cause of stent thrombosis, myocardial infarction, and death after drug-eluting stent (DES) placement. Previous studies of clopidogrel nonadherence after DES placement have had short follow-up and have relied on self-reported adherence. All patients who underwent DES placement from January 2008 to December 2011 at a single safety-net hospital and received medications through the county-subsidized health plan were considered for inclusion; those with <1-year follow-up were excluded. We retrospectively collected 1-year refill data from a large, closed pharmacy system. Our primary outcome was time to failure to obtain a clopidogrel refill, allowing a 5-day grace period. Our study cohort (n = 369) was 34% female, 39% Hispanic, 26% white, and 26% African-American; 26% identified Spanish as their primary language. The time to failure to obtain a clopidogrel refill was 153 days. Cumulative failure to obtain at least 1 refill was 23% for the first refill, increasing to 52% at 6 months and 68% at 1 year. Examining the proportion of days covered (PDC), 21% of patients had 100% coverage, whereas 34% had PDC <80%. There were no independent predictors of nonadherence (PDC <80%). In conclusion, we identified a high rate of clopidogrel nonadherence in a multiethnic urban poor patient population where clopidogrel was provided at discharge and at nominal cost thereafter. In this cohort, prediction models of nonadherence performed poorly. Novel strategies are needed to address this important problem.
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Doença da Artéria Coronariana/terapia , Stents Farmacológicos , Hospitais Urbanos , Cooperação do Paciente , Ticlopidina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Clopidogrel , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Ticlopidina/uso terapêutico , Fatores de Tempo , Suspensão de TratamentoRESUMO
OBJECTIVES: To provide a review of the outcomes and costs in patients seen by Clinical Pharmacy Specialist (CPS) Certified Diabetes Educators in ambulatory care for diabetes management. STUDY DESIGN: A retrospective chart review. METHODS: All patients discharged by a CPS for diabetes management between January 1, 2010, and December 31, 2013, were included. RESULTS: A total of 915 patients were discharged from CPS services. The majority of patients had type 2 diabetes (98.7%) and were female (63.1%), Hispanic (53.3%), and on average, were aged 56 years. The patients were seen by the CPS for approximately 5.3 face-to-face visits, and by their provider for 1.9 face-to-face visits. The average difference from baseline for glycated hemoglobin was -2.6%, while the average systolic and diastolic blood pressures improved by -8 mm Hg and -3 mm Hg, respectively. The major lipid parameters also reported improvement, averaging -23 mg/dL for total cholesterol, -54 mg/dL for triglycerides, -15 mg/dL for low-density lipoprotein cholesterol, -23 mg/dL for non-high-density lipoprotein cholesterol (non-HDL-C), and +0.8 mg/dL for HDL-C. Overall, the average difference from baseline to final visit for the numbers and costs of medications and diabetes supplies per patient increased slightly. Medication adherence also improved each year in patients with diabetes. CONCLUSIONS: The CPSs directly impact patient care through improvements in clinical outcomes. They help patients achieve disease-state goals for diabetes, hypertension, and dyslipidemia through a variety of clinical interventions and by promoting medication adherence. These data demonstrate the significant positive impact to the institution that clinical pharmacy services have in diabetes management.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/economia , Hipoglicemiantes/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Serviço de Farmácia Hospitalar/organização & administração , Cuidados de Saúde não Remunerados/economia , Adulto , Idoso , Assistência Ambulatorial/organização & administração , Análise Custo-Benefício , Bases de Dados Factuais , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Seguimentos , Humanos , Hipoglicemiantes/economia , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Melhoria de Qualidade , Estudos Retrospectivos , Resultado do Tratamento , Cuidados de Saúde não Remunerados/estatística & dados numéricos , Estados UnidosRESUMO
BACKGROUND: Little is known about the use and effectiveness of over-the-counter (OTC) fish oil supplements for triglyceride (TG) lowering. OBJECTIVES: To (1) perform a medication-use evaluation (MUE) and (2) assess the efficacy of OTC fish oil. METHODS: Retrospective, observational cohort study using electronic medical records and the pharmacy database from Parkland Health and Hospital System in Dallas, Texas. Parkland is a tax-supported county institution that provides patients with single-brand OTC fish oil. Two separate analyses were conducted. Six hundred seventeen patients (prescribed fish oil between July 1, 2012, and August 31, 2012) were included in the MUE analysis and 235 patients (109 fish oil, 72 fenofibrate, and 54 gemfibrozil, prescribed between January 1, 2012, and July 31, 2013) were included in the efficacy analysis. The main outcome measure for the MUE was fish oil prescribing habits including dosages and patient adherence, as defined by medication possession ratio. The main outcome measure for the efficacy analysis was change in lipids measured using the last value before fish oil treatment and the first value after fish oil treatment. RESULTS: MUE: 617 patients received prescriptions for OTC fish oil. Sixty-four percent were prescribed a total daily dose of 2000 mg. Only 25% of patients were adherent. Efficacy analysis: despite being prescribed suboptimal doses, fish oil reduced TGs by 29% (95% confidence interval, 34.3-22.7). Compared with fish oil therapy, fibrate therapy resulted in a greater TG reduction: 48.5% (55.1-41.0) with fenofibrate and 49.8% (57.6-40.5) with gemfibrozil (P < .0001, both medications compared with fish oil). CONCLUSIONS: Health care providers prescribe suboptimal doses of fish oil, and adherence is poor. Even at low doses (2 g/d), though, fish oil lowers TGs by 29%.
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Óleos de Peixe/administração & dosagem , Hipolipemiantes/administração & dosagem , Medicamentos sem Prescrição/administração & dosagem , Triglicerídeos/sangue , Adulto , Idoso , Feminino , Fenofibrato/administração & dosagem , Genfibrozila/administração & dosagem , Hospitais Públicos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
This article describes the pharmacy management information systems environment currently being implemented at the Australian Department of Veterans' Affairs (DVA), and focuses on the objectives and design of the medication management program's management of information. As the system is new, it is too early to predict the difference that it will make to the operations and policy initiatives within the Medication Management section. The anticipated benefits are discussed. The user reaction, and the uses of these management data, are part of an ongoing benefits realisation study and the subject of a future article.