SLC6A8 creatine transporter deficiency can be detected by plasma creatine and creatinine concentrations.

Creatine transporter deficiency has been described with normal or uninformative levels of creatine and creatinine in plasma, while urine has been the preferred specimen type for biochemical diagnosis. We report a cohort of untreated patients with creatine transporter deficiency and abnormal plasma creatine panel results, characterized mainly by markedly decreased plasma creatinine. We conclude that plasma should be considered a viable specimen type for the biochemical diagnosis of this disorder, and abnormal results should be followed up with further confirmatory testing.

Interventions for Behaviour Change and Self-Management of Risk in Stroke Secondary Prevention: An Overview of Reviews.

INTRODUCTION: Optimised secondary prevention strategies that include lifestyle change are recommended after stroke. While multiple systematic reviews (SRs) address behaviour change interventions, intervention definitions, and associated outcomes differ between reviews. This overview of reviews addresses the pressing need to synthesise high-level evidence for lifestyle-based behavioural and/or self-management interventions to reduce risk in stroke secondary prevention in a structured, consistent way. METHODS: Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria were applied to meta-analyses, demonstrating statistically significant effect sizes to establish the certainty of existing evidence. Electronic databases MEDLINE, Embase, Epistemonikos, and the Cochrane Library of Systematic Reviews were systematically searched, current to March 2023. RESULTS: Fifteen SRs were identified following screening, with moderate overlap of primary studies demonstrated (5.84% degree of corrected covered area). Interventions identified could be broadly categorised as multimodal; behavioural change; self-management; psychological talk therapies, albeit with overlap between some theoretical domains. Seventy-two meta-analyses addressing twenty-one preventive outcomes of interest were reported. Best-evidence synthesis identifies that for primary outcomes of mortality and future cardiovascular events post-stroke, moderate certainty GRADE evidence supports multimodal interventions to reduce cardiac events, with no available evidence for outcomes of mortality (all-cause or cardiovascular) or recurrent stroke events. For secondary outcomes addressing risk-reducing behaviours, best-evidence synthesis identifies moderate certainty GRADE evidence for multimodal lifestyle-based interventions to increase physical activity participation, and low certainty GRADE evidence for behavioural change interventions to improve healthy eating post-stroke. Similarly, low certainty GRADE evidence supports self-management interventions to improve preventive medication adherence. For mood self-management post-stroke, moderate GRADE evidence supports psychological therapies for remission and/or reduction of depression and low/very low certainty GRADE evidence for reduction of psychological distress and anxiety. Best-evidence for outcomes addressing proxy physiological measures identified low GRADE evidence supporting multimodal interventions to improve blood pressure, waist circumference, and LDL cholesterol. CONCLUSION: Effective strategies to redress risk-related health behaviours are required in stroke survivors to complement current pharmacological secondary prevention. Inclusion of multimodal interventions and psychological talk therapies in evidence-based stroke secondary prevention programmes is warranted given the moderate GRADE of evidence that supports their role in risk reduction. Given the overlap in primary studies across reviews, often with overlapping theoretical domains between broad intervention categories, further research is required to identify optimal intervention behavioural change theories and techniques employed in behavioural/self-management interventions.

MT-ATP6 mitochondrial disease identified by newborn screening reveals a distinct biochemical phenotype.

Although decreased citrulline is used as a newborn screening (NBS) marker to identify proximal urea cycle disorders (UCDs), it is also a feature of some mitochondrial diseases, including MT-ATP6 mitochondrial disease. Here we describe biochemical and clinical features of 11 children born to eight mothers from seven separate families who were identified with low citrulline by NBS (range 3-5 µM; screening cutoff >5) and ultimately diagnosed with MT-ATP6 mitochondrial disease. Follow-up testing revealed a pattern of hypocitrullinemia together with elevated propionyl-(C3) and 3-hydroxyisovaleryl-(C5-OH) acylcarnitines, and a homoplasmic pathogenic variant in MT-ATP6 in all cases. Single and multivariate analysis of NBS data from the 11 cases using Collaborative Laboratory Integrated Reports (CLIR; https://clir.mayo.edu) demonstrated citrulline <1st percentile, C3 > 50th percentile, and C5-OH >90th percentile when compared with reference data, as well as unequivocal separation from proximal UCD cases and false-positive low citrulline cases using dual scatter plots. Five of the eight mothers were symptomatic at the time of their child(ren)'s diagnosis, and all mothers and maternal grandmothers evaluated molecularly and biochemically had a homoplasmic pathogenic variant in MT-ATP6, low citrulline, elevated C3, and/or elevated C5-OH. All molecularly confirmed individuals (n = 17) with either no symptoms (n = 12), migraines (n = 1), or a neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) phenotype (n = 3) were found to have an A or U mitochondrial haplogroup, while one child with infantile-lethal Leigh syndrome had a B haplogroup.

Proximal urea cycle defects are challenging to detect with newborn screening: Results of a prospective pilot study using post-analytical tools.

The purpose of this pilot project was to evaluate the efficacy of the Collaborative Integrated Laboratory Reports (CLIR) postanalytical tools from Mayo Clinic for detection of newborns with proximal urea cycle disorders (PUCD) in the Georgia newborn screening program that uses the underivatized Neobase2 kit (Perkin Elmer). We evaluated 138,560 newborn screening (NBS) samples (between 125,000 and 130,000 children) and used the CLIR result interpretation guidelines to stratify results. Children at higher risk of having a PUCD received follow-up services including confirmatory lab testing (ammonia, plasma amino acids, urine orotic acid) or a repeat NBS sample. We made multiple adjustments to our CLIR PUCD tool and to our follow-up algorithms in order to reduce false positives. Regardless, a high number of NBS samples resulted with false positives in part due to the glutamine peak also containing lysine. No children were diagnosed with a PUCD during our study period, and the Emory Genetics Metabolic Center is unaware of any children diagnosed outside of the NBS system during that time. Based on our experience, PUCD is not suitable for statewide NBS using Neobase2 and CLIR. Other methodologies that can separate glutamine from other amino acids may have better performance.

Systematic Review of Pooling Sputum as an Efficient Method for Xpert MTB/RIF Tuberculosis Testing during the COVID-19 Pandemic.

GeneXpert-based testing with Xpert MTB/RIF or Ultra assays is essential for tuberculosis diagnosis. However, testing may be affected by cartridge and staff shortages. More efficient testing strategies could help, especially during the coronavirus disease pandemic. We searched the literature to systematically review whether GeneXpert-based testing of pooled sputum samples achieves sensitivity and specificity similar to testing individual samples; this method could potentially save time and preserve the limited supply of cartridges. From 6 publications, we found 2-sample pools using Xpert MTB/RIF had 87.5% and 96.0% sensitivity (average sensitivity 94%; 95% CI 89.0%-98.0%) (2 studies). Four-sample pools averaged 91% sensitivity with Xpert MTB/RIF (2 studies) and 98% with Ultra (2 studies); combining >4 samples resulted in lower sensitivity. Two studies reported that pooling achieved 99%-100% specificity and 27%-31% in cartridge savings. Our results show that pooling may improve efficiency of GeneXpert-based testing.

Increased parental anxiety and a benign clinical course: Infants identified with short-chain acyl-CoA dehydrogenase deficiency and isobutyryl-CoA dehydrogenase deficiency through newborn screening in Georgia.

The long-term consequences and need for therapy in children with short-chain acyl-CoA dehydrogenase deficiency (SCADD) or isobutyryl-CoA dehydrogenase deficiency (IBDD) identified via newborn screening (NBS) remains controversial. Initial clinical descriptions were severe; however, while most cases identified through NBS have remained asymptomatic, clinical concerns have been raised in these populations. It is not clear whether these children are asymptomatic because of the success of NBS, or because the normal clinical course of these disorders is relatively benign. To evaluate these possibilities in our program, we evaluated the clinical outcomes of children with SCADD or IBDD identified by the Georgia NBS compared to the health status of a healthy age-matched control group. We also assessed parental anxiety during a phone interview both subjectively and objectively using the Pediatric Inventory for Parents (PIP), a validated measure of illness-related parental stress. The general health of 52 SCADD and nine IBDD cases from 2007 to 2016 were compared to the general health of unaffected control children obtained through the Centers for Disease Control and Prevention (CDC) parent listserv. We also collected statements from parents who participated in a phone survey regarding events they experienced during and after their diagnostic process. Overall, the children with SCADD and IBDD had no major health problems. There was no significant difference in cognitive development (p = .207). We identified a slightly higher incidence of reported neonatal hypoglycemia in the SCADD group; two of these occurred in the context of maternal diabetes. All interviewed parents reported extreme anxiety during the diagnostic period and current feelings of uncertainty about their child's future. PIP scores for all six caregivers who responded to that portion of the survey were consistent with some degree of parental stress. The greatest reported stressor was the unknown long-term impact of the illness. All children with SCADD and IBDD had no significant long-term sequelae. The phone interviews revealed substantial parental anxiety about the identification and follow-up of SCADD and IBDD. Based on our findings, the anxiety parents experience may be unwarranted given that we see no disease-associated morbidity or mortality in these children. Consideration should be given to the removal of these conditions from NBS panels, or if that is not possible, clinicians could educate parents on the benign nature of these diagnoses and release them from follow-up without treatment.

The Impact of Cognitive Impairment on Poststroke Outcomes: A 5-Year Follow-Up.

AIM: To explore the impact of cognitive impairment poststroke on outcomes at 5 years. METHODS: Five-year follow-up of the Action on Secondary Prevention Interventions and Rehabilitation in Stroke (ASPIRE-S) prospective cohort. Two hundred twenty-six ischemic stroke survivors completed Montreal Cognitive Assessments at 6 months poststroke. Outcomes at 5 years included independence in activities of daily living, receipt of informal care, quality of life, and depressive symptoms. Data were analyzed using logistic and linear regression models. Adjusted odds ratios (ORs; 95% confidence interval [CI]) and ß coefficients (95% CI) are reported. RESULTS: One hundred one stroke survivors were followed up at 5 years. Cognitive impairment at 6 months was independently associated with worse quality of life (B [95% CI]: -0.595 [-0.943 to -0.248]), lower levels of independence (B [95% CI]: -3.605 [-5.705 to -1.505]), increased likelihood of receiving informal care (OR [95% CI]: 6.41 [1.50-27.32]), and increased likelihood of depressive symptoms (OR [95% CI]: 4.60 [1.22-17.40]). Conclusion: Cognitive impairment poststroke is associated with a range of worse outcomes. More effective interventions are needed to improve outcomes for this vulnerable group of patients.

Implementation of an acute DVT ambulatory care pathway in a large urban centre: current challenges and future opportunities.

BACKGROUND: Ambulatory management of isolated acute deep venous thrombosis (DVT) is the recommended standard of care in selected populations. However, in practice a significant number of patients continue to be managed as in-patients. OBJECTIVES: In this study we aimed to evaluate acute DVT treatment pathways in our emergency department (ED) in practice and to identify barriers to outpatient management. METHODS: This study was a cross-sectional analysis of prospectively collected data pertaining to consecutive patients presenting to the ED of a large, city center, academic teaching hospital over a 46 week period who were diagnosed with DVT. RESULTS: Implementation of an outpatient care pathway led to the majority of patients presenting with DVT in our institution being treated without hospital admission. Forty percent (31/78) of patients with DVT were treated with a direct oral anticoagulant (DOAC) as an outpatient in line with international best practice guidelines. CONCLUSION: The study provides a clear picture of the clinical profile and management of patients in clinical practice. Due to the lack of resources and supported infrastructure it is difficult to effectively implement outpatient venous thromboembolism (VTE) management to its full potential. Directing resources towards strategies which facilitate outpatient DVT treatment among vulnerable patient groups could represent a means of reducing hospital admissions for DVT in urban centers. Our study highlights the success and clinical limitations of the outpatient treatment model, which should become standard as part of wider VTE care.

Moonlighting newborn screening markers: the incidental discovery of a second-tier test for Pompe disease.

PURPOSE: To describe a novel biochemical marker in dried blood spots suitable to improve the specificity of newborn screening for Pompe disease. METHODS: The new marker is a ratio calculated between the creatine/creatinine (Cre/Crn) ratio as the numerator and the activity of acid α-glucosidase (GAA) as the denominator. Using Collaborative Laboratory Integrated Reports (CLIR), the new marker was incorporated in a dual scatter plot that can achieve almost complete segregation between Pompe disease and false-positive cases. RESULTS: The (Cre/Crn)/GAA ratio was measured in residual dried blood spots of five Pompe cases and was found to be elevated (range 4.41-13.26; 99%ile of neonatal controls: 1.10). Verification was by analysis of 39 blinded specimens that included 10 controls, 24 samples with a definitive classification (16 Pompe, 8 false positives), and 5 with genotypes of uncertain significance. The CLIR tool showed 100% concordance of classification for the 24 known cases. Of the remaining five cases, three p.V222M homozygotes, a benign variant, were classified by CLIR as false positives; two with genotypes of unknown significance, one likely informative, were categorized as Pompe disease. CONCLUSION: The CLIR tool inclusive of the new ratio could have prevented at least 12 of 13 (92%) false-positive outcomes.

Urine oligosaccharide screening by MALDI-TOF for the identification of NGLY1 deficiency.

N-glycanase deficiency (NGLY1 deficiency, NGLY1-CDDG), the first autosomal recessive congenital disorder of N-linked deglycosylation (CDDG), is caused by pathogenic variants in NGLY1. The majority of affected individuals have been identified using exome or genome sequencing. To date, no reliable, clinically available biomarkers have been identified. Urine oligosaccharide analysis was included as part of a routine evaluation for possible biomarkers in patients with confirmed NGLY1-CDDG. During the qualitative review of oligosaccharide profiles by an experienced laboratory director an abnormal analyte with a proposed structure of Neu5Ac1Hex1GlcNAc1-Asn was identified in NGLY1-CDDG patient urine samples. The same species has been observed in profiles from individuals affected with aspartylglucosaminuria, although the complete spectra are not identical. Additional studies using tandem mass spectrometry confirmed the analyte's structure. In addition to the known NGLY1-CDDG patients identified by this analysis, a single case was identified in a population referred for clinical testing who subsequently had a diagnosis of NGLY1-CDDG confirmed by molecular testing. Urine oligosaccharide screening by MALDI-TOF MS can identify individuals with NGLY1-CDDG. In addition, this potential biomarker might also be used to monitor the effectiveness of therapeutic options as they become available.

Acute liver failure in neonates with undiagnosed hereditary fructose intolerance due to exposure from widely available infant formulas.

Hereditary fructose intolerance (HFI) is an autosomal recessive disorder caused by aldolase B (ALDOB) deficiency resulting in an inability to metabolize fructose. The toxic accumulation of intermediate fructose-1-phosphate causes multiple metabolic disturbances, including postprandial hypoglycemia, lactic acidosis, electrolyte disturbance, and liver/kidney dysfunction. The clinical presentation varies depending on the age of exposure and the load of fructose. Some common infant formulas contain fructose in various forms, such as sucrose, a disaccharide of fructose and glucose. Exposure to formula containing fructogenic compounds is an important, but often overlooked trigger for severe metabolic disturbances in HFI. Here we report four neonates with undiagnosed HFI, all caused by the common, homozygous mutation c.448G>C (p.A150P) in ALDOB, who developed life-threatening acute liver failure due to fructose-containing formulas. These cases underscore the importance of dietary history and consideration of HFI in cases of neonatal or infantile acute liver failure for prompt diagnosis and treatment of HFI.

Cognitive Impairment, Vulnerability, and Mortality Post Ischemic Stroke: A Five-Year Follow-Up of the Action on Secondary Prevention Interventions and Rehabilitation in Stroke (ASPIRE-S) Cohort.

BACKGROUND: The aim of this study was to examine predictors of mortality in patients 5 years after ischemic stroke, focusing on cognitive impairment, vulnerability, and vascular risk factors assessed at 6 months post stroke. MATERIALS AND METHODS: Patients from the Action on Secondary Prevention Interventions and Rehabilitation in Stroke (ASPIRE-S) cohort were followed up 5 years post ischemic stroke. Vascular risk factors, cognitive impairment, and vulnerability were assessed at 6 months post stroke. Cognitive impairment was assessed using a cutoff score lower than 26 on the Montreal Cognitive Assessment (MoCA). Vulnerability was defined as a score of 3 or higher on the Vulnerable Elders Scale (VES). Mortality and date of death were ascertained using hospital records, death notifications, and contact with general practitioners. Predictors of mortality were explored using multivariate Cox proportional hazards models. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) are presented. RESULTS: Sixty-three of 256 patients (24.6%) assessed at 6 months post stroke had died within 5 years. Cognitive impairment (HR [95% CI]: 2.19 [1.42-3.39]), vulnerability (HR [95% CI]: 5.23 [2.92-9.36]), atrial fibrillation (AF) (HR [95% CI]: 2.31 [1.80-2.96]), and dyslipidemia (HR [95% CI]: 1.90 [1.10-3.27]) were associated with increased risk of 5-year mortality. DISCUSSION: Vulnerability, cognitive impairment, AF, and dyslipidemia at 6 months were associated with increased risks of mortality 5 years post ischemic stroke. CONCLUSION: Identification and management of these risk factors should be emphasized in poststroke care.

PGM3 mutations cause a congenital disorder of glycosylation with severe immunodeficiency and skeletal dysplasia.

Human phosphoglucomutase 3 (PGM3) catalyzes the conversion of N-acetyl-glucosamine (GlcNAc)-6-phosphate into GlcNAc-1-phosphate during the synthesis of uridine diphosphate (UDP)-GlcNAc, a sugar nucleotide critical to multiple glycosylation pathways. We identified three unrelated children with recurrent infections, congenital leukopenia including neutropenia, B and T cell lymphopenia, and progression to bone marrow failure. Whole-exome sequencing demonstrated deleterious mutations in PGM3 in all three subjects, delineating their disease to be due to an unsuspected congenital disorder of glycosylation (CDG). Functional studies of the disease-associated PGM3 variants in E. coli cells demonstrated reduced PGM3 activity for all mutants tested. Two of the three children had skeletal anomalies resembling Desbuquois dysplasia: short stature, brachydactyly, dysmorphic facial features, and intellectual disability. However, these additional features were absent in the third child, showing the clinical variability of the disease. Two children received hematopoietic stem cell transplantation of cord blood and bone marrow from matched related donors; both had successful engraftment and correction of neutropenia and lymphopenia. We define PGM3-CDG as a treatable immunodeficiency, document the power of whole-exome sequencing in gene discoveries for rare disorders, and illustrate the utility of genomic analyses in studying combined and variable phenotypes.

Variants of uncertain significance in newborn screening disorders: implications for large-scale genomic sequencing.

PURPOSE: As exome and genome sequencing using high-throughput sequencing technologies move rapidly into the diagnostic process, laboratories and clinicians need to develop a strategy for dealing with uncertain findings. A commitment must be made to minimize these findings, and all parties may need to make adjustments to their processes. The information required to reclassify these variants is often available but not communicated to all relevant parties. METHODS: To illustrate these issues, we focused on three well-characterized monogenic, metabolic disorders included in newborn screens: classic galactosemia, caused by GALT variants; phenylketonuria, caused by PAH variants; and medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, caused by ACADM variants. In 10 years of clinical molecular testing, we have observed 134 unique GALT variants, 46 of which were variants of uncertain significance (VUS). In PAH, we observed 132 variants, including 17 VUS, and for ACADM, we observed 64 unique variants, of which 33 were uncertain. CONCLUSION: After this review, 17 VUS (37%; 7 in ACADM, 9 in GALT, and 1 in PAH) were reclassified from uncertain (6 to benign or likely benign and 11 to pathogenic or likely pathogenic). We identified common types of missing information that would have helped make a definitive classification and categorized this information by ease and cost to obtain.Genet Med 19 1, 77-82.

'Betwixt and between health and illness' - women's narratives following acute coronary syndrome.

AIMS AND OBJECTIVES: This study investigated experiences of women with a primary diagnosis of ACS (NSTEMI and Unstable Angina) in the 6-8 week period following discharge from hospital. The aim was to report the experience of the mediating impact of a newly-diagnosed disease. BACKGROUND: Cardiovascular disease is the main cause of mortality in women. Treatment modalities have improved health outcomes and survival rates, however, quality of life and ongoing morbidity after discharge is not clearly understood from a gender specific perspective. DESIGN: A naturalistic case study design guided this study. METHODS: Thirty women participated (n = 30); a within-case followed by a cross-case analysis provided meticulous knowledge of each case. Data collection included participant diaries and face to face interviews. Data were analysed using modified analytic induction which allowed the emergence of theoretical insights. The theoretical concepts, liminality and transitioning were used to inform the analysis. Within-methods triangulation captured the depth and breadth of the women's experiences. RESULTS: The data provide an insight into women's experiences following ACS and highlight a need for support structures and services after discharge. Many women reported a period of disrupted normality following discharge from hospital. While a number of women had transitioned towards recovery, many remained in a liminal space 'betwixt and between' health and illness. Cardiac rehabilitation was reported as a positive experience for those who were attending. CONCLUSIONS: The findings provide a platform for a wider discourse on the needs of women with ACS in the immediate period after discharge from hospital. Women may benefit from gender-specific, appropriately timed, and targeted interventions to facilitate recovery and adaptation to living with CHD. RELEVANCE TO CLINICAL PRACTICE: It is essential that secondary prevention services are modelled and tailored to meet the needs of women and evaluated appropriately to ensure positive outcomes. Nursing could have a key role to play in managing and providing this support.

Access to Rehabilitation at Six Months Post Stroke: A Profile from the Action on Secondary Prevention Interventions and Rehabilitation in Stroke (ASPIRE-S) Study.

BACKGROUND AND PURPOSE: Stroke is the third leading cause of death and disability. Few studies have assessed the profile and adequacy of access to rehabilitation services after ischaemic stroke both in the inpatient and community setting. The objectives of the Action on Secondary Prevention Interventions and Rehabilitation in Stroke (ASPIRE-S) study were to assess the disability and rehabilitation profile, adherence with rehabilitation recommendations and needs of patients 6 months following hospital admission for stroke. METHODS: A rehabilitation prescription was completed before hospital discharge for each participant, and adherence to this prescription was assessed at 6 months to determine whether patients received their recommended rehabilitation needs. RESULTS: Two hundred and fifty six patients were recruited to ASPIRE-S. The average age was 69 (SD 12.8). A majority (n = 221, 86%) were referred to the hospital multidisciplinary team, 59% (n = 132) were referred to all services (physiotherapy (PT), occupational therapy (OT), speech and language therapy (SLT)). Fifty-four percent (n = 119) of patients (seen by the multidisciplinary team) were referred for further rehabilitation in the community on discharge. Of these 119 patients, 112 (95%) recalled receiving community rehabilitation services. However, while most (68%) patients were referred for several disciplines (PT, OT, SLT), the most commonly recalled therapy (55%) was from a single discipline. The most commonly recommended frequency of therapy required was on a weekly basis. Sixty-one patients (51%) reported a delay in services, with some still awaiting services at 6 months. CONCLUSION: Results from this prospective study revealed that a significant number of patients (57%) did not receive the therapy recommended on discharge. Future initiatives should include the development of policies, which support more effective, equitable multidisciplinary rehabilitation for stroke patients in the community.

Continuous age- and sex-adjusted reference intervals of urinary markers for cerebral creatine deficiency syndromes: a novel approach to the definition of reference intervals.

BACKGROUND: Urinary concentrations of creatine and guanidinoacetic acid divided by creatinine are informative markers for cerebral creatine deficiency syndromes (CDSs). The renal excretion of these substances varies substantially with age and sex, challenging the sensitivity and specificity of postanalytical interpretation. METHODS: Results from 155 patients with CDS and 12 507 reference individuals were contributed by 5 diagnostic laboratories. They were binned into 104 adjacent age intervals and renormalized with Box-Cox transforms (Ξ). Estimates for central tendency (µ) and dispersion (σ) of Ξ were obtained for each bin. Polynomial regression analysis was used to establish the age dependence of both µ[log(age)] and σ[log(age)]. The regression residuals were then calculated as z-scores = {Ξ - µ[log(age)]}/σ[log(age)]. The process was iterated until all z-scores outside Tukey fences ±3.372 were identified and removed. Continuous percentile charts were then calculated and plotted by retransformation. RESULTS: Statistically significant and biologically relevant subgroups of z-scores were identified. Significantly higher marker values were seen in females than males, necessitating separate reference intervals in both adolescents and adults. Comparison between our reconstructed reference percentiles and current standard age-matched reference intervals highlights an underlying risk of false-positive and false-negative events at certain ages. CONCLUSIONS: Disease markers depending strongly on covariates such as age and sex require large numbers of reference individuals to establish peripheral percentiles with sufficient precision. This is feasible only through collaborative data sharing and the use of appropriate statistical methods. Broad application of this approach can be implemented through freely available Web-based software.

Cognitive impairment six months after ischaemic stroke: a profile from the ASPIRE-S study.

BACKGROUND: Cognitive impairment commonly occurs in the acute phase post-stroke, but may persist with over half of all stroke survivors experiencing some form of long-term cognitive deficit. Recent evidence suggests that optimising secondary prevention adherence is a critical factor in preventing recurrent stroke and the incidence of stroke-related cognitive impairment and dementia. The aim of this study was to profile cognitive impairment of stroke survivors at six months, and to identify factors associated with cognitive impairment post-stroke, focusing on indicators of adequate secondary prevention and psychological function. METHODS: Participants were assessed at six months following an ischaemic stroke as part of the Action on Secondary Prevention Interventions and Rehabilitation in Stroke study (ASPIRE-S), which examined the secondary preventive and rehabilitative profile of patients in the community post-stroke. Cognitive impairment was measured using the Montreal Cognitive Assessment (MoCA). RESULTS: Two-hundred and fifty-six stroke patients were assessed at six months. Over half of the sample (56.6%) were found to have cognitive impairment, with significant associations between cognitive impairment and female sex (odds ratio (OR) = 1.6, 95% CI 1.01-2.57) and history of cerebrovascular disease (OR = 2.22, 95% CI 1.38-3.59). Treatment with antihypertensive medications (OR = .65, 95% CI .44-.96) and prescription of anticoagulant therapy (OR = .41, 95% CI .26-.68) were associated with reduced likelihood of cognitive impairment, however increasing number of total prescribed medications was moderately associated with poorer cognitive impairment (OR = 1.12, 95% CI 1.04-1.19). CONCLUSIONS: Findings reveal levels of cognitive impairment at 6 months post-stroke that are concerning. Encouragingly, aspects of secondary prevention were identified that may be protective in reducing the incidence of cognitive impairment post-stroke. Neuropsychological rehabilitation post-stroke is also required as part of stroke rehabilitation models to meet the burden of post-stroke cognitive impairment.

Secondary prevention after ischaemic stroke: the ASPIRE-S study.

BACKGROUND: Survivors of ischaemic stroke (IS) are at high-risk for future vascular events. Comprehensive information on the adequacy of secondary prevention after IS is lacking despite the knowledge that appropriate secondary prevention improves long-term patient outcomes. ASPIRE-S (Action on Secondary Prevention Interventions and Rehabilitation in Stroke) aimed to prospectively assess secondary prevention in patients 6 months following IS. METHODS: Consenting patients admitted with IS to three Dublin hospitals were recruited over 1 year, from October 2011. At 6 months post IS a comprehensive assessment was completed, modelled on the EUROASPIRE protocol for evaluation of the adequacy of secondary prevention in post-discharge cardiac patients. This assessment included measurements of blood pressure, body mass index and fasting lipid and glucose profiles. Secondary preventive medications and smoking status were also documented. RESULTS: Three hundred two patients (58 % male) participated, of whom 256 (85 %) were followed-up at 6 months. Mean age was 69 years (range 22-95). At follow-up, 68 % of patients had a BMI >25 kg/m(2) and 16.4 % were still smoking. Almost two-thirds (63.4 %) had a blood pressure >140/90 and 23 % had low-density-lipoprotein >2.5 mmol/L. 28 % of diabetic patients had HbA1c ≥ 7 %. Ninety seven percent of patients were on anti-platelet and/or anticoagulant therapy. Of those with atrial fibrillation, 82 % were anti-coagulated (mean INR of 2.4). Ninety-five percent were on lipid-lowering therapy and three-quarters were on anti-hypertensive therapy. CONCLUSION: This prospective multi-centre survey of IS patients demonstrated a high prevalence of remaining modifiable risk factors at 6 months post stroke, despite the widespread prescription of secondary preventive medications. There is scope to improve preventive measures after IS (in particular blood pressure) by incorporating evidence-based guidelines into quality assurance cycles in stroke care.