An evaluation of elderly people’s understanding of pharmacotherapy among those treated in the Primary Healthcare System in Belo Horizonte, Brazil

Isabela Vaz Leite Pinto Adriano Max Moreira Reis Celline Cardoso Almeida-Brasil Micheline Rosa da Silveira Marina Guimarães Lima Maria das Graças Braga Ceccato About the authors

Resumo

Os idosos apresentam maior número de doenças, levando a maior uso de medicamentos e a farmacoterapia mais complexa. O objetivo do estudo foi avaliar o nível de compreensão da farmacoterapia entre idosos e fatores associados. Realizou-se estudo transversal analítico em Unidades Básicas de Saúde. Foram investigadas as características sociodemográficas, clínicas, funcionais e relativas ao uso de medicamentos. O nível de compreensão foi obtido após a análise de concordância entre a resposta do entrevistado e a informação contida na prescrição para: nome do medicamento, dose, frequência, indicação, precauções e efeitos adversos. O nível global de compreensão foi classificado como insuficiente em caso de discordância ≥ 30%. Dos 227 idosos entrevistados, 51,1% apresentaram compreensão insuficiente em relação aos medicamentos. Realizou-se regressão logística multivariada para observar os fatores associados à compreensão da farmacoterapia, sendo menor escolaridade e dependência para uso dos medicamentos os que apresentaram associação com a compreensão insuficiente (p < 0,05). É necessário implementar estratégias para aumentar a qualidade das orientações fornecidas aos idosos e garantir seu cumprimento.

Compreensão; Conhecimento do paciente sobre a medicação; Farmacoterapia; Idoso; Atenção Primária à Saúde

Abstract

There are a greater number of elderly people with diseases which has led to a greater use in medication and complexity in pharmacotherapy. The aim of this study was to understand the level of understanding on pharmacotherapy amongst the elderly and associated factors. An analytical transversal study was carried out in the Primary Health Care Units. Sociodemographic, clinical, and functional characteristics relative to the use of medication were explored. The level of understanding was obtained after a concordance analysis had been done based on the responses from the interviewees and the information on the medical prescriptions such as: name of medication, dosage, frequency, indication, precautions and side effects. The global level of understanding was classified as insufficient in cases where the discordance was ≥ 30%. Of the 227 elderly people interviewed, 51.1% showed an insufficient understanding in relation to their medication. We carried out multivariate logistic regression to observe the factors associated with an understanding of pharmacotherapy. We noted that those with a low level of education and a dependency on the use of medication showed insufficient understanding. (p < 0,05). It is necessary to implement strategies to increase the quality of the guidance given to the elderly and to ensure compliance.

Comprehension; Patient medication knowledge; Drug therapy; Aged; Primary Health Care

Introduction

The increase in the elderly population and general life expectancy that can be seen in Brazil and in the world and has been called the Longevity Revolution11. Kalache A. Respondendo à revolução da longevidade. Cien Saude Colet 2014; 19(8):3306-3307.. A policy that takes into account the longevity revolution ought to be accompanied by 4 key elements so that people can age well: primary health care (PHC), access to knowledge, financial conditions and support and care from family, friends and those close to the individual22. Minayo MCS, Gualhano L. Cuidados frente à revolução da longevidade. Cien Saude Colet 2014; 19(8).. PHC is one of the essential strategies for the promotion of health for older people since aging is a dynamic process that brings vulnerabilities and greater incidents of morbidity. During the process of aging, morphological alterations occur as well as physiological, biochemical and psychological changes in the individual. This results in the progressive loss of capacity to adapt to the environment33. Rocha CH, Oliveira APS, Ferreira CF, Faggiani, CF, Schroeter G, Souza ACA, DeCarli GA, Morrone FB, Werlang MC. Adesão à prescrição médica em idosos de Porto Alegre-RS. Cien Saude Colet 2008; 13(Supl.):703-710. and it explains the prevalence of the chronic diseases44. Instituto Brasileiro de Geografia e Estatística (IBGE). Coordenação de População e Indicadores Sociais. Indicadores sociodemográficos e de saúde no Brasil: 2009/IBGE. Rio de Janeiro: IBGE; 2009. [acessado 2015 jan 05]. Disponível em: http://www.ibge.gov.br/home/estatistica/populacao/indic_sociosaude/2009/
http://www.ibge.gov.br/home/estatistica/...
and the use of various medications simultaneously55. Jyrkkä J, Enlund H, Korhonen MJ, Sulkava R, Hartikainen S. Patterns of drug use and factors associated with polypharmacy and excessive polypharmacy in elderly persons: results of the Kuopio 75+ study: a cross-sectional analysis. Drugs Aging 2009; 26(6):493-503..

The use of multiple medications can bring about clinical implications in relation to effectiveness, safety and adherence as well as having economic impacts55. Jyrkkä J, Enlund H, Korhonen MJ, Sulkava R, Hartikainen S. Patterns of drug use and factors associated with polypharmacy and excessive polypharmacy in elderly persons: results of the Kuopio 75+ study: a cross-sectional analysis. Drugs Aging 2009; 26(6):493-503.. In order for the medication to be adequate, it is necessary that the patient has the necessary information so that can use it in compliance with the medical prescription66. Fröhlich SE, Dal Pizzol TS, Mengue SS. Instrumento para avaliação do nível de conhecimento da prescrição na atenção primária. Rev Saude Publica 2010; 44(6):1046-1054.,77. Silva T, Schenkel EP, Mengue SS. Nível de informação a respeito de medicamentos a pacientes ambulatoriais de hospital universitário. Cad Saude Publica 2000; 16(2): 449-455.. The person should know the dosage to take, the frequency and the importance of the medication that is being used88. Hope CJ, Wu J, Tu W, Young J, Murray MD. Association of medication adherence, knowledge and skills with emergency department visits by adults 50 years or older with congestive heart failure. Am J Health-Syst Pharm 2004; 61(19):2043-2049..

The lack of effective strategies for the transmission of information from health care professionals to patients and/or the non-understanding of such information can bring serious consequences such as inadequate adherence, that can worsen the clinical state of the patients99. Ceccato MGB, Acúrcio FA, Cesar CC, Bonolo PF, Guimarães MDC. Compreensão de terapia anti-retroviral: uma aplicação do modelo de traço latente. Cad Saude Publica 2008; 24(7):1689-1698.

10. Chau I, Korb-Savoldelli V, Trinquart L, Caruba T, Prognon P, Durieux P, Piketty C, Sabatier B. Knowledge of oral drug treatment in immunocompromised patients on hospital discharge. Swiss Med Wkly 2011; 141:w13204.
-1111. Oenning D, Oliveira BV, Blatt CR. Conhecimento dos pacientes sobre os medicamentos prescritos após consulta médica e dispensação. Cien Saude Colet 2011; 16(7):3277-3283.. The non-understanding of the prescribed therapy can be a reason why the medication that has been recognized as effective under control conditions, becomes ineffective when used on the population at large66. Fröhlich SE, Dal Pizzol TS, Mengue SS. Instrumento para avaliação do nível de conhecimento da prescrição na atenção primária. Rev Saude Publica 2010; 44(6):1046-1054..

The understanding of pharmacotherapy means that the patients should know: the name of the medication, indication, frequency of use, side effects or special instructions in relation to its use1212. Ascione FJ, Kirscht JP, Shimp LA. An assessment of different components of patient medication knowledge. Med Care 1986; 24(Supl.):1018-1027.. The understanding of pharmacotherapy can be influenced by different factors such as those related to the individual, the therapy itself, the health care professional and the health service99. Ceccato MGB, Acúrcio FA, Cesar CC, Bonolo PF, Guimarães MDC. Compreensão de terapia anti-retroviral: uma aplicação do modelo de traço latente. Cad Saude Publica 2008; 24(7):1689-1698.. The factors related to having the worse understanding of pharmacotherapy described in the research studies published are: being male1313. Guénette L, Moisan J. Elderly people’s knowledge of the purpose of their medicines. Am J Geriatr Pharmacotherapy 2011; 9(1):49-57.

14. Cruzeta APS, Dourado ACL, Monteiro MTM, MartinS RO, Calegario TA, Galato D. Fatores associados a compreensão da prescrição médica no sistema único de saúde de um município do sul do Brasil. Cien Saude Colet 2013; 18(12):3731-3737.
-1515. Okuyan B, Sancar M, Izzettin FV. Assessment of medication knowledge and adherence among patients under oral chronic medication treatment in community pharmacy settings. Pharmacoepidemiol and Drug Saf 2013; 22(2):209-214., advanced age1515. Okuyan B, Sancar M, Izzettin FV. Assessment of medication knowledge and adherence among patients under oral chronic medication treatment in community pharmacy settings. Pharmacoepidemiol and Drug Saf 2013; 22(2):209-214.

16. Ponnusankar S, Surulivelrajan M, Anandamoorthy N, Suresh B. Assessment of impact of medication counseling on patients’ medication knowledge and compliance in an outpatient clinic in south India. Patient Educ Couns 2004; 54(1):55-60.

17. Gallagher R, Warwick M, Chenoweth L, Stein-Parbury J, Milton-Wildey K. Medication knowledge, adherence and predictors among people with heart failure and chronic obstructive pulmonary disease. J Nursing Healthcare Chronic Illness 2010; 3(1):30-40.
-1818. Motter FR, Olinto MTA, Paniz VMV. Conhecimento sobre a farmacoterapia por portadores de hipertensão arterial sistêmica. Cien Saude Colet 2013; 18(8):2263-2274., low level of schooling1515. Okuyan B, Sancar M, Izzettin FV. Assessment of medication knowledge and adherence among patients under oral chronic medication treatment in community pharmacy settings. Pharmacoepidemiol and Drug Saf 2013; 22(2):209-214.

16. Ponnusankar S, Surulivelrajan M, Anandamoorthy N, Suresh B. Assessment of impact of medication counseling on patients’ medication knowledge and compliance in an outpatient clinic in south India. Patient Educ Couns 2004; 54(1):55-60.

17. Gallagher R, Warwick M, Chenoweth L, Stein-Parbury J, Milton-Wildey K. Medication knowledge, adherence and predictors among people with heart failure and chronic obstructive pulmonary disease. J Nursing Healthcare Chronic Illness 2010; 3(1):30-40.

18. Motter FR, Olinto MTA, Paniz VMV. Conhecimento sobre a farmacoterapia por portadores de hipertensão arterial sistêmica. Cien Saude Colet 2013; 18(8):2263-2274.
-1919. Chan FW, Wong FY, So WY, Kung K, Wong CK. How much do elders with chronic conditions know about their medications? BMC Geriatrics 2013; 13:59., poor socioeconomic status1313. Guénette L, Moisan J. Elderly people’s knowledge of the purpose of their medicines. Am J Geriatr Pharmacotherapy 2011; 9(1):49-57.,1414. Cruzeta APS, Dourado ACL, Monteiro MTM, MartinS RO, Calegario TA, Galato D. Fatores associados a compreensão da prescrição médica no sistema único de saúde de um município do sul do Brasil. Cien Saude Colet 2013; 18(12):3731-3737., cognitive deficit1313. Guénette L, Moisan J. Elderly people’s knowledge of the purpose of their medicines. Am J Geriatr Pharmacotherapy 2011; 9(1):49-57.,2020. Sela-Katz P, Rabinowitz I, Shugaev I, Shigorina G. Basic knowledge of the medication regimen correlates with performance on cognitive function tests and diagnosis of dementia in elderly patients referred to a geriatric assessment unit. Gerontology 2010; 56(5):491-495., presence of comorbidities1717. Gallagher R, Warwick M, Chenoweth L, Stein-Parbury J, Milton-Wildey K. Medication knowledge, adherence and predictors among people with heart failure and chronic obstructive pulmonary disease. J Nursing Healthcare Chronic Illness 2010; 3(1):30-40., use of multiple medications1818. Motter FR, Olinto MTA, Paniz VMV. Conhecimento sobre a farmacoterapia por portadores de hipertensão arterial sistêmica. Cien Saude Colet 2013; 18(8):2263-2274.,1919. Chan FW, Wong FY, So WY, Kung K, Wong CK. How much do elders with chronic conditions know about their medications? BMC Geriatrics 2013; 13:59.,2121. Modig S, Kristensson J, Ekwall AK, Hallberg IR, Midlov P. Frail elderly patients in primary care-their medication knowledge and beliefs about prescribed medicines. Eur J Clin Pharmacol 2009; 65(2):151-155., great complexity of the pharmacotherapy66. Fröhlich SE, Dal Pizzol TS, Mengue SS. Instrumento para avaliação do nível de conhecimento da prescrição na atenção primária. Rev Saude Publica 2010; 44(6):1046-1054.,2222. Spiers MV, Kutzik DM, Lamar M. Variation in medication understanding among the elderly. Am J Health-Syst Pharm 2004; 61(4):373-380. and low adherence to pharmacotherapy1515. Okuyan B, Sancar M, Izzettin FV. Assessment of medication knowledge and adherence among patients under oral chronic medication treatment in community pharmacy settings. Pharmacoepidemiol and Drug Saf 2013; 22(2):209-214.,2222. Spiers MV, Kutzik DM, Lamar M. Variation in medication understanding among the elderly. Am J Health-Syst Pharm 2004; 61(4):373-380..

International research that studied the understanding of pharmacotherapy in the elderly doesn’t show methodological homogeneity and presents varied results2121. Modig S, Kristensson J, Ekwall AK, Hallberg IR, Midlov P. Frail elderly patients in primary care-their medication knowledge and beliefs about prescribed medicines. Eur J Clin Pharmacol 2009; 65(2):151-155.

22. Spiers MV, Kutzik DM, Lamar M. Variation in medication understanding among the elderly. Am J Health-Syst Pharm 2004; 61(4):373-380.

23. Tordoff JM, Bagge ML, Gray AR, Campbell AJ, Norris PT. Medicine-taking practices in community-dwelling people aged ≥ 75 years in New Zealand. Age and Ageing 2010; 39(5):574-580.
-2424. Mosher HJ, Lund BC, Kripalani S, Kaboli PJ. Association of health literacy with medication knowledge, adherence, and adverse drug events among elderly veterans. J Health Commun 2012; 17(Supl. 3):241-251.. This makes it difficult to make comparisons and to come up with definitions that encapsulate the knowledge of therapeutic regimes. In Brazil, research that focuses on the aspects relative to the information obtained by patients on their prescribed medication and their understanding of this information is scarce. We weren’t able to find publications exploring the understanding of the elderly in relation to medication66. Fröhlich SE, Dal Pizzol TS, Mengue SS. Instrumento para avaliação do nível de conhecimento da prescrição na atenção primária. Rev Saude Publica 2010; 44(6):1046-1054.,77. Silva T, Schenkel EP, Mengue SS. Nível de informação a respeito de medicamentos a pacientes ambulatoriais de hospital universitário. Cad Saude Publica 2000; 16(2): 449-455.,1111. Oenning D, Oliveira BV, Blatt CR. Conhecimento dos pacientes sobre os medicamentos prescritos após consulta médica e dispensação. Cien Saude Colet 2011; 16(7):3277-3283.,1414. Cruzeta APS, Dourado ACL, Monteiro MTM, MartinS RO, Calegario TA, Galato D. Fatores associados a compreensão da prescrição médica no sistema único de saúde de um município do sul do Brasil. Cien Saude Colet 2013; 18(12):3731-3737.,1818. Motter FR, Olinto MTA, Paniz VMV. Conhecimento sobre a farmacoterapia por portadores de hipertensão arterial sistêmica. Cien Saude Colet 2013; 18(8):2263-2274.,2525. Ceccato MGB, Acurcio FA, Bonolo PF, Rocha GM, Guimarães MDC. Compreensão de informações relativas ao tratamento anti-retroviral entre indivíduos infectados pelo HIV. Cad Saude Publica 2004; 20(5):1388-1397..

In the context of assistance given through PHC, it is important to evaluate the understanding of the medical prescription by patients. However in research studies published, there is no consensus on what constitutes this knowledge of the therapeutic regime nor is there information on what to do in relation to measuring knowledge levels. Nevertheless, knowledge of the level of understanding of pharmacotherapy in patients that are elderly and who are attended to by the PHC and identifying the characteristics that influence this understanding, are central aspects in analyzing this area and intervening effectively in the process of using the medication.

In this way, this study aimed to evaluated the level of understanding of pharmacotherapy and the associated factors amongst older people in two Primary Health Care Units in Belo Horizonte.

Methods

A transversal analytical study was carried out in two Primary Health Care Units (PHUs) in the municipality of Belo Horizonte MG from November 2013 to April 2014. The following was the eligibility criteria for inclusion: being 60 years old or over, an user of the PHC in Belo Horizonte, receiving medication in the pharmacies of the PHUs that were studied and, at the moment of the interview, carry in their hands at least one medication. The receipt of the medication in the PHU pharmacy is only permitted if the person is a resident of Belo Horizonte. Also the patient must be: registered on the electronic system in municipality, have identification documentation and have a prescription from a professional that works in the public or private health sector. The individuals were invited to participate in the research when they were in the queue in the pharmacy waiting to obtain their medication.

In order to calculate the sample we used information from the pharmacy information system at the PHU (SISREDE). Based on this information, we found out that the monthly mean number of elderly people being served by the pharmacies in the PHU from January to October 2013 was 483 individuals. With this monthly service being carried out in the PHUs, we adopted the premise that those being seen were regulars to the pharmacies and attend the pharmacies once a month to receive the chronic use drugs. Considering the finite population of 483 individual, there was a prevalence of 50% for all of the characteristics observed, 5% level of significance, confidence interval (IC) of 95% and a 10% possibility of loss, the sample was estimated at 237 older people. The selection of the sample was done consecutively for convenience. The individuals that fulfilled the inclusion criteria were selected after signing a Consent Form. The project was duly approved by the Ethics Committee on Research in the institutions that were involved in this study.

The collection of data was based on the use of structured interviews with patients which were carried out from November 2013 to April 2014. The questionnaire contained questions covering: sociodemographic, clinical and functional characteristics and information related to the use of the medication. All of the interviews were carried out by a principal researcher, resident pharmacists and academics studying pharmacy and medicine who had been previously trained on the procedures to be used. With the objective of evaluating the inter-interviewer reliability, approximately 10% of the participants (n = 20) were re-interviewed 2 times by different interviewers. A consistency analysis was done which obtained a kappa value = 0.835.

The level of understanding of the elderly on pharmacotherapy was evaluated based on the proposal of Silva et al.77. Silva T, Schenkel EP, Mengue SS. Nível de informação a respeito de medicamentos a pacientes ambulatoriais de hospital universitário. Cad Saude Publica 2000; 16(2): 449-455. and Ceccato et al.2525. Ceccato MGB, Acurcio FA, Bonolo PF, Rocha GM, Guimarães MDC. Compreensão de informações relativas ao tratamento anti-retroviral entre indivíduos infectados pelo HIV. Cad Saude Publica 2004; 20(5):1388-1397.. This was done through questions in relation to all of the prescribed medication that the individual had in their hand at the time of the interview covering the following items: name of the drug, dosage, frequency of use, indication, side effects and precautions (Chart 1). Medication that was used based on self-medication was not evaluated. At the time of the interview the individual was permitted to look at the prescription or the medication packaging or any notes that they had in their hands.

The responses to the questions were transcribed and interpreted by 2 revisers who evaluated concordance between the information provided by the patient with the instructions on the medical prescription, medical records and/or guidance from the National Therapeutic Form2626. Brasil. Ministério da Saúde (MS). Secretaria de Ciência, Tecnologia e Insumos Estratégicos. Departamento de Assistência Farmacêutica e Insumos Estratégicos. Formulário Terapêutico Nacional 2010. 2ª ed. Brasília: MS; 2010., for medication shown at the time of the interview. Where there was discordance amongst them, a third reviser was used. Differences in the technical and popular terminology were accepted as well as differences between the terminology on the medical prescription and the description given by the participant. The responses were considered as dichotomous (correct/wrong) and we adopted the following scoring for each item that was considered as correct: i. name of thedrug, dosage and frequency of use = 2 points for each, whereas items considered of great importance for the safe use of the medication; side effects and precautions = 1 point for each of the aforementioned. “Zero” was given for cases where the participant didn’t know the responses for the specific item or when the person responded incorrectly. The maximum score would be equal to 9 points where correct responses were given for all of the items. After this we calculated the level of understanding of the pharmacotherapy for each medication that was presented. Subsequently the global level of understanding on the treatment for each individual based on the mean values obtained for each medication. The level of global understanding of the prescription was classified as “insufficient” for individuals that obtained a score of less than 70.0% of the points (< 6.3 points) according to Ceccato et al.2525. Ceccato MGB, Acurcio FA, Bonolo PF, Rocha GM, Guimarães MDC. Compreensão de informações relativas ao tratamento anti-retroviral entre indivíduos infectados pelo HIV. Cad Saude Publica 2004; 20(5):1388-1397. proposition.

The investigated explicable variables were group namely: i. sociodemographic characteristics (gender, age, level of education, living alone, income measured in minimum salaries, marital status and race), ii. clinical characteristics (comorbidities, depression, self-perception of health, cognition), iii. functional characteristics (basic and instrumental activities of daily living) and iv. characteristics related to the use of the medication (number of medication, complexity of the pharmacotherapy, adherence, independence in administering the medication and guidance received from the health care professionals). We use validated scales and/or adapted scales for the Brazilian context for the evaluation of variables: depression - the Geriatric Depression Scale of 15 items2727. Paradela EM, Lourenço RA, Veras RP. Validação da escala de depressão geriátrica em um ambulatório geral. Rev Saude Publica 2005; 39(6):918-923. (individuals with symptoms of depression: ≥ 6 points), cognition -MiniMental State Examination2828. Lourenço RA, Veras RP. Mini-exame do estado mental: características psicométricas em idosos ambulatoriais. Rev Saude Publica 2006; 40(4):712-719.,2929. Bertolucci PH, Brucki SMD, Campacci SR, Juliano Y. O mini-exame do estado mental em uma população geral: impacto da escolaridade. Arq Neuropsiquiatr 1994; 52(1):1-7. (individuals with cognitive incapacity: ≤ 13 points for illiteracy: ≤ 18 points for individuals with 1 to 8 years of schooling and ≤ 24 points for individuals with more than 8 years of schooling2929. Bertolucci PH, Brucki SMD, Campacci SR, Juliano Y. O mini-exame do estado mental em uma população geral: impacto da escolaridade. Arq Neuropsiquiatr 1994; 52(1):1-7.), adherence - the therapeutic Scale of adherence with 8 items proposed by Moriskyet al.3030. Oliveira-Filho AD, Barreto-Filho JA, Neves SJF, Lyra-Junior DP. Relação entre a escala de adesão terapêutica de oito itens de Morinsky (MMAS-8) e o controle da pressão arterial. Arq Bras Cardiol 2012; 99(1):649-668.; complexity of pharmacotherapy - Medication Regimen Complexity Index3131. Melchiors AC, Correr CJ, Fernández-Llimos F. Tradução e validação para o português do Medication Regimen Complexity Index. Arq Bras Cardiol 2007; 89(4):210-218.; basic activities of daily living- Katz3232. Lino VTS, Pereira SRM, Camacho LAB, Ribeiro-Filho STR, Buksman S. Adaptação transcultural da escala de independência em atividades da vida diária (escala de Katz). Cad Saude Publica 2008; 24(1):103-112. Scale and the instrumental activities of daily life – Brody & Lawton Scale (independent individuals = 21 points)3333. Santos RL, Virtuoso-Junior JS. Confiabilidade da versão brasileira da escala de atividades de vida diária. RBPS 2008; 21(4):290-296.. The medication present in the medical prescription which was shown by the individual was classified by the Anatomical Therapeutic Chemical – ATC3434. World Health Organization (WHO). ATC/DDD Index 2014. [acessado 2014 mar 01]. Disponível em: http://www.whocc.no/atc_ddd_index/
http://www.whocc.no/atc_ddd_index/...
, at the levels of 1º and 5º (the principal anatomical group and sub-chemical group respectively). The evaluation of the dependency on the use of medication was carried out using the following question: “Mr/Ms, do you rely on the support of someone to take your medication?”. It was considered dependent on the individual who answered “yes” to the question.

A database was created in the Epi Info Program version 3.5.4 (Center for Disease Control and Prevention, Atlanta, United States). We carried out quality control for the typing up of the data with the replication being 10% of that which was digitized. The analysis of the reliability of the typist was carried out using the kappa statistics where kappa = 1.0 would indicate excellent concordance.

In order to conduct a descriptive analysis of data, we determined the frequency, measurements of central tendency and dispersion for the studied characteristics. The continuous variables were dichotomized based on the median and Pearson’s chi-squared test was applied to the comparison of proportions. The magnitude of the association of the global level of understanding of the elderly people and the expected variables were estimated through the use of the Odds Ratio (OR) with the interval of 95% of confidence (IC95%) using the univariate logistic regression and multivariate analysis.

The variables that obtained p-value ≤ 0.25 in the Wald test in the univariate analysis were selected to the multivariate model. The variables that were clinically and epidemiologically relevant, were selected manually to start the multivariate model, using step by step procedures with the selections underlying our research. In the final model the variables that were obtained with the value of p < 0.05 were kept. We used the Likelihood Ratio test to compare the models. The adequacy of the final model was evaluated by the Hosmer-Lemeshow test. Statistical Analysis was done using the software Statistical Package for Social Sciences® (SPSS®) 21.

Results

Of the 230 elderly people that were invited to take part of the study, 3 of them were excluded as they didn’t meet the inclusion criteria, which left 227 eligible participants. Of these, 221 (97.4%) responded to the questionnaire without any help from a caregiver. We observed that the majority of the respondents were women (70.9%), individuals that were aged up to 79 (84.1%), with up to 8 years of schooling (75.7%), who lived alone (76.2%) and with an income of up to 2 minimum salaries (60.9%) (Table 1). The mean age amongst the participants was 71.4 years old (DP = 7.5; Coefficient variation-CV = 10,6%).

In relation to clinical characteristics, 23% presented symptoms of depression. The self-referred health was as positive (excellent, very good or good) for 70% of the participants (Table 1). The illnesses that were most prevalent amongst the elderly were: systemic arterial hypertension (n = 196; 22.2%), dyslipidemia (n = 131; 14.8%); others cardiovascular diseases (n = 79; 8.9%), illnesses affecting the joints (n = 79; 8.9%), Diabetes mellitus (n = 74; 8.4%) and psychiatric disorders (n = 59; 6.7%).

In relation to the functional characteristics, 13.9% of the older people showed signs of cognitive incapacity. 76.5% were considered independent to do basic activities of daily living, 22.9% were considered to be independent to do instrumental activities of daily living and the rest of the participants shown to be partially dependent on someone to perform such activities (Table 1).

In relation to the use of medication, we identified a total of 1176 prescription drugs. The mean daily prescription drugs was 5.3 (DP = 2.3, CV = 44.1) and 58.6% (n = 133) of the individuals used 5 or more prescription drugs. The rate of complexity of the prescriptions had a mean value of 22.7 (DP = 10.9, CV = 48.0%) with a minimum of 4.0 and a maximum of 65.5. The most common medications used were medications for: cardiovascular system (50.4%; n = 593), alimentary tract and metabolism (17.1%; n = 201), nervous system (13.0%; n = 153) and blood system and blood forming organs (8.0%; n = 94). Amongst the different types of medications used the most common that were on the prescriptions were: hydrochlorothiazide (7.8%, n = 92), simvastatin (7.7%, n = 91), losartan (7.6%, n = 89), amlodipine (6.0%, n = 71) and acetylsalicylic acid (5.9%, n = 70).

In relation to the adherence to the pharmacotherapy, only 29.6% of the participants showed high levels of this. About 83% stated that they didn’t need help to take their medication and 72.6% stated that they had already received guidance from a health care professional in relation to their pharmacotherapy. Amongst the professionals that gave guidance, the following were mentioned: doctors (n = 147), nurses (n = 12) and pharmacist (n = 11). When patients were asked about whether they understood the guidance, 84.7% (n = 144) of the participants stated that they understood everything or a lot. Out of all of the participants in the study, only 20.6% considered that they needed more information to understand the treatment with medication (Table 1).

The level of understanding was evaluated for a total of 629 drugs that were presented at the moment of the interview. Table 2 has the frequency of the correct answers for the items used in the evaluation of understanding referring to the medication presented by the participants. We observed a rate of concordance of 86.2% in relation to the doses, 84.4% for the indication, 82.7% for the frequency of administration, 75.8% for the name of the drug, 24.0% for the precautions with the medication and only 6.9% for the side effects.

116 elderly people (51.1%) presented insufficient understanding (< 6.3 points) in relation to the pharmacotherapy. The mean level of global understanding amongst participants was 6.02 (DP = 1.5, CV = 24.6%) which represents 66.9% of correct answers.

In Table 3 we observed the distribution of the level of understanding of the classes of medication in accordance with the ATC 1 classification level and the 20 medicines presented with the greatest frequency. The highest scores were observed for the classes of drug that act on the sensory organs and the blood as well as for the drugs: metformin, acetylsalicylic acid, atenolol and clonazepam. The medicines acetaminophen, carvedilol, glyburide and ibuprofen presented the worse mean scores. The classes of the anti-infectives and dermatological medications presented the lowest scores.

In the univariate analysis, insufficient understanding was associated with having only been in formal education up to4 years, presenting symptoms of depression, having a partial dependency for the instrumental activities of daily living, using 5 or more medications, mean or low adherence to the treatment and being dependent on the use of the medication (Table 4). The clinical and/or epidemiologically relevant variables were included: age, the index of complexity, cognition and the receipt of guidance from health care professionals. After the adjusted analysis, individuals with up to 4 year of education had double the chances of having insufficient understanding in relation to those with more than 4 years of education. In addition, for those that did not have independence in the use of their medication, they had 3 times more chances of having insufficient understanding (Table 4).

Discussion

It was identified in the study that more than half of the participants (51.1%) presented a level of understanding of their pharmacotherapy that was considered insufficient which triggered our attention to the consequences concerning the effectiveness and safety in the use of medication for older people in the context of primary health care. In spite of the lacuna found, for the understanding of patients, the majority of them thought that they understood a lot or everything concerning the guidance received from the health care professionals and that they didn’t need further information on their medication. In this way, it was observed that the participants, in their great majority, didn’t have an adequate perception of their own knowledge regarding the use of their medication.

Older people use medication extensively and as a result have a higher risk of suffering adverse reactions to the medication because of pharmacokinetics and pharmacodynamic alterations when aging33. Rocha CH, Oliveira APS, Ferreira CF, Faggiani, CF, Schroeter G, Souza ACA, DeCarli GA, Morrone FB, Werlang MC. Adesão à prescrição médica em idosos de Porto Alegre-RS. Cien Saude Colet 2008; 13(Supl.):703-710.. Aside from this, there was a higher prevalence of cognitive incapacity amongst people in this age group, which made understanding difficult as well as hindering the adherence to the pharmacotherapy. This makes the use of medication amongst older people a critical situation2020. Sela-Katz P, Rabinowitz I, Shugaev I, Shigorina G. Basic knowledge of the medication regimen correlates with performance on cognitive function tests and diagnosis of dementia in elderly patients referred to a geriatric assessment unit. Gerontology 2010; 56(5):491-495.. A fact worth highlighting is that the characteristics found in the present study are similar to the sociodemographic characteristics of Brazilian elderly3535. Loyola-Filho AI, Uchoa E, Lima-Costa MF. Estudo epidemiológico de base populacional sobre uso de medicamentos entre idosos na região metropolitana de Belo Horizonte, Minas Gerais, Brasil. Cad Saude Publica 2006; 22(12):2657-2667.,3636. Victor JF, Ximenes LB, Almeida PC, Vasconcelos FF. Perfil sociodemográfico e clínico de idosos atendidos em Unidade Básica de Saúde da Família. Acta Paul Enferm 2009; 22(1):49-54..

We compared the percentage of concordance between the information related to the medical prescription and the information given by the patient for the medication presented at the moment of the interview. Amongst the items considered to be very important for the use of medication – name, dose and frequency – it was observed that there was a low proportion of concordance for the medicine’s name. The proportion of the low concordance for the name of the medication (24.4%) was about 2 times greater than what was found for the dosage (13.8%) and about 1.5 times greater than what was found for the frequency (17.3%). This fact was found in previousstudies77. Silva T, Schenkel EP, Mengue SS. Nível de informação a respeito de medicamentos a pacientes ambulatoriais de hospital universitário. Cad Saude Publica 2000; 16(2): 449-455.,2525. Ceccato MGB, Acurcio FA, Bonolo PF, Rocha GM, Guimarães MDC. Compreensão de informações relativas ao tratamento anti-retroviral entre indivíduos infectados pelo HIV. Cad Saude Publica 2004; 20(5):1388-1397. and it probably owes itself to the great complexity of the names of the drugs. Frequently, the names are not similar to any word in the patient’s vocabulary. They are not familiar with the names and they have difficulties in memorizing and pronouncing them. It’s important to state that in this study we accepted differences amongst the technical and popular terminology, and the participant could look at either the medication packaging, the medical description or any notes that they had in their hands during the interview. There was low concordance for the side effects item which was the case for other similar studies66. Fröhlich SE, Dal Pizzol TS, Mengue SS. Instrumento para avaliação do nível de conhecimento da prescrição na atenção primária. Rev Saude Publica 2010; 44(6):1046-1054.,1111. Oenning D, Oliveira BV, Blatt CR. Conhecimento dos pacientes sobre os medicamentos prescritos após consulta médica e dispensação. Cien Saude Colet 2011; 16(7):3277-3283.,1919. Chan FW, Wong FY, So WY, Kung K, Wong CK. How much do elders with chronic conditions know about their medications? BMC Geriatrics 2013; 13:59.,2525. Ceccato MGB, Acurcio FA, Bonolo PF, Rocha GM, Guimarães MDC. Compreensão de informações relativas ao tratamento anti-retroviral entre indivíduos infectados pelo HIV. Cad Saude Publica 2004; 20(5):1388-1397.. This situation can be explained, in part, by the fact that health care professionals, many times, did not write down any information on the prescriptions for fear of alarming the patients and this led to non-adherence to the treatment1919. Chan FW, Wong FY, So WY, Kung K, Wong CK. How much do elders with chronic conditions know about their medications? BMC Geriatrics 2013; 13:59.. Aside from this, the medical appointments were short in terms of time which meant that the health care professional gave priority in providing information such as: name, dose and frequency of use of the medication, at the detriment of information on possible side effects1212. Ascione FJ, Kirscht JP, Shimp LA. An assessment of different components of patient medication knowledge. Med Care 1986; 24(Supl.):1018-1027.,1919. Chan FW, Wong FY, So WY, Kung K, Wong CK. How much do elders with chronic conditions know about their medications? BMC Geriatrics 2013; 13:59.. The low amount of knowledge of the side effects is a worrying fact that requires attention. Patients that are not familiar with such effects present a greater risk of having serious complications since some of these side effects can lead to the person being hospitalized and they may even die1919. Chan FW, Wong FY, So WY, Kung K, Wong CK. How much do elders with chronic conditions know about their medications? BMC Geriatrics 2013; 13:59.. It is important to emphasize that knowledge of the side effects may contribute to relations being improved between health care professionals and patients since patients will have the liberty to inform the health care professional when one of the such effects occurs.

The understanding of every class of medication in accordance with the first ATC level presented a low score for medication frequently used in acute conditions or used sporadically such as ibuprofen, paracetamol, or anti-infectives or dermatological drugs. In past studies66. Fröhlich SE, Dal Pizzol TS, Mengue SS. Instrumento para avaliação do nível de conhecimento da prescrição na atenção primária. Rev Saude Publica 2010; 44(6):1046-1054., it was observed that less knowledge was associated with the use of anti-infective medication and drugs for the respiratory system. Also, found that there was greater knowledge of medication used for chronic problems when compared to medication used in a sporadic way1010. Chau I, Korb-Savoldelli V, Trinquart L, Caruba T, Prognon P, Durieux P, Piketty C, Sabatier B. Knowledge of oral drug treatment in immunocompromised patients on hospital discharge. Swiss Med Wkly 2011; 141:w13204.. Probably, it occurs because the medication used for chronic problems are used for a prolonged period of time and as a consequent the patient becomes more familiar with it and their understanding of it is better.

The index of complexity for the pharmacotherapy is an important tool since the simple acting of counting the medication in itself is not sufficient to measure the complexity of the medication usage regime3737. Mansur N, Weiss A, Beloosesky Y. Looking beyond polypharmacy: quantification of medication regimen complexity in the elderly. Am J Geriatr Pharmacother 2012; 10(4):223-229.. In previous studies, an association of low understanding of pharmacotherapy with the greater complexity of the problem was found66. Fröhlich SE, Dal Pizzol TS, Mengue SS. Instrumento para avaliação do nível de conhecimento da prescrição na atenção primária. Rev Saude Publica 2010; 44(6):1046-1054.,2222. Spiers MV, Kutzik DM, Lamar M. Variation in medication understanding among the elderly. Am J Health-Syst Pharm 2004; 61(4):373-380.. This occurs because the greater the quantity of information to be assimilated, greater the difficulty in memorizing the instructions66. Fröhlich SE, Dal Pizzol TS, Mengue SS. Instrumento para avaliação do nível de conhecimento da prescrição na atenção primária. Rev Saude Publica 2010; 44(6):1046-1054.. It is important to highlight that the tool for evaluating the complexity used in this study3131. Melchiors AC, Correr CJ, Fernández-Llimos F. Tradução e validação para o português do Medication Regimen Complexity Index. Arq Bras Cardiol 2007; 89(4):210-218. was presented as a continuous variable. The mean found for the index of complexity of the pharmacotherapy in the sample studied, was close to a study carried out on older people in the United States3838. Linnebur SA, Vande-Griend JP, Metz KR, Hosokawa PW, Hirsch JD, Libby AM. Patient-level medication regimen complexity in older adults with depression. Clin Ther 2014; 36(11):1538-1546.. However, what was not clear was the score that ought to be reached for a prescription to be considered complex.

A low level of education and the dependency on the use of medication were factors independently associated with an understanding of the pharmacotherapy. The association of the level of education with the understanding of the pharmacotherapy was demonstrated in previous studies with adults66. Fröhlich SE, Dal Pizzol TS, Mengue SS. Instrumento para avaliação do nível de conhecimento da prescrição na atenção primária. Rev Saude Publica 2010; 44(6):1046-1054.,1414. Cruzeta APS, Dourado ACL, Monteiro MTM, MartinS RO, Calegario TA, Galato D. Fatores associados a compreensão da prescrição médica no sistema único de saúde de um município do sul do Brasil. Cien Saude Colet 2013; 18(12):3731-3737.,1515. Okuyan B, Sancar M, Izzettin FV. Assessment of medication knowledge and adherence among patients under oral chronic medication treatment in community pharmacy settings. Pharmacoepidemiol and Drug Saf 2013; 22(2):209-214.,1818. Motter FR, Olinto MTA, Paniz VMV. Conhecimento sobre a farmacoterapia por portadores de hipertensão arterial sistêmica. Cien Saude Colet 2013; 18(8):2263-2274. and older people1919. Chan FW, Wong FY, So WY, Kung K, Wong CK. How much do elders with chronic conditions know about their medications? BMC Geriatrics 2013; 13:59.. Patients with a low level of education showed difficulties in reading, memorizing and understanding the instructions as well as having a poor understanding of the information given by the health care professionals66. Fröhlich SE, Dal Pizzol TS, Mengue SS. Instrumento para avaliação do nível de conhecimento da prescrição na atenção primária. Rev Saude Publica 2010; 44(6):1046-1054.,1414. Cruzeta APS, Dourado ACL, Monteiro MTM, MartinS RO, Calegario TA, Galato D. Fatores associados a compreensão da prescrição médica no sistema único de saúde de um município do sul do Brasil. Cien Saude Colet 2013; 18(12):3731-3737.. Health Literacy means having the ability to obtain, process and understand basic information and services that are necessary in order to take adequate decisions regarding health care3939. Passamai MPB, Sampaio HAC, Dias AMI, Cabral LA. Letramento funcional em saúde: reflexões e conceitos sobre seu impacto na interação entre usuários, profissionais e sistema de saúde. Interface (Botucatu) 2012; 16(41):301-314.. Health literacy can be worse than general literacy. An individual may be able to understand a material of something that is common to them but have to major effort to understand materials in vocabulary or concepts that are unfamiliar to them, such as those used in medical prescriptions3939. Passamai MPB, Sampaio HAC, Dias AMI, Cabral LA. Letramento funcional em saúde: reflexões e conceitos sobre seu impacto na interação entre usuários, profissionais e sistema de saúde. Interface (Botucatu) 2012; 16(41):301-314.. The worse health literacy is associated with low levels of knowledge related to health and a poor control of chronic diseases2424. Mosher HJ, Lund BC, Kripalani S, Kaboli PJ. Association of health literacy with medication knowledge, adherence, and adverse drug events among elderly veterans. J Health Commun 2012; 17(Supl. 3):241-251.. Therefore it is recommended that the medical team be attentive to the patients with little education. They should be prepared to serve them individually using accessible vocabulary that is written legibly and when necessary, strategies for improving understanding of the pharmacotherapy should be implemented with the use of designs, colors and symbols. One important action to improve the knowledge of older people in relation to medication is the insertion of pharmacists in the multi-professional health care team. It is known that the guidance given by pharmacist contributes to increasing understanding and as a consequence, increases the compliance with medication treatment1111. Oenning D, Oliveira BV, Blatt CR. Conhecimento dos pacientes sobre os medicamentos prescritos após consulta médica e dispensação. Cien Saude Colet 2011; 16(7):3277-3283.,1616. Ponnusankar S, Surulivelrajan M, Anandamoorthy N, Suresh B. Assessment of impact of medication counseling on patients’ medication knowledge and compliance in an outpatient clinic in south India. Patient Educ Couns 2004; 54(1):55-60.,2525. Ceccato MGB, Acurcio FA, Bonolo PF, Rocha GM, Guimarães MDC. Compreensão de informações relativas ao tratamento anti-retroviral entre indivíduos infectados pelo HIV. Cad Saude Publica 2004; 20(5):1388-1397.. In 2008 pharmaceutical assistance was included as one of the strategic areas for the actions of the Núcleos de Apoio à Saúde da Família, a team of professionals that act as support for the PHCTeams4040. Brasil. Ministério da Saúde (MS). Portaria nº 154, de 24 de janeiro de 2008. Cria o Núcleo de Apoio à Saúde da Família – NASF. Diário Oficial da União 2008; 25 jan.. The pharmaceutical professional in NASF should develop focused actions in patient care and they should not be limited to administrative activities4141. Brasil. Ministério da Saúde (MS). Secretaria de Ciência, Tecnologia e Insumos Estratégicos. Departamento de Assistência Farmacêutica e Insumos Estratégicos. Serviços farmacêuticos na atenção básica à saúde. Brasília: MS; 2014.. In spite of important advances, the number of pharmacist in PHC is incipient with only one responsible professional for a population that has approximately 20 to 40,000 people4242. Brasil. Ministério da Saúde (MS). Portaria nº 2.488, de 21 de outubro de 2011. Aprova a Política Nacional de Atenção Básica, estabelecendo a revisão de diretrizes e normas para a organização da Atenção Básica, para a Estratégia Saúde da Família (ESF) e o Programa de Agentes Comunitários de Saúde (PACS). Diário Oficial da União 2011; 22 out.. This low number of pharmacists in the PHC may explain the fact that these professionals have not been mentioned much as responsible for giving guidance in relation to medication. The pharmacist, for being the reference for various PHC teams4242. Brasil. Ministério da Saúde (MS). Portaria nº 2.488, de 21 de outubro de 2011. Aprova a Política Nacional de Atenção Básica, estabelecendo a revisão de diretrizes e normas para a organização da Atenção Básica, para a Estratégia Saúde da Família (ESF) e o Programa de Agentes Comunitários de Saúde (PACS). Diário Oficial da União 2011; 22 out., often carries out clinical appointments with individual patients that are a part of specific risk groups. Therefore, the insertion of pharmacists in sufficient numbers in the health services can contribute to improving the adherence and understanding of pharmacotherapy and thus contribute to the reaching of the objectives of the pharmacotherapy.

It was noted in one study that the 55 and over who had good functional capabilities, presented the best knowledge on the pharmacotherapy1717. Gallagher R, Warwick M, Chenoweth L, Stein-Parbury J, Milton-Wildey K. Medication knowledge, adherence and predictors among people with heart failure and chronic obstructive pulmonary disease. J Nursing Healthcare Chronic Illness 2010; 3(1):30-40.. In this study, the older people that used medicines in an independent way had a better understanding of the medication treatment. The probably explanation for this is the fact that when the individual depends on the help of a caregiver to administer the drug, he possibly will make less of an effort to understand the pharmacotherapy and as a result will have less understanding. Thus we highlight the importance of health care professionals providing guidance in relation to the medication of caregivers of older people as they are often responsible for the pharmacotherapy of older people. In the face of this scenario what emerges as a perspective is an investigation of the understanding of caregivers on treatment with medicines.

The understanding of pharmacotherapy is not described as a single concept in research studies published. It is looked on as embracing different aspects of pharmacotherapy that are not equivalent, in order to get a representation of the overall concept99. Ceccato MGB, Acúrcio FA, Cesar CC, Bonolo PF, Guimarães MDC. Compreensão de terapia anti-retroviral: uma aplicação do modelo de traço latente. Cad Saude Publica 2008; 24(7):1689-1698.,1212. Ascione FJ, Kirscht JP, Shimp LA. An assessment of different components of patient medication knowledge. Med Care 1986; 24(Supl.):1018-1027.. It is evident that there is a tendency for the inclusion in the studies of evaluating understanding of pharmacotherapy and the relative aspects such as: indication, frequency, name and dose of the medication. These items are considered essential for the safe use of medication. In the studies, the approach of the questions relative to conduct covers: what to do when forget a dose, safety, duration of the treatment, storage and medication interaction are reduced. These items can be judged as being relevant for the rational use of the medication. One point to be evidenced is that in spite of having various studies that evaluate understanding of pharmacotherapy, none of them used valid tools. The validation of a tool for the measurement of understanding of the pharmacotherapy is relevant for clinical and epidemiological research as it permits the obtaining of results that are more reproducible and there would be uniformity in the methodologies that would contribute to a wider level of knowledge. A valid tool can be applied to clinical practices with the provision of resources with the assurance of the detection of patients at risk of not understanding the pharmacotherapy.

It is important to highlight that this study is one of the first in Brazil that deals with the evaluation of understanding of pharmacotherapy amongst older people. In the international medical journals, such studies are scarce with few variables being analyzed1313. Guénette L, Moisan J. Elderly people’s knowledge of the purpose of their medicines. Am J Geriatr Pharmacotherapy 2011; 9(1):49-57.,1919. Chan FW, Wong FY, So WY, Kung K, Wong CK. How much do elders with chronic conditions know about their medications? BMC Geriatrics 2013; 13:59.,2020. Sela-Katz P, Rabinowitz I, Shugaev I, Shigorina G. Basic knowledge of the medication regimen correlates with performance on cognitive function tests and diagnosis of dementia in elderly patients referred to a geriatric assessment unit. Gerontology 2010; 56(5):491-495.,2121. Modig S, Kristensson J, Ekwall AK, Hallberg IR, Midlov P. Frail elderly patients in primary care-their medication knowledge and beliefs about prescribed medicines. Eur J Clin Pharmacol 2009; 65(2):151-155.,2222. Spiers MV, Kutzik DM, Lamar M. Variation in medication understanding among the elderly. Am J Health-Syst Pharm 2004; 61(4):373-380.,2323. Tordoff JM, Bagge ML, Gray AR, Campbell AJ, Norris PT. Medicine-taking practices in community-dwelling people aged ≥ 75 years in New Zealand. Age and Ageing 2010; 39(5):574-580., 3434. World Health Organization (WHO). ATC/DDD Index 2014. [acessado 2014 mar 01]. Disponível em: http://www.whocc.no/atc_ddd_index/
http://www.whocc.no/atc_ddd_index/...
. The covering of the evaluated items in the definition from Ascione et al.1212. Ascione FJ, Kirscht JP, Shimp LA. An assessment of different components of patient medication knowledge. Med Care 1986; 24(Supl.):1018-1027., was highlighted.

A limitation of this study was the evaluation of understanding of pharmacotherapy for medication that individuals carried with them at the moment of the interview. In this case, the participant could not always have, to hand, all of the drugs that they normally used. We obtain a sample of convenience on the assumption that all elderly people were the same.

The findings of this study are useful for general research purposes and for practical clinical ones since it brings to the attention of health care professionals, managers and researchers the lack of knowledge in the elderly population concerning medication. Interventions need to be carried out so that the existing lacuna can be reduced between the information that the patient really knows and the information that he ought to know in order to safe use of medicines. The elderly that has little education should be prioritized for pharmaceutical clinical services. Guidelines with the focus on the older person should be implemented.

Conclusion

The insufficient understanding of pharmacotherapy was high in this study, principally amongst older people with low levels of education and a dependency in the use of medication. The insufficient understanding on the part of the older person can compromise the rational use of any medication, creating problems in relation to effectiveness and safety. Elderly extensively use medication and are more sensitive to adverse reactions. The services and the health care professionals ought to be prepared to attend to and guide elderly people in relation to medication, principally those that have low formal education.

Acknowledgements

Fundação de Amparo à Pesquisa de Minas Geraisand Pró-reitoria de Pesquisa da Universidade Federal de Minas Gerais.Lázara M. Lopes, Lucas C. B. Ceccato, Mariana C. de Oliveira, Mariane S. Garcia, Rachel C. C. Pereira and Thayane O. dos Santos for contribuition in research.

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Publication Dates

  • Publication in this collection
    Nov 2016

History

  • Received
    06 July 2015
  • Reviewed
    27 Nov 2015
  • Accepted
    29 Nov 2015
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