KNOWLEDGE OF COMMONLY PRESCRIBED MEDICATIONS TO OCTOGENARIANS

T.V.N. Didone¹, D. Oliveira de Melo², E. Ribeiro^1,3

1. Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil; 2. Department of Biological Sciences, Institute of Environmental, Chemical and Pharmaceutical Sciences, Federal University of Sao Paulo, Diadema, Brazil; 3. University Hospital, University of Sao Paulo, Sao Paulo, Brazil

Corresponding Author: Thiago Vinicius Nadaleto Didone, Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil, E-mail: tdidone@gmail.com, Phone: 55-11-3091-9246, Fax: 55-11-3091-9283

J Aging Res Clin Practice 2019;8:70-73
Published online October 1, 2019, http://dx.doi.org/10.14283/jarcp.2019.12

Abstract

Eighty outpatients aged 80 years or more were face-to-face interviewed in order to assess the appropriate recall of six items of information about the 19 most commonly prescribed medications by means of a questionnaire cross-culturally adapted into Brazilian Portuguese. In some cases, the caregiver was interviewed instead. The frequency of medications whose information was appropriately recalled ranged from 36% to 100%, 36% to 100%, 18% to 90%, 9% to 63%, 0 to 25%, and 0 to 10% for respectively the following items dosage, form of administration, indication, storage, side effects, and precautions and warnings, indicating poor overall knowledge. The lowest frequency of dosage and form of administration was seen for alendronic acid (36% each), and the highest frequency of side effects was found for donepezil (25%). Octagenarians and their caregivers should be constantly counseled on medication information.

Key words: Aged, 80 and over, drug storage, health knowledge, attitudes, practice, patient education as topic, patient medication knowledge.

Introduction

The world’s population is ageing with the feature that the number of people aged ≥80 years is growing even faster than the number of older people overall (1). By 2035, the number of octogenarians in Brazil will double, rising from the current 2.0% to 3.8% of the population (2). Older individuals use more drugs (1) and have less knowledge of them (3, 4) in comparison to younger people. Among the elderly, octogenarians may have still even less medication knowledge. Primary care patients aged ≥80 years presented 53% less chance of appropriately recall the indications of medications in use than the ones aged 60 to 69 years (5). This reaffirm the fact that medication knowledge among older patients is insufficient (3, 5-7), which may lead to medication non-adherence (6) and negative clinical implications (4). For instance, 75-year-old patients with adequate knowledge of the indications of the medications they used had 3.7 times more chance to follow the prescribed regimen than the ones with inadequate knowledge (6).
The aim of this study was to evaluate the knowledge octogenarian outpatients had about commonly prescribed medications.

Methods

Patients seen at the outpatient geriatric clinic of the University of Sao Paulo Hospital (São Paulo, Brazil) and having a valid prescription of at least one medication were included at random from March 2013 to February 2014. Patients having communication difficulties or not willing to be interviewed were excluded.
Patients were interviewed face-to-face in order to identify the prescribed medications in last geriatrician appointment and their Anatomical Therapeutic Chemical (ATC) codes (www.whocc.no), time of use, and knowledge. In the case of patients with dementia, we interviewed his/her caregiver responsible by the home organization of medications instead. We allowed interviewees to read the prescription if they felt the need to.
Medication knowledge is the knowledge needed to ensure the appropriate use of the medication. It was obtained for each medication by means of an 11-question Spanish questionnaire cross-culturally adapted into Brazilian Portuguese (8). Each question inquires the interviewee about one item of information on medication. We selected six questions, each one concerning one of the following items: dosage, form of administration, indication, storage, side effects, and precautions and warnings. Answers were classified either correct, incomplete, unknown or incorrect according to its degree of agreement with the UpToDate® database (www.uptodate.com). Two interviewers independently classified the answers and a third one was consulted if necessary.
Knowledge was expressed as the appropriate recall of the items mentioned above, that is when answers were either correct or incomplete (5). We analyzed only medications prescribed to ≥10% of patients. For every one of them, we calculated the frequency of medications appropriately recalled.

Results

We interviewed 80 individuals. There were 19 ATC 5th codes prescribed to ≥10% of patients, which corresponded to 61.5% (305/496) of all medications prescribed. Acetylsalicylic acid was the most prescribed medication (43% of patients) followed by omeprazole (36%) and enalapril (30%). Regarding the time of use, 72.5% (221/305) of the most prescribed medications were being used for more than 6 months. The majority (9/19) of medications acts on the cardiovascular system (ATC 1st code: C). The second most common (5/19) ATC 1st code was A (medications acting on the alimentary tract and metabolism).
Table 1 shows the frequency of medications whose information about dosage, form of administration, indication, storage, side effects, and precautions and warnings was appropriately recalled. Frequencies of these six items of information respectively ranged from 36% to 100%, 36% to 100%, 18% to 90%, 9% to 63%, 0 to 25%, and 0 to 10%. The overall knowledge was intermediate to high regarding information on dosage and form of administration, varied a lot for information on indication and storage, and for information on side effects and precautions and warnings was almost non-existent.
Of note, the lowest appropriate recall of dosage and form of administration was found for alendronic acid. Still, the highest appropriate recall of side effects was seen for donepezil.

Table 1
Frequency of medications whose information was appropriately recalled

It was considered the 19 most commonly prescribed medications and 6 information needed for appropriate use of medications. D: dosage; FA: form of administration; I: indication; S: storage; SE: side effects; PW: precautions and warnings.

Discussion

A few Brazilian studies (9-11) corroborate our findings in spite of having evaluated only one prescribed medication and having had no constraints of age. For instance, in Grão Pará, Santa Catarina, 95.7%, 60.0%, 11.4%, and 0 of primary care outpatients had appropriate knowledge of indication, dosage, precautions and warnings, and side effects, respectively (9).
Patients often demonstrate appropriate knowledge of how much to take of a medication and how to take it, since this information is usually present in prescriptions and constantly required when long-term medications are being used (9, 10). Here, the vast majority of medications has been prescribed for more than 6 months, which might have influenced the high frequencies of appropriate recall of dosage and form of administration. The latter can be explained by the simple instructions usually recommended in order to take oral products in safety (eg. taking with water was an answer good enough to be considered correct). Taking alendronic acid in safety needs more complex directions though. We believe the low appropriate recall of form of administration of alendronic acid resulted from insufficient counselling on this issue by healthcare professionals. In a 3-year trial there was no difference in the incidence of esophageal adverse reactions among individuals receiving placebo, 5, 10, or 20 mg of alendronic acid because they were regularly seeing the physician who reinforced the instructions for the safe use of the medication in every encounter (12).
Although the frequencies of appropriate recall of indication varied widely among medications, the ones for the cardiac medications (ATC 1st code: C) are in line with a Dutch study, which showed that 61.6% of these medications were appropriately recalled by older primary care patients (5). Knowing the indication might be challenging when medications have multiple indications (eg. sertraline), were prescribed to prevent a condition rather than treat one (eg. acetylsalicylic acid) or in an irrational way (eg. omeprazole is not indicated to treat polypharmacy). In addition, this knowledge may be influenced by the amount of time of medication use and the skills needed to use it (5, 10).
Appropriate recall of storage was ≤50% for 16 out of 19 medications, indicating that most of them might have been inadequately stored. This is associated with patients’ age and habits. In Cuité, Northeast Brazil, for example, 203 out of 267 (76.0%) households had medications inadequately stored. Besides, the older the organizer of home medications, the higher the risk of them being inadequately stored (13).
The low frequencies of appropriate recall of side effects and precautions and warnings we found is ordinary. Safety issues are the least known information about medication in older individuals (6, 7, 14). Reasons include not experiencing adverse reactions (10) and lack of counselling by healthcare professionals (7, 9) who fear nocebo effect or medication discontinuation (9). While 72.2% and 70.1% of older outpatients using long-term medications reported receiving information about the form of administration and the indication, 73.0% claimed that they did not receive any information on side effects (14).
Since it is a first-line treatment for Alzheimer’s disease, answers regarding donepezil information were given by caregivers instead of patients. Not surprisingly, they possessed the highest knowledge of side effects as caregivers of dementia patients actively seek key information about medications in use by their care-recipients, especially information on adverse reactions (15).
The lack of knowledge needed for appropriate use of medications may cause negative and significant clinical consequence. Not knowing information about dosage and form of administration may expose patients to adverse events and other risks of not following the prescription. The knowledge of indication may help patients assess the correspondence between indication and treating condition so that they can verify the clinical reasoning of the prescriber. In addition, not knowing storage information increases the odds of consuming badly preserved medications. Besides, patients who has appropriate knowledge of side effects may engage in preventive health behaviors and seek assistance to manage them when they manifest (14). Therefore, healthcare professionals must unquestionably provide reliable written and oral information on medication to patients and caregivers in order to increase their medication knowledge.
Selection bias may arise due to the inclusion not at random of individuals and the exclusion of the ones not willing to participate (eg. patients with gait disorders, caregivers late for work). Besides, it is expected that caregivers possess more medication knowledge than their care-recipients simply due to sociodemographic differences (eg. caregivers are usually women, younger and more educated).

Funding: TVND was granted with a fellowship by Conselho Nacional de Desenvolvimento Científico e Tecnológico – Brasil (CNPq), number 135839/2012-2. CNPq had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; in the preparation of the manuscript; or in the review or approval of the manuscript.

Acknowledgements: None.

Conflict of interest disclosure: TVND, DOM and ER have nothing to disclose.

Ethical standard: The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. The research ethics committee of the University of Sao Paulo (USP) Hospital and the Faculty of Pharmaceutical Sciences of the USP approved the study and all participants gave written informed consent to take part.

References

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DEPRESSIVE SYMPTOMS AND LEVEL OF 25-HYDROXYVITAMIN D IN FREE-LIVING OLDEST OLD

M.T. da Rocha Lima¹, O. Custódio², P. Ferreira do Prado Moreira³, L.M. Quirino Araujo², C. de Mello Almada Filho², M. Seabra Cendoroglo⁴

1. Geriatrics Division, Paulista School of Medicine, Federal University of Sao Paulo, Brazil; 2. Geriatrics Division, Paulista School of Medicine, Federal University of Sao Paulo, Brazil; 3. Nutritionist at the Geriatrics Division, Paulista School of Medicine, Federal University of Sao Paulo, Brazil; 4. Professor at the Geriatrics Division, Paulista School of Medicine, Federal University of Sao Paulo, Brazil

Corresponding Author: Márcio Tomita da Rocha Lima, Rua Professor Francisco de Castro, 105, Vila Clementino, CEP 04020-050, São Paulo – São Paulo, Brazil, Telephone number: +551155764848 – extension line 2298, marciotrl@yahoo.com.br

J Aging Res Clin Practice 2016;5(3):142-146
Published online June 16, 2016, http://dx.doi.org/10.14283/jarcp.2016.101

Abstract

Background: Nowadays, the relation between hypovitaminosis D and depression has been reported and it is estimated that 1 billion people worldwide have vitamin D deficiency or insufficiency. However, the oldest old people are not included or are under-represented in most of the studies. Objective: To examine the association between depressive symptoms and 25-hydroxyvitamin D level (25(OH)Vit D) in elderly aged 80 and over who are physically more active and independent. Design: Cross-sectional study. Setting and Participants: Data collected from 182 oldest old people, aged 80 and over in the Geriatric Division from Federal University of São Paulo. Measurements: The functionality was evaluated by the Instrumental activities of their daily living (IADL). The approach of the depressive symptoms was done by the Geriatric Depression Scale (GDS) in its reduced 15 item version. 25-hydroxyvitamin D (25(OH)Vit D) analyses was done in serum sample refrigerated and protected from solar exposition. We considered deficiency serum level of 25(OH)Vit D <10ng/mL, insufficiency between 10 and 30ng/mL and sufficiency >30ng/mL. Results: According to blood level of 25(OH)Vit D we found difference between GDS score comparing the groups: “deficiency” (U=144,50; z=-3,126; p=0,002) and “insufficiency” groups (U=975,50; z=-2,793; p=0.005) are different than “sufficiency” group. Conclusion: In free-living independent oldest old people the goal of 25(OH)Vit D levels can be higher to avoid depressive symptoms, levels under 30ng/mL can be inadequate. Considering that the costs are low and side effects are not common, 25(OH)Vit D supplementation can be an important public health action.

Key words: Oldest old, aged, 80 and over, vitamin D, depression.

Introduction

The accelerated aging of Brazil has one of its epidemiologic consequences: the increased number of elderly with chronic diseases and incapacities that generate dependency (1). Late-life depression (LLD) affects from 10% to 22% of the growing geriatric population living in the community (2,3), it´s a risk factor for all-cause mortality in the elderly (4) and adults 85 and older appear to be more vulnerable to depression than other age groups (5). Wu et al. (6) demonstrates that the age-related growth of depressive symptoms occurs wholly in the context of medical comorbidity and does not have an independent effect. Weyerer et al. (7) found that the incidence of depression symptoms, measured using the GDS-15 Geriatric Depression Scale, increases significantly with age in non-demented primary care attenders aged 75 years and older. The presence of depressive symptoms as a risk factor for disability occurs in both genders (8) and it is associated with development of cognitive decline in older patients (9).
Nowadays, the relation between hypovitaminosis D and depression has been reported and it is estimated that 1 billion people worldwide have vitamin D deficiency or insufficiency (10). Hoogendijk et al. (11), in a cohort study, found that the lower levels of vitamin D were associated with higher intensity of depression. Milaneschi et al. (12), in 2010, also in a cohort study (InCHIANTI study), evaluated elderly of ages 65 and up and observed that hypovitaminosis D was a risk factor for the development of depressive symptoms in elderly. On the other hand, Toffanello et al. (13), in a prospectively studied population (Pro.V.A. study), showed that there was no direct effect between vitamin D deficiency and the onset of late-life depressive symptoms.
The oldest old people are not included or are under-represented in most of the studies. Because of that, we want to know if there is association between depressive symptoms and vitamin D in elderly aged 80 and over who are physically more active and independent.

Methods

Studied population

The analyzed data is part of a cohort study about free-living independent elderly aged 80 and over. The elderly have been following in the Geriatric Division from Federal University of São Paulo. We didn´t include oldest old people with dementia, cancer, acute disease, dialytic therapy, chemotherapy or radiotherapy.
The studied population included 182 oldest old people evaluated from the period of January 2010 to January 2012. The experimental protocols were approved by the appropriate institutional review committee and meet the guidelines of their responsible governmental agency. Informed consent was obtained from all individual participants included in the study (Federal University of São Paulo Ethical Committee approval number 1532/09).

Clinical assessment

The collected data were sex, age, ethnicity, precedence, smoking history (current, previous or more than one year without smoking, never smoked), alcohol history (drinking any amount of alcohol in the last 10 years), health perception (excellent, good, regular or bad), chronic pain (presence of pain for more than 3 months), and any exposition to sunlight. The neuropsychological evaluation was made by the Mini–mental state examination (MMSE) developed by Folstein and validated in Brazil by Brucki et al. (14). The functionality was evaluated by the Instrumental activities of their daily living (IADL) (15). The nutritional evaluation was made by the means of the Body mass index (BMI) (16), abdominal circumference (AC – we considered as a high AC value in elderly ≥ 102cm in men and ≥ 88cm in women), hip circumference (HC) and waist-to-hip ratio (WHR=CA/HC; WHR > 0,99cm2 in men or > 0,97 in women is associated with an increased cardiovascular risk) (17).
The approach of the depressive symptoms was done by the Geriatric Depression Scale (GDS) in its reduced 15 item version. Paradela et al. (18) validated the Portuguese version of the GDS to track depressive symptoms in ambulatory elderly, with a cut mark at 5/6 showing sensibility of 81% and specificity of 71%.

Biochemical analysis

The biochemical analysis of creatinine, fasting glycemia and serum hemoglobin was measured on a fasting blood specimens (collected after 10-hour fast). 25(OH)VitD analyses was done in serum sample refrigerated and protected from solar exposition. We used the DiaSorin LIAISON® 25(OH)VitD, which one is based on chemiluminescence technology (CLIA). We considered deficiency serum level of 25(OH)VitD <10ng/mL, insufficiency between 10 and 30ng/mL and sufficiency >30ng/mL (10).

Statistical analysis

For data processing we used “Statistical Package for the Social Sciences (SPSS) for Windows” (version 13). A measure of central tendency was represented by median and interquartile amplitude (IA) when appropriate. We used the bootstrapping method for assigning confidence intervals from the proportion and median. Levene’s test was used to assess the equality of variances for a variable calculated for two or more groups. We also used t Student´s test to determine if two sets of data were significantly different from each other, and the non-parametric tests Mann-Whitney (U) and Kruskal-Wallis (KW). When the Kruskal-Wallis (KW) test leads to significant results, Mann-Whitney (U)´s test was used with Bonferroni-corrected significance level. Chi-square test (X2) was used considering the recommendations of Cochran and the Fisher’s exact test when these recommendations were violated.

Results

We studied independent oldest old people, with a IADL median 26,0 (IA 5,0) for men and 24,0 (IA 5,0) for women (p=0,187). Most of them were women and 82% of oldest old women never smoked (Table 1). The women had more depressive symptoms than men. On the other hand, oldest old men had a better performance on MMSE, with a schooling median 4,0 (IA= 5,5) for men and 3,0 (IA 3,3) for women (p=0,09). 83,7% of men and 88,7% of women had insufficiency or deficiency blood levels of 25(OH)Vit D although 52,2% declared sunlight exposition.
We also observed that 66,7% of men and 49,2% of women had excellent or good health perception (p=0,154). 77,6% of men and 62,4% of women did not have chronic pain (p=0,076) and 36,2% of men and 64,6% of women had abdominal circumference increased (X2=11,280; gl=1, p=0,001). There were no differences between serum levels of fasting glycemia of men compared to women (median 87,0 +/- 16,0 and 88,0 +/- 17,0 respectively). However, the men hemoglobin (average 13,7 +/- 1,6) was greater than for women (average 13,2 +/- 1,5; p=0.005).
According to blood level of 25(OH)Vit D (Table 2) we found difference between GDS score comparing the groups: “deficiency” (U=144,50; z=-3,126; p=0,002) and “insufficiency” groups (U=975,50; z=-2,793; p=0.005) are different than “sufficiency” group; but there was no difference between “deficiency” and “insufficiency” groups (U=1460,00; z=-1.263; p=0,206).

Table 1
Characterization of elderly aged 80 years and over according to gender

IA: interquartile amplitude; CI: confidence interval; SD: standard deviation; MMSE: Mini–mental state examination; GDS: Geriatric depression scale; BMI: Body mass index; Missing values a=9; *U=3116,50, z=-0,452; **U=2399,00, z=-2,678; ***U=2444, z=-2,605; ****U=2835,50, z=-0,428; #X2=1,505, gl=2; &Fisher’s exact test.

Table 2
Characterization of elderly aged 80 years and over according to levels of 25(OH)Vit D

IA: interquartile amplitude; CI: confidence interval; SD: standard deviation; MMSE: Mini–mental state examination; GDS: Geriatric depression scale; BMI: Body mass index; WHR= waist-to-hip ratio ; Clearance of creatinine: estimated clearance of creatinine. Missing values a= 9; b= 8; c=8; d=13; e=2. *KW=5,503, gl=2; **KW=1,539, gl=2; ***KW=10,743, gl=2; ****KW=1,954, gl=2; *****KW=9,103, gl=2; ******KW=2,485, gl=2; #X2=1,505, gl=2; ##X2=4,48, gl=2; ###X2=4,249, gl=2; & Fisher’s exact test.

Discussion

In our cross-sectional study, we observed that there was association between worst GDS scores with < 30ng/mL of 25(OH)Vit D in oldest old people. It´s already known that depressive symptoms are associated with clinical 25(OH)Vit D deficiency (levels <10ng/mL) (19) in elderly 65 years of age. This was confirmed in a systematic review and meta-analysis of epidemiological studies: depression risk was found to be inversely associated with serum 25(OH)Vit D in both cross-sectional and cohort studies (20). But it seems that in free-living independent oldest old people the goal of 25(OH)Vit D levels can be higher to avoid depressive symptoms, levels under 30ng/mL can be inadequate. We have to consider that there is a decline of 25(OH)Vit D levels with age and also a gender difference (21) that is going to increase the risk of depression in oldest old age and can compromise functionality.
Low blood levels of 25(OH)Vit D can be related with the inflammatory status observed in depressed patients, because in these conditions, auto-reactive T cells against tissues and synthesis of the interleukins and the pro-inflammatory cytokines (IL-12, interferon gama) are stimulated by the immunologic system (22). Synthesis and metabolism of serotonin (5-hydroxytryptamine) is influenced by cytokine signaling pathways (23). In physiologic conditions, indoleamine 2,3-dioxigenase (IDO) compete by tryptophan hydroxylase (TH) in tryptophan metabolism. The activation of IDO metabolizes the tryptophan in kynurenine and in the end quinolinic acid. It decreases brain tryptophan and the serotonin levels.
The functional reserve decline with age and also the capability to the oldest old to maintain a health life style and independency. It´s interesting to note that these oldest old people are independent, free-living individuals and even so had 25(OH)Vit D levels under 30ng/mL. This was found for others researchers in elderly above 60 years of age (24, 25) despite their high sun exposure during the summer months and regarding the nutritional status (26).
It´s suggested that 25(OH)Vit D supplementation is indicated as a complement of depression treatment (27). Zanetidou et al. (28) demonstrated that administering 25(OH)Vit D to patients 65 years or older as an adjunct to antidepressant therapy was associated with a significant improvement in the depressive symptomatology. Considering that the costs are low and side effects are not common, 25(OH)Vit D supplementation is very cost-effective and can be a good choice to prevent depressive symptoms. This can be an important public health action to avoid depressive humor in oldest old people (29). We already know that to prevent fractures the goal is > 30ng/mL of 25(OH)Vit D (30) and it seems that, in oldest old people these levels are also recommended to avoid depressive symptoms. It´s important to establish if to avoid depressive symptoms in oldest old the goal is also > 30ng/mL of 25(OH)Vit D.
Our study has limitations: selection was by convenience and the GDS is a screening instrument and detect depression symptoms and not the diagnosis of depression. It´s also important to note that 56,9% of the sample had an increased abdominal circumference that can be related with low levels of 25(OH)Vit D and also with a more inflammatory condition.
We conclude that the goal of 25(OH)Vit D levels can be higher to avoid depressive symptoms in free-living independent oldest old people and levels under 30ng/mL can be inadequate. Considering that the costs are low and side effects are not common, 25(OH)Vit D supplementation can be an important public health action.

Funding: This study was funded by FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo – São Paulo Research Funding Foundation) – grant number 2011/12753-8. The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; in the preparation of the manuscript; or in the review or approval of the manuscript.

Acknowledgements: We acknowledge and thank Ana Beatriz Galhardi Di Tommaso, Renato Laks, Paulo Mateus Costa Affonso, and all doctors who contributed in data collection.

Conflict of interest: Márcio Tomita da Rocha Lima, Osvladir Custódio, Patricia Ferreira do Prado Moreira, Lara Miguel Quirino Araujo, Clineu de Mello Almada Filho and Maysa Seabra Cendoroglo have no conflicts of interest to declare.

Ethical standards: This experiment complies with the current laws of the country in which they were performed.

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