Till Örebro universitet

OBJECTIVES: The primary objective of this study was to examine the impact of the COVID-19 pandemic on the quality of stroke care for patients with preexisting dementia, compared with patients who had only stroke. The secondary aim was to investigate how the quality of stroke care changed during the pandemic and post-pandemic periods compared with the pre-pandemic period in patients with preexisting dementia.

DESIGN: A registry-based, nationwide cohort study in Sweden.

SETTING AND PARTICIPANTS: We included patients with a first stroke between 2019 and 2022, both with and without dementia. The study periods were defined as follows: pre-pandemic (January 1, 2019, to February 29, 2020), COVID-19 pandemic (March 1, 2020, to February 24, 2022), and post-COVID-19 pandemic period (February 25, 2022, to September 19, 2022). The outcomes examined were the following quality indicators of stroke care, suggested by the national guideline of stroke care in Sweden: stroke admission site, performance of swallowing assessment, reperfusion treatment, assessment for rehabilitation, and early supported discharge.

METHODS: The associations were studied through group comparisons and binary logistic regressions.

RESULTS: Of the 21,795 stroke patients, 1357 had documented preexisting dementia, and 20,438 had stroke without a dementia diagnosis. Throughout all study periods, a significantly lower proportion of stroke patients with preexisting dementia, compared with stroke-only patients, received reperfusion treatment, assessments for rehabilitation, and early supported discharge from stroke units. In the subgroup of stroke patients with preexisting dementia, no significant associations were found regarding the quality indicators of stroke care before, during, and after the pandemic.

CONCLUSIONS AND IMPLICATIONS: Disparities in quality of stroke care were observed between stroke patients with preexisting dementia and those with only stroke during the COVID-19 pandemic. However, there were no statistically significant differences in stroke care for patients with dementia across the pandemic.

BACKGROUND: There is a need for a prehospital stroke test that in addition to high sensitivity for stroke, also is able to communicate stroke severity similar to the National Institute of Health Stroke Scale (NIHSS).

METHODS: The PreHospital Ambulance Stroke Test (PreHAST), an eight item test based on NIHSS, which scores stroke severity from 0-19 points, was designed and adapted for the ambulance services. In the pilot study the ambulance nurses used PreHAST to assess patients with suspected stroke in the prehospital setting. Regardless of the results after PreHAST testing the patients were triaged with a provisional stroke diagnosis. The PreHAST scores were compared with the final diagnosis and the ability to differentiate stroke and transient ischemic attacks (TIA) with ongoing symptoms at evaluation from non-stroke patients was analysed.

RESULTS: 69 patients were included in the study, 26 had stroke/TIA and 43 other diagnoses. All stroke/TIA patients were identified by PreHAST (sensitivity 100% (95% CI; 87-100%)). The specificity increased with higher PreHAST scores and the discriminative capacity for PreHAST for different cut off values showed an area under the curve of 0.77 (95%CI; 0.66-0.88) in the receiver operating characteristic (ROC) analysis.

DISCUSSION: PreHAST is designed for high sensitivity, screening for a broad range of stroke symptoms including most key components of NIHSS. The promising sensitivity between 87 and 100% in our study has to be confirmed in a larger study also including multiple centres. Higher PreHAST scores implied more typical patterns of stroke and accordingly the proportion of stroke mimics decrease with higher scores. However, also stroke mimics with epilepsy/seizure and patients with deficit after prior stroke could show higher PreHAST scores. Other prehospital stroke tests that evaluate stroke severity have been designed with the main purpose to screen for large vessel occlusion. The advantage of PreHAST is the dual purpose not only to evaluate stroke severity but also to screen for stroke in general.

CONCLUSIONS: PreHAST is a new screening test of stroke adapted for ambulance services that in addition to high sensitivity for stroke, provides a grading system with increasing specificity with higher scores.

OBJECTIVE: To study the occurrence of ischaemic and haemorrhagic stroke in systemic lupus erythematosus (SLE) compared with the general population by age, sex and time since SLE diagnosis METHODS: Adults with incident SLE were identified from the Swedish National Patient Register (NPR, n=3390) and general population comparators from the Total Population Register were matched on age, sex and county (n=16730). Individuals were followed prospectively until first of death, December 2013, emigration or incident stroke (identified from the NPR, Cause of Death Register and the Stroke Register). Incidence rates, rate differences and HR were estimated comparing SLE with non-SLE. Estimates were stratified by sex, age and time since diagnosis.

RESULTS: We observed 126 strokes in SLE and 304 in the general population. Individuals with SLE had a twofold increased rate of ischaemic stroke compared with the general population (HR 2.2; 95% CI 1.7 to 2.8). The HR for intracerebral haemorrhage was 1.4 (95% CI 0.7 to 2.8). There was effect modification by sex and age, with the highest HRs for females and individuals <50 years old. The HR for ischaemic stroke was highest in the first year of follow-up (3.7; 95% CI 2.1 to 6.5).

CONCLUSIONS: The relative risk of ischaemic stroke in SLE was more than doubled compared with the general population, and importantly, the highest relative risks were observed within the first year after SLE diagnosis. Thus, the first encounter with patients presents an opportunity for rheumatologists to screen for risk factors and intervene.

The 2-vessel occlusion approach to produce global ischemia in rats requires concomitant reduction of systemic blood pressure. We have utilized the hypotensive effect of halothane administrated by artificial respiration to prevent respiratory arrest and to ensure stable physiological conditions. Systemic blood pressure was reduced to 40-45 mmHg by instant adjustments of the halothane concentration. Bilateral occlusion of the carotid arteries caused a profound and reproducible ischemia, as analyzed by laser-Doppler flowmetry. In the rats exposed to 11, 12, or 13 min of ischemia, 5% died and 5% developed seizures. The extent of neuronal death in CA1 was highly correlated to the duration of ischemia. Following 11 min of ischemia, CA1 neuronal cell death, as analyzed by Fluoro-Jade, was absent 1 day after injury, variable at day 4, and consistent at day 7. The numbers of cresyl violet- and NeuN-positive neurons at day 7 were 8% and 20% of control, respectively. OX42 immunoreactivity was low and variable at day 4, but pronounced at day 7. In conclusion, this rat global ischemia model is relatively simple to perform, has a low mortality, and produces a profound and highly reproducible delayed cell death of hippocampal CA1 neurons.

The pyramidal neurons of the hippocampal CA1 region are essential for cognitive functions such as spatial learning and memory, and are selectively destroyed after cerebral ischemia. To analyze whether degenerated CA1 neurons are replaced by new neurons and whether such regeneration is associated with amelioration in learning and memory deficits, we have used a rat global ischemia model that provides an almost complete disappearance (to approximately 3% of control) of CA1 neurons associated with a robust impairment in spatial learning and memory at two weeks after ischemia. We found that transient cerebral ischemia can evoke a massive formation of new neurons in the CA1 region, reaching approximately 40% of the original number of neurons at 90 days after ischemia (DAI). Co-localization of the mature neuronal marker neuronal nuclei with 5-bromo-2'-deoxyuridine in CA1 confirmed that neurogenesis indeed had occurred after the ischemic insult. Furthermore, we found increased numbers of cells expressing the immature neuron marker polysialic acid neuronal cell adhesion molecule in the adjacent lateral periventricular region, suggesting that the newly formed neurons derive from this region. The reappearance of CA1 neurons was associated with a recovery of ischemia-induced impairments in spatial learning and memory at 90 DAI, suggesting that the newly formed CA1 neurons restore hippocampal CA1 function. In conclusion, these results show that the brain has an endogenous capacity to form new nerve cells after injury, which correlates with a restoration of cognitive functions of the brain.

Stroke affects both men and women of all ages, although the condition is more common among the elderly. Stroke occurs at an older age among women than among men; although the incidence is lower among women than among men, as women have a longer life expectancy their lifetime risk is slightly higher. Ischemic stroke is the most common type of stroke; and reperfusion treatment is possible if the patient reaches hospital early enough. Thrombolysis and thrombectomy are time-sensitive treatments - the earlier they are initiated the better is the chance of a positive outcome. It is therefore important to identify a stroke as soon as possible. Medical personnel can readily identify typical stroke symptoms but the presentation of non-traditional stroke symptoms, such as impaired consciousness and altered mental status, is often associated with a significant delay in the identification of stroke and thus delay in or inability to provide treatment. Non-traditional stroke symptoms are reported to be more common in women, who are thereby at risk of delayed recognition of stroke and treatment delay.

AIMS: To explore the factors that facilitate or hamper identification of stroke in emergency calls concerning patients with stroke who have fallen or been in a lying position.

BACKGROUND: Early identification of stroke in emergency calls is vital but can be complicated as the patients may be unable to express themselves and the callers generally are bystanders. In a previous study, we found presentation of fall or the patient being in a lying position to be the major problem in 66% of emergency calls concerning, but not dispatched as acute stroke.

DESIGN: A qualitative study using interpretive phenomenology.

METHODS: Analysis of transcribed emergency calls concerning 29 patients with stroke diagnoses at hospital discharge, in 2011 and presented with fall/lying position.

FINDINGS: Patients' ability to express themselves, callers' knowledge of the patient and of stroke, first call-takers' and nurses' authority, nurses' coaching and nurses' expertise skills facilitated or hindered the identification of stroke. Certain aspects are adjustable, but some are determined by the situation or on callers' and patients' abilities and thus difficult to change. Nurses' expertise skills were the only theme found to have a decisive effect of the identification of stroke on its own.

CONCLUSION: To increase identification of stroke in emergency calls concerning stroke, the first call-takers' and nurses' action, competence and awareness of obstacles are crucial and if strengthened would likely increase the identification of stroke in emergency calls. In complicated cases, nurses' expertise skills seem essential for identification of stroke.

BACKGROUND AND PURPOSE: Early initiated treatment of stroke increases the chances of a good recovery. This randomized controlled study evaluates how an increased priority level for patients with stroke, from level 2 to 1, from the Emergency Medical Communication Center influences thrombolysis frequency, time to stroke unit, and whether other medical emergencies reported negative consequences.

METHODS: Patients aged 18 to 85 years in Stockholm, Sweden, with symptoms of stroke within 6 hours were randomized from the Emergency Medical Communication Center or emergency medical services to an intervention group, priority level 1, immediate call of an ambulance, or to a control group with standard priority level, that is, priority level 2 (within 30 minutes). Before study start, an educational program on identification of stroke and importance of early initiated treatment was directed to all medical dispatchers and ambulance and emergency department personnel.

RESULTS: During 2008, 942 patients were randomized of which 53% (n=496) had a final stroke/transient ischemic attack diagnosis. Patients in the Emergency Medical Communication Center randomized intervention group reached the stroke unit 26 minutes earlier than the control group (P<0.001) after the emergency call. Thrombolysis was given to 24% of the patients in the intervention group compared with 10% of the control subjects (P<0.001). The higher priority level showed no negative effect on other critical ill patients requiring priority level 1 prehospital attention.

CONCLUSIONS: This randomized study shows negligible harm to other medical emergencies, a significant increase in thrombolysis frequency, and a shorter time to the stroke unit for patients with stroke upgraded to priority level 1 from the Emergency Medical Communication Center and through the acute chain of stroke care.

BACKGROUND: Prehospital identification of acute stroke increases the possibility of early treatment and good outcome. To increase identification of stroke, the Face Arm Speech Time (FAST) test was introduced in the Emergency Medical Communication Center (EMCC). This substudy aims to evaluate the implementation of the FAST test in the EMCC and the ambulance service.

METHODS: The study was conducted in the region of Stockholm, Sweden during 6 months. The study population consisted of all calls to the EMCC concerning patients presenting at least one FAST symptom or a history/finding making the EMCC or ambulance personnel to suspect stroke within 6 h. Positive FAST was compared to diagnosis at discharge. Positive predictive values (PPV) for a stroke diagnosis at discharge were calculated.

RESULTS: In all, 900 patients with a median age of 71 years were enrolled, 667 (74%) by the EMCC and 233 (26%) by the ambulances. At discharge, 472 patients (52%) were diagnosed with stroke/transient ischemic attack (TIA), 337 identified by the EMCC (71%) and 135 (29%) by the ambulances. The PPV for a discharge diagnosis of stroke/TIA was 51% (CI 47-54%) in EMCC-enrolled and 58% (CI 52-64%) in ambulance-enrolled patients. With a positive FAST the PPV of a correct stroke/TIA diagnosis increased to 56% (CI 52-61%) and 73% (CI 66-80%) in EMCC- and ambulance-enrolled patients, respectively. Positive FAST from EMCC was also found in 44% of patients with a nonstroke diagnosis at discharge. A stroke/TIA diagnosis at discharge but negative FAST was found in 58 and 27 patients enrolled by the EMCC and ambulances, respectively.

CONCLUSIONS: The PPV of FAST is higher when used on the scene by ambulance than by EMCC. FAST may be a useful prehospital tool to identify stroke/TIA but has limitations as the test can be negative in true strokes, can be positive in nonstrokes, and FAST symptoms may be present but not identified in the emergency call. For the prehospital care situation better identification tools are needed.

OBJECTIVES: To evaluate symptoms presented by the caller during emergency calls regarding stroke, and to assess if symptoms in the Face-Arm-Speech-Time Test (FAST) are related to identification of stroke.

SETTING: Emergency calls to the Emergency Medical Communication Center (EMCC) concerning patients discharged with stroke diagnosis in a large teaching hospital in Stockholm, Sweden, in January-June 2011.

PARTICIPANTS: The emergency calls of 179 patients who arrived at hospital by ambulance, and who were discharged with a stroke diagnosis and consented to participate were included in the study.

OUTCOME MEASURES: Frequencies of stroke symptoms presented and a comparison of symptoms presented in calls with dispatch code stroke or other dispatch code.

RESULTS: Of the 179 emergency calls analysed, 64% were dispatched as 'Stroke'. FAST symptoms, that is, facial or arm weakness or speech disturbances, were presented in 64% of the calls and were spontaneously revealed in 90%. Speech disturbance was the most common problem (54%) in all calls, followed by fall/lying position (38%) and altered mental status (27%). For patients with dispatch codes other than stroke, the dominating problem presented was a fall or being in a lying position (66%), followed by speech disturbance (31%) and altered mental status (25%). Stroke-specific symptoms were more common in patients dispatched as stroke. FAST symptoms were reported in 80% of patients dispatched as stroke compared with 35% in those dispatched as something else.

CONCLUSIONS: This study implicates that fall/lying position and altered mental status could be considered as possible symptoms of stroke during an emergency call. Checking for FAST symptoms in these patients might uncover stroke symptoms. Future studies are needed to evaluate if actively asking for FAST symptoms in emergency calls presenting falls or a lying position can improve the identification of stroke.

TRIAL REGISTRATION NUMBER: Stroke2010/703-31/2.

Third-generation cephalosporins in general have few adverse effects and cefotaxime (Claforan) particularly is considered to be a good choice because of the favourable side effect profile. In patients with severe renal failure there have been reports of confusion and psychosis. The manufacturer therefore recommends that half the ordinary dose should be given to patients with severe renal failure. Half the ordinary dose can still be too much. We describe a patient in hemodialysis who reacted with a reversible encephalopathy with psychosis in spite of reduced doses of cefotaxime. The plasma concentration of cefotaxime was high and the reaction was diagnosed as a dose dependent side effect.

The pyramidal neurons of the hippocampal CA1 region are essential for spatial learning and memory and are almost entirely destroyed 7-14 days after transient cerebral ischemia (DAI). Recently, we found that CA1 neurons reappeared at 21-90 DAI, in association with a recovery of ischemia-induced deficits in spatial learning and memory. However, at 125 DAI the number of neurons was fewer than at 90 DAI, suggesting that the new nerve cells undergo neurodegeneration during this time period. We therefore investigated whether neuronal degeneration occurred between 90 and 250 DAI and how this related to learning and memory performance. We found that many of the new CA1 neurons previously seen at 90 DAI had disappeared at 250 DAI. In parallel, large mineralized calcium deposits appeared in the hippocampus and thalamus, in association with neuroinflammatory and astroglial reactions. In spite of the extensive CA1 damage, the ischemic rats showed no deficiencies in spatial learning and memory, as analyzed in the Morris water maze and a complimentary water maze test based on sequential left-right choices. However, ischemia rats showed a general increase in swim length in the Morris water maze suggesting altered search behaviour. Taken together, these results indicate that the CA1 neurons that reappear after transient global ischemia to a large extent degenerate at 125-250 DAI, in parallel with the appearance of a less efficient search strategy.

Kvinnor löper 18 procent högre risk än män att drabbas av en stroke vid förmaksflimmer, men får ändå en lägre andel förebyggande, effektiv medicin. Det är ett tydligt tecken på att kvinnor fortfarande missgynnas inom den svenska hjärtsjukvården.

OBJECTIVES: The aim of this study was to explore whether recording in primary care of a previously recorded hospital diagnosis was associated with increased patient utilisation of recommended medications.

DESIGN: Registry-based prospective cohort study.

SETTING AND PARTICIPANTS: 19 072 patients with a hospital discharge diagnosis of transient ischaemic attack (TIA), stroke or acute coronary syndrome from hospitals in Stockholm County 2010-2013 were included in the study.

MAIN OUTCOME MEASURE: The outcome of the study was medication dispensation as a marker of adherence to recommended medications. Adherence was defined as having had at least two filled prescriptions in the third year following hospital discharge.

RESULTS: Recording a diagnosis was associated with higher utilisation of all recommended medications with the exception of antihypertensives in patients with TIA. The differences between the groups with and without a recorded diagnosis remained after adjusting for age, sex, index year and visits to private practitioners. Dispensation of antithrombotics was high overall, 80%-90% in patients without a recorded diagnosis and 90%-94% for those with a diagnosis. Women with recorded ischaemic stroke/TIA/acute coronary syndrome were dispensed more statins (56%-71%) than those with no recorded diagnosis (46%-59%). Similarly, 68%-83% of men with a recorded diagnosis were dispensed statins (57%-77% in men with no recorded diagnosis). The rate of diagnosis recording spanned from 15% to 47% and was especially low in TIA (men 15%, women 16%).

CONCLUSION: Recording a diagnosis of TIA/stroke or acute coronary syndrome in primary care was found to be associated with higher dispensation of recommended secondary preventive medications. Further study is necessary in order to determine the mechanisms underlying our results and to establish the utility of our findings.

BACKGROUND: The treatment of ischaemic stroke with neuroprotective drugs has been unsuccessful, and whether these compounds can be used to reduce disability after recurrent stroke is unknown. The putative neuroprotective effects of antiplatelet compounds and the angiotensin II receptor antagonist telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial.

METHODS: Patients who had had an ischaemic stroke were randomly assigned in a two by two factorial design to receive either 25 mg aspirin (ASA) and 200 mg extended-release dipyridamole (ER-DP) twice a day or 75 mg clopidogrel once a day, and either 80 mg telmisartan or placebo once per day. The predefined endpoints for this substudy were disability after a recurrent stroke, assessed with the modified Rankin scale (mRS) and Barthel index at 3 months, and cognitive function, assessed with the mini-mental state examination (MMSE) score at 4 weeks after randomisation and at the penultimate visit. Analysis was by intention to treat. The study was registered with ClinicalTrials.gov, number NCT00153062.

FINDINGS: 20,332 patients (mean age 66 years) were randomised and followed-up for a median of 2.4 years. Recurrent strokes occurred in 916 (9%) patients randomly assigned to ASA with ER-DP and 898 (9%) patients randomly assigned to clopidogrel; 880 (9%) patients randomly assigned to telmisartan and 934 (9%) patients given placebo had recurrent strokes. mRS scores were not statistically different in patients with recurrent stroke who were treated with ASA and ER-DP versus clopidogrel (p=0.38), or with telmisartan versus placebo (p=0.61). There was no significant difference in the proportion of patients with recurrent stroke with a good outcome, as measured with the Barthel index, across all treatment groups. Additionally, there was no significant difference in the median MMSE scores, the percentage of patients with an MMSE score of 24 points or less, the percentage of patients with a drop in MMSE score of 3 points or more between 1 month and the penultimate visit, and the number of patients with dementia among the treatment groups. There were no significant differences in the proportion of patients with cognitive impairment or dementia among the treatment groups.

INTERPRETATION: Disability due to recurrent stroke and cognitive decline in patients with ischaemic stroke were not different between the two antiplatelet regimens and were not affected by the preventive use of telmisartan.

INTRODUCTION: Atrial fibrillation (AF) is a major risk factor for ischaemic stroke and transient ischaemic attack (TIA), and AF detection can be challenged by asymptomatic and paroxysmal presentation. Long-term ECG monitoring after ischaemic stroke or TIA is recommended by all major societies in cardiology and cerebrovascular medicine as a secondary prophylactic measure. However, data on stroke reduction are lacking, and the recommendations show significant diversity.

METHODS AND ANALYSIS: AF SPICE is a multicentre, national, investigator-initiated, randomised, parallel-group, register-based trial comparing extended ECG monitoring versus standard ECG monitoring in patients admitted with ischaemic stroke or TIA, with a composite endpoint of stroke, all-cause-mortality and intracerebral bleeding. Patients aged ≥70 years without previous AF will be randomised 1:1 to control (standard ECG monitoring) or intervention (extended ECG monitoring). In the control arm, patients will undergo 48±24 hours (ie, a range of 24-72 hours) of continuous ECG monitoring according to national recommendations. In the intervention arm, patients will undergo 14+14 days of continuous ECG monitoring 3 months apart using an ECG patch device, which will provide an easy-accessed, well-tolerated 14-day continuous ECG recording. All ECG patch recordings will be read in a core facility. In cases of AF detection, oral anticoagulation will be recommended if not contraindicated. A pilot phase has been concluded in 2022, which will transcend into the main trial during 2023-2026, including approximately 30 stroke units. The sample size was calculated to be 3262 patients. The primary outcome will be collected from register data during a 36-month follow-up.

ETHICS AND DISSEMINATION: Ethical approval has been provided by the Swedish Ethical Review Authority, reference 2021-02770. The trial will be conducted according to the ethical principles of the Declaration of Helsinki and national regulatory standards. Positive results from the study have the potential for rapid dissemination in clinical practice.

TRIAL REGISTRATION NUMBER: NCT05134454.

OBJECTIVES: To present the 'Wise List' (a formulary of essential medicines for primary and specialised care in Stockholm Healthcare Region) and assess adherence to the recommendations over a 15-year period.

DESIGN: Retrospective analysis of all prescription data in the Stockholm Healthcare Region between 2000 and 2015 in relation to the Wise List recommendations during the same time period.

SETTING: All outpatient care in the Stockholm Healthcare Region.

PARTICIPANTS: All prescribers in the Stockholm Healthcare Region.

MAIN OUTCOME MEASURES: The number of core and complementary substances included in the Wise List, the adherence to recommendations by Anatomic Therapeutic Chemical (ATC) 1st level using defined daily doses (DDDs) adjusted to the DDD for 2015, adherence to recommendations over time measured by dispensed prescriptions yearly between 2002 and 2015.

RESULTS: The number of recommended core substances was stable (175-212). Overall adherence to the recommendations for core medicines for all prescribers increased from 75% to 84% (2000 to 2015). The adherence to recommendations in primary care for core medicines increased from 80% to 90% (2005 to 2015) with decreasing range in practice variation (32% to 13%). Hospital prescriber adherence to core medicine recommendations was stable but increased for the combination core and complementary medicines from 77% to 88% (2007 to 2015). Adherence varied between the 4 therapeutic areas studied.

CONCLUSIONS: High and increasing adherence to the Wise List recommendations was seen for all prescriber categories. The transparent process for developing recommendations involving respected experts and clinicians using strict criteria for handling potential conflicts of interests, feedback to prescribers, continuous medical education and financial incentives are possible contributing factors. High-quality evidence-based recommendations to prescribers, such as the Wise List, disseminated through a multifaceted approach, will become increasingly important and should be developed further to include recommendations and introduction protocols for new expensive medicines.

PURPOSE: To describe patients initiating dimethyl fumarate (DMF) and measure persistence with DMF, discontinuation, and switching in treatment-naïve DMF patients and patients switching to DMF from other multiple sclerosis disease-modifying treatments (DMTs).

METHODS: A population-based cohort study of all Stockholm County residents initiating DMF from 9 May 2014 until 31 May 2017. All data were derived from a regional database that collects individual-level data on healthcare and drug utilization of all residents. The study outcomes were persistence with DMF and DMF discontinuation and switching to other DMTs. Persistence was measured as the number of days until either DMF discontinuation (treatment gap ≥ 60 days) or switching to another DMT.

RESULTS: The study included 400 patients (median follow-up = 2.5 years). The majority had previously been treated with other DMTs (61%). Throughout the follow-up period, 124 patients (31%) discontinued DMF and 114 patients (29%) switched treatment. Overall, 34% of patients initiating DMF stopped treatment within 1 year and only 43% of patients remained on DMF at 2 years from treatment initiation.

CONCLUSIONS: DMF had a rapid market uptake likely due to high expectations held by both patients and clinicians. However, persistence with DMF in routine clinical practice was found to be low.

PURPOSE: The purpose of this study is to describe the utilization of disease-modifying treatments (DMTs) in relapsing-remitting multiple sclerosis (MS) and assess the impact of both the introduction of new drugs and treatment recommendations (local recommendation on rituximab use issued at the largest MS clinic in Stockholm and regional Drug and Therapeutics Committee (DTC) recommendation on how dimethyl fumarate should be used).

METHODS: Interrupted time series analyses using monthly data on all MS patients treated with DMTs in the Stockholm County, Sweden, from January 2011 to December 2017.

RESULTS: There were 4765 individuals diagnosed with MS residing in the Stockholm County from 2011 to 2017. Of these, 2934 (62%) were treated with an MS DMT. Since 2011, fingolimod, alemtuzumab, teriflunomide, dimethyl fumarate, peginterferon beta-1a, and daclizumab were introduced. Only fingolimod and dimethyl fumarate significantly impacted MS DMT utilization. In parallel, the use of rituximab off-label increased steadily, reaching 58% of all DMT-treated MS patients by the end of the study period. The local recommendation on rituximab was associated with an increase in rituximab use. The regional DTC recommendation on dimethyl fumarate was associated with a decrease in dimethyl fumarate use.

CONCLUSIONS: Three MS DMTs-fingolimod, dimethyl fumarate, and rituximab off-label-impacted MS DMT utilization in the Stockholm County. The associations between the treatment recommendations and the subsequent changes in MS DMT utilization indicate that such interventions can influence the uptake and utilization of new drugs used in the specialized care setting.

BACKGROUND: Early awareness and alert systems have been established in many countries but evidence on their ability to accurately prioritize new medicines (for early assessment) is limited.

OBJECTIVE: The purpose of this study was to assess whether the Swedish Early Awareness and Alert System identified and prioritized (i.e., produced early assessment reports for) new medicines that would go on to have substantial economic impact.

METHODS: We adapted a study design commonly used in the assessment of diagnostic test accuracy. The prioritization made by the Swedish Early Awareness and Alert System prior to marketing authorization comprised the index test and the national drug sales data in the second year post-authorization served as the reference standard. All initial marketing authorization applications for medicinal products processed by the European Medicines Agency between 2010 and 2015 (study population) were classified using the index test and the reference standard.

RESULTS: Two hundred and fifty-three new medicinal products processed by the European Medicines Agency comprised the study population. Of these, 71 were prioritized by the Swedish Early Awareness and Alert System and 21 were classified as having substantial economic impact. The sensitivity and positive predictive value were 76.2% and 22.5%, respectively. Subgroup analyses showed that the accuracy of prioritization, in terms of sensitivity, was 100% for antineoplastic/immunomodulating agents.

CONCLUSIONS: The Swedish Early Awareness and Alert System identified all new medicines that would go on to have substantial economic impact and prioritized most of these medicines. Our findings provide reassurance to decision makers who rely on the outputs of the Swedish Early Awareness and Alert System to keep informed about new medicines. Moreover, this study also provides valuable insights to stakeholders willing to establish or evaluate their own early awareness and alert activities and systems.

The Swedish EAA System started as a regional initiative and rapidly grew to become a national level activity. An important feature of the system today is its complete integration into the national process for managed introduction and follow-up of new medicines. The system will continue to evolve as a response both to the changing landscape of health innovations and to new policy initiatives at the regional, national and international level.

Background: Stroke incidence, care, and survival show continuous improvements in Sweden, including no or decreasing disparities between men and women. In this study, we aimed to estimate and compare the risk of stroke recurrence in men and women over time, accounting for the competing risk of death.

Methods and Results: We included adult patients with first-time stroke (ischemic or intracerebral hemorrhage) registered in Riksstroke (the Swedish Stroke Register), 2012 to 2020, and followed until December 2020. Stroke recurrences included new events registered in Riksstroke from 28 days after stroke. To account for the competing risk of death, we used the cumulative incidence function to estimate crude incidences, and multivariable Cox regression to estimate cause-specific hazard ratios (HRs) adjusting for differences in patients' risk factor profiles. The study included 72 148 (53.5%) men and 62 689 (46.5%) women. We observed 10 925 stroke recurrences and 81 811 deaths following the initial 28 days after the first stroke. The cumulative incidence of stroke recurrence was 3.7% (95% CI, 3.6-3.8) after 1 year, 7.0 (95% CI, 6.8-7.1) after 3 years, and 9.1% (95% CI, 8.9-9.3) after 5 years. The incidence decreased substantially during the study period (HR, 2019-2020 versus 2012, 0.824 [95% CI, 0.759-0.894]). Overall, men had a lower risk of stroke recurrence. After adjustments for differences in patient characteristics, men had a slightly higher risk of recurrence (of any type) after an ischemic stroke (HR, 1.090 [95% CI, 1.045-1.138]) and a lower risk after hemorrhagic stroke (HR, 0.880 [95% CI, 0.781-0.991]) compared with women.

Conclusions: The risk of stroke recurrence has decreased in both men and women. Women's higher age and other differences in risk factors partly explain their higher risk of stroke recurrence compared with men.

BACKGROUND AND PURPOSE: Previous studies of stroke management and outcome in Sweden have revealed differences between men and women. We aimed to analyze if differences in stroke incidence, care, and outcome have altered over time.

METHODS: All stroke events registered in the Swedish Stroke Register 2005 to 2018 were included. Background variables and treatment were collected during the acute hospital stay. Survival data were obtained from the national cause of death register by individual linkage. We used unadjusted proportions and estimated age-adjusted marginal means, using a generalized linear model, to present outcome.

RESULTS: We identified 335 183 stroke events and a decreasing incidence in men and women 2005 to 2018. Men were on average younger than women (73.3 versus 78.1 years) at stroke onset. The age-adjusted proportion of reperfusion therapy 2005 to 2018 increased more rapidly in women than in men (2.3%-15.1% in men versus 1.4%-16.9% in women), but in 2018, women still had a lower probability of receiving thrombolysis within 30 minutes. Among patients with atrial fibrillation, oral anticoagulants at discharge increased more rapidly in women (31.2%-78.6% in men versus 26.7%-81.9% in women). Statins remained higher in men (36.9%-83.7% in men versus 32.3%-81.2% in women). Men had better functional outcome and survival after stroke. After adjustment for women's higher age, more severe strokes, and background characteristics, the absolute difference in functional outcome was <1% and survival did not differ.

CONCLUSIONS: Stroke incidence, care, and outcome show continuous improvements in Sweden, and previously reported differences between men and women become less evident. More severe strokes and older age in women at stroke onset are explanations to persisting differences.

Background and Purpose: The purpose of this study was to investigate the impact of improved antithrombotic treatment in atrial fibrillation after the introduction of non-vitamin K antagonist oral anticoagulants on the incidence of stroke and bleeding in a real-life total population, including both primary and secondary care.

Methods: All resident and alive patients with a recorded diagnosis for atrial fibrillation during the preceding 5 years in the Stockholm County Healthcare database (Vårdanalysdatabasen) were followed for clinical outcomes during 2012 (n=41 008) and 2017 (n=49 510).

Results: Pharmacy claims for oral anticoagulants increased from 51.6% to 73.8% (78.7% among those with CHA₂DS₂-VASc ≥2). Non-vitamin K antagonist oral anticoagulant claims increased from 0.4% to 34.4%. Ischemic stroke incidence rates decreased from 2.01 per 100 person-years in 2012 to 1.17 in 2017 (incidence rate ratio, 0.58; 95% CI, 0.52-0.65). The largest increases in oral anticoagulants use and decreases in ischemic strokes were seen in patients aged ≥80 years who had the highest risk of stroke and bleeding. The incidence rates for major bleeding (2.59) remained unchanged (incidence rate ratio, 1.00; 95% CI, 0.92-1.09) even in those with a high bleeding risk. Poisson regression showed that 10% of the absolute ischemic stroke reduction was associated with increased oral anticoagulants treatment, whereas 27% was related to a generally decreased risk for all stroke.

Conclusions: Increased oral anticoagulants use contributed to a marked reduction of ischemic strokes without increasing bleeding rates between 2012 and 2017. The largest stroke reduction was seen in elderly patients with the highest risks for stroke and bleeding. These findings strongly support the adoption of current guideline recommendations for stroke prevention in atrial fibrillation in both primary and secondary care.

Sedan introduktionen av NOAK (non-vitamin K antagonist oral anticoagulants) som trombosprofylax vid förmaksflimmer har det skett en markant ökning av antalet diagnostiserade patienter med förmaksflimmer i Stockholms läns landsting. Andelen som är behandlade med antikoagulantia har samtidigt ökat från 47 till 58 procent. Vid nyinsättning är NOAK lika vanliga som warfarin i nuläget. Förskrivningen av ASA sjunker kraftigt. NOAK-förskrivningen har varit avvaktande avseende de äldsta patienterna med hög risk för stroke, blödning och nedsatt njurfunktion.

BACKGROUND: Earlier validation studies of risk scoring by CHA2DS2VASc for assessments of appropriateness of warfarin treatment in patients with atrial fibrillation have been performed solely with diagnoses recorded in hospital based care, even though many patients to a large extent are managed in primary care.

METHODS: Cross-sectional registry study of all 43 353 patients with a diagnosis of non-valvular atrial fibrillation recorded in inpatient care, specialist ambulatory care or primary care in the Stockholm County during 2006-2010.

RESULTS: The mean CHA2DS2VASc score was 3.82 (4.67 for women and 3.14 for men). 64% of the entire cohort of patients with atrial fibrillation had the diagnosis in primary care (12% only there). The mean CHA2DS2VASc score of patients with a diagnosis only in inpatient care or specialist ambulatory care increased from 3.63 to 3.83 when comorbidities registered in primary care were added. In 2010 warfarin prescriptions were claimed by 47.2%, and ASA by 41.6% of the entire cohort. 34% of patients with CHA2DS2VASc=1 and 20% with CHA2DS2VASc=0 had warfarin treatment. ASA was more frequently used instead of warfarin among women and elderly patients.

CONCLUSIONS: Registry CHA2DS2VASc scores were underestimated without co-morbidity data from primary care. Many individuals with scores 0 and 1 were treated with warfarin, despite poor documentation of clinical benefit. In contrast, warfarin appears to be underused and ASA overused among high risk atrial fibrillation patients. Lack of diagnoses from primary care underestimated CHA2DS2VASc scores and may thereby have overestimated treatment benefits in low-risk patients in earlier studies.

PURPOSE: This study evaluated the benefits of and possible contraindications to warfarin treatment in patients with atrial fibrillation (AF) prior to the introduction of new oral anticoagulants using health registry data from inpatient care, specialist ambulatory care, and primary care.

METHODS: This is a cohort study including all patients in the region of Stockholm, Sweden (2.1 million inhabitants) with a diagnosis of non-valvular AF (n = 41 810) recorded during 2005-2009. The risks of suffering ischemic stroke, bleeding, or death with warfarin, aspirin, or no antithrombotic treatment during 2010 were related to CHA2DS2VASc scores, age, and complicating co-morbidities.

RESULTS: One-year risks for ischemic stroke were 1.0-1.2 % with aspirin, 0-0.3 % with warfarin, and 0.1-0.2 % without treatment at CHA2DS2VASc scores 0-1. Among the aspirin-treated patients with CHA2DS2VASc scores ≥2, half had possible contraindications and high risks for ischemic stroke (5.2 %), bleeding (5.0 %), and death (19.3 %). The other half of the patients with no identified contraindications had a high risk for ischemic stroke (4.0 %) but a low bleeding risk (1.8 %) and a moderate mortality rate (8.4 %).

CONCLUSIONS: The present observations confirm earlier findings of undertreatment with warfarin and half of the high-risk patients treated with aspirin were obvious candidates for anticoagulant treatment. However, the other half of the patients had complicating co-morbidities, high bleeding risk, and poor prognosis. This and possible overtreatment of low-risk patients should be taken into account when considering more aggressive use of anticoagulant treatment.

PURPOSE: Triptans are widely used in acute migraine, and in some countries, they are also available over-the-counter (OTC). In Sweden, sales have increased for both prescription and OTC triptans. This study aimed to describe current prescribing and utilisation patterns of prescription and OTC triptans in Stockholm, Sweden.

METHODS: Register data from 4759 patients dispensed triptans in 2014 were used to study documented diagnosis of migraine, concomitant acute and preventive treatment for migraine, and contraindications. Survey data from 49 patients purchasing OTC triptans in three pharmacies were used to capture physician-diagnosed migraine, concomitant acute and preventive treatment for migraine, a behaviour of combining or alternating between prescription and OTC triptans, and pharmacy counselling rates.

RESULTS: Among the prescription triptan users, 52 % had a recorded diagnosis of migraine, 48 % had no other acute treatment, preventive treatment was rare (12 %) and contraindications were found in 2 % of the patients. Among the OTC triptan users, the majority (63 %) had been diagnosed by a physician and had a history of prescription triptan use, but combining or alternating between OTC and prescription triptans was rare. Concomitant acute treatment was reported in 53 % and preventive treatment was rare (4 %), despite high self-reported migraine frequencies. Some off-label use was detected, despite moderate to high counselling rates.

CONCLUSION: Triptans are prescribed with attention to safety but with poor recording of migraine diagnosis. OTC triptan users generally have a history of prescription triptan use. Preventive treatment rates are low in both groups. Strategies to discern patients who need other treatment options should be considered.

OBJECTIVES: To explore the association between prestroke mobility dependency and dementia on functioning and mortality outcomes after stroke in patients>65 years of age.

DESIGN: Longitudinal cohort study based on SveDem, the Swedish Dementia Registry and Riksstroke, the Swedish Stroke Registry.

PARTICIPANTS: A total of 1689 patients with dementia >65 years of age registered in SveDem and suffering a first stroke between 2007 and 2014 were matched with 7973 controls without dementia with stroke.

MEASUREMENTS: Odds ratios (ORs) and 95% confidence intervals (CIs) for intrahospital mortality, and functioning and mortality outcomes at 3 months were calculated. Functioning included level of residential assistance (living at home without help, at home with help, or nursing home) and mobility dependency (independent, needing help to move outdoors, or needing help indoors and outdoors).

RESULTS: Prestroke dependency in activities of daily living and mobility were worse in patients with dementia than controls without dementia. In unadjusted analyses, patients with dementia were more often discharged to nursing homes (51% vs 20%; P < .001). Mortality at 3 months was higher in patients with dementia (31% vs 23% P < .001) and fewer were living at home without help (21% vs 55%; P < .001). In adjusted analyses, prestroke dementia was associated with higher risk of 3-month mortality (OR 1.34; 95% CI 1.18-1.52), requiring a higher level of residential assistance (OR 4.07; 3.49-.75) and suffering from more dependency in relation to mobility (OR 2.57; 2.20-3.02). Patients with dementia who were independent for mobility prestroke were more likely to be discharged to a nursing home compared with patients without dementia with the same prestroke mobility (37% vs 16%; P < .001), but there were no differences in discharge to geriatric rehabilitation (19% for both; P = .976). Patients, who moved independently before stroke, were more often discharged home (60% vs 28%) and had lower mortality. In adjusted analyses, prestroke mobility limitations were associated with higher odds for poorer mobility, needing more residential assistance, and death.

CONCLUSIONS: Patients with mobility impairments and/or dementia present a high burden of disability after a stroke. There is a need for research on stroke interventions among these populations.

Background: Improving use of anticoagulants in atrial fibrillation (AF) patients in primary care has proved challenging. Anticoagulants are often prescribed by primary care physicians in the long term. Suboptimal anticoagulant use may be partly due to physicians' non-prescribing. One potential way of targeting physician prescribing behavior is “audit & feedback”. The documented use of audit and feedback in research aimed at increasing use of anticoagulants in primary care is limited. The objective was to test if an audit & feedback intervention aimed at directors in primary care centers could increase the use of anticoagulants in patients with AF.

Methods: Database generated quality reports with primary care center specific data on recommended medication use in their patients with previous stroke or atrial fibrillation were sent to intervention centers.

Results: 94 centers received the intervention, 102 centers were controls. 31,477 patients in total were included. Use of anticoagulants in all primary care centers increased from 76% before to 82% after the intervention. Patients in intervention centers were more likely than patients in control centers to use anticoagulants after the intervention, adjusted odds ratio increasing slightly from 1.04 (95%, CI, 0.98–1.10) before to 1.08 (95% CI, 1.02–1.15) after the intervention.

Conclusions: An audit & feedback intervention with quality reports in primary care had only a small effect on anticoagulant use in patients with AF. A combined and more complex intervention may have a greater effect in improving anticoagulation use. 

OBJECTIVES: To analyse if there are sociodemographic differences in the utilisation of statins 9-12 months after ischaemic stroke or transitory ischaemic attack.

METHODS: Anonymised linkage of registry data on all patients >18 years discharged from the hospitals in Stockholm, Sweden 2006-2010 with diagnosis of ischaemic stroke (ICD-10: I63.0-9) or TIA (ICD-10: G45.9) was performed. Data on hospitalisations and diagnoses were collected from the Stockholm County Council administrative databases on healthcare consumption. Dispensed prescriptions with statins and, for comparative purposes, antihypertensive agents 9-12 months after discharge were acquired from the National Swedish Prescribed Drug Register. Data about socioeconomic factors were obtained from Statistics Sweden. The dispensing of statins and antihypertensive agents, relative to sociodemographic variables were analysed. Using logistic regression odds ratios, crude, and adjusted with education, income, origin of birth, age, and sex as predictors where calculated.

RESULTS: Of 24 312 patients with ischaemic stroke/TIA, 19 335 were alive 12 months after discharge. Statins were dispensed to 44% of all patients in the cohort, more frequently to men of all age groups, to patients with higher education, and to those with higher income. Antihypertensive agents were dispensed to 68% of all patients and there were no differences related to sex and income whilst patients with lower education were dispensed with antihypertensives more frequently.

CONCLUSION: We find a low utilisation of statins one year after ischaemic stroke/TIA. Patients with low education, low income, and female sex were dispensed fewer prescriptions of statins indicating a need for improvement.

OBJECTIVES: The clinical benefits of use of secondary preventive pharmacotherapy in ischemic stroke/TIA have been previously demonstrated. A potential target for facilitating the use of recommended medications is primary care physicians. Therefore, we carried out an audit and feedback intervention aimed at primary care centers. The aim was to improve the use of secondary preventive stroke medications and diagnosis recording in ischemic stroke/TIA.

MATERIALS AND METHODS: The intervention consisted of structured, healthcare database-derived quality reports on secondary preventive medication use and diagnosis recording, sent in 2015 to half of the primary care centers in Stockholm County, with information specific to each primary care center. Medication dispensation (primary outcome) for statins, antihypertensives, antiplatelets, and anticoagulants, as well as diagnosis recording (secondary outcome), was compared between intervention centers and control centers in the 18 months following the intervention. Outcome data were derived from the healthcare databases of Stockholm County (VAL).

RESULTS: Dispensation of medications to the 12 766 patients analyzed in the study was high. Over 77% of patients used antihypertensives and antithrombotics, and 65%-68% used statins. After the intervention, no differences in medication dispensation were seen between the intervention and control centers, even after adjusting for potential confounders.

CONCLUSIONS: A simple audit and feedback intervention directed toward physicians in primary care did not improve medication dispensation to ischemic stroke/TIA patients 18 months later. Any future audit and feedback intervention aimed at improving adherence to guidelines for secondary prevention in primary care should consider multiple and continuous reminders, the graphical appeal, and widening the recipients to include patients.

PURPOSE: To perform a meta-analysis on how the admissions of stroke and transient ischemic attack (TIA) changed during the Corona Virus infection-19 (COVID-19) pandemic and evaluate if the effect was depending on stroke severity.

METHODS: Observational cohort studies comparing the number of stroke and/or TIA admissions during a period of the pandemic compared to a period before the pandemic were identified in PubMed and Embase. After excluding studies with overlapping populations and studies without satisfactory case ascertainment, data was extracted and meta-analyzed.

FINDINGS: A total of 59 studies were included. During the pandemic, there was a decrease in admissions of ischemic stroke (admission rate ratio (ARR) = 0.77, 95% confidence interval (CI): 0.72, 0.82), intracerebral hemorrhage (ARR = 0.79, 95% CI: 0.70, 0.90) and TIA (ARR = 0.66, 95% CI: 0.58, 0.75). Albeit admission rates of both mild (ARR = 0.61, 95% CI: 0.49, 0.77) and severe (ARR = 0.82, 95% CI = 0.71, 0.95) strokes decreased, milder strokes decreased more (proportion ratio (PR) = 0.76, 95% CI: 0.65, 0.89).

DISCUSSION: Potential causes for the admission reduction could be strict prioritizations within the health care, patients' fear of acquiring COVID-19, or decreased access to health care due to lockdowns.

CONCLUSION: During the COVID-19 pandemic, there was a reduction in admissions of stroke and TIA, possibly caused by reluctance to seek medical care.

The aim was to present and evaluate the impact of a comprehensive strategy over 10 years to select, communicate and achieve adherence to essential drug recommendations (EDR) in ambulatory care in a metropolitan healthcare region. EDRs were issued and launched as a 'Wise List' by the regional Drug and Therapeutics Committee in Stockholm. This study presents the concept by: (i) documenting the process for selecting, communicating and monitoring the impact of the 'Wise List'; (ii) analysing the variation in the number of drug substances recommended between 2000 and 2010; (iii) assessing the attitudes to the 'Wise List' among prescribers and the public; (iv) evaluating the adherence to recommendations between 2003 and 2009. The 'Wise List' consistently contained 200 drug substances for treating common diseases. The drugs were selected based on their efficacy, safety, suitability and cost-effectiveness. The 'Wise List' was known among one-third of a surveyed sample of the public in 2002 after initial marketing campaigns. All surveyed prescribers knew about the concept and 81% found the recommendations trustworthy in 2005. Adherence to recommendations increased from 69% in 1999 to 77% in 2009. In primary care, adherence increased from 83% to 87% from 2003 to 2009. The coefficient of variation (CV%) decreased from 6.1% to 3.8% for 156 healthcare centres between these years. The acceptance of the 'Wise List' in terms of trust among physicians and among the public and increased adherence may be explained by clear criteria for drug recommendations, a comprehensive communication strategy, electronic access to recommendations, continuous medical education and involvement of professional networks and patients.

BACKGROUND: Adverse drug reactions (ADRs) are common in elderly patients. There are various reasons for this, including age- and disease-related alterations in pharmacokinetics and pharmacodynamics as well as the common practice of polypharmacy. The decline in renal function in elderly patients may also predispose them to pharmacological ADRs (type A, augmented). Patients receiving home healthcare may be at even higher risk.

OBJECTIVES: To study ADRs as a cause of acute hospital admissions in a defined cohort of elderly patients (aged >or=65 years) registered to receive home healthcare services, with special reference to impaired renal function as a possible risk factor.

METHODS: This was a retrospective study of 154 elderly patients aged >or=65 years admitted to the emergency department of a university hospital in Stockholm, Sweden, in October-November 2002. Estimated creatinine clearance (eCL(CR)) was calculated from the Cockcroft-Gault formula, and estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease (MDRD) equation. ADRs were defined according to WHO criteria. All medications administered to patients at admission and at discharge were collated. These and other data were collected from computerized hospital records.

RESULTS: ADRs were judged to contribute to or be the primary cause of hospitalization in 22 patients, i.e. 14% of 154 patients registered to receive home healthcare. Eleven of the 22 patients were women. All but one ADR were type A. Excessive doses or drugs unsuitable in renal insufficiency were present in seven patients in the ADR group compared with only four patients in the group without ADRs (p = 0.0001). Patients with ADRs did not differ significantly from those without ADRs in relation to age, plasma creatinine, eCL(CR), weight or number of drugs prescribed at admission. However, women with ADRs were significantly older than women without ADRs (mean +/- SD age 88.8 +/- 5.7 years vs 82.5 +/- 8.0 years, respectively; p = 0.014) and had significantly lower mean +/- SD eCL(CR) values (25.5 +/- 10.8 and 37.1 +/- 17.1 mL/min, respectively; p = 0.035). Median MDRD eGFR was significantly higher than median eCL(CR) (59 [range 6-172] mL/min/1.73 m2 vs 38 [range 5-117] mL/min, respectively; p = 0.0001).

CONCLUSIONS: In elderly patients registered to receive home healthcare, 14% of hospital admissions were primarily caused by ADRs. One-third of these ADRs were related to impaired renal function, generally in very old women. These ADRs may be avoided by close monitoring of renal function and adjustments to pharmacotherapy (drug selection and dose), particularly in very elderly women.

OBJECTIVES: The thrombin inhibitor dabigatran is mainly excreted by the kidneys. We investigated whether the recommended method for estimation of renal function used in the clinical trials, the Cockcroft-Gault (CGold) equation and the estimated glomerular filtration rate (eGFR) modification of diet in renal disease equation 4 (MDRD4), differ in elderly participants, resulting in erroneously higher dose recommendations of dabigatran, which might explain the serious, even fatal, bleeding reported. The renally excreted drugs gabapentin and valaciclovir were also included for comparison.

DESIGN: A retrospective data simulation study.

PARTICIPANTS: Participants 65 years and older included in six different studies.

MAIN OUTCOME MEASURE: Estimated renal function by CG based on uncompensated ('old Jaffe' method) creatinine (CGold) or by MDRD4 based on standardised compensated P-creatinine traceable to isotope-dilution mass spectrometry, and the resulting doses.

RESULTS: 790 participants (432 females), mean age (±SD) 77.6±5.7 years. Mean estimated creatinine clearance (eCrCl) by the CGold equation was 44.2±14.8 ml/min, versus eGFR 59.6±20.7 ml/min/1.73 m(2) with MDRD4 (p<0.001), absolute median difference 13.5, 95% CI 12.9 to 14.2. MDRD4 gave a significantly higher mean dose (valaciclovir +21%, dabigatran +25% and gabapentin +37%) of all drugs (p<0.001). With MDRD4 58% of the women would be recommended a full dose of dabigatran compared with 18% if CGold is used.

CONCLUSIONS: MDRD4 would result in higher recommended doses of the three studied drugs to elderly participants compared with CG, particularly in women, and thus increased the risk of dose and concentration-dependent adverse reactions. It is important to know which method of estimation of renal function the Summary of Products Characteristics was based on, and use only that one when prescribing renally excreted drugs with narrow safety window. Doses based on recently developed methods for estimation of renal function may be associated with considerable risk of overtreatment in the elderly.

We have analyzed the binding properties of the selective D3 receptor agonist [3H]PD 128907 in 120 days old rats. In tissue sections, we found high numbers of binding sites for [3H]PD 128907 both in the islands of Calleja and the caudate-putamen (Bmax values being 500 and 1000 fmol/mg protein, respectively). The KD values were higher in the caudate-putamen than in the islands of Calleja. Similar regional differences in Bmax and KD values were observed in membranes from the caudate-putamen and the subcortical limbic region. The distribution of [3H]PD 128907 in adult rats is markedly different from that observed in young rats. Taken together, the present results suggest a prominent presence of D3 receptors in the caudate-putamen of adult, but not young, rats. Hence, these findings may have important physiological, pathophysiological, and clinical implications.

The introduction of NOACs has put a focus on stroke prevention in atrial fibrillation (AF). The number of patients in Stockholm diagnosed with non-valvular AF increased from 41 008 in 2011 to 51 266 in 2017 and their treatment has been markedly improved. Between 2011 and 2017 total oral anticoagulant treatment increased from 51.6% (warfarin) to 77.3% (31% warfarin, 46.3% NOACs) and aspirin decreased from 31.6% to 7.2%. Treatment was especially improved among patients with CHA2DS2-VASc scores ≥2 and elderly high risk patients. We found an excellent persistence with OAC treatment (88% at 1 year and 83% at 2 years). A comparative effectiveness study showed that NOACs were at least as effective and safe as warfarin even among patients ≥80 years or with previous serious bleeds. After a gradual introduction of NOACs with many educational activities apixaban is now the first-line choice for stroke prevention in AF in Stockholm. Swedish guideline goals are fulfilled and outcomes are improved.

BACKGROUND: Stroke and dementia are frequent comorbidities. Dementia possibly increases total costs of stroke care, especially cost of institutionalization and informal medical care. However, stroke rehabilitation costs in dementia patients are understudied.

OBJECTIVE: To estimate inpatient stroke rehabilitation costs for Swedish dementia patients in comparison with non-dementia patients.

METHODS: A longitudinal cohort study with linked data from the Swedish Dementia Register and the Swedish Stroke Register was conducted. Patients diagnosed with dementia who suffered a first ischemic stroke between 2010 and 2014 (n = 138) were compared with non-dementia patients (n = 935). Cost analyses were conducted from a Swedish health care perspective. The difference of rehabilitation costs between the two groups was examined via simple linear regression (before and after matching by propensity scores of dementia) and multiple linear regression.

RESULTS: Mean inpatient rehabilitation costs for dementia and non-dementia patients were SEK 103,693/$11,932 and SEK 130,057/$14,966, respectively (median SEK 92,183/$10,607 and SEK 106,365/$12,239) (p = 0.001). Dementia patients suffered from more comorbidities and experienced lower functioning, compared to non-dementia patients. The inpatient rehabilitation cost for patients with known dementia was 0.84 times the cost in non-dementia individuals.

CONCLUSION: Dementia diagnosis was significantly associated with lower inpatient stroke rehabilitation costs. This might be explained by physicians' beliefs on the limited effectiveness of rehabilitation in dementia patients. Further research on cost-effectiveness of stroke rehabilitation and patients' satisfaction with stroke rehabilitation is necessary.

BACKGROUND: Patient dissatisfaction with stroke care is associated with poor self-rated health and unmet care needs. Dementia patients' satisfaction with stroke care is understudied.

OBJECTIVE: To compare satisfaction with stroke care in patients with and without dementia.

METHODS: This longitudinal cohort study included 5,932 dementia patients (2007-2017) who suffered a first stroke after dementia diagnosis and 39,457 non-dementia stroke patients (2007-2017). Data were retrieved by linking the Swedish Stroke Register, the Swedish Dementia Register, the Swedish National Patient Register, and the Swedish Prescribed Drug Register. The association between dementia and satisfaction was analyzed with ordinal logistic regression.

RESULTS: When dementia patients answered themselves, they reported significantly lower odds of satisfaction with acute stroke care (OR: 0.71; 95% CI: 0.60-0.85), healthcare staff's attitude (OR: 0.79; 95% CI: 0.66-0.96), communication with doctors (OR: 0.78; 95% CI: 0.66-0.92), stroke information (OR: 0.62; 95% CI: 0.52-0.74); but not regarding inpatient rehabilitation (OR: 0.93; 95% CI: 0.75-1.16), or outpatient rehabilitation (OR: 0.93; 95% CI: 0.73-1.18). When patients answered with caregivers' help, the association between dementia status and satisfaction remained significant in all items. Subgroup analyses showed that patients with Alzheimer's disease and mixed dementia reported lower odds of satisfaction with acute care and healthcare staff's attitude when they answered themselves.

CONCLUSION: Patients with dementia reported lower satisfaction with stroke care, revealing unfulfilled care needs among dementia patients, which are possibly due to different (or less) care, or because dementia patients require adaptations to standard care.

Cerebral microemboli are frequently observed during coronary angiography (CA) and percutaneous coronary intervention (PCI), and their numbers have been related to the vascular access site used. Although cerebral microemboli can cause silent cerebral lesions, their clinical impact is debated. To study this, 93 patients referred for CA or PCI underwent serial cognitive testing using the Montreal Cognitive Assessment (MoCA) test to detect postprocedural cognitive impairment. Patients were randomized to radial or femoral access. In a subgroup of 35 patients, the number of cerebral microemboli was monitored with transcranial Doppler technique. We found the median precatheterization result of the MoCA test to be 27, and it did not change significantly 4 and 31 days, respectively, after the procedure. There was no significant correlation between the number of cerebral microemboli and the difference between preprocedural and postprocedural MoCA tests. The test results did not differ between vascular access sites. One-third of the patients had a precatheterization median MoCA test result <26 corresponding to mild cognitive impairment. In conclusion, using the MoCA test, we could not detect any cognitive impairment after CA or PCI, and no significant correlations were found between the results of the MoCA test and cerebral microemboli or vascular access site, respectively. In patients with suspected coronary heart disease, mild cognitive impairment was common.

BACKGROUND: The effect of calcium channel blockers (CCB) on mortality and ischaemic stroke risk in dementia patients is understudied.

OBJECTIVES: To calculate the risk of death and ischaemic stroke in dementia patients treated with CCBs, considering individual agents and dose response.

METHODS: Longitudinal cohort study with 18 906 hypertensive dementia patients from the Swedish Dementia Registry (SveDem), 2008-2014. Other Swedish national registries contributed information on comorbidities, dispensed medication and outcomes. Individual CCB agents and cumulative defined daily doses (cDDD) were considered.

RESULTS: In patients with hypertension and dementia, nifedipine was associated with increased mortality risk (aHR 1.32; CI 1.01-1.73; P < 0.05) compared to non-CCB users. Patients diagnosed with Alzheimer's dementia (AD) or dementia with Lewy bodies/Parkinson's disease dementia (DLB-PDD) taking amlodipine had lower mortality risk (aHR, 0.89; CI, 0.80-0.98; P < 0.05 and aHR 0.58; CI, 0.38-0.86; P < 0.01, respectively), than those taking other CCBs. Amlodipine was associated with lower stroke risk in patients with Alzheimer's dementia compared to other CCBs (aHR 0.63; CI, 0.44-0.89; P < 0.05). Sensitivity analyses with propensity score-matched cohorts repeated the results for nifedipine (aHR 1.35; 95% CI, 1.02-1.78; P < 0.05) and amlodipine in AD (aHR, 0.87; CI, 0.78-0.97; P < 0.05) and DLB-PDD (aHR, 0.56, 95%CI, 0.37-0.85; P < 0.05).

CONCLUSION: Amlodipine was associated with reduced mortality risk in dementia patients diagnosed with AD and DLB-PDD. AD patients using amlodipine had a lower risk of ischaemic stroke compared to other CCB users.

Objective: In November 2014, the European Medicines Agency (EMA) strengthened restrictions on the use of valproic acid in girls and women of childbearing potential. The objective of this study was to determine whether there has been a change in initiations of valproic acid treatment to females after the regulatory restrictions and to assess if such changes differed between indications (epilepsy and psychiatric disorder).

Methods: An interrupted time-series analysis was conducted using all initiations of valproic acid in Stockholm, Sweden. from January 2011 to June 2017. Female and male patients aged 0-45 years with a recorded diagnosis of epilepsy and/or a psychiatric disorder were compared.

Results: Before the EMA warning, a decline in trend of valproic acid initiations was seen in patients with epilepsy. After the warning, a significant decrease of valproic acid initiations was seen in women with a psychiatric disorder, but not in women with epilepsy.

Significance: The regulatory warning appeared to have significantly influenced valproic acid initiations in women of childbearing age with a psychiatric disorder. No effect was seen in women with epilepsy, probably because the decline had started long before.