ORCID Profile
0000-0003-1830-9930
Current Organisation
Universidade Federal do Rio de Janeiro
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Publisher: Springer Science and Business Media LLC
Date: 31-08-2020
DOI: 10.1007/S40520-019-01336-X
Abstract: The objective of this study is to investigate the association between multiple antihypertensive use and mortality in residents with diagnosed hypertension, and whether dementia and frailty modify this association. This is a two-year prospective cohort study of 239 residents with diagnosed hypertension receiving antihypertensive therapy across six residential aged care services in South Australia. Data were obtained from electronic medical records, medication charts and validated assessments. The primary outcome was all-cause mortality and the secondary outcome was cardiovascular-related hospitalizations. Inverse probability weighted Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. Covariates included age, sex, dementia severity, frailty status, Charlson's comorbidity index and cardiovascular comorbidities. The study s le (mean age of 88.1 ± 6.3 years 79% female) included 70 (29.3%) residents using one antihypertensive and 169 (70.7%) residents using multiple antihypertensives. The crude incidence rates for death were higher in residents using multiple antihypertensives compared with residents using monotherapy (251 and 173/1000 person-years, respectively). After weighting, residents who used multiple antihypertensives had a greater risk of mortality compared with monotherapy (HR 1.40, 95%CI 1.03-1.92). After stratifying by dementia diagnosis and frailty status, the risk only remained significant in residents with diagnosed dementia (HR 1.91, 95%CI 1.20-3.04) and who were most frail (HR 2.52, 95%CI 1.13-5.64). Rate of cardiovascular-related hospitalizations did not differ among residents using multiple compared to monotherapy (rate ratio 0.73, 95%CI 0.32-1.67). Multiple antihypertensive use is associated with an increased risk of mortality in residents with diagnosed hypertension, particularly in residents with dementia and among those who are most frail.
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.SAPHARM.2016.08.005
Abstract: Pharmacist-led medication review is a collaborative service which aims to identify and resolve medication-related problems. To critically evaluate published systematic reviews relevant to pharmacist-led medication reviews in community settings. MEDLINE, EMBASE, International Pharmaceutical Abstracts (IPA), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane Database of Systematic Reviews (CDSR) were searched from 1995 to December 2015. Systematic reviews of all study designs and outcomes were considered. Methodological quality was assessed using the 11-item Assessment of Multiple Systematic Reviews (AMSTAR) tool. Systematic reviews of moderate or high quality (AMSTAR ≥ 4) were included in the data synthesis. Data extraction and quality assessment was performed independently by two investigators. Of the 35 relevant systematic reviews identified, 24 were of moderate and seven of high quality and were included in the data synthesis. The largest overall numbers of unique primary research studies with favorable outcomes were for diabetes control (78% of studies reporting the outcome), blood pressure control (74%), cholesterol (63%), medication adherence (56%) and medication management (47%). Significant reductions in medication and/or healthcare costs were reported in 35% of primary research studies. Meta-analysis was performed in 12 systematic reviews. Results from the meta-analyses suggested positive impacts on glycosylated hemoglobin, blood pressure, cholesterol, and number and appropriateness of medications. Conflicting findings were reported in relation to hospitalization. No meta-analyses reported reduced mortality. Moderate and high quality systematic reviews support the value of pharmacist-led medication review for a range of clinical outcomes. Further research including more rigorous cost analyses are required to determine the impact of pharmacist-led medication reviews on humanistic and economic outcomes. Future systematic reviews should consider the inclusion of both qualitative and quantitative studies to comprehensively evaluate medication review.
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.SAPHARM.2018.07.001
Abstract: Evidence is accumulating globally on harms from extramedical prescription opioid analgesic (POA) use. The aim of this scoping review was to explore harms and documented risk factors associated with extramedical POA use in Australia. MEDLINE, EMBASE, PsycINFO and CINAHL were searched for original studies published between January 2000 and February 2018. Studies were eligible for inclusion if: 1) POA use was explicitly reported, 2) extramedical use was evident 3) harm was explicitly reported, 4) data were collected in/after 2000, 5) conducted in adults and 6) undertaken in Australia. We identified 560 articles and 16 met the inclusion criteria. Harms reported from extramedical POA use included: increased health service utilization (n = 5), non-fatal overdose (n = 6), fatal overdose (n = 5), injection-related injuries or diseases (n = 4), engagement in crime (n = 2), loss of employment (n = 1), and foreign body pulmonary embolization (n = 1). Multiple drug toxicity was reported as the cause of death in up to 83% of fatal overdose cases. Risk factors for harm included being male, aged 31-49 years, a history of chronic non-cancer pain, mental health disorders and/or substance abuse, and concomitant use of benzodiazepines, antidepressants or other centrally-acting substances. Extramedical use of POAs is associated with a range of harms, including fatal and non-fatal overdose. Polysubstance use with other centrally-acting substances was often implicated. No published studies used linked data sources to provide a comprehensive overview of the extent of POA use or harm in Australia. Future research should focus on undertaking longitudinal cohort studies with linked data sources.
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.SAPHARM.2015.06.007
Abstract: Clinical medication review (CMR) is a structured and collaborative service aimed at identifying and resolving medication-related problems (MRPs). This is the first systematic review of CMR research in Australia. To systematically review the processes and outcomes of CMR in community-settings in Australia. MEDLINE, EMBASE, International Pharmaceutical Abstracts (IPA), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library and the grey literature were searched from 2000 to February 2015. All study designs were considered. Data extraction and quality assessment were performed independently by two investigators. Nine controlled studies, 34 observational and uncontrolled studies, 11 qualitative studies (focus groups and interviews) and nine survey studies were included. The CMRs resulted in identification of MRPs (n = 15 studies, mean 3.6 MPRs per CMR) and improved adherence (n = 3). Reductions in numbers of medications prescribed (n = 3 studies), hospitalizations (n = 3), potentially inappropriate prescribing (n = 3) and costs (n = 6) were demonstrated. Comparisons to a control group, predominately non-recipients of CMR, were made in eleven of 43 studies. Evidence supports additional models that promote interprofessional collaboration and timely referral following hospital discharge. Qualitative research identified low awareness of CMR among eligible non-recipients, while benefits were perceived to outweigh barriers to implementation. Underserved populations include indigenous and culturally and linguistically erse people, recipients of palliative care, those recently discharged from hospital, people with poor medication adherence, those in rural and remote areas, older males, and younger people with long-term, persistent or serious health problems. The available evidence suggests CMR is beneficial in improving the quality use of medications and health outcomes. However, lack of comparator groups in many observational studies limited the strength of conclusions in relation to the impact on clinical outcomes. Addressing access gaps for underserved populations, implementing additional referral pathways, and facilitating greater collaboration between the health professionals represent opportunities for further improvement.
Publisher: Elsevier BV
Date: 06-2016
Publisher: Wiley
Date: 19-12-2016
DOI: 10.1111/JGS.14682
Abstract: To systematically review clinical outcomes associated with medication regimen complexity in older people. Systematic review of EMBASE, MEDLINE, International Pharmaceutical Abstracts, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane library. Hospitals, home, and long-term care. 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. Quality assessment was conducted using an adapted version of the Joanna Briggs Institute critical appraisal tool. 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. 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.
Publisher: Springer Science and Business Media LLC
Date: 06-11-2017
Publisher: Springer Science and Business Media LLC
Date: 09-05-2015
Publisher: American Chemical Society (ACS)
Date: 16-11-2010
DOI: 10.1021/IC101433T
Abstract: Purple acid phosphatases (PAPs) are a group of metallohydrolases that contain a dinuclear Fe(III)M(II) center (M(II) = Fe, Mn, Zn) in the active site and are able to catalyze the hydrolysis of a variety of phosphoric acid esters. The dinuclear complex [(H(2)O)Fe(III)(μ-OH)Zn(II)(L-H)](ClO(4))(2) (2) with the ligand 2-[N-bis(2-pyridylmethyl)aminomethyl]-4-methyl-6-[N'-(2-pyridylmethyl)(2-hydroxybenzyl) aminomethyl]phenol (H(2)L-H) has recently been prepared and is found to closely mimic the coordination environment of the Fe(III)Zn(II) active site found in red kidney bean PAP (Neves et al. J. Am. Chem. Soc. 2007, 129, 7486). The biomimetic shows significant catalytic activity in hydrolytic reactions. By using a variety of structural, spectroscopic, and computational techniques the electronic structure of the Fe(III) center of this biomimetic complex was determined. In the solid state the electronic ground state reflects the rhombically distorted Fe(III)N(2)O(4) octahedron with a dominant tetragonal compression aligned along the μ-OH-Fe-O(phenolate) direction. To probe the role of the Fe-O(phenolate) bond, the phenolate moiety was modified to contain electron-donating or -withdrawing groups (-CH(3), -H, -Br, -NO(2)) in the 5-position. The effects of the substituents on the electronic properties of the biomimetic complexes were studied with a range of experimental and computational techniques. This study establishes benchmarks against accurate crystallographic structural information using spectroscopic techniques that are not restricted to single crystals. Kinetic studies on the hydrolysis reaction revealed that the phosphodiesterase activity increases in the order -NO(2) ←Br ←H ←CH(3) when 2,4-bis(dinitrophenyl)phosphate (2,4-bdnpp) was used as substrate, and a linear free energy relationship is found when log(k(cat)/k(0)) is plotted against the Hammett parameter σ. However, nuclease activity measurements in the cleavage of double stranded DNA showed that the complexes containing the electron-withdrawing -NO(2) and electron-donating -CH(3) groups are the most active while the cytotoxic activity of the biomimetics on leukemia and lung tumoral cells is highest for complexes with electron-donating groups.
Publisher: BMJ
Date: 03-2021
DOI: 10.1136/BMJOPEN-2020-046142
Abstract: Antimicrobial resistance is a growing global health threat, driven by increasing inappropriate use of antimicrobials. High prevalence of unnecessary use of antimicrobials in residential aged care facilities (RACFs) has driven demand for the development and implementation of antimicrobial stewardship (AMS) programmes. The Stepped-wedge Trial to increase antibiotic Appropriateness in Residential aged care facilities and model Transmission of antimicrobial resistance (START) will implement and evaluate the impact of a nurse-led AMS programme on antimicrobial use in 12 RACFs. The START trial will implement and evaluate a nurse-led AMS programme via a stepped-wedge cluster randomised controlled trial design in 12 RACFs over 16 months. The AMS programme will incorporate education, aged care-specific treatment guidelines, documentation forms, and audit and feedback strategies that will target aged care staff, general practitioners, pharmacists, and residents and their families. The intervention will primarily focus on urinary tract infections, lower respiratory tract infections, and skin and soft tissue infections. RACFs will transition from control to intervention phases in random order, two at a time, every 2 months, with a 2-month transition, wash-in period. The primary outcome is the cumulative proportion of residents within each facility prescribed an antibiotic during each month and total days of antibiotic use per 1000 occupied bed days. Secondary outcomes include the number of courses of systemic antimicrobial therapy, antimicrobial appropriateness, antimicrobial resistant organisms, Clostridioides difficile infection, change in antimicrobial susceptibility profiles, hospitalisations and all-cause mortality. Analyses will be conducted according to the intention-to-treat principle. Ethics approval has been granted by the Alfred Hospital Human Research Ethics Committee (HREC/18/Alfred/591). Research findings will be disseminated through peer-reviewed publications, conferences and summarised reports provided to participating RACFs. NCT03941509 .
Publisher: Bentham Science Publishers Ltd.
Date: 20-08-2015
DOI: 10.2174/157488471003150820145539
Abstract: There is uncertainty in relation to the effect of alcohol consumption on the incidence of dementia and cognitive decline. This review critically evaluated published systematic reviews on the epidemiology of alcohol consumption and the risk of dementia or cognitive decline. MEDLINE, EMBASE and PsycINFO were searched from inception to February 2014. Systematic reviews of longitudinal observational studies were considered. Two reviewers independently completed the 11-item Assessment of Multiple Systematic Reviews (AMSTAR) tool to assess the quality. We identified three moderate quality systematic reviews (AMSTAR score 4-6) that included a total of 45 unique studies. Two of the systematic reviews encompassed a meta-analysis. Light to moderate drinking may decrease the risk of Alzheimer's disease (AD) (pooled risk ratio [RR] 0.72 95% confidence interval [CI] 0.61-0.86) and dementia (RR 0.74 95%CI 0.61-0.91) whereas heavy to excessive drinking does not affect the risk (RR 0.92 95%CI 0.59-1.45 and RR 1.04 95%CI 0.69-1.56, respectively). One systematic review identified two studies that reported a link between alcohol consumption and the development of AD. No systematic review categorised former drinkers separately from lifetime abstainers in their analysis. Definitions of alcohol consumption, light to moderate drinking and heavy-excessive drinking varied and drinking patterns were not considered. Moderate quality (AMSTAR score 4-6) systematic reviews indicate that light to moderate alcohol consumption may protect against AD and dementia. However, the importance of drinking patterns and specific beverages remain unknown. There is insufficient evidence to suggest abstainers should initiate alcohol consumption to protect against dementia.
Publisher: Public Library of Science (PLoS)
Date: 24-04-2015
Publisher: Bentham Science Publishers Ltd.
Date: 20-08-2015
DOI: 10.2174/157488471003150820144958
Abstract: Pain is a frequent cause of discomfort and distress in residents in residential aged care facilities (RACFs). Despite the benefits of adequate pain management, there is inconsistency in the literature regarding analgesic use and pain in residents with dementia. The aim of this systematic review was to determine the prevalence of analgesic drug use among residents with and without dementia or cognitive impairment in RACFs. A systematic search of MEDLINE and EMBASE (inception to January 2014) was conducted using Medical Subject Headings and Emtree terms, respectively. Studies were included if they reported prevalence of analgesic use for residents both with and without dementia within the same study. Data extraction and quality assessment was performed independently by two investigators. Data on the prevalence of analgesic use, pain and painful conditions were extracted. Meta-analyses were performed using random effect models. The 7 included studies were of high quality (≥ 5 out of 7 on the adapted Newcastle-Ottawa Scale). Analgesic use in residents with and without dementia or cognitive impairment ranged from 20.2% to 61.2% and 38.8% to 79.6%, respectively. Paracetamol was the most prevalent analgesic in people with and without dementia. Residents with dementia or cognitive impairment had a significantly lower prevalence of analgesic use (odds ratio [OR] 0.576, 95% confidence interval [CI] = 0.406-0.816) and of self-reported and clinician-observed pain (OR 0.355, 95% CI = 0.278-0.454) than residents without cognitive impairment, despite a comparable prevalence of painful conditions. These findings may indicate under-reporting and under-detection of pain in persons with dementia, and subsequent suboptimal treatment.
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.SAPHARM.2015.04.004
Abstract: There is increasing awareness that medications can contribute to cognitive decline. Prospective cohort studies are rich sources of clinical data. However, investigating the contribution of medications to cognitive decline is challenging because both medication exposure and cognitive impairment can be associated with attrition of study participants, and medication exposure status may change over time. The objective of this review was to investigate the statistical methods in prospective cohort studies assessing the effect of medications on cognition in older people. A systematic literature search was conducted to identify prospective cohort studies of at least 12 months duration that investigated the effect of common medications or medication classes (anticholinergics, antihistamines, hypnotics, sedatives, opioids, statins, estrogens, testosterone, antipsychotics, anticonvulsants, antidepressants, anxiolytics, antiparkinson agents and bronchodilators) on cognition in people aged 65 years and older. Data extraction was performed independently by two investigators. A descriptive analysis of the statistical methods was performed. A total of 44 articles were included in the review. The most common statistical methods were logistic regression (24.6% of all reported methods), Cox proportional hazards regression (22.8%), linear mixed-effects models (21.1%) and multiple linear regression (14.0%). The use of advanced techniques, most notably linear mixed-effects models, increased over time. Only 6 articles (13.6%) reported methods for addressing missing data. A variety of statistical methods have been used for investigating the effect of medications on cognition in older people. While advanced techniques that are appropriate for the analysis of longitudinal data, most notably linear mixed-effects models, have increasingly been employed in recent years, there is an opportunity to implement alternative techniques in future studies that could address key research questions.
Publisher: Springer Science and Business Media LLC
Date: 30-11-2020
Publisher: Springer Science and Business Media LLC
Date: 05-04-2019
DOI: 10.1007/S40266-019-00656-X
Abstract: One quarter of residents in long-term care facilities (LTCFs) have a diagnosis of CHD or stroke and over half use at least one preventative cardiovascular medication. There have been no studies that have investigated the longitudinal change in secondary preventative cardiovascular medication use in residents in LTCFs over time. The aim of this study was to investigate the change in cardiovascular medication use among residents with coronary heart disease (CHD) and prior stroke in nursing homes (NHs) and assisted living facilities (ALFs) in Finland over time, and whether this change differs according to dementia status. Three comparable cross-sectional audits of cardiovascular medication use among residents aged 65 years and over with CHD or prior stroke in NHs in 2003 and 2011 and ALFs in 2007 and 2011 were compared. Logistic regression analyses adjusted for gender, age, mobility, cancer and length of stay were performed to examine the effect of study year, dementia and their interaction on medication use. Cardiovascular medication use among residents with CHD (NHs: 89% vs 70% ALFs: 89% vs 84%) and antithrombotic medication use among residents with stroke (NHs: 72% vs 63% ALFs: 78% vs 69%) declined between 2003 and 2011 in NHs and 2007 and 2011 in ALFs. Decline in the use of diuretics, nitrates and digoxin were found in both groups and settings. Cardiovascular medication use among residents with CHD and dementia declined in NHs (88% [95% CI 85-91] in 2003 vs 70% [95% CI 64-75] in 2011) whereas there was no change among people without dementia. There was no change in cardiovascular medication use among residents with CHD in ALFs with or without dementia over time. Antithrombotic use was lower in residents with dementia compared with residents without dementia in NHs (p < 0.001) and ALFs (p = 0.026) however, the interaction between dementia diagnosis and time was non-significant. The decline in cardiovascular medication use in residents with CHD and dementia suggests Finnish physicians are adopting a more conservative approach to the management of cardiovascular disease in the NH population.
Publisher: Wiley
Date: 25-01-2016
DOI: 10.1111/JEP.12514
Abstract: The prevalence of polypharmacy in residential aged care facilities (RACFs) is high and increasing. Although not necessarily inappropriate, polypharmacy has been associated with drug interactions, adverse drug events, geriatric syndromes and hospital admissions. The aim of this study was to identify and prioritize factors contributing to the increasing prevalence of polypharmacy in RACFs. Seventeen health care professionals from metropolitan and regional Victoria and South Australia identified and prioritized factors using a modified nominal group technique. The top five factors ranked from most important to fifth most important were 'changes in resident mix', 'increasing numbers of prescribers and the reluctance of one prescriber to discontinue a medicine commenced by another prescriber', 'better adherence to clinical practice guidelines', 'increasing reliance on locums' and 'greater recognition and pharmacological management of pain'. Reasons for the increase in polypharmacy are multifactorial. Understanding the factors contributing to polypharmacy may help to guide future research and develop interventions to manage polypharmacy in RACFs.
Publisher: Elsevier BV
Date: 12-2015
Publisher: Springer Science and Business Media LLC
Date: 27-03-2023
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.SAPHARM.2016.06.003
Abstract: Polypharmacy is highly prevalent in residential aged care facilities (RACFs). Although polypharmacy is sometimes unavoidable, polypharmacy has been associated with increased morbidity and mortality. To identify and prioritize a range of potential interventions to manage polypharmacy in RACFs from the perspectives of health care professionals, health policy and consumer representatives. Two nominal group technique (NGT) sessions were convened in August 2015. A purposive s le (n = 19) of clinicians, researchers, managers and representatives of consumer, professional and health policy organizations were asked to nominate interventions to address the prevalence and appropriateness of medication use. Participants were then asked to prioritize five interventions suitable for possible implementation at the system level. Six of 16 potential interventions were prioritized highest for possible implementation in clinical practice, with two interventions prioritized as second highest. The top interventions in rank order were 'implementation of a pharmacist-led medication reconciliation service for new residents,' 'conduct facility-level audits and feedback to staff and health care professionals,' 'develop deprescribing scripts to assist clinician-resident discussion,' 'develop or revise prescribing guidelines specific to older people with multimorbidity in RACFs,' 'implement electronic medication charts and records' and 'better support Medication Advisory Committees (MACs) to address medication appropriateness.' This study prioritized a range of potential interventions that may be used to assist clinicians and policy makers develop a comprehensive strategy to manage polypharmacy in RACFs.
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.JAMDA.2015.03.003
Abstract: The objective of the study was to investigate the prevalence of, and factors associated with, polypharmacy in long-term care facilities (LTCFs). MEDLINE, EMBASE, International Pharmaceutical Abstracts, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library were searched from January 2000 to September 2014. Primary research studies in English were eligible for inclusion if they fulfilled the following criteria: (1) polypharmacy was quantitatively defined, (2) the prevalence of polypharmacy was reported or could be extracted from tables or figures, and (3) the study was conducted in a LTCF. Methodological quality was assessed using an adapted version of the Joanna Briggs Institute Critical Appraisal Checklist. Forty-four studies met the inclusion criteria and were included. Polypharmacy was most often defined as 5 or more (n = 11 studies), 9 (n = 13), or 10 (n = 11) medications. Prevalence varied widely between studies, with up to 91%, 74%, and 65% of residents taking more than 5, 9, and 10 medications, respectively. Seven studies performed multivariate analyses for factors associated with polypharmacy. Positive associations were found for recent hospital discharge (n = 2 studies), number of prescribers (n = 2), and comorbidity including circulatory diseases (n = 3), endocrine and metabolic disorders (n = 3), and neurological motor dysfunctioning (n = 3). Older age (n = 5), cognitive impairment (n = 3), disability in activities of daily living (n = 3), and length of stay in the LTCF (n = 3) were inversely associated with polypharmacy. The prevalence of polypharmacy in LTCFs is high, varying widely between facilities, geographical locations and the definitions used. Greater use of multivariate analysis to investigate factors associated with polypharmacy across a range of settings is required. Longitudinal research is needed to explore how polypharmacy has evolved over time.
No related grants have been discovered for Natali Jokanovic.