1.
Saulo, Eleonor C., et al.
(author)
Willingness and ability to pay for artemisinin-based combination therapy in rural Tanzania
2008
In: Malaria Journal. - London : BioMed Central. - 1475-2875. ; 7, s. 227-
Journal article (peer-reviewed) abstract
The aim of this study was to analyse willingness to pay (WTP) and ability to pay (ATP) for ACT for children below five years of age in a rural setting in Tanzania before the introduction of artemisinin-based combination therapy (ACT) as first-line treatment for uncomplicated malaria. Socio-economic factors associated with WTP and expectations on anti-malaria drugs, including ACT, were also explored.MethodsStructured interviews and focus group discussions were held with mothers, household heads, health-care workers and village leaders in Ishozi, Gera and Ishunju wards in north-west Tanzania in 2004. Contingent valuation method (CVM) was used with "take-it-or-leave-it" as the eliciting method, expressed as WTP for a full course of ACT for a child and households' opportunity cost of ACT was used to assess ATP. The study included descriptive analyses with multivariate adjustment for potential confounding factors.ResultsAmong 265 mothers and household heads, 244 (92%, CI = 88%–95%) were willing to pay Tanzanian Shillings (TSh) 500 (US$ 0.46) for a child's dose of ACT, but only 55% (49%–61%) were willing to pay more than TSh 500. Mothers were more often willing to pay than male household heads (adjusted odds ratio = 2.1, CI = 1.2–3.6). Socio-economic status had no significant effect on WTP. The median annual non-subsidized ACT cost for clinical malaria episodes in an average household was calculated as US$ 6.0, which would represent 0.9% of the average total consumption expenditures as estimated from official data in 2001. The cost of non-subsidized ACT represented 7.0% of reported total annual expenditure on food and 33.0% of total annual expenditure on health care."Rapid effect," "no adverse effect" and "inexpensive" were the most desired features of an anti-malarial drug.ConclusionWTP for ACT in this study was less than its real cost and a subsidy is, therefore, needed to enable its equitable affordability. The decision taken in Tanzania to subsidize Coartem® fully at governmental health care facilities and at a consumer price of TSh 300–500 (US$ 0.28–0.46) at special designated shops through the programme of Accredited Drug Dispensing Outlets (ADDOs) appears to be well founded.
2.
Di Gennaro, A., et al.
(author)
Cysteinyl leukotriene receptor 1 antagonism prevents experimental abdominal aortic aneurysm
2018
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 115:8, s. 1907-1912
Journal article (peer-reviewed) abstract
Cysteinyl-leukotrienes (cys-LTs) are 5-lipoxygenase-derived lipid mediators involved in the pathogenesis and progression of inflammatory disorders, in particular asthma. We have previously found evidence linking these mediators to increased levels of proteolytic enzymes in tissue specimens of human abdominal aortic aneurysm (AAA). Here we show that antagonism of the CysLT1 receptor by montelukast, an established antiasthma drug, protects against a strong aorta dilatation (>50% increase = aneurysm) in a mouse model of CaCl2-induced AAA at a dose comparable to human medical practice. Analysis of tissue extracts revealed that montelukast reduces the levels of matrix metalloproteinase-9 (MMP-9) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the aortic wall. Furthermore, aneurysm progression was specifically mediated through CysLT1 signaling since a selective CysLT2 antagonist was without effect. A significantly reduced vessel dilatation is also observed when treatment with montelukast is started days after aneurysm induction, suggesting that the drug not only prevents but also stops and possibly reverts an already ongoing degenerative process. Moreover, montelukast reduced the incidence of aortic rupture and attenuated the AAA development in two additional independent models, i.e., angiotensin II- and porcine pancreatic elastase-induced AAA, respectively. Our results indicate that cys-LTs are involved in the pathogenesis of AAA and that antagonism of the CysLT1 receptor is a promising strategy for preventive and therapeutic treatment of this clinically silent and highly lethal disease.
3.
Svedbo Engström, Maria, 1980, et al.
(author)
A disease-specific questionnaire for measuring patient-reported outcomes and experiences in the Swedish National Diabetes Register: Development and evaluation of content validity, face validity, and test-retest reliability
2018
In: Patient Education and Counseling. - : Elsevier BV. - 0738-3991 .- 1873-5134. ; 101:1, s. 139-146
Journal article (peer-reviewed) abstract
Objective: To describe the development and evaluation of the content and face validity and test-retest reliability of a disease-specific questionnaire that measures patient-reported outcomes and experiences for the Swedish National Diabetes Register for adult patients who have type 1 or type 2 diabetes. Methods: In this methodological study, a questionnaire was developed over four phases using an iterative process. Expert reviews and cognitive interviews were conducted to evaluate content and face validity, and a postal survey was administered to evaluate test-retest reliability. Results: The expert reviews and cognitive interviews found the disease-specific questionnaire to be understandable, with relevant content and value for diabetes care. An item-level content validity index ranged from 0.6-1.0 and a scale content validity/average ranged from 0.7-1.0. The fourth version, with 33 items, two main parts and seven dimensions, was answered by 972 adults with type 1 and type 2 diabetes (response rate 61%). Weighted Kappa values ranged from 0.31-0.78 for type 1 diabetes and 0.27-0.74 for type 2 diabetes. Conclusions: This study describes the initial development of a disease-specific questionnaire in conjunction with the NDR. Content and face validity were confirmed and test-retest reliability was satisfactory. Practice implications: With the development of this questionnaire, the NDR becomes a clinical tool that contributes to further understanding the perspectives of adult individuals with diabetes. (c) 2017 Elsevier B.V. All rights reserved.
4.
Nijsingh, Niels, 1977, et al.
(author)
Managing pollution from antibiotics manufacturing: charting actors, incentives and disincentives
2019
In: Environmental health. - : Springer Science and Business Media LLC. - 1476-069X. ; 18
Journal article (peer-reviewed) abstract
Background Emissions of high concentrations of antibiotics from manufacturing sites select for resistant bacteria and may contribute to the emergence of new forms of resistance in pathogens. Many scientists, industry, policy makers and other stakeholders recognize such pollution as an unnecessary and unacceptable risk to global public health. An attempt to assess and reduce such discharges, however, quickly meets with complex realities that need to be understood to identify effective ways to move forward. This paper charts relevant key actor-types, their main stakes and interests, incentives that can motivate them to act to improve the situation, as well as disincentives that may undermine such motivation. Methods The actor types and their respective interests have been identified using research literature, publicly available documents, websites, and the knowledge of the authors. Results Thirty-three different actor-types were identified, representing e.g. commercial actors, public agencies, states and international institutions. These are in complex ways connected by interests that sometimes may conflict and sometimes pull in the same direction. Some actor types can act to create incentives and disincentives for others in this area. Conclusions The analysis demonstrates and clarifies the challenges in addressing industrial emissions of antibiotics, notably the complexity of the relations between different types of actors, their international dependency and the need for transparency. The analysis however also suggests possible ways of initiating incentive-chains to eventually improve the prospects of motivating industry to reduce emissions. High-resource consumer states, especially in multinational cooperation, hold a key position to initiate such chains.
5.
Turanli, Beste, et al.
(author)
Drug Repositioning for Effective Prostate Cancer Treatment
2018
In: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9
Journal article (peer-reviewed) abstract
Drug repositioning has gained attention from both academia and pharmaceutical companies as an auxiliary process to conventional drug discovery. Chemotherapeutic agents have notorious adverse effects that drastically reduce the life quality of cancer patients so drug repositioning is a promising strategy to identify non-cancer drugs which have anti-cancer activity as well as tolerable adverse effects for human health. There are various strategies for discovery and validation of repurposed drugs. In this review, 25 repurposed drug candidates are presented as result of different strategies, 15 of which are already under clinical investigation for treatment of prostate cancer (PCa). To date, zoledronic acid is the only repurposed, clinically used, and approved non-cancer drug for PCa. Anti-cancer activities of existing drugs presented in this review cover diverse and also known mechanisms such as inhibition of mTOR and VEGFR2 signaling, inhibition of PI3K/Akt signaling, COX and selective COX-2 inhibition, NF-kappa B inhibition, Wnt/beta - Catenin pathway inhibition, DNMT1 inhibition, and GSK-3 beta inhibition. In addition to monotherapy option, combination therapy with current anti-cancer drugs may also increase drug efficacy and reduce adverse effects. Thus, drug repositioning may become a key approach for drug discovery in terms of time- and cost-efficiency comparing to conventional drug discovery and development process.
6.
7.
Altay, Özlem, et al.
(author)
Current Status of COVID-19 Therapies and Drug Repositioning Applications
2020
In: Iscience. - : Elsevier BV. - 2589-0042. ; 23:7
Journal article (peer-reviewed) abstract
The rapid and global spread of a new human coronavirus (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19. Drug repositioning is an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. Here, we review current information concerning the global health issue of COVID-19 including promising approved drugs and ongoing clinical trials for prospective treatment options. In addition, we describe computational approaches to be used in drug repurposing and highlight examples of in silico studies of drug development efforts against SARS-CoV-2.
8.
Mohammadi, Elyas, et al.
(author)
Applications of Genome-Wide Screening and Systems Biology Approaches in Drug Repositioning
2020
In: Cancers. - : MDPI AG. - 2072-6694. ; 12:9, s. 1-24
Research review (peer-reviewed) abstract
Simple Summary Drug repurposing is an accelerated route for drug development and a promising approach for finding medications for orphan and common diseases. Here, we compiled databases that comprise both computationally- or experimentally-derived data, and categorized them based on quiddity and origin of data, further focusing on those that present high throughput omic data or drug screens. These databases were then contextualized with genome-wide screening methods such as CRISPR/Cas9 and RNA interference, as well as state of art systems biology approaches that enable systematic characterizations of multi-omic data to find new indications for approved drugs or those that reached the latest phases of clinical trials. Modern drug discovery through de novo drug discovery entails high financial costs, low success rates, and lengthy trial periods. Drug repositioning presents a suitable approach for overcoming these issues by re-evaluating biological targets and modes of action of approved drugs. Coupling high-throughput technologies with genome-wide essentiality screens, network analysis, genome-scale metabolic modeling, and machine learning techniques enables the proposal of new drug-target signatures and uncovers unanticipated modes of action for available drugs. Here, we discuss the current issues associated with drug repositioning in light of curated high-throughput multi-omic databases, genome-wide screening technologies, and their application in systems biology/medicine approaches.
9.
Forslund, Sofia K., et al.
(author)
Combinatorial, additive and dose-dependent drug–microbiome associations
2021
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 600:7889, s. 500-505
Journal article (peer-reviewed) abstract
During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1–5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug–host–microbiome interactions in cardiometabolic disease.
10.
11.
Sjölander, Maria, 1970-
(author)
Use of secondary preventive drugs after stroke
2013
Doctoral thesis (other academic/artistic) abstract
Background Stroke is a serious condition that can have significant impact on an individual’s health and is a significant burden on public health and public finances. Secondary preventive drug treatment after stroke is important for decreasing the risk of recurrent strokes. Non-adherence to drug treatment hampers the treatment effect, especially in long-term preventive treatments. The aim of this thesis was to study the use of secondary preventive drugs after stroke among Swedish stroke patients in terms of inequalities in implementation in clinical practice and patient adherence to treatment over time.Methods Riks-Stroke, the Swedish stroke register, was used to sample stroke patients and as a source of information on background characteristics and medical and health care-related information including information on prescribed preventive drugs. The patients that were included had a stroke between 2004 and 2012. Individual patient data on prescriptions filled in Swedish pharmacies were retrieved from the Swedish Prescribed Drug Register and used to estimate patient adherence to drug treatment. Data on education, income, and country of birth were included from the LISA database at Statistics Sweden. A questionnaire survey was used to collect information about patients’ perceptions about stroke, beliefs about medicines, and self-reported adherence.Results Results showed that a larger proportion of men than women were prescribed statins and warfarin after stroke. There was also a social stratification in the prescribing of statins. Patients with higher income and a higher level of education were more likely to be prescribed a statin compared to patients with low income and low level of education. Statins were also more often prescribed to patients born in Nordic countries, Europe, or outside of Europe compared to patients born in Sweden. Primary non-adherence (not continuing treatment at all within 4 months of discharge from hospital) was low for preventive drug treatment after stroke. Data on filled prescriptions, however, indicated that the proportion of patients who continued to use the drugs declined during the first 2 years after stroke. For most drugs, refill adherence in drug treatment was associated with female sex, good self-rated health, and living in institutions and (for antihypertensive drugs and statins) having used the drug before the stroke. For statins and warfarin, a first-ever stroke was also associated with continuous drug use. Self-reported adherence 3 months after stroke also showed associations with patients’ personal beliefs about medicines; non-adherent patients scored higher on negative beliefs and lower on positive beliefs about medicines.Conclusion Inequalities between men and women and between different socioeconomic groups were found in the prescribing of secondary preventive drugs after stroke. Only a small proportion of Swedish stroke patients did not continue treatment after discharge from hospital, but the proportion of non-adherent patients increased over time. Poor adherence to preventive drug treatment after stroke is a public health problem, and improving adherence to drug treatment requires consideration of patients’ personal beliefs and perceptions about drugs.
12.
Centanni, Maddalena, 1994-
(author)
Model-based evaluation of biomarkers for dose-individualization in oncology
2024
Doctoral thesis (other academic/artistic) abstract
In contemporary cancer care, several issues are garnering increasing attention. First, significant inter-individual variability among patients challenges the effectiveness of a uniform dosing approach. Second, the escalating costs of treatments necessitate careful consideration when selecting doses and other clinical modalities, including biomarkers, while balancing economic constraints. The objective of this thesis was to evaluate techniques for tailoring doses and guiding clinical decisions for cancer patients through the development and implementation of various models, with the aim of improving treatment outcomes in terms of both efficacy and safety. Through a model-based framework integrating sunitinib pharmacokinetics (PK), adverse events, biomarkers, tumor dynamics and their correlation with overall survival, different treatment schedules and biomarkers for dose individualization were explored. Based on the proposed threshold values, neutrophil count (ANC) and the biomarker sVEGFR-3 were identified as offering the best balance between safety and efficacy for sunitinib in gastro-intestinal stromal tumors (GIST) and could thus serve as viable guides for dose individualization in clinical practice. Given its routine measurement, dose adjustments guided by ANC may be preferable in clinical settings. The feasibility of utilizing diastolic blood pressure (dBP) for personalized dose optimization of tyrosine-kinase inhibitors in clinical settings is constrained due to its reliance on repeated measurements taken at consistent intervals. For axitinib and sunitinib, model-based predictions using multiple clinical measurements were more accurate than single sample measurements. For drugs with high unexplained inter-individual variability (IIV), low residual variability (RUV), and low inter-occasional variability (IOV), therapeutic drug monitoring (TDM) provided a more accurate measure of exposure. Conversely, for drugs with low IIV and high RUV and IOV, pharmacogenetic profiling was more suitable. However, the prevalence of pharmacogenetic subtypes and the challenge of measuring exposure metrics like AUC through limited sampling also influence these approaches.This research further emphasizes how model structure affects the outcomes of cost-effectiveness analyses and consequently the potential implications for regulatory decisions. Although creating mechanistic models for these analyses demands substantial initial effort, the growing need for model-based analyses in drug approval is likely to make these models more accessible for future compounds. Moreover, such models are expected to be more biologically plausible and therefore more reflective of reality and offer flexibility for exploring alternative dosages with limited additional effort.Using model-based assessments, the relationship between the PK and PK-pharmacodynamic (PKPD) profiles of adverse events arising from therapies for acute lymphocytic leukemia were established. For PEG-asparaginase, the PK model categorized 93% of patients who experienced inactivation against PEG-asparaginase as having an increased clearance, and 86% of patients who did not experience hypersensitivity as maintaining stable clearance throughout their asparaginase treatment. This approach marks a potential method for predicting inactivation by identifying early changes in clearance. For vincristine, model-informed precision dosing was shown to reduce the incidence of vincristine-induced peripheral neuropathy (VIPN) from 62.1% to 53.9%, though the clinical impact remains modest.
13.
Malmqvist, Erik, et al.
(author)
Pharmaceutical Pollution from Human use and the Polluter Pays Principle
2023
In: Public Health Ethics. - 1754-9973 .- 1754-9981. ; 16:2, s. 152-164
Journal article (peer-reviewed) abstract
Human consumption of pharmaceuticals often leads to environmental release of residues via urine and faeces, creating environmental and public health risks. Policy responses must consider the normative question how responsibilities for managing such risks, and costs and burdens associated with that management, should be distributed between actors. Recently, the Polluter Pays Principle (PPP) has been advanced as rationale for such distribution. While recognizing some advantages of PPP, we highlight important ethical and practical limitations with applying it in this context: PPP gives ambiguous and arbitrary guidance due to difficulties in identifying the salient polluter. Moreover, when PPP does identify responsible actors, these may be unable to avoid or mitigate their contribution to the pollution, only able to avoid/mitigate it at excessive cost to themselves or others, or excusably ignorant of contributing. These limitations motivate a hybrid framework where PPP, which emphasizes holding those causing large-scale problems accountable, is balanced by the Ability to Pay Principle (APP), which emphasizes efficiently managing such problems. In this framework, improving wastewater treatment and distributing associated financial costs across water consumers or taxpayers stand out as promising responses to pharmaceutical pollution from human use. However, sound policy depends on empirical considerations requiring further study.
14.
Lesén, Eva, 1982, et al.
(author)
Is the level of patient co-payment for medicines associated with refill adherence in Sweden?
2014
In: European Journal of Public Health. - : Oxford University Press (OUP). - 1101-1262 .- 1464-360X. ; 24:1, s. 85-90
Journal article (peer-reviewed) abstract
In the Swedish reimbursement scheme, the co-payment is based on the price of the product and decreases in a stepwise manner as the total accumulated co-payment increases. The aim of this study was to analyse how refill adherence in Sweden varies according to patient's co-payment level for medicines, with antiepileptic drug (AED) use as an example.
15.
Bjerkeli, Pernilla J., et al.
(author)
Overuse of methylphenidate : an analysis of Swedish pharmacy dispensing data
2018
In: Clinical Epidemiology. - : Dove Press. - 1179-1349. ; 10, s. 1657-1665
Journal article (peer-reviewed) abstract
Purpose: To identify overuse of methylphenidate and to investigate patterns of overuse in relation to sociodemographic and clinical characteristics. Patients and methods: Swedish national, pharmacy dispensing data were analyzed for all 56,922 individuals aged 6-79 years, who filled a methylphenidate prescription between 2010 and 2011. Overuse was defined as having above 150% days covered by the dispensed amount during 365 days from the first prescription fill, assuming use at the maximum recommended daily dose. Results: In total, 4,304 individuals (7.6% of the methylphenidate users) were categorized as overusers. The risk of overuse increased with age (OR for 46-65 years vs 6-12 years 17.5, 95% CI 14.3-21.3), and was higher in men (OR 1.4, 95% CI 1.3-1.5) and individuals with low income (OR 1.1, 95% CI 1.0-1.2), as well as in individuals with an attention deficit hyperactivity disorder (ADHD) diagnosis (OR 1.4, 95% CI 1.3-1.6), health care visits (OR 1.3, 95% CI 1.2-1.4), previous ADHD medication use (OR 2.6, 95% CI 2.4-2.8), and previous diagnosis of mental and behavioral disorders due to psychoactive substance use (OR 2.1 95% CI 2.0-2.3). Conclusion: Among individuals using methylphenidate in Sweden, 7.6% receive amounts that are larger than what they should have a medical need for, assuming that they were using the maximum recommended daily dose 365 days per year. Notably, the prevalence of overuse was associated with previous diagnosis of alcohol and drug misuse. The prevalence was also positively associated with higher age and previous use of ADHD medication. These findings may point toward a link between exposure time and overuse. However, future studies with long-term data are needed to investigate this.
16.
Lin, Chung-Ying, et al.
(author)
Validation of the 5-Item Medication Adherence Report Scale in Older Stroke Patients in Iran
2018
In: Journal of Cardiovascular Nursing. - : Lippincott Williams & Wilkins. - 0889-4655 .- 1550-5049. ; 33:6, s. 536-543
Journal article (peer-reviewed) abstract
Background: There is a lack of feasible and validated measures to self-assess medication adherence for older patients with stroke. In addition, the potential determinants of medication adherence for older patients with stroke remain unclear. Objectives: The aims of this study were to (1) examine the psychometric properties of a 5-item questionnaire on medication adherence, specifically the 5-item Medication Adherence Report Scale (MARS-5), and (2) explore the determinants of medication adherence. Methods: Stroke patients older than 65 years (N = 523) filled out the MARS-5 and the Hospital Anxiety and Depression Scale. The medication possession rate (MPR) was calculated to measure the objective medication adherence. Several clinical characteristics (stroke types, blood pressure, comorbidity, HbA1c, quantity of prescribed drugs, fasting blood glucose, and total cholesterol) and background information were collected. We used Rasch analysis with a differential item functioning test to examine psychometric properties. Results: All 5 items in the MARS-5 fit in the same construct (ie, medication adherence), no differential item functioning items were displayed in the MARS-5 across gender, and the MARS-5 total score was strongly correlated with the MPR (r = 0.7). Multiple regression models showed that the MARS-5 and the MPR shared several similar determinants. In addition, the variance of the MARS-5 (R-2 = 0.567) was more than that of the MPR (R-2 = 0.300). Conclusions: The MARS-5 is a feasible and valid self-assessed medication adherence for older patients with stroke. In addition, several determinants were found to be related to medication adherence for older patients with stroke. Healthcare providers may want to take heed of these determinants to improve medication adherence for this population.
17.
Alin, Rebecca, 1989, et al.
(author)
A Preparatory Study for a Randomized Controlled Trial of Dietary Fiber Intake During Adult Pelvic Radiotherapy
2021
In: Frontiers in Nutrition. - : Frontiers Media SA. - 2296-861X. ; 8
Journal article (peer-reviewed) abstract
Background: Patients undergoing pelvic radiotherapy are often advised to omit fiber-rich foods from their diet to reduce the adverse effects of treatment. Scientific evidence supporting this recommendation is lacking, and recent studies on animals and humans have suggested that there is a beneficial effect of dietary fiber for the alleviation of symptoms. Randomized controlled studies on dietary fiber intake during pelvic radiotherapy of sufficient size and duration are needed. As preparation for such a large-scale study, we evaluated the feasibility, compliance, participation rate, and logistics and report our findings here in this preparatory study. Methods: In this preparatory study of a fiber intervention trial, Swedish gynecological cancer patients scheduled for radiotherapy were recruited between January 2019 and August 2020. During the intervention, the participants filled out questionnaires and used an application. They also consumed a fiber supplement at first in powder form, later in capsules. Blood- and fecal samples were collected. The study is registered in clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT04534075?cond=fidura&draw=2&rank=1). Results: Among 136 approached patients, 57 started the study and the participation rate for primary outcomes was 63% (third blood sample) and 65% (third questionnaire). Barely half of the participants provided fecal samples. Providing concise and relevant information to the patients at the right time was crucial in getting them to participate and stay in the study. The most common reasons for declining participation or dropping out were the expected burden of radiotherapy or acute side effects. Tailoring the ambition level to each patient concerning the collection of data beyond the primary endpoints was an important strategy to keep the dropout rate at an acceptable level. Using capsules rather than psyllium in powder form made it much easier to document intake and to create a control group. During the course of the preparatory study, we improved the logistics and for the last 12 participants included, the participation rate was 100% for the earliest primary outcome. Conclusion: A variety of adjustments in this preparatory study resulted in an improved participation rate, which allowed us to set a final protocol and proceed with the main study.
18.
19.
Lindblad, Marléne, 1963-, et al.
(author)
Identifying no-harm incidents in home healthcare : a cohort study using trigger tool methodology
2020
In: BMC Health Services Research. - : Springer. - 1472-6963. ; 20:1, s. 1-11
Journal article (peer-reviewed) abstract
BackgroundPatient safety in home healthcare is largely unexplored. No-harm incidents may give valuable information about risk areas and system failures as a source for proactive patient safety work. We hypothesized that it would be feasible to retrospectively identify no-harm incidents and thus aimed to explore the cumulative incidence, preventability, types, and potential contributing causes of no-harm incidents that affected adult patients admitted to home healthcare.MethodsA structured retrospective record review using a trigger tool designed for home healthcare. A random sample of 600 home healthcare records from ten different organizations across Sweden was reviewed.ResultsIn the study, 40,735 days were reviewed. In all, 313 no-harm incidents affected 177 (29.5%) patients; of these, 198 (63.2%) no-harm incidents, in 127 (21.2%) patients, were considered preventable. The most common no-harm incident types were “fall without harm,” “deficiencies in medication management,” and “moderate pain.” The type “deficiencies in medication management” was deemed to have a preventability rate twice as high as those of “fall without harm” and “moderate pain.” The most common potential contributing cause was “deficiencies in nursing care and treatment, i.e., delayed, erroneous, omitted or incomplete treatment or care.”ConclusionThis study suggests that it is feasible to identify no-harm incidents and potential contributing causes such as omission of care using record review with a trigger tool adapted to the context. No-harm incidents and potential contributing causes are valuable sources of knowledge for improving patient safety, as they highlight system failures and indicate risks before an adverse event reach the patient.
20.
Håkansson, Samuel, 1996, et al.
(author)
Potential for improved retention rate by personalized antiseizure medication selection: A register-based analysis
2021
In: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 62:9, s. 2123-2132
Journal article (peer-reviewed) abstract
Objective The first antiseizure medication (ASM) is ineffective or intolerable in 50% of epilepsy cases. Selection between more than 25 available ASMs is guided by epilepsy factors, but also age and comorbidities. Randomized evidence for particular patient subgroups is seldom available. We asked whether register data could be used for retention rate calculations based on demographics, comorbidities, and ASM history, and quantified the potential improvement in retention rates of the first ASM in several large epilepsy cohorts. We also describe retention rates in patients with epilepsy after traumatic brain injury and dementia, patient groups with little available evidence. Methods We used medical, demographic, and drug prescription data from epilepsy cohorts from comprehensive Swedish registers, containing 6380 observations. By analyzing 381 840 prescriptions, we studied retention rates of first- and second-line ASMs for patients with epilepsy in multiple sclerosis (MS), brain infection, dementia, traumatic brain injury, or stroke. The rank of retention rates of ASMs was validated by comparison to published randomized control trials. We identified the optimal stratification for each brain disease, and quantified the potential improvement if all patients had received the optimal ASM. Results Using optimal stratification for each brain disease, the potential improvement in retention rate (percentage points) was MS, 20%; brain infection, 21%; dementia, 14%; trauma, 21%; and stroke, 14%. In epilepsy after trauma, levetiracetam had the highest retention rate at 80% (95% confidence interval [CI] = 65-89), exceeding that of the most commonly prescribed ASM, carbamazepine (p = .04). In epilepsy after dementia, lamotrigine (77%, 95% CI = 68-84) and levetiracetam (74%, 95% CI = 68-79) had higher retention rates than carbamazepine (p = .006 and p = .01, respectively). Significance We conclude that personalized ASM selection could improve retention rates and that national registers have potential as big data sources for personalized medicine in epilepsy.
21.
Svensson, Staffan, 1972
(author)
Medication adherence, side effects and patient-physician interaction in hypertension
2006
Doctoral thesis (other academic/artistic) abstract
Hypertension is an important risk factor for cardiovascular disease, the incidence of which it is possible to reduce by prophylactic treatment with antihypertensive drugs. In clinical practice, however, only a minority of patients reach target blood pressure levels. The resulting gap between actual and potential health gains has been attributed to the fact that many patients do not take prescribed treatment as recommended, i.e. ”medication non-adherence”. This phenomenon is, however, insufficiently understood. We investigated the topic of adherence by way of a randomised questionnaire material comprising 1013 patients, and audio-recordings of 51 patient-physician consultations and 33 interviews with the patients made after the consultations. All patients came for regular follow-up appointments with their physicians and were under treatment with antihypertensives. In the questionnaire material, we found that patients who reported side effects of their drugs tended to rate their future risk of cardiovascular complications as being higher. Analysis of the interview data showed that patients had various reasons for sticking to the treatment recommendations: trust in physicians and wanting to avoid sequelae of hypertension were common arguments for doing so, while having side effects and disliking pharmaceuticals in general were reasons against. In the follow-up appointments, we found that the determinants of treatment decisions, i.e. the measured blood pressure values and (suspected) side effects, were defined through negotiation between patients and physicians. On the whole, patients and physicians were more in agreement about the interpretation of blood pressure values than of side effects, and physicians had the last say in the decision-making. We concluded that the antecedents of decisions about using medication are surrounded by uncertainty, and that it is the patient's interpretation of the ”facts” that, ultimately, determines if and how antihypertensive medications will be taken.
22.
Krigsman, Kristin, et al.
(author)
Refill non-adherence to repeat prescriptions leads to treatment gaps or to high extra costs.
2007
In: Pharmacy World & Science. - : Springer Netherlands. - 0928-1231 .- 1573-739X. ; 29:1, s. 19-24
Journal article (peer-reviewed) abstract
OBJECTIVE: To determine the nature and extent of undersupply and the economic consequences of oversupply of medication among non-adherent patients. METHODS: This study used copies of repeat prescriptions (= multiple dispensations), collected during 1 week in 2002 at 16 Swedish community pharmacies. For patients with a refill adherence below 80%, treatment gaps were defined as the number of days they had no drug available. The cost of drug oversupply (i.e., refill adherence > 120%) was calculated from the prices of the drug packages dispensed. RESULTS: The number of collected repeat prescriptions was 3,636. The median of treatment gaps among patients with a refill adherence below 80% was 53 days per 90-100 days treatment period and the corresponding median for oversupply was 40 days. The cost of oversupply for exempt patients (i.e., patients who have paid 1,800 SEK (Euro 196; US$ 243) per year for medicines) was 32,000 SEK (Euro 3,500; US$ 4,300) higher than for non-exempt patients. An extrapolation to all Sweden indicates that exemption from charges leads to an additional oversupply of about 142 million SEK (Euro 15 million; US$ 19 million) per year above that of non-exempt patients. CONCLUSION: Both undersupply and oversupply of prescribed medicines are common in Sweden. Patients with a refill adherence below 80% seem to have less than half of the prescribed treatment available. Oversupply or drug stockpiling occurs more frequently among exempt than among non-exempt patients, and this oversupply leads to high unnecessary costs.
23.
Miller, Frank, et al.
(author)
A decision theoretical modeling for Phase III investments and drug licensing
2018
In: Journal of Biopharmaceutical Statistics. - : Informa UK Limited. - 1054-3406 .- 1520-5711. ; 28:4, s. 698-721
Journal article (peer-reviewed) abstract
For a new candidate drug to become an approved medicine, several decision points have to be passed. In this article, we focus on two of them: First, based on Phase II data, the commercial sponsor decides to invest (or not) in Phase III. Second, based on the outcome of Phase III, the regulator determines whether the drug should be granted market access. Assuming a population of candidate drugs with a distribution of true efficacy, we optimize the two stakeholders' decisions and study the interdependence between them. The regulator is assumed to seek to optimize the total public health benefit resulting from the efficacy of the drug and a safety penalty. In optimizing the regulatory rules, in terms of minimal required sample size and the Type I error in Phase III, we have to consider how these rules will modify the commercial optimization made by the sponsor. The results indicate that different Type I errors should be used depending on the rarity of the disease.
24.
Tjäderborn, Micaela, 1983-
(author)
Psychoactive prescription drug use disorders, misuse and abuse : Pharmacoepidemiological aspects
2016
Doctoral thesis (other academic/artistic) abstract
Background: There is a widespread and increasing use of psychoactive prescription drugs, such as opioid analgesics, anxiolytics, hypnotics and anti-epileptics, but their use is associated with a risk of drug use disorder, misuse and abuse. Today, these are globally recognized and emerging public health concerns.Aim: The aim of this thesis is to estimate the prevalence of psychoactive prescription drug (PPD) use disorders, misuse and abuse, and to investigate the association with some potential risk factors.Methods: A study using register data from forensic cause of death investigations investigated and described cases of fatal unintentional intoxication with tramadol (Study I). Based on register data on spontaneously reported adverse drug reactions (ADRs) reported cases of tramadol dependence were investigated and summarised (Study II). In a study in suspected drug-impaired drivers with a toxicology analysis confirming the intake of one out of five pre-specified PPDs, the prevalence of non-prescribed use was assessed and associated factors were investigated (Study III). From a cohort of patients initiating prescribed treatment with pregabalin, using data on prescription fills, a study investigated longitudinal utilisation patterns during five years with regards to use of the drug above the maximum approved daily dose (MAD), and factors associated with the utilisation patterns (Study IV).Results: In the first study, 17 cases of unintentional intoxications were identified, of which more concerned men, the median age was 44 years and the majority used multiple psychoactive substances (alcohol, illicit drugs and prescription drugs). The second study identified 104 spontaneously reported cases of tramadol dependence, in which more concerned women, the median age was 45 years, and a third reported a history of substance abuse and 40% of past psychoactive medication use. In the third study, more than half of the individuals suspected of drug-impaired driving used the drug without a recent prescription. Non prescribed use was most frequent in users of benzodiazepines and tramadol, and was more likely in younger individuals and in multiple-substance users. In the last paper five longitudinal utilisation patterns were found in pregabalin users, with two patterns associated with a particularly high risk of doses above the maximum approved dosing recommendation. This pattern of use was associated with male sex, younger age, non-urban residency and a recent prescribed treatment with an antiepileptic or opioid analgesic drug.Conclusions: This thesis shows that psychoactive prescription drug use disorders, misuse and abuse occur and may have serious and even fatal consequences. The prevalence varies between different drugs and populations. Abuse and misuse seem to be more common in young people. Fatal intoxications and misuse of prescribed drugs may be more common in men, while drug use disorders following prescribed treatment may be more common in women and non-prescribed use equally distributed between women and men. Individuals with a history of mental illness, substance use disorder or abuse, or of past use of psychoactive medications are likely important risk groups. In summary, the findings suggest a potential for improvements in the utilisation of psychoactive prescription drugs. The results may be useful in the planning of clinical and regulatory preventive interventions to promote the rational, individualised and safe use of such drugs.
25.
Xin, D. L., et al.
(author)
Effectiveness of conservative interventions for sickness and pain behaviors induced by a high repetition high force upper extremity task
2017
In: BMC Neuroscience. - : BioMed Central. - 1471-2202. ; 18
Journal article (peer-reviewed) abstract
Background: Systemic inflammation is known to induce sickness behaviors, including decreased social interaction and pain. We have reported increased serum inflammatory cytokines in a rat model of repetitive strain injury (rats perform an upper extremity reaching task for prolonged periods). Here, we sought to determine if sickness behaviors are induced in this model and the effectiveness of conservative treatments.Methods: Experimental rats underwent initial training to learn a high force reaching task (10 min/day, 5 days/week for 6 weeks), with or without ibuprofen treatment (TRHF vs. TRHF + IBU rats). Subsets of trained animals went on to perform a high repetition high force (HRHF) task for 6 or 12 weeks (2 h/day, 3 days/week) without treatment, or received two secondary interventions: ibuprofen (HRHF + IBU) or a move to a lower demand low repetition low force task (HRHF-to-LRLF), beginning in task week 5. Mixed-effects models with repeated measures assays were used to assay duration of social interaction, aggression, forepaw withdrawal thresholds and reach performance abilities. One-way and two-way ANOVAs were used to assay tissue responses. Corrections for multiple comparisons were made.Results: TRHF + IBU rats did not develop behavioral declines or systemic increases in IL-1beta and IL-6, observed in untreated TRHF rats. Untreated HRHF rats showed social interaction declines, difficulties performing the operant task and forepaw mechanical allodynia. Untreated HRHF rats also had increased serum levels of several inflammatory cytokines and chemokines, neuroinflammatory responses (e.g., increased TNFalpha) in the brain, median nerve and spinal cord, and Substance P and neurokinin 1 immunoexpression in the spinal cord. HRHF + IBU and HRHF-to-LRLF rats showed improved social interaction and reduced inflammatory serum, nerve and brain changes. However, neither secondary treatment rescued HRHF-task induced forepaw allodynia, or completely attenuated task performance declines or spinal cord responses.Conclusions: These results suggest that inflammatory mechanisms induced by prolonged performance of high physical demand tasks mediate the development of social interaction declines and aggression. However, persistent spinal cord sensitization was associated with persistent behavioral indices of discomfort, despite use of conservative secondary interventions indicating the need for prevention or more effective interventions.
26.
Nijsingh, Niels, 1977, et al.
(author)
Justifying Antibiotic Resistance Interventions: Uncertainty, Precaution and Ethics
2020
In: Jamrozik E., Selgelid M.J. (eds) Ethics and Drug-Resistance: Collective Responsibility for Global Public Health. - Cham, Switzerland : Springer. - 2211-6680. - 9783030278731
Book chapter (peer-reviewed) abstract
This chapter charts and critically analyses the ethical challenge of assessing how much (and what kind of) evidence is required for the justification of interventions in response antibiotic resistance (ABR), as well as other major public health threats. Our ambition here is to identify and briefly discuss main issues, and point to ways in which these need to be further advanced in future research. This will result in a tentative map of complications, underlying problems and possible challenges. This map illustrates that the ethical challenges in this area are much more complex and profound than is usually acknowledged, leaving no tentatively plausible intervention package free of downsides. This creates potentially overwhelming theoretical conundrums when trying to justify what to do. We therefore end by pointing out two general features of the complexity we find to be of particular importance, and a tentative suggestion for how to create a theoretical basis for further analysis.
27.
Pestoff, Rebecka, et al.
(author)
Genetic counsellors in Sweden : their role and added value in the clinical setting.
2016
In: European Journal of Human Genetics. - : Nature Publishing Group. - 1018-4813 .- 1476-5438. ; 24:3, s. 350-355
Journal article (peer-reviewed) abstract
Genetic testing is becoming more commonplace in general and specialist health care and should always be accompanied by genetic counselling, according to Swedish law. Genetic counsellors are members of the multi-disciplinary team providing genetic counselling. This study examined the role and added value of genetic counsellors in Sweden, using a cross-sectional on-line survey. The findings showed that the genetic counsellors added value in the clinical setting by acting as the 'spider-in-the-web' regarding case management, having a more holistic, ethical and psychological perspective, being able to offer continuous support and build a relationship with the patient, and being more accessible than medical geneticists. The main difference between a genetic counsellor and medical geneticist was that the doctor had the main medical responsibility. Thus genetic counsellors in Sweden contribute substantially to the care of patients in the clinical genetic setting.
28.
Tyrberg, Erika, et al.
(author)
Higher plasma drug levels in elderly people living with HIV treated with darunavir
2021
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:2
Journal article (peer-reviewed) abstract
Background The proportion of elderly people living with HIV-1 (PLHIV) is rising. In older patients, comorbidities and concomitant medications are more frequent, increasing the risk of potential drug-drug interactions (PDDIs). Data on the pharmacokinetics of ART in individuals aged >= 65 years of age are scarce. We compared plasma drug levels of ART, PDDIs, and side-effects in PLHIV aged >= 65 years of age, with controls <= 49 years of age. Methods Patients >= 65 years of age and controls <= 49 years of age, all of whom were on stable treatment with atazanavir (ATV), darunavir (DRV), or efavirenz (EFV) were included cross-sectionally. Plasma drug levels of ART were analyzed, comorbidities, concomitant medication, adherence, and side-effects recorded, and PDDIs analyzed using drug interactions databases. Results Between 2013 and 2015, we included 100 individuals >= 65 years of age (study group) and 99 controls (<= 49 years of age). Steady-state DRV concentrations were significantly higher in the study group than in the control group (p = 0.047). In the ATV group there was a trend towards a significant difference (p = 0.056). No significant differences were found in the EFV arm. The DRV arm had a higher frequency of reported side-effects than the ATV and EFV arms in the study group (36.7% vs. 0% and 23.8% respectively (p = 0.014), with significant differences between DRV vs. ATV, and EFV vs. ATV). Conclusions Higher steady-state plasma levels of DRV and ATV (but not EFV) were found in PLHIV aged >= 65 years of age, compared to controls <= 49 years of age.
29.
Ekqvist, David, et al.
(author)
Safety and pharmacokinetics-pharmacodynamics of a shorter tuberculosis treatment with high-dose pyrazinamide and rifampicin : a study protocol of a phase II clinical trial (HighShort-RP)
2022
In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:3
Journal article (peer-reviewed) abstract
Introduction: Increased dosing of rifampicin and pyrazinamide seems a viable strategy to shorten treatment and prevent relapse of drug-susceptible tuberculosis (TB), but safety and efficacy remains to be confirmed. This clinical trial aims to explore safety and pharmacokinetics-pharmacodynamics of a high-dose pyrazinamide-rifampicin regimen.Methods and analysis: Adult patients with pulmonary TB admitted to six hospitals in Sweden and subjected to receive first-line treatment are included. Patients are randomised (1:3) to either 6-month standardised TB treatment or a 4-month regimen based on high-dose pyrazinamide (40 mg/kg) and rifampicin (35 mg/kg) along with standard doses of isoniazid and ethambutol. Plasma samples for measurement of drug exposure determined by liquid chromatography tandem-mass spectrometry are obtained at 0, 1, 2, 4, 6, 8, 12 and 24 hours, at day 1 and 14. Maximal drug concentration (C-max) and area under the concentration-time curve (AUC(0-24h)) are estimated by non-compartmental analysis. Conditions for early model-informed precision dosing of high-dose pyrazinamide-rifampicin are pharmacometrically explored. Adverse drug effects are monitored throughout the study and graded according to Common Terminology Criteria for Adverse Events V.5.0. Early bactericidal activity is assessed by time to positivity in BACTEC MGIT 960 of induced sputum collected at day 0, 5, 8, 15 and week 8. Minimum inhibitory concentrations of first-line drugs are determined using broth microdilution. Disease severity is assessed with X-ray grading and a validated clinical scoring tool (TBscore II). Clinical outcome is registered according to WHO definitions (2020) in addition to occurrence of relapse after end of treatment. Primary endpoint is pyrazinamide AUC(0-24h) and main secondary endpoint is safety.Ethics and dissemination: The study is approved by the Swedish Ethical Review Authority and the Swedish Medical Products Agency. Informed written consent is collected before study enrolment. The study results will be submitted to a peer-reviewed journal.
30.
Svensberg, Karin, et al.
(author)
Nordic Pharmacy Students' Opinions of their Patient Communication Skills Training
2018
In: American Journal of Pharmaceutical Education. - : American Association of Colleges of Pharmacy (AACP). - 0002-9459 .- 1553-6467. ; 82:2, s. 152-165
Journal article (peer-reviewed) abstract
Objective. To describe Nordic pharmacy students' opinions of their patient communication skills training (PCST), and the association between course leaders' reports of PCST qualities and students' perceptions of their training. Secondary objective was to determine what factors influence these associations. Methods. A cross-sectional questionnaire-based study was performed. The various curricula were categorized into three types (basic, intermediate and innovative training) and students were divided into three groups according to the type of training they had received. Multivariable logistic regression models were fitted with different opinions as outcomes and three types of training as exposure, using generalized estimation equations. Results. There were 370 students who responded (response rate: 77%). Students within the innovative group were significantly more likely to agree that they had received sufficient training, and to agree with the assertion that the pharmacy school had contributed to their level of skills compared to students in the basic group. Conclusion. There appears to be an association between larger and varied programs of training in patient communication skills and positive attitudes toward this training on the part of the students, with students reporting that they received sufficient training, which likely enhanced their skills.
31.
Andersson Sundell, Karolina, 1978, et al.
(author)
Factors associated with switching and combination use of antidepressants in young Swedish adults.
2013
In: International journal of clinical practice. - : Hindawi Limited. - 1742-1241 .- 1368-5031. ; 67:12, s. 1302-10
Journal article (peer-reviewed) abstract
Little is known on factors associated with switching and combination use of antidepressants. Our aim was to describe such use and to analyse the association with socioeconomic factors and level of care in Swedish adults aged 20-34years.
32.
Qvarnström, Miriam, et al.
(author)
Medication persistence to antihypertensive drug treatment : a cross-sectional study of attitudes towards hypertension and medication in persistent and non-persistent patients
2019
In: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 28:5, s. 309-316
Journal article (peer-reviewed) abstract
Purpose: To study the differences in attitudes towards hypertension and drug treatment between patients persistent and non-persistent to antihypertensive drug treatment.Materials and methods: Cross-sectional study on patients with hypertension treated at 25 primary healthcare centres in Stockholm, Sweden. Questionnaires were sent to the patients 3-12 months after initiation of antihypertensive drug treatment. Persistent medication users, defined as patients with less than 30 days without tablet supply between prescription refills, were compared with non-persistent users by scores from Likert scales: Brief-Illness Perception Questionnaire (Brief IPQ, 0-10) and Beliefs about Medicines Questionnaire (BMQ General, 4-20 and BMQ Specific, 5-25).Results: A total of 711 patients were included in the final analyses (mean age: 62 years; 50% women), of whom 609 (86%) were classified as persistent and 102 (14%) as non-persistent by analyses of their filled prescriptions. Likert scales from the Brief-IPQ showed (all p<0.02) that persistent patients believed that hypertension was a chronic condition (median 6 vs. 4), that hypertension had less consequences on their life (median 2 vs. 3) and that they can prevent cardiovascular disease by taking antihypertensive treatment (median 7 vs. 5). Likert scales from the BMQ General showed (all p<0.02) that persistent patients believed that there are potential benefits from taking the treatment (median 16 vs. 16), and they did not believe that the doctors put too much trust in drugs (median 12 vs. 13). Further, results from the BMQ Specific showed that they believed that the antihypertensive drugs are necessary for them in order to maintain or improve their own health (median 17 vs. 16).Conclusions: Primary healthcare providers should further emphasize the chronicity of hypertension diagnosis and the benefits of treatment, to improve the patients' medication persistence to antihypertensive treatment.
33.
Ekedahl, Anders, et al.
(author)
Impact of postal and telephone reminders on pick-up rates of unclaimed e-prescriptions.
2008
In: Pharmacy World & Science. - : Springer Netherlands. - 0928-1231 .- 1573-739X. ; 30:5, s. 503-508
Journal article (peer-reviewed) abstract
OBJECTIVE: To investigate the impact of a reminder (i.e., a mailed letter or short telephone call) from the pharmacy to patients, compared with no reminder in a control group, on the pick-up rates of unclaimed e-prescriptions. METHOD: Patients, with e-prescriptions transmitted to four large community pharmacies in two counties in northern Sweden and remaining unclaimed after 4 weekdays, were randomised to one of two intervention groups (a mailed reminder or a short telephonic reminder) or a control group. MAIN OUTCOME MEASURES: Rates of patients' pick-up of their e-prescriptions at follow-up after about 1, 2 and 3 weeks. RESULTS: Altogether, 320 patients with e-prescriptions, transmitted from March 21 through April 6 and not picked-up or dispensed, were identified and randomised to the study. There were no statistically significant differences in overall pick-up rates between the groups or with respect to gender. However, pick-up rates increased with increasing age. Higher pick-up rates were observed for two subgroups (but only in the mailed reminder group compared with controls)--for cardiovascular drugs to men and for respiratory drugs to adolescents and young adults. CONCLUSION: A reminder (i.e., a mailed letter or short telephone call) from the pharmacy to the patient had no statistically significant effect on overall pick-up rates of unclaimed e-prescriptions compared with no reminders.
34.
Canevelli, Marco, et al.
(author)
Race reporting and disparities in clinical trials on Alzheimer's disease : A systematic review
2019
In: Neuroscience and Biobehavioral Reviews. - : Elsevier BV. - 0149-7634 .- 1873-7528. ; 101, s. 122-128
Research review (peer-reviewed) abstract
Introduction: Race is an important health determinant and should adequately be considered in research and drug development protocols targeting Alzheimer's disease (AD).Methods: A systematic review of available randomized controlled trials (RCTs) on the currently marketed treatments for AD was conducted with the aim of 1) documenting the reporting of race, and 2) exploring the impact of race on the efficacy and safety/tolerability of the considered medications.Results: Overall, 59.2% of the 49 retained RCTs reported information concerning the race of participants. Only a striking minority of enrolled patients was constituted of blacks and Hispanics. None on the retained studies reported results on the efficacy and safety/tolerability of the tested treatment separately for racial groups nor performed sensitivity analyses accounting for the race of participants.Discussion: Race has insufficiently been reported in previous interventional studies on AD. Its potential association with the effectiveness and safety/tolerability of the tested medications has completely been neglected.
35.
Bondesson, Åsa ÅB, et al.
(author)
A structured questionnaire to assess patient compliance and beliefs about medicines taking into account the ordered categorical structure of data
2009
In: Journal of Evaluation In Clinical Practice. - : Wiley. - 1356-1294 .- 1365-2753. ; 15:4, s. 713-723
Journal article (peer-reviewed) abstract
RATIONALE, AIMS AND OBJECTIVE: The objectives were to describe and evaluate the structured medication questionnaire and to improve data handling of results from the Morisky four-item scale for patient compliance and Beliefs about Medicines Questionnaire-specific (BMQ-specific). METHODS: A questionnaire was developed with the purpose of being used when identifying medication errors and assessing patient compliance to and beliefs about medicines. RESULTS: A majority of the respondents (62%; CI 45-77%) had at least one medication error. Assuming that all items are equally important in the Morisky four-item scale we presented four alternative ways to create a unidimensional global scale. A two-dimensional global scale was also constructed. The results from the BMQ-specific were presented in different ways, all taking into account that the scale has ordered verbal categories: at the level addressing each specific question, at the sub-scales 'concern' and 'necessity' level and at the global level. CONCLUSIONS: The structured medication questionnaire can be used in daily practice as a tool to identify drug-related problems. The choice of how to use and present data from those scales in research depends on patient characteristics and how discriminating one would like the scales to be.
36.
Salomé, Nicolas, et al.
(author)
Anorexigenic and electrophysiological actions of novel ghrelin receptor (GHS-R1A) antagonists in rats
2009
In: European Journal of Pharmacology. - : Elsevier. - 0014-2999 .- 1879-0712. ; 612:1-3, s. 167-173
Journal article (peer-reviewed) abstract
Here we provide the first pharmacological exploration of the impact of acute central nervous system exposure to three recently developed ghrelin receptor (GHS-R1A) ligands on food intake and on the electrical activity of the target cells for ghrelin in the hypothalamus. Central (i.c.v) injection of GHS-R1A antagonists to rats suppressed food intake induced by i.c.v ghrelin injection (1 mu g) in a dose-dependent manner with a total blockade at concentraions of 0.4 mu g and 8 mu g for JMV 3002 and JMV 2959 respectively. JMV 2810, a partial agonist, also suppressed ghrelin-induced food intake (range: 0.02-2 mu g). Moreover all three compounds reduced fasting-induced food intake in rats (i.e. the amount of food eaten during the first hour of food exposure after a 16 h fast). At the single cell level we also explored the effects of the compounds to suppress ghrelin (0.5 mu M)-induced changes in electrical activity of arcuate nucleus cells recorded extracellularly in a slice preparation. Preincubation followed by perfusion with the GHS-R1A ligands suppressed the responsiveness of arcuate cells to ghrelin. Thus, the recently developed GHS-R1A ligands (JMV 3002, 2959 and 2810) suppress ghrelin-induced and fasting-induced food intake at the level of the central nervous system. This appears to be mediated, at least in part, by a modulation of the activity of ghrelin-responsive arcuate nucleus cells. As the central ghrelin signalling system has emerged as an important pro-obesity target, it will be important to establish the efficacy of these GHS-R1A ligands to reduce fast mass in clincal studies.
37.
Hellström, Lina, 1975-, et al.
(author)
Clinical implementation of systematic medication reconciliation and review as part of the Lund Integrated Medicines Management model – impact on all cause emergency department revisits
2012
In: Journal of Clinical Pharmacy and Therapeutics. - : Hindawi Limited. - 0269-4727 .- 1365-2710. ; 37:6, s. 686-692
Journal article (peer-reviewed) abstract
What is known and objective: Interventions involving medication reconciliation and review by clinical pharmacists can reduce drug-related problems and improve therapeutic outcomes. The objective of this study was to examine the impact of routine admission medication reconciliation and inpatient medication review on emergency department (ED) revisits after discharge. Secondary outcomes included the combined rate of post-discharge hospital revisits or death.Methods: This prospective, controlled study included all patients hospitalised in three internal medicine wards in a university hospital, between January 1 2006 and May 31 2008. Medication reconciliation on admission and inpatient medication review, conducted by clinical pharmacists in a multiprofessional team, were implemented in these wards at different times during 2007 and 2008 (intervention periods). A discharge medication reconciliation was undertaken in all the study wards, during both control and intervention periods. Patients were included in the intervention group (n=1216) if they attended a ward with medication reconciliation and review, whether they had received the intervention or not. Control patients (n=2758) attended the wards before implementation of the intervention. Results: No impact of medication reconciliation and reviews on ED revisits (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.86-1.04) or event-free survival (HR, 0.96; 95% CI, 0.88-1.04) was demonstrated. In the intervention group, 594 patients (48.8%) visited the ED, compared to 1416 (51.3%) control patients. In total, 716 intervention (58.9%) and 1688 (61.2%) control patients experienced any event (ED visit, hospitalisation or death). Because the time to a subsequent ED visit was longer for the control as well as the intervention groups in 2007 than in 2006 (p<0.05), we re-examined this cohort of patients; the proportion of patients revisiting the ED was similar in both groups in 2007 (p=0.608).What is new and conclusion: Routine implementation of medication reconciliation and reviews on admission and during the hospital stay did not appear to have any impact on ED revisits, rehospitalisations or mortality over six months' follow-up.
38.
Hellström, Lina, 1975-, et al.
(author)
Errors in medication history at hospital admission: prevalence and predicting factors
2012
In: BMC Clinical Pharmacology. - : Springer Science and Business Media LLC. - 1472-6904. ; 12, s. Article ID: 9-
Journal article (peer-reviewed) abstract
Background: An accurate medication list at hospital admission is essential for the evaluation and further treatment of patients. The objective of this study was to describe the frequency, type and predictors of errors in medication history, and to evaluate the extent to which standard care corrects these errors.Methods:A descriptive study was carried out in two medical wards in a Swedish hospital using Lund Integrated Medicines Management (LIMM)-based medication reconciliation. A clinical pharmacist identified each patient's most accurate pre-admission medication list by conducting a medication reconciliation process shortly after admission. This list was then compared with the patient's medication list in the hospital medical records. Addition or withdrawal of a drug or changes to the dose or dosage form in the hospital medication list were considered medication discrepancies. Medication discrepancies for which no clinical reason could be identified (unintentional changes) were considered medication history errors.Results: The final study population comprised 670 of 818 eligible patients. At least one medication history error was identified by pharmacists conducting medication reconciliations for 313 of these patients (47%; 95% CI 43-51%). The most common medication error was an omitted drug, followed by a wrong dose. Multivariate logistic regression analysis showed that a higher number of drugs at admission (odds ratio [OR] per 1 drug increase = 1.10; 95% CI 1.06 - 1.14; p<0.0001) and the patient living in their own home without any care services (OR1.58; 95% CI 1.02 - 2.45; p = 0.042) were predictors for medication history errors at admission. The results further indicated that standard care by non-pharmacist ward staff had partly corrected the errors in affected patients by four days after admission, but a considerable proportion of the errors made in the initial medication history at admission remained undetected by standard care (OR for medication errors detected by pharmacists' medication reconciliation carried out on days 4 - 11 compared to days 0 - 1 = 0.52; 95% CI 0.30 - 0.91; p = 0.021).Conclusions: Clinical pharmacists conducting LIMM-based medication reconciliations have a high potential for correcting errors in medication history for all patients. In an older Swedish population, those prescribed many drugs seem to benefit most from admission medication reconciliation.
39.
Hughes, Carmel M, et al.
(author)
Provision of pharmaceutical care by community pharmacists : a comparison across Europe
2010
In: Pharmacy World & Science. - : Springer Science and Business Media LLC. - 0928-1231 .- 1573-739X. ; 32:4, s. 472-487
Journal article (peer-reviewed) abstract
Objective To investigate the provision of pharmaceutical care by community pharmacists across Europe and to examine the various factors that could affect its implementation. Methods A questionnaire-based survey of community pharmacies was conducted within 13 European countries. The questionnaire consisted of two sections. The first section focussed on demographic data and services provided in the pharmacy. The second section was a slightly adapted version of the Behavioral Pharmaceutical Care Scale (BPCS) which consists of three main dimensions (direct patient care activities, referral and consultation activities and instrumental activities). Results Response rates ranged from 10–71% between countries. The mean total score achieved by community pharmacists, expressed as a percentage of the total score achievable, ranged from 31.6 (Denmark) to 52.2% (Ireland). Even though different aspects of pharmaceutical care were implemented to different extents across Europe, it was noted that the lowest scores were consistently achieved in the direct patient care dimension (particularly those related to documentation, patient assessment and implementation of therapeutic objectives and monitoring plans) followed by performance evaluation and evaluation of patient satisfaction. Pharmacists who dispensed higher daily numbers of prescriptions in Ireland, Germany and Switzerland had significantly higher total BPCS scores. In addition, pharmacists in England and Ireland who were supported in their place of work by other pharmacists scored significantly higher on referral and consultation and had a higher overall provision of pharmaceutical care. Conclusion The present findings suggest that the provision of pharmaceutical care in community pharmacy is still limited within Europe. Pharmacists were routinely engaged in general activities such as patient record screening but were infrequently involved in patient centred professional activities such as the implementation of therapeutic objectives and monitoring plans, or in self-evaluation of performance.
40.
Wisell, Kristin, 1980-, et al.
(author)
The Raison D’être for the Community Pharmacy and the Community Pharmacist in Sweden: : A Qualitative Interview Study
2016
In: Pharmacy. - : MDPI AG. - 2226-4787. ; 4:1
Journal article (peer-reviewed) abstract
Community pharmacies are balancing between business (selling medicines and other products) and healthcare (using the pharmacists’ knowledge in order to improve drug utilization). This balance could be affected by regulations decided upon by politicians, but also influenced by others. The aim of this study was to explore important stakeholders’ views on community pharmacy and community pharmacists in Sweden. The method used was that of semi-structured qualitative interviews. Political, professional, and patient organization representatives were interviewed.The results show that informants who are pharmacists or representatives of a professional pharmacist organization generally have a healthcare-centered view on community pharmacy/pharmacists. However, different views on how this orientation should be performed were revealed, ranging from being specialists to dealing with uncomplicated tasks. Political organization representatives generally had a more business-oriented view, where competition in the market was believed to be the main driving force for development. A third dimension in which competition was not stressed also emerged; that community pharmacies should primarily distribute medicines. This dimension was most prevalent among the political and patient organization representatives. One conclusion to be drawn is that no stakeholder seemed to have a clear vision or was willing to take the lead for the development of the community pharmacy sector.
41.
Lytsy, Per, 1968-
(author)
Power of the Pill : Views about Cardiovascular Risk and the Risk-reducing Effect of Statins
2010
Doctoral thesis (other academic/artistic) abstract
Medical treatments with statins are prescribed to patients with increased risk of cardiovascular events. The benefits from statin treatment are well documented in clinical trials, but long-term adherence in patients is low, indicating that patients have an uncertainty about the necessity and benefits of treatment. The aims of this thesis were to investigate how patients and doctors view different aspects of statin treatment. Further aims were to investigate if the cardiovascular risk level in patients affects their views about different aspects of statin treatment. Yet further aims were to compare health behaviours and views about risk factors in patients using statins to a non-treated population. Data was obtained from patients (n = 829), doctors (n = 330) and a population sample (n = 720) using postal questionnaires. Views about the effect of statin treatment were assessed in different ways for patients and doctors. Patients based their assessments on their own situation, and doctors’ treatment decisions and assessments of anticipated effect of treatment were based on two hypothetical patient cases. The results indicate that patients greatly overestimate the general effect of statins, compared to efficacy results reported from clinical trials. Patients’ previous coronary heart disease or high overall risk were factors not associated with their views and expectations of treatment effect. Statin users with an internally perceived health control and patients satisfied with their doctor’s treatment explanation reported higher beliefs in treatment necessity and benefits. Statin users reported having better health behaviours and generally rated risk factors as more important than the non-treated population. Doctors had suboptimal understanding of the number of patients expected to benefit following five years of statin treatment and had a varying understanding of statins’ ability to prolong life. Overall the results illustrate that patients and doctors have different perspectives and views of the benefits from statin treatment which puts emphasis on how statin treatment is discussed in the clinical setting.
42.
Gyllensten, Hanna, 1979, et al.
(author)
Cost of illness of patient-reported adverse drug events: a population-based cross-sectional survey.
2013
In: BMJ open. - : BMJ. - 2044-6055. ; 3:6
Journal article (peer-reviewed) abstract
To estimate the cost of illness (COI) of individuals with self-reported adverse drug events (ADEs) from a societal perspective and to compare these estimates with the COI for individuals without ADE. Furthermore, to estimate the direct costs resulting from two ADE categories, adverse drug reactions (ADRs) and subtherapeutic effects of medication therapy (STE).
43.
Gyllensten, Hanna, 1979, et al.
(author)
Economic Impact of Adverse Drug Events – A Retrospective Population-Based Cohort Study of 4970 Adults
2014
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:3
Journal article (peer-reviewed) abstract
Background The aim was to estimate the direct costs caused by ADEs, including costs for dispensed drugs, primary care, other outpatient care, and inpatient care, and to relate the direct costs caused by ADEs to the societal COI (direct and indirect costs), for patients with ADEs and for the entire study population. Methods We conducted a population-based observational retrospective cohort study of ADEs identified from medical records. From a random sample of 5025 adults in a Swedish county council, 4970 were included in the analyses. During a three-month study period in 2008, direct and indirect costs were estimated from resource use identified in the medical records and from register data on costs for resource use. Results Among 596 patients with ADEs, the average direct costs per patient caused by ADEs were USD 444.9 [95% CI: 264.4 to 625.3], corresponding to USD 21 million per 100 000 adult inhabitants per year. Inpatient care accounted for 53.9% of all direct costs caused by ADEs. For patients with ADEs, the average societal cost of illness was USD 6235.0 [5442.8 to 7027.2], of which direct costs were USD 2830.1 [2260.7 to 3399.4] (45%), and indirect costs USD 3404.9 [2899.3 to 3910.4] (55%). The societal cost of illness was higher for patients with ADEs compared to other patients. ADEs caused 9.5% of all direct healthcare costs in the study population. Conclusions Healthcare costs for patients with ADEs are substantial across different settings; in primary care, other outpatient care and inpatient care. Hence the economic impact of ADEs will be underestimated in studies focusing on inpatient ADEs alone. Moreover, the high proportion of indirect costs in the societal COI for patients with ADEs suggests that the observed costs caused by ADEs would be even higher if including indirect costs. Additional studies are needed to identify interventions to prevent and manage ADEs.
44.
Wastesson, Jonas W., et al.
(author)
Trends in Use of Paracetamol in the Nordic Countries
2018
In: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7835 .- 1742-7843. ; 123:3, s. 301-307
Journal article (peer-reviewed) abstract
Paracetamol (acetaminophen) is one of the most commonly used analgesics in Europe; however, both the safety and efficacy of paracetamol have recently been questioned. Little is known about cross-national differences in the sales of paracetamol. Using national wholesale statistics and nationwide prescription drug registers, we investigated trends in total and prescribed use of paracetamol in the Nordic countries. The total sales of paracetamol (Anatomical Therapeutic Chemical (ATC) classification system code: N02BE01) measured as defined daily doses (DDD) per 1000 inhabitants/day, and the sales by prescription (users per 1000 inhabitants/year), increased in the Nordic countries from 2000 to 2015. The total sales were highest in Denmark throughout the period, with 65 DDD per 1000 inhabitants/day and lowest in Iceland with 30 DDD per 1000 inhabitants/day in 2015. The cross-national difference in total sales of paracetamol was smaller in 2015 than in 2000. The proportion of paracetamol (DDD per 1000 inhabitants/day) sold by prescription was also highest in Denmark (78%), compared with 75% in Finland, 69% in Sweden, 61% in Norway and 38% in Iceland. Paracetamol by prescription was more common at older ages and among women. Total and prescribed sales of paracetamol have increased in all five Nordic countries over time. Cross-national differences exist, with highest sales per capita in Denmark throughout the period.
45.
46.
47.
Schildmeijer, Kristina, 1959-, et al.
(author)
Adverse events in patients in home healthcare : A retrospective record review using trigger tool methodology
2018
In: BMJ Open. - : BMJ Publishing Group. - 2044-6055. ; 8:1
Journal article (peer-reviewed) abstract
Objective Home healthcare is an increasingly common part of healthcare. The patients are often aged, frail and have multiple diseases, and multiple caregivers are involved in their treatment. This study explores the origin, incidence, types and preventability of adverse events (AEs) that occur in patients receiving home healthcare. Design A study using retrospective record review and trigger tool methodology. Setting and methods Ten teams with experience of home healthcare from nine regions across Sweden reviewed home healthcare records in a two-stage procedure using 38 predefined triggers in four modules. A random sample of records from 600 patients (aged 18 years or older) receiving home healthcare during 2015 were reviewed. Primary and secondary outcome measures The cumulative incidence of AEs found in patients receiving home healthcare; secondary measures were origin, types, severity of harm and preventability of the AEs. Results The patients were aged 20-79 years, 280 men and 320 women. The review teams identified 356 AEs in 226 (37.7%; 95% CI 33.0 to 42.8) of the home healthcare records. Of these, 255 (71.6%; 95% CI 63.2 to 80.8) were assessed as being preventable, and most (246, 69.1%; 95% CI 60.9 to 78.2) required extra healthcare visits or led to a prolonged period of healthcare. Most of the AEs (271, 76.1%; 95% CI 67.5 to 85.6) originated in home healthcare; the rest were detected during home healthcare but were related to care outside home healthcare. The most common AEs were healthcare-associated infections, falls and pressure ulcers. Conclusions AEs in patients receiving home healthcare are common, mostly preventable and often cause temporary harm requiring extra healthcare resources. The most frequent types of AEs must be addressed and reduced through improvements in interprofessional collaboration. This is an important area for future studies.
48.
Axelsson, K. F., et al.
(author)
Hip fracture risk and safety with alendronate treatment in the oldest-old
2017
In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 282:6, s. 546-559
Journal article (peer-reviewed) abstract
Background. There is high evidence for secondary prevention of fractures, including hip fracture, with alendronate treatment, but alendronate's efficacy to prevent hip fractures in the oldest-old (80 years old), the population with the highest fracture risk, has not been studied. Objective. To investigate whether alendronate treatment amongst the oldest-old with prior fracture was related to decreased hip fracture rate and sustained safety. Methods. Using a national database of men and women undergoing a fall risk assessment at a Swedish healthcare facility, we identified 90 795 patients who were 80 years or older and had a prior fracture. Propensity score matching (four to one) was then used to identify 7844 controls to 1961 alendronate-treated patients. The risk of incident hip fracture was investigated with Cox models and the interaction between age and treatment was investigated using an interaction term. Results. The case and control groups were well balanced in regard to age, sex, anthropometrics and comorbidity. Alendronate treatment was associated with a decreased risk of hip fracture in crude (hazard ratio (HR) 0.62 (0.49-0.79), P < 0.001) and multivariable models (HR 0.66 (0.51-0.86), P < 0.01). Alendronate was related to reduced mortality risk (HR 0.88 (0.82-0.95) but increased risk of mild upper gastrointestinal symptoms (UGI) (HR 1.58 (1.12-2.24). The alendronate association did not change with age for hip fractures or mild UGI. Conclusion. In old patients with prior fracture, alendronate treatment reduces the risk of hip fracture with sustained safety, indicating that this treatment should be considered in these high-risk patients.
49.
Alrifaiy, Ahmed, et al.
(author)
A lab-on-a-chip for hypoxic patch clamp measurements combined with optical tweezers and spectroscopy : first investigations of single biological cells
2015
In: Biomedical engineering online. - : Springer Science and Business Media LLC. - 1475-925X. ; 14
Journal article (peer-reviewed) abstract
The response and the reaction of the brain system to hypoxia is a vital research subject that requires special instrumentation. With this research subject in focus, a new multifunctional lab-on-a-chip (LOC) system with control over the oxygen content for studies on biological cells was developed. The chip was designed to incorporate the patch clamp technique, optical tweezers and absorption spectroscopy. The performance of the LOC was tested by a series of experiments. The oxygen content within the channels of the LOC was monitored by an oxygen sensor and verified by simultaneously studying the oxygenation state of chicken red blood cells (RBCs) with absorption spectra. The chicken RBCs were manipulated optically and steered in three dimensions towards a patch-clamp micropipette in a closed microfluidic channel. The oxygen level within the channels could be changed from a normoxic value of 18% O 2 to an anoxic value of 0.0-0.5% O 2. A time series of 3 experiments were performed, showing that the spectral transfer from the oxygenated to the deoxygenated state occurred after about 227 ± 1 s and a fully developed deoxygenated spectrum was observed after 298 ± 1 s, a mean value of 3 experiments. The tightness of the chamber to oxygen diffusion was verified by stopping the flow into the channel system while continuously recording absorption spectra showing an unchanged deoxygenated state during 5400 ± 2 s. A transfer of the oxygenated absorption spectra was achieved after 426 ± 1 s when exposing the cell to normoxic buffer. This showed the long time viability of the investigated cells. Successful patching and sealing were established on a trapped RBC and the whole-cell access (Ra) and membrane (Rm) resistances were measured to be 5.033 ± 0.412 M Ω and 889.7 ± 1.74 M Ω respectively.
50.
Lindström, Kjell, 1946-, et al.
(author)
Can selective serotonin inhibitor drugs in elderly patients in nursing homes be reduced?
2007
In: Scandinavian Journal of Primary Health Care. - London : Informa Healthcare. - 0281-3432 .- 1502-7724. ; 25:1, s. 3-8
Journal article (peer-reviewed) abstract
OBJECTIVE: To investigate whether treatment with selective serotonin reuptake inhibitors (SSRIs) could be withdrawn for elderly residents who had been on treatment for at least one year and to evaluate a method for systematic drug review. DESIGN: Open, prospective, interventional study. SETTING: Four counties in Sweden. SUBJECTS: Elderly residents at 19 nursing homes, with ongoing treatment with SSRIs for more than one year. MAIN OUTCOME MEASURES: Clinical evaluation, registration of drugs used and rating with Montgomery-Asberg Depression Rating Scale (MADRS). A semi-structured telephone interview with 15 participating physicians and 19 nurses. RESULTS: About one-third of all 822 residents in the nursing homes had ongoing antidepressant treatment, predominantly with SSRIs; 75% of them had been treated with SSRIs for at least one year and 119 (60%) of these were considered eligible for the study. The intervention was judged successful in 52% of these residents of whom 88% had a MADRS rating of less than 20 points. The GPs and the nurses experienced the method as practicable. CONCLUSIONS: Withdrawal of SSRI treatment was successful in the majority of cases. The MADRS may be a valuable addition to clinical evaluation when deciding whether to end or continue SSRI treatment.
