Methodological quality of 100 recent systematic reviews of health-related outcome measurement instruments: an overview of reviews.

PURPOSE: Systematic reviews evaluating and comparing the measurement properties of outcome measurement instruments (OMIs) play an important role in OMI selection. Earlier overviews of review quality (2007, 2014) evidenced substantial concerns with regards to alignment to scientific standards. This overview aimed to investigate whether the quality of recent systematic reviews of OMIs lives up to the current scientific standards. METHODS: One hundred systematic reviews of OMIs published from June 1, 2021 onwards were randomly selected through a systematic literature search performed on March 17, 2022 in MEDLINE and EMBASE. The quality of systematic reviews was appraised by two independent reviewers. An updated data extraction form was informed by the earlier studies, and results were compared to these earlier studies' findings. RESULTS: A quarter of the reviews had an unclear research question or aim, and in 22% of the reviews the search strategy did not match the aim. Half of the reviews had an incomprehensive search strategy, because relevant search terms were not included. In 63% of the reviews (compared to 41% in 2014 and 30% in 2007) a risk of bias assessment was conducted. In 73% of the reviews (some) measurement properties were evaluated (58% in 2014 and 55% in 2007). In 60% of the reviews the data were (partly) synthesized (42% in 2014 and 7% in 2007); evaluation of measurement properties and data syntheses was not conducted separately for subscales in the majority. Certainty assessments of the quality of the total body of evidence were conducted in only 33% of reviews (not assessed in 2014 and 2007). The majority (58%) did not make any recommendations on which OMI (not) to use. CONCLUSION: Despite clear improvements in risk of bias assessments, measurement property evaluation and data synthesis, specifying the research question, conducting the search strategy and performing a certainty assessment remain poor. To ensure that systematic reviews of OMIs meet current scientific standards, more consistent conduct and reporting of systematic reviews of OMIs is needed.

Caregiver strain and fatigue are independent determinants of anxiety among patients early after stroke.

Anxiety and depression are common mental health disorders in stroke patients, and often co-occur. However, in contrast to depression, there is limited research about anxiety after stroke, although impact of anxiety can be substantial. Therefore, this cross-sectional observational study investigated determinants of anxiety after stroke and compared them with determinants of depression after stroke. Stroke surviving patients (n = 284) were seen six weeks after discharge from the hospital or rehabilitation setting. Of these, 238 patients answered all questions of the Hospital Anxiety and Depression Scale measuring anxiety (HADS-a) and 239 patients answered all questions measuring depression (HADS-d). Step-wise regression was used to identify independent determinants of anxiety and depression after stroke. Higher levels of anxiety were associated with a higher caregiver strain (p < 0.01) and more fatigue (p < 0.05). In contrast, higher levels of depression were associated with lower life satisfaction (p < 0.001) and less daily activities (p < 0.05), but also more fatigue (p < 0.001). Hence, our results show that both fatigue and caregiver strain are associated with higher levels of anxiety, but of these only fatigue is also associated with higher levels of depression. Practitioners should therefore ask for both anxiety and depression symptoms in stroke patients.

Measurement properties and interpretability of the PROMIS item banks in stroke patients: a systematic review.

PURPOSE: Both the International Consortium for Health Outcomes Measurement and the National Institutes of Health recommend the use of Patient-Reported Outcomes Measurement Information System (PROMIS®) measures in clinical care and research for stroke patients. This study aimed to systematically review the literature on the measurement properties and interpretability of PROMIS measures in stroke patients. METHODS: Nine databases were searched from January 1st, 2007 till April 12th, 2021 for studies concerning the measurement properties and interpretability of PROMIS measures in stroke patients. The findings of these studies were analyzed according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guideline for systematic reviews of Patient-Reported Outcome Measures (PROMs). RESULTS: Ten studies were included. The PROMIS Global Health was studied the most: its two subscales had sufficient structural validity in one study of very good quality, sufficient construct validity with > 75% of hypotheses tested confirmed (high GRADE rating), sufficient internal consistency, i.e. α ≥ 0.70 in two studies (high GRADE rating), sufficient reliability, i.e. ICC ≥ 0.70 in one study of doubtful quality, and indeterminate responsiveness in one study of inadequate quality. For other PROMIS measures, the measurement properties and interpretability were limitedly studied. CONCLUSION: The PROMIS Global Health showed sufficient structural and construct validity and internal consistency in stroke patients. There is a need for further research on content validity, structural validity, and measurement invariance of PROMIS measures in stroke patients. Trial Registration Information: CRD42020203044 (PROSPERO).

Patient Activation During the First 6 Months After the Start of Stroke Rehabilitation.

OBJECTIVE: To examine patient activation from the start of stroke rehabilitation and its course up until the 6-month follow-up. DESIGN: Inception cohort study with a follow-up of 6 months. SETTING: Multidisciplinary rehabilitation facility. PARTICIPANTS: A total of 478 patients (N=478) with stroke who received inpatient or outpatient rehabilitation, with a median age of 63.0 years (interquartile range, 56.0-70.0 years) with 308 (64.2%) being men. The study was completed by 439 patients (91.8%). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patient activation was measured with the Patient Activation Measure (PAM) (score 0-100, 4 levels, where a higher score and level denotes more patient activation). The PAM was measured at the start of the rehabilitation (baseline) and 3 and 6 months thereafter and was analyzed using the multivariate mixed model analysis. RESULTS: At baseline, the mean PAM score was 60.2±14.3, with the number of patients in PAM levels 1, 2, 3, and 4 being 76 (17.8%), 85 (19.9%), 177 (41.4%), and 90 (21.0%), respectively. The multivariate mixed-model analysis demonstrated that the PAM score increased over time (baseline 60.2±14.3 vs 3 months 60.7±14.8 vs 6 months 61.9±18.0; P.007). Between baseline and 6 months, 122 patients (41.4%) remained at the same PAM level, 105 patients (35.6%) increased, and 68 patients (23.1%) decreased. At all time points, >35% of patients were in level 1 or 2. CONCLUSIONS: PAM scores increased slightly over time from the start of rehabilitation up to the 6-month follow-up. However, more than one-third of patients remained at low levels (ie, level 1 and 2) of patient activation, which indicates that specific interventions during rehabilitation to increase patient activation might be of value.

Are There Differences in Long-Term Functioning and Recovery Between Hemorrhagic and Ischemic Stroke Patients Receiving Rehabilitation?

OBJECTIVE: Previous research suggested better recovery in functioning of patients with hemorrhagic as compared to ischemic stroke. Now that more effective acute treatment for ischemic stroke, i.e. thrombolysis and thrombectomy, has become available, this observational cohort study aimed to examine if current rehabilitation outcomes differ between patients with hemorrhagic and ischemic stroke. MATERIALS AND METHODS: The Barthel Index, 4 domains of the Stroke Impact Scale (SIS) and the EuroQol 5Dimensions were completed in all consecutive patients who received stroke rehabilitation at start of rehabilitation and during follow-up (for Barthel Index at discharge, SIS and EuroQol 5D after three and six months). Outcomes and recovery (i.e. change of scores between baseline and last follow-up) were compared between patients with hemorrhagic stroke and ischemic stroke (total and categorized by initial hospital treatment) using the Kruskall Wallis test. In addition, recovery was compared between ischemic and hemorrhagic stroke in multiple regression analyses with bootstrapping. RESULTS: Baseline functioning did not differ between 117 patients with a hemorrhagic stroke, 118 ischemic stroke patient treated with reperfusion therapy, and 125 ischemic stroke patients without reperfusion therapy. There were no differences in functioning at follow-up nor in recovery concerning the Barthel Index, SIS domains 'mobility', 'communication', 'memory and thinking' and 'mood and emotions', and EuroQoL 5D between the three categories. CONCLUSIONS: In a rehabilitation population the recovery and functioning at three or six months did not differ between ischemic stroke patients and hemorrhagic stroke patients, regardless of the hospital treatment they had received.

Reliability parameters of the Timed 25-Foot-Walk (T25FW) in patients with Multiple Sclerosis: Lower walking speed is associated with greater Smallest Detectable Change.

BACKGROUND: Reliability parameters of clinical measures should be sufficient in order to adequately monitor disease course and evaluate treatment in patients with Multiple Sclerosis (MS). The aim of this study was to assess the reliability of the Timed 25-Foot-Walk (T25FW) in patients with MS. METHODS: MS patients performed the T25FW twice with approximately one year in between. After the second measurement, they answered an anchor question using a three-point Likert scale. Taking the non-normal distribution of the T25FW into account, intraclass correlation coefficient (ICCagreement), standard error of the mean (SEMagreement) and smallest detectable change (SDC) were computed. RESULTS: 118 MS patients (76.3 % females, mean age 48.2 years) were included. Of these patients, 73 reported no change on the anchor question. They completed the T25FW at baseline in 4.7s (IQR 4.3-5.4s, n = 72) and at follow-up in 4.9s (IQR 4.3-5.9s, n = 73). The ICCagreement was 0.895, the SEMagreement was 0.037. The SDC was higher for higher mean T25FW and can be computed for each mean T25FW by 0.23*mean T25FW. CONCLUSION: Overall, in patients with MS, the T25FW has a sufficient reliability as measured with the ICC, however the SDC of the T25FW increased when patients perform worse on the T25FW (i.e. have a lower walking speed). Because this test is often used in MS patients with limited walking ability, these findings are important to keep in mind when interpreting the re-test scores of the T25FW.

The psychometric properties of the PROMIS® profile CAT in people with stroke.

BACKGROUND: The Patient-Reported Outcomes Measurement Information System® (PROMIS) Profile Computer Adaptive Testing (CAT) consists of seven CATs and one single item measuring most relevant aspects of health-related quality of life (HRQoL). The aim of our study was to determine construct validity and floor and ceiling effects of the PROMIS Profile CAT in Dutch people with stroke. METHODS: People with stroke receiving rehabilitation completed the PROMIS Profile CAT and the EuroQol-5 dimensions (EQ5D). Construct validity was evaluated with hypotheses testing based on expected correlations between the profile domains and the domains of the EQ5D. The proportion of participants with the lowest and highest scores were calculated for each profile domain to assess floor and ceiling effects. RESULTS: 160 participants were included (median age 61 years, 41.9% female). For the PROMIS Profile domains Physical Function, Anxiety, Depression, Sleep Disturbance, Pain Interference, and Pain Intensity > 75% of the results met our hypotheses. For Fatigue and Ability to Participate in Social Roles and Activities only 60% of hypotheses were met. No floor or ceiling effects were found, with the exception of a floor effect for Pain Intensity which probably indicates that many participants had no pain. CONCLUSION: Most domains of the PROMIS Profile CAT showed sufficient construct validity and no problematic floor or ceiling effects in people with stroke. These CATs and the single item Pain Intensity can be used to efficiently measure HRQoL in people with stroke.

The trajectory of pain and pain intensity in the upper extremity after stroke over time: a prospective study in a rehabilitation population.

PURPOSE: To assess the presence of upper extremity pain after stroke over time and the course of its intensity in patients with persistent pain. MATERIALS AND METHODS: Patients with stroke completed a question on the presence of upper extremity pain (yes/no) and rated its intensity with a visual analogue scale (0-10) at 3, 18, and 30 months after starting multidisciplinary rehabilitation. The presence of upper extremity pain and its intensity over time were analysed with Generalized Estimating Equations models and Linear Mixed Models, respectively. RESULTS: 678 patients were included. The proportions of patients reporting upper extremity pain were 41.8, 36.0, and 32.7% at 3, 18, and 30 months, respectively, with the decline in proportions reaching statistical significance (odds ratio 0.82, 95% confidence interval 0.74-0.92, p < 0.001). At all time points, in those reporting pain the median intensity was 5.0 (interquartile ranges (IQR) 4.0-7.0 at 3 and 3.0-6.0 at 18 and 30 months). In the 73 patients with persistent pain, there was no significant change in intensity over time. CONCLUSIONS: The proportion of patients reporting upper extremity pain after stroke was considerable, despite a significant decrease in 2.5 years. In patients reporting persistent pain, the intensity did not change over time.IMPLICATIONS FOR REHABILITATIONAbout one-third of patients with stroke reported upper extremity pain at 30 months after starting rehabilitation.In patients with stroke who reported persistent upper extremity pain, there was no significant change in pain intensity over time.There is room for improvement of diagnosis and treatment of upper extremity pain in patients with stroke.

Stroke survivors' long-term participation in paid employment.

BACKGROUND: Knowledge on long-term participation is scarce for patients with paid employment at the time of stroke. OBJECTIVE: Describe the characteristics and the course of participation (paid employment and overall participation) in patients who did and did not remain in paid employment. METHODS: Patients with paid employment at the time of stroke completed questions on work up to 30 months after starting rehabilitation, and the Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-P, Frequency, Restrictions and Satisfaction scales) up to 24 months. Baseline characteristics of patients with and without paid employment at 30 months were compared using Fisher's Exact Tests and Mann-Whitney U Tests. USER-P scores over time were analysed using Linear Mixed Models. RESULTS: Of the 170 included patients (median age 54.2 interquartile range 11.2 years; 40% women) 50.6% reported paid employment at 30 months. Those returning to work reported at baseline more working hours, better quality of life and communication, were more often self-employed and in an office job. The USER-P scores did not change statistically significantly over time. CONCLUSION: About half of the stroke patients remained in paid employment. Optimizing interventions for returning to work and achieving meaningful participation outside of employment seem desirable.

Functioning and recovery during stroke rehabilitation: a comparison between pre-stroke frail and non-frail patients.

PURPOSE: Pre-stroke frailty in older adults is associated with adverse outcomes after stroke in community-based and hospital-based populations. The aim of our study was to investigate the prevalence of pre-stroke frailty among older stroke survivors receiving medical specialistic rehabilitation and its association with outcomes and recovery. METHODS: Pre-stroke frailty was measured by the Groningen Frailty Indicator (GFI, score ≥ 4 indicates frailty) in patients ≥ 65 years receiving stroke medical specialistic rehabilitation. Baseline, follow-up and change (i.e. recovery) scores of the Barthel index (BI), Stroke Impact Scale (SIS) 'mobility', 'communication', and 'memory and thinking', Hospital Anxiety and Depression Scale (HADS) and the EuroQoL-5 dimensions (EQ-5D) were compared between frail and non-frail patients with a multivariable regression model adjusting for confounders. RESULTS: Of 322 included patients (34.2% females, median age 70 years), 43 (13.4%) patients reported pre-stroke frailty. There were no differences in BI or in destination of discharge between pre-stroke frail and non-frail stroke survivors receiving inpatient rehabilitation. However, pre-stroke frailty was associated with worse follow-up scores for all other measures. Recovery in pre-stroke frail patients was less favorable compared to non-frail patients for SIS mobility, HADS subscales and EQ-5D index and visual analogue scale. CONCLUSION: Pre-stroke frailty was present in a minority of older stroke survivors receiving medical specialistic rehabilitation. BI and destination of discharge did not differ. Nevertheless, pre-stroke frailty was associated with worse functioning at follow-up for most measures of health status and with smaller improvements in mobility, mood and quality of life.

Translation and cross-cultural adaptation of the ICHOM standard set for stroke: the Dutch version.

INTRODUCTION: The International Consortium for Health Outcomes Measurement (ICHOM) developed a standard set of patient-centered outcome measures for use in stroke patients. In addition to the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health, it is comprised of 25 questions that are not part of a specific questionnaire. This study aimed to translate these 25 single questions into Dutch. METHODS: Two native Dutch-speaking translators independently translated the original ICHOM questions into Dutch. A consensus translation was made by these translators and a third person. This translation was subsequently translated back to English independently by two native English-speaking translators. Afterwards a pre-final version was made by consensus of a committee. After field-testing among 30 stroke patients, a final version was made. RESULTS: The forward and backward translations led to eight cross-cultural adaptations. Based on the interviews with stroke patients, 12 questions were changed to enhance comprehensibility leading to a final Dutch translation of the 25 single questions. CONCLUSIONS: A Dutch translation of the 25 single questions of the ICHOM Standard Set for Stroke was developed. Now a complete ICHOM Standard Set for Stroke can be used in Dutch populations allowing comparison and improvement of stroke care.

A frequent variant in the ABCA1 gene is associated with increased coronary heart disease risk and a better response to statin treatment in familial hypercholesterolemia patients.

AIMS: Statins are essential for the reduction of risk of coronary heart disease (CHD) in familial hypercholesterolemia (FH). One of many genes influenced by statin treatment is the ATP-binding cassette transporter A1 (ABCA1) gene, which plays an important role in metabolism of high-density lipoprotein (HDL). The present aim was to test if the ABCA1 C69T polymorphism influences CHD risk and response to statin treatment. METHODS AND RESULTS: In a large cohort of 1686 FH patients without a history of CHD before 1 January 1990, we analysed statin-ABCA1 C69T polymorphism interaction by comparing treated and untreated patients. We used a Cox proportional hazard model adjusted for sex, birth year, and smoking. In analyses restricted to untreated patients, the TT genotype was associated with 1.7 times higher CHD risk than the CC genotype (hazard ratio (HR) =1.65, 95% confidence interval (95% CI): 1.08-2.53; P = 0.02). Conversely, in statin-treated FH patients, CHD risk in TT individuals was not increased (HR: 0.65, 95% CI: 0.35-1.24; P = 0.2). Formal testing confirmed this interaction (P = 0.03). HDL-cholesterol levels were significantly more raised in statin-treated patients with the TT than with the CC genotype (two-way ANOVA, P = 0.045). CONCLUSION: In untreated FH patients, the TT genotype of the ABCA1 C69T polymorphism was associated with increased CHD risk. However, in statin-treated patients, CHD risk was no longer significantly different between genotypes, at least partially explained by a higher rise in HDL-cholesterol levels during statin treatment in TT individuals.

Determining the minimal important change of the 6-minute walking test in Multiple Sclerosis patients using a predictive modelling anchor-based method.

BACKGROUND: The minimal important change (MIC) of the 6-minute walk test (6MWT) is not clear for patients with Multiple Sclerosis (MS), hampering treatment evaluation. The aim of our study was therefore to determine the MIC of the 6MWT in MS patients. METHODS: MS patients did the 6MWT using the instruction to walk at comfortable speed twice with approximately one year in between. After the second 6MWT they completed 3-point anchor question. The MICadjusted with a 95% confidence interval (CI) was calculated with the predictive modelling method with bootstrapping. RESULTS: 118 MS patients (mean age 48.2 years, 23.7% men) were included between September 2018 and October 2019. Mean 6MWT distance was 468 ± 112 m at baseline and 469 ± 115 m one year later. Twenty-three (19.5%) patients answered their walking distance improved, 43 (36.4%) answered it worsened. A MICadjusted for improvement of 19.7 m (95%CI 9.8-30.9 m) was found, and for deterioration of 7.2 m (95%CI -3.3-18.2 m). CONCLUSIONS: Using the most sophisticated statistical method, the MICadjusted of the 6MWT in MS patients was 19.7 m for improvement, and 7.2 m for deterioration. This knowledge allows physiotherapists and physicians to evaluate if their treatment has led to a meaningful improvement for their MS patients or if walking of their patients has deteriorated.

Use of Patient-Reported Outcomes Measurement Information System Measures in Clinical Research in Patients With Stroke: A Systematic Literature Review.

Objective: To systematically describe the use and outcomes of Patient-Reported Outcomes Measurement Information System (PROMIS) measures in clinical studies in populations with stroke. Data Sources: A systematic search on the use of PROMIS measures in clinical stroke studies in 9 electronic databases. Study Selection: Studies had to be original, reporting on outcome data using PROMIS measures in populations with stroke (ischemic and/or hemorrhagic), from January 1st, 2007. Initially, 174 unique studies met the inclusion criteria. In 2 steps, titles, abstracts and full-text articles were screened for eligibility (2 authors independently). Data Extraction: From the selected articles, study characteristics, type of PROMIS measures, and its outcomes were extracted by 2 authors independently. The authors discussed their views to achieve consensus. A third author was consulted if necessary. Data Synthesis: In total, 27 studies (24,366 patients) were included, predominantly from the United States (22); most study populations were hospital-based (20); the number of patients ranged from 30-3283. In general, patients had no or mild symptoms (median modified Rankin scale 1). Two different generic PROMIS measures were reported (PROMIS Global Health, PROMIS 29) and 9 PROMIS measures focusing on specific domains (sleep, pain, physical functioning, self-efficacy, satisfaction with social roles, depression, anxiety, cognition, fatigue). These match the International Classification of Functioning, Disability, and Health (ICF) domains mentioned in the Core Set for Stroke. The measures were administered 1-55 months after stroke. Outcome data are provided. Pooling of data was not achieved because of a large variety in study characteristics (inclusion criteria, follow-up moments, data processing). Conclusions: The PROMIS measures in this review could be relevant from a patient's perspective, covering ICF core set domains for patients with stroke. The large variety in study characteristics hampers comparisons across populations. Many different outcome measures are used to report results of stroke rehabilitation studies.

The risk of tendon xanthomas in familial hypercholesterolaemia is influenced by variation in genes of the reverse cholesterol transport pathway and the low-density lipoprotein oxidation pathway.

AIMS: The presence of tendon xanthomas is a marker of high risk of cardiovascular disease (CVD) among patients with familial hypercholesterolaemia (FH). Therefore, xanthomas and atherosclerosis may result from the same pathophysiological mechanisms. Reverse cholesterol transport (RCT) and low-density lipoprotein (LDL) oxidation are pathophysiological pathways of atherosclerosis, and it is well established that genetic variation in these pathways influences CVD risk. We therefore determined whether genetic variation in these pathways is also associated with the occurrence of tendon xanthomas in FH patients. METHODS AND RESULTS: Four genetic variants in each pathway were genotyped in 1208 FH patients. We constructed a gene-load score for both pathways. The odds of xanthomas increased with the number of the risk alleles in the RCT pathway (OR 1.21, 95% CI 1.08-1.36, P(trend) = 0.0014). Similarly, higher numbers of risk alleles in the LDL oxidation pathway were associated with the presence of xanthomas (OR 1.24, 95% CI 1.08-1.41, P(trend) = 0.0015). CONCLUSION: The presence of tendon xanthomas in FH patients is associated with genetic variation in the RCT and LDL oxidation pathways. These results support the hypothesis that xanthomas and atherosclerosis share pathophysiological mechanisms.

Aging With Cerebral Palsy: A Photovoice Study Into Citizenship.

Background: Adults with cerebral palsy (CP) may experience an increasing impact of their disability on daily life and this may interfere with their citizenship. Citizenship is a layered construct. Next to formal and theoretical significations, and civil rights acts such as the UN Convention on the Rights for Persons with Disabilities (CRPD), the meaning of citizenship is formed by the person themselves. The present study aimed to gain insight into what citizenship means for adults with CP 40 years or older and what is needed to support and pursue their citizenship to improve person-centered rehabilitation which can facilitate this process. Methods: Adults with CP (>40 years) without intellectual disability were recruited from medical records of a large rehabilitation center to participate in a qualitative study using the photovoice method. Participants were asked to take photos of objects or life situations that constituted citizenship for them; these photos were then the prompts for the semi-structured interviews that were held face-to-face at their homes. Background and clinical characteristics were gathered using a short face-to-face questionnaire. Data were analyzed through inductive thematic analysis. Results: Nineteen adults participated [mean age (SD) 57.8 (9.4) years (range 44-79), six men]. From the analysis four themes emerged: (a) Meanings of citizenship; (b) Citizenship: Facilitator and barriers; (c) Paradoxes of support and participation; and (d) Future. Furthermore, next to the ability to participate in society without restrictions, sense of belonging was reported to be an important aspect of "meanings of citizenship." The physiotherapist was perceived as an important health professional to maintain physical activity and deal with the impact of aging with CP on daily activities. Complex healthcare and support services regulations and aging affected citizenship negatively. Conclusion: Middle-aged and older adults with CP view citizenship as the ability to participate and belong in society. To optimize their citizenship the challenges and individual needs must be seen and supported by person-centered rehabilitation and support services. Simplification of complex healthcare and services regulations can further improve citizenship.

Replication study of 10 genetic polymorphisms associated with coronary heart disease in a specific high-risk population with familial hypercholesterolemia.

AIMS: Recent large association studies have revealed associations between genetic polymorphisms and myocardial infarction and coronary heart disease (CHD). We performed a replication study of 10 polymorphisms and CHD in a population with familial hypercholesterolemia (FH), individuals at extreme risk of CHD. METHODS AND RESULTS: We genotyped 10 polymorphisms in 2145 FH patients and studied the association between these polymorphisms and CHD in Cox proportional hazards models. We confirmed the associations between four polymorphisms and CHD, the rs1151640 polymorphism in the olfactory receptor family 13 subfamily G member 1 (OR13G1) gene (HR 1.14, 95% CI 1.01-1.28, P = 0.03), the rs11881940 polymorphism in the heterogeneous nuclear ribonucleoprotein U-like 1 (HNRPUL1) gene (HR 1.27, 95% CI 1.07-1.51, P = 0.007), the rs3746731 polymorphism in the complement component 1 q subcomponent receptor 1 (CD93) gene (HR 1.26, 95% CI 1.06-1.49, P = 0.01), and the rs10757274 polymorphism near the cyclin-dependent kinase N2A and N2B (CDKN2A and CDKN2B) genes (HR 1.39, 95% CI 1.15-1.69, P < 0.001). CONCLUSION: We confirmed previously found associations between four polymorphisms and CHD, but refuted associations for six other polymorphisms in our large FH population. These findings stress the importance of replication before genetic information can be implemented in the prediction of CHD.

Depression is an independent determinant of life satisfaction early after stroke.

OBJECTIVE: Life satisfaction is reduced in stroke patients. However, as a rule, rehabilitation goals are not aimed at life satisfaction, but at activities and participation. In order to optimize life satisfaction in stroke patients, rehabilitation should take into account the determinants of life satisfaction. The aim of this study was therefore to determine what factors are independent determinants of life satisfaction in a large group of patients early after stroke. METHODS: Stroke-surviving patients were examined by a specialized nurse 6 weeks after discharge from hospital or rehabilitation setting. A standardized history and several screening lists, including the Lisat-9, were completed. Step-wise regression was used to identify independent determinants of life satisfaction. RESULTS: A total of 284 stroke-surviving patients were included in the study. Of these, 117 answered all of the Lisat-9 questions. Most patients (66.5%) rated their life as a whole as "satisfying" or "very satisfying". More depressive symptoms were independently associated with lower life satisfaction (p < 0.001). CONCLUSION: Most stroke-surviving patients are satisfied with their life early after a stroke. The score on the Hospital Anxiety and Depression Scale depression items is independently associated with life satisfaction. Physicians should therefore pay close attention to the mood of these patients.

Identifying genetic risk variants for coronary heart disease in familial hypercholesterolemia: an extreme genetics approach.

Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a disorder characterized by coronary heart disease (CHD) at young age. We aimed to apply an extreme sampling method to enhance the statistical power to identify novel genetic risk variants for CHD in individuals with FH. We selected cases and controls with an extreme contrast in CHD risk from 17,000 FH patients from the Netherlands, whose functional LDLR mutation was unequivocally established. The genome-wide association (GWA) study was performed on 249 very young FH cases with CHD and 217 old FH controls without CHD (above 65 years for males and 70 years of age for females) using the Illumina HumanHap550K chip. In the next stage, two independent samples (one from the Netherlands and one from Italy, Norway, Spain, and the United Kingdom) of FH patients were used as replication samples. In the initial GWA analysis, we identified 29 independent single nucleotide polymorphisms (SNPs) with suggestive associations with premature CHD (P<1 × 10(-4)). We examined the association of these SNPs with CHD risk in the replication samples. After Bonferroni correction, none of the SNPs either replicated or reached genome-wide significance after combining the discovery and replication samples. Therefore, we conclude that the genetics of CHD risk in FH is complex and even applying an 'extreme genetics' approach we did not identify new genetic risk variants. Most likely, this method is not as effective in leveraging effect size as anticipated, and may, therefore, not lead to significant gains in statistical power.

Anxiety and low life satisfaction associate with high caregiver strain early after stroke.

OBJECTIVE: Caregivers play an important role in the well-being of stroke patients, and are known to experience considerable strain 3 months or more after patient discharge. The aim of this study was to determine the prevalence and determinants of caregiver strain early after discharge. METHODS: Six weeks after discharge from the hospital or rehabilitation setting stroke-surviving patients and their caregivers were seen by a specialized nurse. Several screening lists, including the Caregiver Strain Index (CSI), were completed. Step-wise logistic regression was used to analyse which determinants independently contribute to caregiver strain. RESULTS: A total of 284 stroke-surviving patients were included in the study. Of the 179 caregivers who completed the CSI, 23 (12.8%) experienced considerable strain. A higher level of anxiety symptoms and lower life satisfaction in patients are independently associated with higher caregiver strain (p = 0.000007 and p = 0.0031, respectively). CONCLUSION: High strain is experienced by 12.8% of caregivers shortly after discharge of a stroke-surviving patient. More anxiety symptoms and lower life satisfaction in patients are independently associated with a higher level of strain in caregivers. Treating patient anxiety at an early stage might therefore lead to a decrease in long-term caregiver strain.