| 1. |
- Kindstedt, Jonas, 1986-
(författare)
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Medication-related problems and psychotropic drug use in vulnerable older populations : a focus on acute hospital admissions and cognitive impairment
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The ageing process involves several physiological changes that affect both pharmacodynamics and pharmacokinetics and that, in combination with a heavier disease burden and more extensive use of medicines, put older people at higher risk of medication-related problems and associated clinical outcomes. The older population is often treated as a homogenous group, when in fact there are factors that render certain individuals more vulnerable to adverse drug effects and other types of medication-related problems. Older people encountered in the acute medical care setting and/or individuals with varying degrees of cognitive impairment are especially vulnerable in that context. The overall aim of this thesis was to describe and understand medication use in certain vulnerable subgroups of older people, which in turn might identify suitable target populations in which medication-related problems can be prevented or managed through interventions or similar efforts.Paper I presented, in the form of a study protocol, a clinical pharmacist intervention intended to reduce the risk of medication-related readmission to hospital among people aged 75 years or older during transitions of care. Based on 300 participants from the intervention study, approximately 50% had been readmitted to hospital within 180 days of being discharged from the hospital. Both heart failure and cognitive impairment, the latter identified through a four-item test, were predictors of early readmission. Altogether, the study population seems relevant for the purpose of the intervention; whether the intervention model is effective remains to be determined.Based on the same sample of study participants, paper II found that approximately one third of the 300 index hospital admissions were possibly medication related. Moreover, possibly medication-related hospital admissions were negatively associated with the fewest positive/correct answers on the four-item screening tool for cognitive impairment, which suggests that those clinical events might be less prevalent among people with cognitive impairment when exploring the association cross-sectionally. Both papers III and IV were registry-based studies, and their overall objective can be summarized as to describe psychotropic drug use and associated factors among older people with major neurocognitive disorder (NCD). Paper III focused on differences between major NCD subtypes, whereas paper IV compared people with major NCD against matched references from the total older population. In brief, overall psychotropic drug use was notably higher among people with major NCD, although generally in line with national treatment guidelines in terms of individual drugs of choice. The use of hypnotic drugs was also extensive in the reference group, and deprescribing efforts seem warranted, although longitudinal studies that focus on long-term use could provide a better picture of the potential problem. Nursing home stay was also positively associated with psychotropic drug use for all classes of psychotropic drugs, and the difference was most prominent for antipsychotic drugs. In that context, over 1,200 people in the reference population, most of them nursing home residents, had filled prescriptions for antipsychotic drugs, a figure indicating that the management of neuropsychiatric symptoms might also be an issue among older people who, due to various circumstances, have not been examined and diagnosed with neurocognitive disorders. Regarding major NCD subtypes, individuals with Lewy body dementia had, except for antidementia drugs, higher odds of psychotropic drug use than did those with Alzheimer’s disease. For example, the odds of antipsychotic drug use were more than twice as high, which is a worrying figure given that people with Lewy body dementia are extremely sensitive to the adverse effects of those specific drugs.In conclusion, this thesis illustrates the heterogeneity of demographics and drug use among older people and indicates that certain types of medication-related problems may be more relevant in certain older subpopulations. Medicines appear to be involved in many hospital admissions of older people, and the acute medical setting and subsequent care transitions are likely an important focus of pharmaceutical interventions. However, psychotropic drugs are probably not a major issue in that specific context. Efforts to reduce psychotropic drug use are likely more relevant to people with major NCD, especially in the nursing home setting. Antipsychotic drug exposure among persons with Lewy body dementia could be one such focus, especially since there are other better-balanced pharmacological treatment options for these individuals in terms of efficacy and safety profile.
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| 2. |
- Norberg, Helena, 1984-
(författare)
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Bridging the gap between clinical trials and clinical practice : sacubitril-valsartan in heart failure as a model
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- When novel treatments prove more effective than standard therapies, a swift and effective implementation is needed to reach cost-effectiveness and to benefit eligible patients. Meanwhile, women and elderly are often under-represented in clinical trials, which creates a knowledge gap on how to optimize treatment in clinical practice. The arrival of the angiotensin receptor-neprilysin inhibitor sacubitril-valsartan to patients with chronic heart failure and reduced ejection fraction (HFrEF) offered an opportunity to develop and test a new systematic introduction approach, as well as to investigate eligibility and management of sacubitril-valsartan in clinical practice. The aims of this thesis were to investigate obstacles to implement sacubitril-valsartan in a real-world heart failure population, as well as to develop a systematic and effective method to implement novel treatments in patients with chronic disease.With an observational cross-sectional study design, patients were retrospectively included if they had a heart failure diagnosis, living within the Umeå University Hospital catchment area, and had at least one visit at the Heart Centre or Department of internal medicine between January 2010 and March 2016. Eligibility to sacubitril-valsartan was based on the enrollment criteria applied in the landmark trial, PARADIGM-HF. We showed that the primary obstacle to implement sacubitril-valsartan was that only a quarter of the real-world HFrEF population was eligible. The most prominent difference was that real-world patients were significantly older compared with the PARADIGM-HF population. Disproportionally many patients, especially women, were ineligible for sacubitril-valsartan due to intolerance of renin-angiotensin system inhibitors in target doses. With multivariable linear regression analyses, we showed that the lower target doses in women were explained by biological sex differences.Management of heart failure treatment involve many titration steps that risk stressing the resources of both healthcare and patients. We prospectively investigated a direct switch to maximum dose sacubitril-valsartan in patients who tolerated target dose renin-angiotensin system inhibitors (equivalent to enalapril 10 mg twice daily). We showed that the simplified introduction was safe and generally well tolerated during the first year.The systematic introduction approach is a seven-step procedure:1) define a few main criteria2) primary scan patients with the one or two main criteria using computerized medical records/databases/clinical registries3) identify patients applying the other predefined criteria4) evaluate if any examinations/laboratory test updates are required5) summon identified patients with an information letter6) discuss treatment with the patient and prescribe if appropriate7) follow-up on initiated therapy and evaluate the process.We evaluated the approach with a mixed method, including both a case study of the sacubitril-valsartan implementation and an interview study with qualitative content analysis. The new systematic introduction approach effectively implemented sacubitril-valsartan in clinical practice, by identifying eligible patients with limited resources and time. The patients were overall satisfied with the new approach and their confidence in healthcare was maintained.In conclusion, we found that the strict inclusion criteria in the PARADIGM-HF trial would exclude a majority of patients with heart failure if they are implemented and that these criteria have an inherent bias versus the old and the frail, which in turn disproportionately affects women. We further found that patients who are on maximum recommended dose of renin-angiotensin system inhibitors can be safely switched to maximum dose sacubitril-valsartan and that our method of systematic introduction was effective in implementing sacubitril-valsartan to a heart failure population.The approach is a promising example of how to reduce the gap between clinical trials and clinical practice in patients with chronic disease.
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| 3. |
- Sjölander, Maria, 1970-
(författare)
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Use of secondary preventive drugs after stroke
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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.
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| 4. |
- Bråndal, Anna, 1966-
(författare)
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Rehabilitation after stroke with focus on early supported discharge and post-stroke fatigue
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Stroke is a major cause of disability worldwide. After treatment in a specialized stroke unit, early supported discharge (ESD) followed by home rehabilitation has shown to be an effective way to improve patient outcome and quality of care for persons with mild to moderate stroke. ESD service is recommended in the national and international guidelines for stroke care, but has only partially been implemented in Sweden. Following stroke, fatigue is a common consequence that often becomes more evident when the patient comes home. Currently, there is insufficient evidence about how to measure, treat and handle post-stroke fatigue. The overall aim of this thesis was to evaluate and implement early supported discharge (ESD) based on stroke patients experience after discharge from the stroke unit and local conditions. The aim was also to evaluate post-stroke fatigue with a potentially valid and reliable scale and finally to prepare for a study to evaluate cardiorespiratory training as a part of ESD service for patients with post-stroke fatigue.Methods In paper I, nine strategically chosen patients were interviewed of their experience of falling ill, the hospital stay, discharge, contact with health care after discharge and their request of support. Papers II-III describe and evaluate the development, content, implementation and effects of a locally adopted method for early supported discharge (Umeå Stroke Center ESD) in modern stroke care. Paper II included 153 consecutive patients and paper III, 30 232 patients with first-ever stroke registered in the Riksstroke registry in Sweden. Paper II evaluated number of patients/year, clinical and functional health status, satisfaction in relation to needs, accidental falls/other injuries and resources with the result summarized in a value compass. The implementation process was evaluated retrospectively by means of Consolidated Framework for Implementation (CFIR). Paper III evaluated patient reported outcome measurements (PROMs) at 3 months. The primary outcome in paper III was satisfaction with the rehabilitation after discharge. Secondary outcomes were information about stroke provided, tiredness/fatigue, pain, dysthymia/depression, general health status and dependence in activities of daily living (mobility, toilet hygiene and dressing). Multivariable logistic regression models for each PROM was used to analyze associations between PROMs and ESD/no ESD. In Paper IV, the Fatigue Assessment scale (FAS) was translated into Swedish and evaluated regarding psychometric properties when self-administered by persons with mild to moderate stroke. 72 consecutively patients selected from the stroke unit admission register received a letter including three questionnaires: the FAS, the Short Form Health Survey (SF-36) subscale for vitality and the Geriatric Depression Scale GDS-15. A second letter with FAS was sent within 2 weeks, for re-test evaluation. Paper V is a study protocol for a planned randomized controlled trial (RCT) of 50 consecutive stroke patients will who receive stroke unit care followed by ESD-service at Umeå Stroke Center, University Hospital, Umeå, Sweden. Paper V will investigate if a structured cardiorespiratory interval training program (CITP) added to the ESD-service may result in relieved post-stroke fatigue and increased oxygen uptake.Results The interviews in Paper I revealed three main categories with subcategories: “Responsible and implicated”, “Depersonalized object for caring measures” and “The striving for repersonalization and autonomy”. The findings indicate that coming home gave the informants’ important insights and understanding of the stroke, its consequences and was also an important factor for the recovery. Paper II-III showed that it is possible to develop and implement an adapted ESD service for stroke patients based on the patients’ experiences and requests, evidence-based recommendations and local conditions. The ESD service reduced dependence of activity, increased mobility with seemingly no increased risk of accidental falls or other injuries. The patient satisfaction in relation to needs regarding the ESD was high. Paper III showed that patients that received ESD were more satisfied with rehabilitation after discharge, had less need for assistance with ADL and less dysthymia/depression compared to patients that did not receive ESD. Study IV showed that the Swedish FAS used at home as a selfadministered questionnaire is a reliable and valid questionnaire for measuring fatigue in persons with mild to moderate stroke. The internal consistency was good, the agreement between the test and retest reliability for individual items (weighted kappa) was for the majority of items good or moderate. The relative reliability for total scores was good and the absolute reliability was 9 points. The Swedish FAS had no floor nor ceiling effects and correlated both with the SF-36, subscale for vitality and the GDS-15 indicating convergent construct validity, but not divergent construct validity.Conclusion It is possible to develop and implement ESD care for stroke patients based on patients’ experience and needs, evidence-based principles and local conditions. Early supported discharge (ESD) in the setting of modern stroke unit care appears to have positive effects on rehabilitation in the subacute phase. The Swedish FAS used at home as a self-administered questionnaire is reliable and valid for measuring fatigue in persons with mild to moderate stroke.
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| 5. |
- Darehed, David, 1986-
(författare)
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The impact of organizational and temporal factors on acute stroke care in Sweden
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Acute stroke carries a high risk of morbidity and death, but early treatment can improve outcomes. Intravenous stroke thrombolysis (IVT) is one such treatment, it is however time-sensitive and show better outcomes the sooner it is given. Most studies on time to IVT so far have looked at fixed time-intervals, and studies of short delays in clinical practice are relatively scarce. Another well-established treatment is managing acute stroke patients in stroke units (SU). Admission rates to a SU as first destination of hospital care have improved over time in Sweden. In the past decade however, the rates have leveled out at around 75-80% without further improvement. A hypothesis is that in-hospital overcrowding contributes. Previous studies have shown that outcomes after stroke differ between hospital types, and also vary depending on time of admission, with higher mortality seen for off-hours, weekend and winter admissions. The reasons behind temporal variations are not fully understood, but it has been proposed that environmental, patient-related and organizational factors contribute. The overall aim of this thesis was to study the effect of organizational factors on quality of care and outcomes after stroke, primarily focusing on the role of in-hospital overcrowding, in-hospital time to IVT and time of admission, while also studying differences between hospitals.Methods: All papers in this thesis were based on data from the Swedish stroke register (Riksstroke), a national quality register that holds data on patient related factors, acute care and outcomes. Paper I included 13,955 patient admissions from 14 hospitals in Region Norrbotten and Region Skåne from 2011-2014, enriched with data on in-hospital bed occupancy. Papers II-IV included all 72 Swedish hospitals caring for patients with acute stroke. Paper II included data from 2011-2015 (N=113,862), paper III from 2011-2016 (N=132,744) and paper IV from 2010-2017 (N=14,132). Analyses included descriptive statistics, unadjusted analyses and multivariable adjusted analyses.Results: We found that each percent increase in in-hospital bed occupancy above 85% decreased admission rates to a SU as first destination of hospital care by 1.5% (odds ratio (OR) 0.985, 95% confidence interval (CI) 0.978-0.992), with significant differences between hospitals. Admission rates were also lower off-hours, compared to on-hours (OR 0.73, 95% CI 0.70-0.75). Over time, admission rates to a SU as first destination of hospital care decreased in university hospitals, while they increased in specialized non-university hospitals and community hospitals. Each minute delay in door-to-needle time (DNT) decreased the odds of 90-day survival by 0.6% (OR 0.994, 95% CI 0.992-0.996), increased the odds of ICH within 36 hours by 0.3% (OR 1.003, 95% CI 1.000-1.006), and led to significantly higher odds of a worsening in functional outcomes at 3 months by 0.3-0.4%. DNT within 30 minutes was most likely daytime, and varied between hospital types. 90-day survival was lowest for patients admitted in January (81.5%), and highest for those admitted in May (84.1%) (OR 1.28, 95% CI 1.17-1.40).Conclusion: We found that in-hospital overcrowding decrease admission rates to a SU as first destination of hospital care, and that even short delays in DNT decreases survival, increases ICH complications and leads to a worsening in functional outcomes in routine clinical practice. We also found that quality of care varied depending on time of admission and between hospitals, indicating unequal care. Organizational differences should be accessible through quality improvement efforts aiming to implement robust local guidelines for in-hospital stroke treatment.
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| 6. |
- Lindmark, Anita, 1986-
(författare)
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Statistical methods for register based studies with applications to stroke
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis adds to the area of register based research, with a particular focus on health care quality and (in)equality. Contributions are made to the areas of hospital performance benchmarking, mediation analysis, and regression when the outcome variable is limited, with applications related to Riksstroke (the Swedish stroke register).An important part of quality assurance is to identify, follow up, and understand the mechanisms of inequalities in outcome and/or care between different population groups. The first paper of the thesis uses Riksstroke data to investigate socioeconomic differences in survival during different time periods after stroke. The second paper focuses on differences in performance between hospitals, illustrating the diagnostic properties of a method for benchmarking hospital performance and highlighting the importance of balancing clinical relevance and the statistical evidence level used.Understanding the mechanisms behind observed differences is a complicated but important issue. In mediation analysis the goal is to investigate the causal mechanisms behind an effect by decomposing it into direct and indirect components. Estimation of direct and indirect effects relies on untestable assumptions and a mediation analysis should be accompanied by an analysis of how sensitive the results are to violations of these assumptions. The third paper proposes a sensitivity analysis method for mediation analysis based on binary probit regression. This is then applied to a mediation study based on Riksstroke data.Data registration is not always complete and sometimes data on a variable are unavailable above or below some value. This is referred to as censoring or truncation, depending on the extent to which data are missing. The final two papers of the thesis are concerned with the estimation of linear regression models for limited outcome variables. The fourth paper presents a software implementation of three semi-parametric estimators of truncated linear regression models. The fifth paper extends the sensitivity analysis method proposed in the third paper to continuous outcomes and mediators, and situations where the outcome is truncated or censored.
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