liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Inappropriate prescribing, non-adherence to long-term medications and related morbidities: Pharmacoepidemiological aspects
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0002-4642-4592
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Inappropriate use of medications (IUM), in particular inappropriate prescribing and non-adherence to prescribed medications, are important causes of drug-related morbidities (DRMs). They are increasing problems with the ageing populations and the growing burden of chronic conditions. However, research is needed on the association of IUMs with DRMs in outpatient settings and in the general population.

Aim: The aim of this thesis is to estimate and analyse the burden of potentially inappropriate prescriptions (PIPs) in the elderly and non-adherence to long-term medications among adults across care settings, and to investigate how IUM is associated to DRMs.

Methods: A meta-analysis summarised the previous evidence on the percentage of adverse drug reactions (ADRs) associated to IUM across healthcare settings (Study I). From a cohort in the general population, using medical records and register data, the prevalence of PIPs in the elderly and its association with ADRs were estimated retrospectively (Study II). From the same cohort, the factors associated with refill non-adherence to antihypertensive therapy, considering the use of multiple medications, and the association between non-adherence and sub-therapeutic effects (STEs) were investigated (Study III). A survey assessed the refill behaviour to antihypertensive, lipid lowering and oral antidiabetic medications (undersupply, adequate supply and oversupply), and its association with perceived ADRs and STEs (Study IV).

Results: IUM was the cause 52% and 45% of ADRs occurring in adult outpatients and inpatients respectively. Across healthcare settings, 46% of the elderly refilled PIPs over a 6-month period; PIPs were considered the cause of 30% of all ADRs; and the elderly who were prescribed PIPs had increased odds to experience ADRs (OR 2.47, 95% CI 1.65-3.69). In total, 35% was nonadherent to the full multidrug therapy and 13% was non-adherent to any medication (complete non-adherence).  Sociodemographic factors (working age and lower income) were associated with non-adherence to any medication, while clinical factors (use of specialised care, use of multiple medications, and being a new user) with non-adherence to the full multidrug therapy. STEs were associated with non-adherence to any medication a month prior to a healthcare visit (OR 3.27, 95% CI 1.27-8.49), but not with long-term measures of non-adherence. Among survey respondents, 22% of the medications were oversupplied and 12% were undersupplied. Inadequate refill behaviour was not associated with reporting ADRs or STEs (p<0.05).

Conclusions: A large proportion of ADRs occurring in hospital is caused by IUM, but more knowledge is needed in other settings. PIPs are common in the elderly general population and associated with ADRs. Therefore decreasing PIPs could contribute towards ADR prevention. Considering the use of multiple medications may help to better understand the factors associated with non-adherence to a multidrug therapy for tailoring the interventions to patient needs. Monitoring the adherence prior to a healthcare visit may facilitate interpreting STEs. Yet, the absence of an association between long-term measures of refill non-adherence with clinical and perceived DRMs suggest the need to enhance the knowledge of this association in clinical practice. In summary, this thesis shows a significant potential for improvements of medication use and outcomes.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2015. , 100 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1469
Keyword [en]
Drug-related morbidity, medication adherence, inappropriate prescribing, elderly, drug utilisation, pharmacoepidemiology
National Category
Pharmaceutical Sciences Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
URN: urn:nbn:se:liu:diva-122266DOI: 10.3384/diss.diva-122266ISBN: 978-91-7519-025-9 (print)OAI: oai:DiVA.org:liu-122266DiVA: diva2:864346
Public defence
2015-12-04, Originalet, Qulturum, Rybohov sjukhus, Jönköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2015-10-26 Created: 2015-10-26 Last updated: 2015-11-13Bibliographically approved
List of papers
1. Percentage of patients with preventable adverse drug reactions and preventability of adverse drug reactions - a meta-analysis
Open this publication in new window or tab >>Percentage of patients with preventable adverse drug reactions and preventability of adverse drug reactions - a meta-analysis
2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 3, 1-9 p., e33236Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Numerous observational studies suggest that preventable adverse drug reactions are a significant burden in healthcare, but no meta-analysis using a standardised definition for adverse drug reactions exists. The aim of the study was to estimate the percentage of patients with preventable adverse drug reactions and the preventability of adverse drug reactions in adult outpatients and inpatients.

METHODS: Studies were identified through searching Cochrane, CINAHL, EMBASE, IPA, Medline, PsycINFO and Web of Science in September 2010, and by hand searching the reference lists of identified papers. Original peer-reviewed research articles in English that defined adverse drug reactions according to WHO's or similar definition and assessed preventability were included. Disease or treatment specific studies were excluded. Meta-analysis on the percentage of patients with preventable adverse drug reactions and the preventability of adverse drug reactions was conducted.

RESULTS: Data were analysed from 16 original studies on outpatients with 48797 emergency visits or hospital admissions and from 8 studies involving 24128 inpatients. No studies in primary care were identified. Among adult outpatients, 2.0% (95% confidence interval (CI): 1.2-3.2%) had preventable adverse drug reactions and 52% (95% CI: 42-62%) of adverse drug reactions were preventable. Among inpatients, 1.6% (95% CI: 0.1-51%) had preventable adverse drug reactions and 45% (95% CI: 33-58%) of adverse drug reactions were preventable.

CONCLUSIONS: This meta-analysis corroborates that preventable adverse drug reactions are a significant burden to healthcare among adult outpatients. Among both outpatients and inpatients, approximately half of adverse drug reactions are preventable, demonstrating that further evidence on prevention strategies is required. The percentage of patients with preventable adverse drug reactions among inpatients and in primary care is largely unknown and should be investigated in future research.

Place, publisher, year, edition, pages
Public Library of Science, 2012
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-76102 (URN)10.1371/journal.pone.0033236 (DOI)000303309000014 ()22438900 (PubMedID)
Available from: 2012-03-27 Created: 2012-03-27 Last updated: 2017-12-07
2. Potentially inappropriate prescribing and adverse drug reactions in the elderly: a population-based study
Open this publication in new window or tab >>Potentially inappropriate prescribing and adverse drug reactions in the elderly: a population-based study
Show others...
2015 (English)In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 71, no 12, 1525-1533 p.Article in journal (Refereed) Published
Abstract [en]

Purpose

Potentially inappropriate prescriptions (PIPs) criteria are widely used for evaluating the quality of prescribing in elderly. However, there is limited evidence on their association with adverse drug reactions (ADRs) across healthcare settings. The study aimed to determine the prevalence of PIPs, defined by the Screening Tool of Older Persons’ potentially inappropriate Prescriptions (STOPP) criteria, in the Swedish elderly general population and to investigate the association between PIPs and occurrence of ADRs.

Method

Persons ≥65 years old were identified from a random sample of 5025 adults drawn from the Swedish Total Population Register. A retrospective cohort study was conducted among 813 elderly with healthcare encounters in primary and specialised healthcare settings during a 3-month period in 2008. PIPs were identified from the Swedish Prescribed Drug Register, medical records and health administrative data. ADRs were independently identified by expert reviewers in a stepwise manner using the Howard criteria. Multivariable logistic regression examined the association between PIPs and ADRs.

Results

Overall, 374 (46.0 %) persons had ≥1 PIPs and 159 (19.5 %) experienced ≥1 ADRs during the study period. In total, 29.8 % of all ADRs was considered caused by PIPs. Persons prescribed with PIPs had more than twofold increased odds of experiencing ADRs (OR 2.47; 95 % CI 1.65–3.69). PIPs were considered the cause of 60 % of ADRs affecting the vascular system, 50 % of ADRs affecting the nervous system and 62.5 % of ADRs resulting in falls.

Conclusion

PIPs are common among the Swedish elderly and are associated with increased odds of experiencing ADRs. Thus, interventions to decrease PIPs may contribute to preventing ADRs, in particular ADRs associated with nervous and vascular disorders and falls.

Place, publisher, year, edition, pages
Springer, 2015
Keyword
Inappropriate prescribing – Elderly – Adverse drug reactions – Retrospective study – Medical records – Registries
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:liu:diva-121823 (URN)10.1007/s00228-015-1950-8 (DOI)000365179600013 ()26407684 (PubMedID)
Available from: 2015-10-08 Created: 2015-10-08 Last updated: 2017-12-01Bibliographically approved
3. Adherence to Antihypertensive Therapy and Elevated Blood Pressure: Should We Consider the Use of Multiple Medications?
Open this publication in new window or tab >>Adherence to Antihypertensive Therapy and Elevated Blood Pressure: Should We Consider the Use of Multiple Medications?
Show others...
2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 9, e0137451Article in journal (Refereed) Published
Abstract [en]

Background

Although a majority of patients with hypertension require a multidrug therapy, this is rarely considered when measuring adherence from refill data. Moreover, investigating the association between refill non-adherence to antihypertensive therapy (AHT) and elevated blood pressure (BP) has been advocated.

Objective

Identify factors associated with non-adherence to AHT, considering the multidrug therapy, and investigate the association between non-adherence to AHT and elevated BP.

Methods

A retrospective cohort study including patients with hypertension, identified from a random sample of 5025 Swedish adults. Two measures of adherence were estimated by the proportion of days covered method (PDC≥80%): (1) Adherence to any antihypertensive medication and, (2) adherence to the full AHT regimen. Multiple logistic regressions were performed to investigate the association between sociodemographic factors (age, sex, education, income), clinical factors (user profile, number of antihypertensive medications, healthcare use, cardiovascular comorbidities) and non-adherence. Moreover, the association between non-adherence (long-term and a month prior to BP measurement) and elevated BP was investigated.

Results

Non-adherence to any antihypertensive medication was higher among persons < 65 years (Odds Ratio, OR 2.75 [95% CI, 1.18–6.43]) and with the lowest income (OR 2.05 [95% CI, 1.01–4.16]). Non-adherence to the full AHT regimen was higher among new users (OR 2.04 [95% CI, 1.32–3.15]), persons using specialized healthcare (OR 1.63, [95% CI, 1.14–2.32]), and having multiple antihypertensive medications (OR 1.85 [95% CI, 1.25–2.75] and OR 5.22 [95% CI, 3.48–7.83], for 2 and ≥3 antihypertensive medications, respectively). Non-adherence to any antihypertensive medication a month prior to healthcare visit was associated with elevated BP.

Conclusion

Sociodemographic factors were associated with non-adherence to any antihypertensive medication while clinical factors with non-adherence to the full AHT regimen. These differing findings support considering the use of multiple antihypertensive medications when measuring refill adherence. Monitoring patients' refill adherence prior to healthcare visit may facilitate interpreting elevated BP.

Place, publisher, year, edition, pages
´PLoS, 2015
National Category
Social and Clinical Pharmacy
Identifiers
urn:nbn:se:liu:diva-121822 (URN)10.1371/journal.pone.0137451 (DOI)000361043100040 ()26359861 (PubMedID)
Available from: 2015-10-08 Created: 2015-10-08 Last updated: 2017-12-01
4. Refill adherence and self-reported adverse drug reactions and sub-therapeutic effects: a population-based study
Open this publication in new window or tab >>Refill adherence and self-reported adverse drug reactions and sub-therapeutic effects: a population-based study
Show others...
2013 (English)In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 22, no 12, 1317-1325 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: To assess refill adherence to dispensed oral long-term medications among the adult population and to investigate whether the percentages of self-reported adverse drug reactions (ADRs) and sub-therapeutic effects (STEs) differed for medications with adequate refill adherence, oversupply, and undersupply.

METHOD: Survey responses on self-reported ADRs and STEs were linked to the Swedish Prescribed Drug Register in a cross-sectional population-based study. Refill adherence to antihypertensive, lipid-lowering, and oral anti-diabetic medications was measured using the continuous measure of medication acquisition (CMA). The percentages of self-reported ADRs and STEs were compared between medications with adequate refill adherence (CMA 0.8-1.2), oversupply (CMA > 1.2), and undersupply (CMA < 0.8).

RESULTS: The study included 1827 persons, and the refill adherence was measured for 3014 antihypertensive, 839 lipid lowering, and 253 oral anti-diabetic medications. Overall, 65.7% of the medications had adequate refill adherence, 21.9% oversupply, and 12.4% undersupply. The percentages of self-reported ADRs and STEs were respectively 2.6%, 2.7%, and 2.1% (p > 0.5) for ADRs and 1.1%, 1.6%, and 1.5% (p > 0.5) for STEs.

CONCLUSIONS: Adequate refill adherence was found in two thirds of the medication therapies. ADRs and STEs were unexpectedly equally commonly reported for medications with adequate refill adherence, oversupply, and undersupply. These results suggest that a better understanding of patients' refill behaviors and their perceived medication adverse outcomes is needed and should be considered in improving medication management. The impact of individual and healthcare factors that may influence the association between refill adherence and reported medication adverse outcomes should be investigated in future studies. Copyright © 2013 John Wiley & Sons, Ltd.

Place, publisher, year, edition, pages
John Wiley & Sons, 2013
Keyword
adverse drug reaction, oversupply, pharmacoepidemiology, refill adherence, self-report, therapeutic failure, undersupply
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-99892 (URN)10.1002/pds.3528 (DOI)000327446700010 ()24127242 (PubMedID)
Available from: 2013-10-23 Created: 2013-10-23 Last updated: 2017-12-06

Open Access in DiVA

fulltext(1061 kB)285 downloads
File information
File name FULLTEXT01.pdfFile size 1061 kBChecksum SHA-512
05c8450a679310978aa956438802ea25f46fb031d0f7f9237e5d431ce230571bf2fe4bf98af4741510b95fbe86db479fe1245ff1eb0eae48fb1e1d26397ae4ca
Type fulltextMimetype application/pdf
omslag(20 kB)13 downloads
File information
File name COVER01.pdfFile size 20 kBChecksum SHA-512
9813fff21bb822519709c4f30adeefcbc4f4bcd30aba93e7653f1185fab9cb0bad3875942464dcf610d23e792c80503e5fede5334e22aea95f7b7632012026f9
Type coverMimetype application/pdf

Other links

Publisher's full text

Authority records BETA

Hedna, Khedidja

Search in DiVA

By author/editor
Hedna, Khedidja
By organisation
Division of Drug ResearchFaculty of Medicine and Health Sciences
Pharmaceutical SciencesPublic Health, Global Health, Social Medicine and Epidemiology

Search outside of DiVA

GoogleGoogle Scholar
Total: 285 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
isbn
urn-nbn

Altmetric score

doi
isbn
urn-nbn
Total: 1829 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf